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The influence of delay time on the survival of patients with carcinoma of the breast in British Columbia Moorehead, William P. 1978

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THE INFLUENCE OF DELAY TIME ON THE SURVIVAL OF PATIENTS WITH CARCINOMA OF THE BREAST IN BRITISH COLUMBIA by WILLIAM P. MOOREHEAD MB Bch Bao Queens U n i v e r s i t y B e l f a s t 1962 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE i n THE FACULTY OF GRADUATE STUDIES (Dept. of Health Care and Epidemiology) We accept t h i s t h e s i s as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA September 1978 © William P. Moorehead, 1978 In presenting th i s thes is in pa r t i a l fu l f i lment of the requirements for an advanced degree at the Univers i ty of B r i t i s h Columbia, I agree that the L ibrary shal l make it f ree ly ava i lab le for reference and study. I fur ther agree that permission for extensive copying of th is thesis for scho lar ly purposes may be granted by the Head of my Department or by his representat ives. It is understood that copying or pub l i cat ion of th is thes is for f inanc ia l gain sha l l not be allowed without my writ ten permission. W i l l i a m P. Moorehead Department of H e a l t h Care and Epidemiology The Univers i ty of B r i t i s h Columbia 2075 Wesbrook Place Vancouver, Canada V6T 1W5 Date September 15, 1978 0 i i ABSTRACT The question asked i n t h i s thesis i s , "What i s the influence of delay time on the su r v i v a l of patients with carcinoma of the breast i n B r i t i s h Columbia"? A preliminary data review was ca r r i e d out on records of the Cancer Control Agency of B r i t i s h Columbia for the years I960, 1961 and 1970 to explore possible changes i n delay time and the methodology of the present study. The years 1960 to 1964 in c l u s i v e and the two delay periods, under one month and one year and over, were chosen f o r study. A t o t a l of 456 cases from both delay periods was available for comparison. L i f e Tables were used for analysis of the two delay periods and t h e i r s u r v i v a l from date of diagnosis and date of f i r s t symptom. No strong r e l a t i o n s h i p was found between short delay and s u r v i v a l . In fact, i n the i n i t i a l years, those who had long delay appeared to do better, although i n the long term short delay appeared to have an advantage. Again with L i f e Tables, the two delay periods and surv i v a l were explored i n each of the four c l i n i c a l stages of the disease. This showed that i n c l i n i c a l stages I and I I , the long delay group survived longer. The opposite was true i n c l i n i c a l stages I I I and IV. The implications for health planning are discussed. O F C O N T E N T S I N T R O D U C T I O N P R E L I M I N A R Y D A T A R E V I E W L I T E R A T U R E R E V I E W T H E R E L A T I O N S H I P O F D E L A Y T I M E T O S U R V I V A L F A C T O R S I N F L U E N C I N G D E L A Y T I M E C H A R A C T E R I S T I C S O F D E L A Y I N R E C E N T Y E A R S A N D F A C T O R S I N F L U E N C I N G T H E C O U R S E A N D S U R V I V A L O F B R E A S T C A N C E R O T H E R T H A N T R E A T M E N T M E T H O D O L O G Y O F R E S E A R C H O B J E C T I V E S O F S T U D Y D A T A S O U R C E S M E T H O D S O F A N A L Y S I S R E S U L T S T H E D I S T R I B U T I O N O F D E L A Y T I M E S B Y Y E A R O F D I A G N O S I S , A G E , F I V E Y E A R A G E G R O U P S , C L I N I C A L S T A G E , P A T H O -L O G I C A L S T A G E , B R E A S T I N V O L V E D , S I T E I N V O L V E D , H I S T O L O G I C A L D E S C R I P -T I O N , M A R I T A L S T A T U S A N D S O C I O -E C O N O M I C S T A T U S T H E A N A L Y S I S O F T H E A S S O C I A T I O N O F D E L A Y T I M E O N S U R V I V A L F R O M Y E A R O F D I A G N O S I S T H E A N A L Y S I S O F T H E A S S O C I A T I O N O F D E L A Y T I M E O N S U R V I V A L F R O M D A T E O F F I R S T S Y M P T O M T H E A N A L Y S I S O F T H E A S S O C I A T I O N B E T W E E N D E L A Y T I M E A N D S U R V I V A L W I T H C O N T R O L F O R O T H E R F A C T O R S i v 6.0 CONCLUSION 6.1 METHODOLOGICAL ASPECTS OF THE STUDY 6.2 DISTRIBUTION OF DELAY TIME 6.3 ANALYSIS OF SURVIVAL 6.4 INTERPRETATION 6.5 IMPLICATIONS FOR HEALTH PLANNING 6.6 POLICIES AND OBJECTIVES OF HEALTH PLANNING 7.0 BIBLIOGRAPHY V LIST OF TABLES NUMBER OF CASES WITH DISTRIBUTION OF AGES DURATION OF DELAY IN MONTHS AMD NUMBER OF CASES 1960 DURATION OF DELAY IH MONTHS AND NUMBER OF CASES 1961 DURATION OF DELAY IN MONTHS AND NUMBER OF CASES 1970 PERCENTAGE OF CASES FOR EACH PERIOD OF DELAY TIME FOR AGE STRATIFICATIONS 1960 PERCENTAGE OF CASES FOR EACH PERIOD OF DELAY TIME FOR AGE STRATIFICATIONS 1961 PERCENTAGE OF CASES FOR EACH PERIOD OP DELAY TIME FOR AGE STRATIFICATIONS 1970 A COMPARISON OP TWO DELAY PERIODS, UNDER 3 MONTHS, ONE YEAR AMD OVER WITH AGE STRATIFICATIONS FOR 1960, 1961 AND 1970 COMPARISON OF TWO DELAY PERIODS, LESS THAN ONE MONTH, ONS YEAR AND OVER. WITH AGE STRATIFICATIONS FOR 1960, 1961 AND 1970 COMPARING THE TOTAL PERCENTAGES IN EACH YEAR EXAMINED FOR DELAY PERIODS LESS THAN ONE MONTH AND 01® YEAR AND OVER THE DISTRIBUTIONS OF DELAY TIMES WITHIN THE THREE AGE GROUPS FOR THE YEARS 1960, 1961 AND 1970 COMBINED BY PERCENTAGES SHEET FOR COLLECTING DATA CLINICAL STAGING OF BREAST CARCINOMA PATHOLOGICAL STAGING OF BREAST CARCINOMA DISTRIBUTION OF DELAY BY YEAR OF DIAGNOSIS THE DISTRIBUTION OF CASES IN THE DELAY PERIOD ONS YEAR AND OVER BY DELAY TIME DISTRIBUTION OF DELAY IN FIVE YEAR AGE GROUPS AGE DISTRIBUTION OF CASES AND DELAY IN RELATION TO AGE CLINICAL STAGING IN RELATION TO DELAY TIME v i XX. PATHOLOGICAL STAGING IN RELATION TO DELAY TIME XXI. THE DISTRIBUTION OF CASES BY BREAST AND DELAY TIME XXII. THE DISTRIBUTION OF CASES BY SITE AND DELAY TIME XXIII. HISTOLOGICAL DESCRIPTIVE TERM GROWTH IN RELATION TO DELAY XXIV. HISTOLOGICAL DESCRIPTIVE TERM TYPE IN RELATION TO DELAY XXV. PATHOLOGICAL DESCRIPTIVE TERMS IN RELATION TO DELAY XXVI. MARITAL STATUS IN RELATION TO DELAY XXVII. SOCIO-ECONOMIC STATUS AS DEFINED BY HUSBAND'S OCCUPATION IN RELATION TO DELAY XXVIII. SOCIO-ECONOMIC STATUS AS DEFINED BY PATIENT'S OCCUPATION IN RELATION TO DELAY XXIX. THE OUTCOME IN RELATION TO THE TWO DELAY PERIODS IN 456 CASES EXAMINED AS OF JUNE 1 9 7 7 XXX. LIFE TABLE OF SHORT DELAY FRCM YEAR OF DIAGNOSIS -NUMBERS OF DEATHS NOT INCLUDING CASES WHICH DIED OF COMPETING RISK XXXI. LIFE TABLE OF SHORT DELAY FROM YEAR OF DIAGNOSIS -NUMBERS OF DEATHS INCLUDING CASES WHICH DIED OF COMPETING RISK XXXII. LIFE TABLE OF LONG DELAY FROM YEAR OF DIAGNOSIS -NUMBERS OF DEATHS NOT INCLUDING CASES WHICH DIED OF COMPETING RISK XXXIII. LIFE TABLE OF LONG DELAY FROM YEAR OF DIAGNOSIS -NUMBERS OF DEATHS INCLUDING CASES WHICH DIED OF COMPETING RISK XXXIV. SHORT DELAY FROM DATE OF DIAGNOSIS - RELATIVE SURVIVAL RATES XXXV. LONG DELAY FROM DATE OF DIAGNOSIS - RELATIVE SURVIVAL RATES XXXVI. COMPARISON OF RELATIVE SURVIVAL RATES FOR LONG AND SHORT DELAY FROM DATE OF DIAGNOSIS v i i X X X V I I . L I F E T A B L E OF SHORT D E L A Y FROM D A T E OF F I R S T SYMPTOM - NUMBER OF DEATHS NOT I N C L U D I N G C A S E S WHICH D I E D OF C O M P E T I N G R I S K X X X V I I I . L I F E T A B L E OF SHORT D E L A Y FROM D A T E OF F I R S T SYMPTOM - NUMBER OF DEATHS I N C L U D I N G C A S E S WHICH D I E D OF COMPETING R I S K X X X I X . L I F E T A B L E OF LONG D E L A Y FROM D A T E OF F I R S T SYMPTOM - NUMBER OF DEATHS NOT I N C L U D I N G C A S E S WHICH D I E D OF COMPETING R I S K X X X X . L I F E T A B L E OF LONG D E L A Y FROM D A T E OF F I R S T SYMPTOM - NUMBER OF DEATHS I N C L U D I N G C A S E S WHICH D I E D OF COMPETING R I S K X X X X I . SHORT D E L A Y FROM D A T E OF F I R S T SYMPTOM - R E L A T I V E S U R V I V A L R A T E S X X X X I I . LONG D E L A Y FROM D A T E OF F I R S T SYMPTOM - R E L A T I V E S U R V I V A L R A T E S X X X X I I I . COMPARISON OF R E L A T I V E S U R V I V A L R A T E S FOR LONG AND SHORT D E L A Y FROM D A T E OF F I R S T SYMPTOM X X X X I V . CORRECTED OBSERVED S U R V I V A L R A T E S FOR LONG D E L A Y FROM F I R S T SYMPTOM X X X X V . CORRECTED R E L A T I V E S U R V I V A L R A T E S FOR LONG D E L A Y FROM F I R S T SYMPTOM X X X X V I . COMPARISON OF R E L A T I V E S U R V I V A L R A T E S FOR C L I N I C A L S T A G E I I N SHORT AND LONG D E L A Y X X X X V I I . COMPARISON OF R E L A T I V E S U R V I V A L RATES FOR C L I N I C A L S T A G E I I I N SHORT AND LONG D E L A Y X X X X V I I I . COMPARISON OF R E L A T I V E S U R V I V A L R A T E S FOR C L I N I C A L S T A G E I I I I N SHORT AND LONG D E L A Y X X X X I X . COMPARISON OF R E L A T I V E S U R V I V A L R A T E S FOR C L I N I C A L S T A G E I V I N SHORT AND LONG D E L A Y v i i i L I S T O F F I G U R E S A M D I L L U S T R A T I O N S 1 . D I S T R I B U T I O N O F D E L A Y T I M E S W I T H I N T H E T H R E E A G E G R O U P S F O R T H E Y E A R S 1 9 6 0 , 1 9 6 1 A N D 1 9 7 0 C O M B I N E D B Y P E R C E N T A G E S 2 . D E L A Y P A T T E R N B Y P E R C E N T A G E S F O R T H E Y E A R S 1 9 6 0 , 1 9 6 1 A N D 1 9 7 0 3. A C O M P A R I S O N O F R E L A T I V E S U R V I V A L R A T E S F O R L O N G A N D S H O R T D E L A Y F R O M D A T E O F D I A G N O S I S 4. A C O M P A R I S O N O F R E L A T I V E S U R V I V A L R A T E S F O R L O N G A N D S H O R T D E L A Y F R O M D A T E O F F I R S T S Y M P T O M 5 . C O M P A R I S O N O F S H O R T D E L A Y R E L A T I V E S U R V I V A L R A T E S A N D C O R R E C T E D R E L A T I V E S U R V I V A L R A T E S F O R L O N G D E L A Y F R O M F I R S T S Y M P T O M 6 . C O M P A R I S O N O F R E L A T I V E S U R V I V A L R A T E S F O R C L I N I C A L S T A G E I I N S H O R T A N D L O N G D E L A Y 7 . C O M P A R I S O N O F R E L A T I V E S U R V I V A L R A T E S F O R C L I N I C A L S T A G E I I I N S H O R T A N D L O N G D E L A Y 8. C O M P A R I S O N O F R E L A T I V E S U R V I V A L R A T E S F O R C L I N I C A L S T A G E I I I I N S H O R T A N D L O N G D E L A Y AC raroWLEDGEMENT I wish t o acknowledge the guidance and h e l p g i v e n b y t h e chairman and members o f my t h e s i s committee. Chairman: J . Mark Elwood, M.B., M.D., F.R.C.P. (C) , Head., D i v i s i o n o f E p i d e m i o l o g y . C a n c e r C o n t r o l Agency o f B r i t i s h C o l u m b i a J , M, Robin s o n , M.B., D.P.H., F.R.C.P.(C). A s s i s t a n t P r o f e s s o r . Department o f H e a l t h C are and Epidemiology. U n i v e r s i t y o f B r i t i s h Columbia G.. M. C r a w f o r d . M.D., F.R.C.P. (C) . Rad .lother a p i s t , C a n c e r C o n t r o l Agency o f B r i t i s h C o l u m b i a 1 1.0 INTRODUCTION The c o r n e r s t o n e o f t r e a t m e n t o f c a n c e r i s e a r l y d i a g -n o s i s and t r e a t m e n t . Carcinoma o f t h e b r e a s t i s no excep-t i o n t o t h e r u l e and modern d i a g n o s t i c t e c h n i q u e s such as mammography (1) (2) and thermography (3) have been used t o t h a t end. H e a l t h e d u c a t i o n has propagated s e l f - e x a m i n a t i o n and e a r l y a t t e n d a n c e w i t h symptoms t o t h e d o c t o r . I n t h e p a s t , i t has been suggested, t h a t tumours have a " b i o l o g i c p r e d e t e r m i n i s m (4) (5) (MacDonald 1951, 1958) and t h a t t h e c o u r s e o f c a n c e r o f t h e b r e a s t i s u n i n f l u e n c e d by t r e a t m e n t (6) ( P a r k and Lees 1951). They p o i n t out t h a t tumours w h i c h have t h e a b i l i t y t o m e t a s t a s i z e may have done so a t a v e r y e a r l y s t a g e i n t h e l i f e o f t h e tumour, b e f o r e d i a g n o s i s and t r e a t m e n t i s p o s s i b l e . I n 1951 a t t h e ti m e o f p u b l i s h i n g " A b s o l u t e C u r a b i l i t y o f Cancer o f B r e a s t " t h e y remark on t h e p a u c i t y o f r e f e r e n c e s t o t h e fun d a m e n t a l r e l a -t i o n s h i p o f d e l a y t i m e and s u . r v i v a l and o f t h e absence o f i n t e r e s t i n t h e m a t t e r . T w e n t y - f i v e y e a r s l a t e r , t h e same i n t e r e s t i s l a c k i n g and t h e r e a r e s t i l l v e r y few r e f e r e n c e s t o t h i s r e l a t i o n s h i p . D e l a y has been examined i n every c h a r a c t e r i s t i c t o a i d t h e h e a l t h e d u c a t i o n i s t t o i t s s h o r t -e n i n g and e a r l i e r t r e a t m e n t i n t e r v e n t i o n . V e r y few have l o o k e d a t d e l a y and s u r v i v a l o f c a n c e r o f b r e a s t i n t h e l i g h t o f t h e sta t e m e n t mace by Park and Lees - " i f t h e r e i s no e m p i r i c a l c o n f i r m a t i o n t h a t " d e l a y i n t r e a t m e n t l o w e r s t h e c u r a b i l i t y " most o f c a n c e r t r e a t m e n t l o s e s i t s r a t i o n a l e " . I t i s w i t h t h i s s t a tement i n mind t h a t t h e q u e s t i o n i n t h i s 2 t h e s i s i s a s k e d . What i s t h e i n f l u e n c e o f d e l a y time on t h e s u r v i v a l o f p a t i e n t s w i t h c a r c i n o m a o f t h e b r e a s t i n B r i t i s h Columbia? A s t u d y w i l l be made on t h e r e l a t i o n s h i p between d e l a y t i m e , d e f i n e d as t h e time from t h e f i r s t symptom (which i n most p a t i e n t s i s d i s c o v e r y o f a lump) (5) t o f i r s t t r e a t -ment. The f i r s t treatment w i l l be t h e d a t e o f b i o p s y o r b i o p s y / s u r g e r y . S u r v i v a l w i l l be t h e t i m e f rom b i o p s y t o d e a t h o r a g i v e n d a t e o f c o l l e c t i o n o f d a t a . T h i s t h e s i s w i l l be based on a r e t r o s p e c t i v e s t u d y on medical r e c o r d s i n t h e l a r g e s t cancer t r e a t m e n t f a c i l i t y i n t h e P r o v i n c e . I n i t i a l l y t h e p r o c e d u r e f o r t e s t i n g t h e hypo-t h e s i s w i l l be a p r e l i m i n a r y review o f t h e d a t a a v a i l a b l e i n t h e c l i n i c a l r e c o r d s o f t h e Cancer C o n t r o l Agency, o f p r i m a r y cases w i t h Ccircinoma o f t h e b r e a s t . T h i s w i l l d e f i n e t h e q u a l i t y o f t h e data, t h e d i s t r i b u t i o n o f p a t i e n t d e l a y times w i t h i n a g i v e n year, t h e number o f c a s e s a v a i l a b l e and i f d e l a y has changed w i t h time. The l a s t i s e s p e c i a l l y impor-t a n t i n t h a t i f d e l a y does change w i t h t i m e a b r o a d e r range o f d a t a y e a r s w i l l need r e v i e w i n g . As w e l l as r e v i e w i n g d e l a y and s u r v i v a l , t h e f o l l o w i n g v a r i a b l e s which are p o s s i b l y a s s o c i a t e d w i t h t h e above w i l l be i n c l u d e d i n t h e d a t a c o l l e c t e d : - age, c l i n i c a l s t a g e , p a t h o l o g i c a l s t a g e , p o s i t i o n o f tumour, outcome, h i s t o l o g y , m a r i t a l s t a t u s , and s o c i o - e c o n o m i c i n d e x as d e f i n e d by B l i s h e n ( 3 3 ) . The p a t i e n t s from t h e Cancer Agency w i l l be r e a s o n a b l y r e p r e s e n t a t i v e o f t h e t o t a l p o p u l a t i o n w i t h c a r c i n o m a o f t h e b r e a s t as approximately 70% o f nev/ cases a r e seen i n t h e agency. We w i l l t r y t o ensure t h a t t h e r e p r e s e n t -a b i l i t y i s c o n f i r m e d by comparing s u r v i v a l s f r om our s e r i e s o f p a t i e n t s t o t h o s e r e c o r d e d by t h e P r o v i n c i a l r e g i s t r y o f a l l c a s e s . 4 2.0 PRELXJ1IHARY DATA R E V I E W A p r e l i m i n a r y d a t a review wan n e c e s s a r y t o d e f i n e the q u a l i t y o f t h e r e c o r d s i n t h e Cancer Agency, and t o examine the g e n e r a l c h a r a c t e r i s t i c s o f t h e d a t a w i t h r e s p e c t t o age, d e l a y t i m e and i t s d i s t r i b u t i o n . Change o f d e l a y w i t h age and o v e r t i m e were c o n s i d e r e d t o be i m p o r t a n t v a r i a b l e s . These are changes t h a t might o c c u r and c o u l d a f f e c t t h e c h o i c e and e x t e n t o f d a t a t o be c o l l e c t e d . The c o n c l u s i o n s t h e r e f o r e on t h a t c h o i c e o f d a t a w i t h i t s i m p l i c a t i o n s f o r t h e f u t u r e c o u l d be c o n f i d e n t l y a p p l i e d . My i n t e r e s t w i l l be i n p r i m a r y cases o f carcinoma o f the b r e a s t . Primary cases are t h o s e d e f i n e d as diagnosed and t r e a t e d i n t h a t y e a r by the Cancer C l i n i c o r on immediate r e f e r r a l a f t e r t r e a t m e n t o r d i a g n o s i s elsewhere. The p r e l i m i n a r y d a t a r e v i e w w i l l h e l p t o f o r m u l a t e t h e methodology w h i c h w i l l answer t h e h y p o t h e s i s . Three impor-t a n t q u e s t i o n s are t o be answered:-1. Mi at i s t h e d i s t r i b u t i o n o f the primary cases by age and does t h i s change w i t h t i m e ? To f a c i l i t a t e t h i s , I w i l l l o o k at age i n each y e a r chosen, s t r a t i f i e d i n t o t h r e e l e v e l s _ 44, 45 - 64 i n c l u -s i v e and > 65. 2. Miat i s the d i s t r i b u t i o n o f c a s e s by d e l a y t i m e ? T h i s w i l l f o r m u l a t e the b e s t c o m p a r i s o n o f s h o r t d e l a y and l o n g delay times w i t h r e s p e c t to s u r -v i v a l . 5 3. I s t h e r e a change i n t h e character o f d e l a y w i t h time? I f t h e r e i s a change i t w i l l be n e c e s s a r y t o sample more r e c e n t years w i t h c o r r e s p o n d i n g r e d u c t i o n i n f o l l o w up p e r i o d f o r t h o s e y e a r s . T h i s could l e a d t o a b i a s i n comparing t h e i n f l u e n c e o f l o n g and s h o r t d e l a y t i m e s and s u r v i v a l . A s t u d y o f a i l p a t i e n t s d i a g n o s e d i n the f o l l o w i n g y e a r s was chosen t o answer t h e s e t h r e e questions and formulate t h e methodology o f f u r t h e r r e s e a r c h ? i 9 6 0 , 1961 and 1970. On examining t h e number o f primary cases and t h e i r age d i s t r i b -u t i o n ( T a b l e I ) , I f i n d no change i n age d i s t r i b u t i o n be-tween 1960 and. 1970. The t h r e e l e v e l s o f s t r a t i f i c a t i o n have i d e n t i c a l average ages i n 1960, 1961 and 1970. The average age i s 55 y e a r s f o r a l l p a t i e n t s . T h i s i s d e r i v e d , from examining a l l p r i m a r y cases i n 1960 ( 2 4 7 ) , 1961 (224) and. 1970 ( 3 6 7 ) , a t o t a l o f 333 p a t i e n t s . Over h a l f o f t h e p a t i e n t s o c c u r i n t h e mi d d l e age grouping (45 - 64) i n c l u -s i v e i n a l l t h e y e a r s examined. The d i s t r i b u t i o n o f p a t i e n t s a c c o r d i n g t o d e l a y t i m e i s examined b o t h i n t h e s t r a t i f i e d age groups and. i n t o t a l . These are d i s p l a y e d g r a p h i c a l l y by t a b l e s , b a r graphs and l i n e graphs f o r each y e a r . Reviewing T a b l e s I I , I I I and I V , an i n i t i a l peak response f o r t h e f i r s t p e r i o d o f d e l a y t i m e ( l e s s than one month) i s seen. The most common responses from p a t i e n t s r e c o r d e d were e i t h e r a few days o r two t o t h r e e weeks. There was a g r a d u a l 6 f a l l o f f i n each d e l a y p e r i o d u n t i l 12 months and we see a s l i g h t r i s e t h e n a further one a t 24 months. I n 1960 t h e r e were o n l y t h r e e p e o p l e who had d e l a y times l o n g e r t h a n 5 y e a r s (6 y e a r s , 10 y e a r s and. 15 y e a r s ) . Two d e l a y t i m e s were unknown, i n a 93 y e a r o l d woman and a 78 y e a r o l d woman and t h e s e were counted as b e i n g g r e a t e r t h a n two y e a r s . These p a t i e n t s were o m i t t e d i n t h e a n a l y s i s . I n 1961 t h i r t e e n p e o p l e d e l a y e d o v e r 5 y e a r s and o n l y four o f tho s e were i n t h e > 65 group. No d e l a y t i m e s were unknown i n 1961. I n 1970 e i g h t p e o p l e d e l a y e d o v e r 5 y e a r s and f5.ve had a d e l a y t i m e o f 5 y e a r s . Pour cases had no st a t e m e n t on the duration o f d e l a y . It was no t e d in 1970 s i x physicians had c o n t r i b u t e d s i g n i f i c a n t l y t o t h e d e l a y t i m e . T h i s was not p r e s e n t i n t h e 1960 and 1961 f i g u r e s o r n o t commented on. There i s no s i g n i f i c a n c e in t h e s e f i n d i n g s . The i n i -t i a l d a t a d i s p l a y e d on T a b l e s I I , I I I , and I V showed that t h e quality o f r e c o r d s i s h i g h i n t h e Cancer Agency with r e s p e c t t o d e l a y t i m e s . I t would t h e r e f o r e be p r o d u c t i v e to ask t h e q u e s t i o n - "Mlat i s t h e i n f l u e n c e o f d e l a y t i m e on t h e s u r v i v a l o f patients w i t h carcinoma o f t h e b r e a s t i n B r i t i s h Columbia?" T a b l e s V, V I and V I I d e f i n e t h e p e r c e n t a g e o f ca s e s f o r each d e l a y p e r i o d , s t r a t i f i e d i n t o t h r e e age gr o u p s . The d i s t r i b u t i o n i n t h e v a r i o u s d e l a y p e r i o d s f o r each group has changed v e r y l i t t l e between 1960 and 1970. T h i s would r e -a s s u r e us t h a t p o s s i b l y any -further r e s e a r c h c o u l d be p r o -7 j e c t e d t o t h e p r e s e n t day. To d e f i n e t h e p e r i o d s o f d e l a y t h a t might answer t h e h y p o t h e s i s , p a r t i c u l a r p e r i o d s o f d e l a y t i m e were examined. D e l a y p e r i o d s were chosen a t e i t h e r end o f t h e d e l a y t i m e s pectrum and examined i n T a b l e s V I I I , IX and X. I n T a b l e V I I I comparing t h e p e r i o d o f d e l a y t i m e under 3 months w i t h 1 y e a r and over t h e r e i s m i n i m a l d i f f e r e n c e between 1960 and 1970. I n T a b l e I X , I have reduced t h e c o m p a r i s o n t o t h e d e l a y p e r i o d l e s s t h a n one month and compared i t w i t h one y e a r and o v e r . These suggest when comparing 1970 w i t h 1960 some s l i g h t i n c r e a s e i n t h e p r o p o r t i o n i n t h e e a r l y d e l a y p e r i o d ( l e s s t h a n one month) . I f 1961 a l s o i s compared, t h i s im-provement d i s a p p e a r s . I a l s o found no improvement i n t h e l o n g e r d e l a y p e r i o d (one y e a r and over) comparing 1960, 1961 and 1970. I n T a b l e X, I have compared the t o t a l p e r c e n t a g e s i n each y e a r examined f o r d e l a y p e r i o d s l e s s t h a n one month and one y e a r and o v e r . A g a i n , t h e r e i s some i n c r e a s e i n t h e p r o p o r t i o n i n t h e l e s s t h a n one month p e r i o d b u t t h e r e i s a l s o an i n c r e a s e i n t h e one y e a r and o v e r group i n 1970. T a b l e X I and F i g u r e I compare t h e d i s t r i b u t i o n s o f d e l a y t i m e s w i t h i n t h e t h r e e age groups f o r t h e y e a r s 1960, 1961 and 1970 combined by p e r c e n t a g e s . The t a b l e and b a r graph demonstrate t h a t t h e r e i s v e r y l i t t l e d i f f e r e n c e between age groups i n t h e p a t t e r n o f d e l a y . 8 F i g u r e 2 compares t h e t o t a l p e r c e n t a g e f o r each p e r i o d o f d e l a y f o r each y e a r and demonstrates a g a i n t h a t t h e r e i s l i t t l e d i f f e r e n c e i n t h e y e a r s ' d i s t r i b u t i o n o f d e l a y t i m e s I n t h e p r e l i m i n a r y d a t a review the f o l l o w i n g have been demonstrated:- A v e r y h i g h c n i a l i t y o f data f o r d e l a y t i m e s i s a v a i l a b l e ? d e l a y l i a s not changed s i g n i f i c a n t l y w i t h time i n comparing 1960 and 1970; t h e r e i s m i n i m a l d i f f e r e n c e i n d e l a y t i m e s w i t h the t h r e e l e v e l s o f age s t r a t i f i c a t i o n , These f i n d i n g s w i l l be f u r t h e r e x p l o r e d i n t h e s e c t i o n -Methodology o f R e s e a r c h . TABLE I NUMBER OF CASES WITH DISTRIBUTION OF AGES I960 1961 1970 AGE AVERAGE CASES (%) AGE AVERAGE CASES (t) AGE AVERAGE CASES (%) GROUPING AGE GROUPING AGE GROUPING AGE  < 44 38 yrs 52 (21%) < 44 39 yrs 60 (27$) < 44 38 yrs 74 (20%) 45-64 53 yrs 132 (53^) 45-64 54 yrs 107 (U&fo) 45-64 54 yrs 219 (60^) ^ 65 74 yrs 63 (26%) > 65 74 yrs 57 (?~5%) - 65 74 yrs 74 (20%) ALL 55 yrs 247 (100$) ALL 55 yrs 224 (100%) ALL 55 yrs 367 (lOOg) TABLE 11 DURATION OF DELAY IN MONTHS AND NUMBER OF CASES I960 £44 9 13 -ci-lO 4 3 1 2 1 Of -it.. XX+ 3 1 J.O+ 1 Xt$+ ±V+ <iX+ 1 ^+ 2 1 45-64 37 25 16 10 4 4 6 3 2 1 1 7 1 1 1 1 7 5 >65 12 12 10 2 2 2 2 2 1 1 7 1 2 1 1 5 TOTAL: 58 ?6 16 7 8 6 2 1 2 17 2 4 1 1 3 10 11 3 Levels of Stratification Number of Cases TOTAL <44 52 45-64 132 >65 63 247 PERCENTAGE DISTRIBUTION OF CASES: f0 23.5 20 14.6 6,5 3.6 2.8 3.2 2.4 .81 1.2 .40 .81 6.9 0 .31 1.6 .40 .40 1.2 0 0 0 0 0 4.0 4.5 TABLE III DURATION OF DELAY IN MONTHS AND NUMBER OF GASES 1961 MMMM < 1 1+ 2+ 3+ 4+ 5+6+7+8+ 9+ 10+ 11+ 12+ 13+ 14+ 15+ 16+ 17+ 18+ 19+ 20+ 21+ 22+ 23+ 24+ 2 yr+ <44 20 14 10 3 2 1 1 1 1 0 1 0 4 2 45-64 26 24 5 10 5 2 6 1 0 4 1 0 7 2 1 3 10 £65 1 4 8 5 2 1 1 4 5 0 1 2 1 2 1 4 6 TOTAL; 60 46 20 15 8 4 11 7 1 5 4 1 13 1 2 1 7 18 TOTAL <44 60 Levels of Stratification . -Number of Cases ± u / >65 _ _ 224 PERCENTAGE DISTRIBUTION OF CASES % 26.8 20.5 8.9 6.7 3.6 1.8 4.9 3.1 .45 2.2 1.8 .45 5.8 0 .45 0 0 0 .89 .45 0 0 0 3.1 8.0 TABLE I? DURATION OF DELAY IN MONTHS AND NUMBER OF CASES 1970 <1 1+ 2+ 3+ 4+ 5+ 6+ 7+ 8+ 9+ 10+ 11+ 12+ 13+ 14+ 15+ 16+ 17+ 18+ 19+ 20+ 21+ 22+ 23+ 24+ 2 yr+ <44 18 20 7 5 3 1 2 2 1 1 0 0 8 1 2 3 45-64 71 45 17 12 6 8 9 4 3 1 1 1 9 3 2 1 1 10 15 >65 19 7 6 8 3 4 3 1 0 1 0 0 8 6 8 TOTAL:108 72 30 25 12 13 14 7 4 3 1 1 25 4 2 l l 18 26 TOTAL <44 74 3 Levels of Stratification , _ „_ 0 H Number of Cases 4^-64 219 M 36? PERCENTAGE DISTRIBUTION OF CASES % 29.4 19.6 8.2 6.8 3.3 3.5 3.8 1.9 1.1 .82 .27 .27 6.8 0 0 1.1 0 0 .54 0 .2? .27 0 0 4.9 7.1 TABLE V PERCENTAGE OF CASES FOR EACH PERIOD OF DELAY TIME FOR AGE STRATIFICATIONS I960 DELAY MTHS < 1 1+ 2 + 3 + 4 + 5 + 6 + 7 + 8 + 9 + 10+ 11+ 12 >12 <44 17.3$ 25$ 19.2$ 7.7$ 5.8$ 1.9$ 3.8$ 1.9$ 3.8$ 13.5$ 45-64 28$ 18.9$ 12$ 7.6$ 3$ 3$ 4.5$ 2.3$ 1.5$ 0.76$ 0.76$ 5.3$ 12$ >65 19$ 19$ 15.9$ 3.2$ 3.2$ 3.2$ 3.2$ 3.2$ 1.6$ 1.6$ 11.1$ 15.9$ TABLE VI PERCENTAGE OF CASES FOR EACH PERIOD OF DELAY TIME FOR AGE STRATIFICATIONS 1261 DELAY MTHS < 1 1+ 2+ 3+ 4+ 5+ 6+ 7+ 8+ 9+ 10+ 11+ 12 >12 <44 33.3$ 23.3$ 16.7$ 5$ 3.3$ 1.7$ 1.7$ 1.7$ 1.7$ 1.7$ 6.7$ 3.3$ 45-64 24.3$ 22.4$ 4.7$ 9.3$ 4.7$ 1.9$ 5.6$ 0.93$ 3.7$ 0.93$ 6.5$ 15$ >65 24.6$ 14$ 8.8$ 3.5$ 1.8$ 1.8$ 7$ 8.8$ 1.8$ 3.5$ 1.8$ 3.5$ 19.3$ TABLE VII PERCENTAGE OF CASES FOR EACH PERIOD OF DELAY TIME FOR AGE STRATIFICATIONS 1270 DELAY MTHS <1 1+ 2+ 3+ 4+ 5+ 6+ 7+ 8+ 9+ 10+ 11+ 12 >12 <kk 24$ 27% 9.5$ 6.7% 4$ 1.4$ 2.7% 2.7% 1.4$ l.h% 10.8$ 8$ 45-64 32.4$ 20.5$ 7.8$ 5.5$ 2.7$ 3.7$ 4.1$ 1.8$ 1.4$ 4$ 14.* >65 25.7$ 9.5$ 8$ 10.8$ 4$ 5.4$ 4$ 1.4$ 1.4$ 10.8$ 18. c 16 TABLE VIII COMPARISON OF TWO DELAY PERIODS, UNDER 3 MONTHS, ONE YEAR AND OVER WITH AGE STRATIFICATIONS A. DELAY PERIOD < 44 45-64 >65 1960 UNDER 3 MONTHS 61.5% 58.9% 53.9% 1 YEAR AND OVER 17.3% 17.3% 27% 1961 B. DELAY PERIOD <44 45-64 2 65 UNDER 3 MONTHS 73.3% 51.4% 47.4% 1 YEAR AND OVER 10% 21.5% 22.8% 1970 DELAY PERIOD < 44 C. 45-64 > 65 UNDER 3 MONTHS 60.5% 60.7% 43.2% 1 YEAR AND OVER 18.8% 18.6% 29.7% 17 TABLE IX COMPARISON OF TWO DELAY PERIODS, LESS THAN ONE MONTH, ONE YEAR AND OVER WITH AGE STRATIFICATIONS 1960 LESS 1 YEAR THAN AND DELAY PERIOD 1 MTH OVER < 44 17.3% 17.3% 45-64 28% 17.3% >65 19% 27% 1961 DELAY PERIOD LESS THAN 1 MTH 1 YEAR AND OVER <44 33.3% 10% 45-64 24.3% 21.5% >65 24.6% 22.8% 1970 DELAY PERIOD LESS THAN 1 MTH 1 YEAR AND OVER < 44 24% 18.8% 45-64 32.4% 18.6% > 65 25.7% 29.7% 18 TABLE X COMPARING THE TOTAL PERCENTAGES IN EACH YEAR EXAMINED FOR DELAY PERIODS LESS THAN ONE MONTH AND ONE YEAR AND OVER DELAY PERIOD 1960 1961 1970 <1 MTH 23.5% 26.8% 29.4% 1 YEAR AND OVER 19.8% 18.75% 20.98% TABLE XI THE DISTRIBUTIONS OF DELAY TIMES WITHIN THE THREE AGE GROUPS FOR THE YEARS I960, 196l AND 1970 COMBINED BY PERCENTAGES <1 1 2 3 4 5 6 7 8 9 10 11 12 >12 VO £ 6 5 23.1$ 14.2$ 10.9$ 5.8$ 3$ 3.5$ 3.7$ 4.5$ 0$ 2.1$ 1.7$ 1.1$ 8.5$ 18$ 45-64 28.2$ 20.6$ 8.2$ 7.5$ 3.5$ 2.9$ 4.7$ 1.7$ 1.0$ 1.5$ .3$ .2$ 5.3$ 13.9$ <44 24.9$ 25.1$ 15.1$ 6.5$ 4.4$ 1.7$ 2.7$ 2.1$ 1$ .5$ .6$ 0$ 7.1$ 8.3$ 2 0 FIGURE I. DISTRIBUTION OF DELAY TIMES WITHIN THE THREE AGE GROUPS FOR THE YEARS 1960, 1961 AND 1970 COMBINED BY PERCENTAGES 30 2.0 j 10 41 I % 10 ^1 J % 3o Zo io 41 10 II 10 ll IX ><Z MONTHS ll >/Z MOUTHS MotfTKS METRIC 22 3.0 LITERATURE REVIEW 3.1 THE RELATIONSHIP OF DELAY T I M E TO SURVIVAL 3.2 FACTORS INFLUENCING DELAY TIME 3.3 CHARACTERISTICS OF DELAY IN RECENT YEARS AND FACTORS INFLUENCING THE COURSE AND SURVIVAL OF BREAST CANCER OTHER THAN TREATMENT 23 3.1 THE RELATIONSHIP OF DELAY TIME TO SURVIVAL The l i t e r a t u r e on d e l a y i n treatment o f carcinoma o f the b r e a s t i s sparse i n c o n t r a s t t o the importance attached t o the avoidance o f d e l a y . Tv/o d i f f e r e n t approaches are taken. The f i r s t t r i e s t o show a d i r e c t r e l a t i o n s h i p be-tween d e l a y and s u r v i v a l . The second makes a p r i o r assump-t i o n t h a t i n c r e a s i n g d e l a y has an adverse e f f e c t on s u r v i -v a l , and w i t h t h i s assumption t h a t d e l a y must be avoided t h e f a c t o r s i n f l u e n c i n g d e l a y are examined. There i s a t h i r d group o f l i t e r a t u r e which simply d e f i n e s the v a r i o u s c h a r a c t e r i s t i c s o f d e l a y . Parle and Lees (1951) (6) reviewed the e x i s t i n g l i t e r -a t u r e o f the r e l a t i o n s h i p between d e l a y time and s u r v i v a l . They t r i e d t o approach the study o f the a b s o l u t e c u r a b i l i t y of cancer o f the b r e a s t i n two ways - f i r s t , , by showing t h a t the c u r a b i l i t y decreases as the d e l a y i n treatment i n c r e a s e s ? secondly, by f i n d i n g how f a r the index o f e f f e c -t i v e treatment - s u r v i v a l time o r s u r v i v a l r a t e - i s a f u n c t i o n o f t h e i n d i v i d u a l tumour growth r a t e s . They found, r e v i e w i n g the l i t e r a t u r e p r i o r t o 1951, few r e f e r e n c e s t o the fundamental r e l a t i o n s h i p o f d e l a y and s u r v i v a l . They remarked on the absence o f i n t e r e s t i n the matter when the r e l a t i o n s h i p had been noted to be absent o r s m a l l . They r a i s e d the q u e s t i o n " I f t h e r e i s no empir-i c a l c o n f i r m a t i o n t h a t d e l a y i n treatment lowers the c u r -a b i l i t y , most of cancer treatment l o s e s i t s r a t i o n a l e " . From the l i t e r a t u r e they have reviewed they drew these 24 inferences: "Cancer of the breast has a wide range of v a r i a b i l i t y i n behaviour, at least i n so far as concerns the durations between the stages of growth and spread." They suggested there i s a bias i n se l e c t i o n of cases. That good results seem to appear from studies selected from the lower grades of malignancy. Most of these studies defined "cure" as 5 years s u r v i v a l and suggested that the f i v e year cure or s u r v i v a l rate was a date chosen which magnifies the res u l t s of the above chosen cases and comparisons tended to be biased. There seemed to be some evidence that increased delay i n treatment may s l i g h t l y decrease c u r a b i l i t y . The f i n a l conclusion they came to was - " I f there i s a rel a t i o n s h i p between delay i n treatment and c u r a b i l i t y , and, since present day treatment of cancer of the breast i s based on the assumption that t h i s r e l a t i o n s h i p does e x i s t , i f treatment i s e f f e c t i v e at a l l , i t would be expected that t h i s r e l a t i o n s h i p would be empirically demonstrable." These conclusions could equally be applied to a present day review of the l i t e r a t u r e on delay. They concluded that the influence of delay i n treatment upon the c u r a b i l i t y can-not be greater than 5 to 10 percent. I t may be less or may not exi s t at a l l . In 1958 MacDonald (5) reviewed h i s e a r l i e r theory of 25 " B i o l o g i c Predeterminism" (4) , a host-tumor r e l a t i o n s h i p t h a t i s o f g r e a t e r p r o g n o s t i c importance than the time o r type o f treatment. He suggested predeterminism i n b r e a s t cancer i n d i c a t e s grouping by n a t u r a l s e l e c t i o n . He spec-u l a t e d t h a t twenty percent o f b r e a s t l e s i o n s w i l l s t i l l be l i m i t e d t o the b r e a s t 3 o r more years a f t e r onset, 55 per-cent w i l l have developed d i s t a n t metastases i n the p r e -c l i n i c a l phase and i n 25 p e r c e n t t h e r e i s a s e q u e n t i a l time-space r e l a t i o n s h i p , and f o r these women prompt d i a g n o s i s and treatment may be l i f e s a v i n g . U n f o r t u n a t e l y he gave no c r i t e r i a o r p r o o f o f these b i o l o g i c groups t o separate out inhere d e l a y would be important. He was p e s s i m i s t i c even i f the d i f f e r e n t i a t i o n c o u l d be made, t h a t i t would l e a d t o l i t t l e i n c r e a s e i n s u r v i v a l . Bloom (1950) (10) reviewed 565 cases o f carcinoma o f the b r e a s t t r e a t e d at the Middlesex H o s p i t a l d u r i n g the y e a r s 1936 t o 1942. Four hundred and seventy cases were a v a i l a b l e f o r i n v e s t i g a t i o n . The purpose v/as t o examine age o f p a t i e n t , d e l a y i n s e e k i n g treatment and s i z e and s i t e o f tumour i n r e l a t i o n to outcome. The h i s t o l o g i c a l grade o f the tumour was a l s o examined i n r e l a t i o n t o these v a r i a b l e s . Age has been c o n s i d e r e d an important v a r i a b l e i n r e -l a t i o n t o outcome. The younger the p a t i e n t , the more s e r i o u s the o u t l o o k was a view f i r m l y h e l d i n a l a r g e body o f l i t e r -a t ure (10). Bloom i n h i s s e r i e s o f cases found t h a t the younger p a t i e n t s d i d as w e l l as o t h e r s . A l s o the grade o f 26 tumour was evenly d i s t r i b u t e d over the v a r i o u s age groups d i s c o u n t i n g s u g g e s t i o n s t h a t cancer o f b r e a s t was more malignant i n younger p a t i e n t s . In r e v i e w i n g d e l a y and prognosis u s i n g 5 y e a r s u r -v i v a l s , a u n i f o r m s u r v i v a l r a t e was found no matter how l o n g t h e h i s t o r y . T h i s was confirmed when t h e group o f p a t i e n t s were examined from t h e p o i n t o f view o f c l i n i c a l s t a g i n g and h i s t o l o g i c a l g r a d i n g . Bloom f e e l s he was not able t o show t h a t o u t l o o k becomes more gloomy wi t h i n c r e a s -i n g d e l a y . There was a tendency though, l o o k i n g at h i s t o -l o g i c a l g r a d i n g i n t h r e e broad d e l a y groups f o r p a t i e n t s w i t h tumours of h i g h malignancy t o appear e a r l i e r than those with tumours o f low malignancy. T h e r e f o r e the d i s t r i b u t i o n o f the grades tended t o compensate t o some extent f o r the time f a c t o r . I t v/as suggested the c o n f l i c t i n g r e s u l t s found i n t h e l i t e r a t u r e were due t o h i s t o l o g i c a l l y incomparable groups o f cases. Comparing d e l a y i n cases o f same h i s t o -l o g i c a l grade t h e r e appeared t o be some advantage i n grade 1 tumours coming e a r l i e r w i t h 92 percent s u r v i v a l (5-years) f o r l e s s than 6 weeks d e l a y and 72 p e r c e n t s u r v i v a l (5-years) f o r those d e l a y i n g s i x t o twelve months. T h i s was not found i n the o t h e r grades. Bloom t h e r e f o r e i n c o n c l u s i o n f e l t t h a t outcome i n b r e a s t carcinoma was determined l a r g e l y by the h i s t o l o g i c a l type o f growth r a t h e r than d e l a y i n t r e a t -ment, age o f p a t i e n t or s i t e o f primary growth. In s p i t e o f these c o n c l u s i o n s he s t i l l f e l t t h a t 27 campaigns and ed u c a t i o n aimed at s h o r t e n i n g d e l a y should be continued f o r the sake o f those p a t i e n t s w i t h tumours o f low h i s t o l o g i c a l malignancy. Smithers (1958) (7) examined two groups o f p a t i e n t s , one w i t h advanced d i s e a s e who s u r v i v e d f o r many years and another w i t h e a r l y d i s e a s e who d i e d soon a f t e r treatment. The purpose was t o t e s t the two opposing t h e o r i e s - t r e a t -ment has no e f f e c t on the predetermined p a t t e r n o f human b r e a s t tumour behaviour and, on the oth e r hand, e a r l y t r e a t -ment a l t e r s i t s course. He p o i n t e d out re v i e w i n g the R e g i s t r a r General's f i g -u r e s , the unchanging age s p e c i f i c death r a t e s . He r e i t e r -ated the view o f McKinnon (8) t h a t t h i s was evidence o f the f a i l u r e o f h e a l t h e d u c a t i o n and present treatment methods. Smithers used t h e grade and s i z e o f tumour, de-l a y , s i t e o f the tumour, t h e age o f the p a t i e n t and lymph-a t i c involvement as i n d i c e s f o r the b e n e f i t s f o r e a r l y treatment. He demonstrated no d i r e c t r e l a t i o n s h i p between d e l a y and s u r v i v a l but u s i n g the above i n d i c e s o f prognosis suggests t h e r e was i n d i r e c t evidence f o r e a r l y treatment b e i n g b e n e f i c i a l w i t h c a r e f u l s e l e c t i o n o f p a t i e n t s . In 1960 S u t h e r l a n d (9) p u b l i s h e d a book under the t i t l e o f "Cancer, The S i g n i f i c a n c e o f Delay". T h i s was an exten-s i v e review o f the l i t e r a t u r e with an a n a l y s i s o f de l a y . He p o i n t e d out the d i f f i c u l t i e s o f a p p r a i s a l e s p e c i a l l y i n 28 making v a l i d comparisons between one study and another. O b j e c t i v e a p p r a i s a l o f t h e e f f e c t i v e n e s s o f treatment i s d i f f i c u l t . S u t h e r l a n d examined the problems o f d e l a y under t h r e e p r o g n o s t i c v a r i a b l e s , tumour c h a r a c t e r i s t i c s , h o s t charac-t e r i s t i c s and environment. H i s f i n a l c o n c l u s i o n o f tumour c h a r a c t e r i s t i c s - " a t a g i v e n moment o f time, each tumour c h a r a c t e r i s t i c o c c u p i e s i t s own p o s i t i o n on i t s i n d i v i d u a l developmental g r a d i e n t " , p r o b a b l y b e s t summed up the c o n c l u s i o n on the l i t e r a t u r e reviewed. I n the f i n a l chapter, " D u r a t i o n and Problems" Suther-l a n d examined the evidence concerning the p r o g n o s t i c s i g -n i f i c a n c e o f d e l a y . He r e c a l l e d MacDonald (1951) (4) who found t h a t , o f 236 a r t i c l e s t h a t made r e f e r e n c e t o t h e s i g n i f i c a n c e o f e a r l y treatment, o n l y 16 c o n t a i n e d d a t a t h a t made i t p o s s i b l e to c o r r e l a t e end r e s u l t s w i t h e a r l y treatment. Some data a v a i l a b l e appeared t o support the h y p o t h e s i s t h a t treatment soon a f t e r onset o f symptoms improves prog-n o s i s and d e l a y makes i t worse. He suggested the a s s o c i a t i o n was not as c l e a r c u t and t h e r e was o t h e r evidence t h a t prog-n o s i s by no means i n v a r i a b l y and p r o g r e s s i v e l y becomes worse as d e l a y lengthens. Some l i t e r a t u r e showed b e t t e r s u r v i v a l o f p a t i e n t s who delayed a long time compared t o those who came e a r l y . These 29 s u r v i v a l s were c a l c u l a t e d from the day o f treatment which made them more remarkable. T h e r e f o r e to be t r u l y com-p a r a b l e t h e y should be c a l c u l a t e d from date o f onset o f symptoms. B i z a r r e s t a t i s t i c s appear such as the average d u r a t i o n o f s u r v i v a l o f 8.91 y e a r s f o r those who delayed f o u r y e a r s or more and average d u r a t i o n o f s u r v i v a l o f 4.12 y e a r s f o r s h o r t d e l a y cases. I t would seem t h a t from examining the r e l a t i o n s h i p between d e l a y and 5-year s u r v i v a l r a t e s the p a t i e n t s w i t h the b e s t p r o g n o s i s f a l l i n t o two r a d i c a l l y opposed groups: -those t r e a t e d v e r y soon a f t e r onset o f symptoms and those t r e a t e d v e r y l a t e . S u t h e r l a n d p o i n t e d out t h a t those i n the i n t e r m e d i a t e group have t h e worst p r o g n o s i s . He asked the q u e s t i o n s t h a t have been asked b e f o r e . "Does t h i s mean t h a t i n b r e a s t cancer the d e c i s i v e cause o f d i f f e r e n c e i n outcome and i n l e n g t h o f s u r v i v a l i s d i f f e r e n t i n the b i o -l o g i c a l type o f cancer, and t h a t these d i f f e r e n c e s are un-a f f e c t e d by treatment?" (10) (11) (12) S u t h e r l a n d answered the q u e s t i o n by l o o k i n g at the e f f e c t s o f d e l a y on o p e r a b i l i t y , r a d i o c u r a b i l i t y and h o s t -tumour r e l a t i o n s h i p s . He found i n c r e a s i n g d u r a t i o n o f p r e -o p e r a t i v e d e l a y was a s s o c i a t e d w i t h i n c r e a s i n g i n c i d e n c e o f r e g i o n a l and d i s t a n t metastases. I t would seem a d i a g n o s i s as e a r l y as p o s s i b l e was important t o a c e r t a i n y e t unknown, number o f i n d i v i d u a l b r e a s t carcinoma p a t i e n t s . The b e n e f i t from r e d u c i n g d e l a y was moderate. He suggested we ought t o 30 be modest i n our c l a i m s as t o the p o s s i b i l i t y o f m a t e r i a l l y a l t e r i n g the s i t u a t i o n f o r b r e a s t carcinoma by t h i s approach t o t h e problem. E s s e n t i a l l y he b e l i e v e d d e l a y does p l a y a p a r t i n some p a t i e n t ' s s u r v i v a l and i t s r e d u c t i o n i s espe-c i a l l y warranted i n t h e i n t e r m e d i a t e d e l a y group. Rubin (1967) (13) reviewed the assessment o f d e l a y by S u t h e r l a n d and Park and Lees. He suggested the d e c i s i v e answer t o the v a l u e o f treatment i n b r e a s t cancer r e q u i r e s comparison o f s u r v i v a l o f a group o f t r e a t e d p a t i e n t s t o a group o f u n s e l e c t e d u n t r e a t e d p a t i e n t s w i t h b r e a s t cancer. E p i d e m i o l o g i c a l l y I would t h i n k t h i s v e r y u n s a t i s f a c t o r y i n p r e s e n t day i n v e s t i g a t i o n because each would n e c e s s a r i l y be s e l e c t e d and s e l e c t i n g one would exclude the other. Some Authors have used the f o l l o w up o f u n t r e a t e d cases from the p a s t c o n t r a s t i n g t h e i r s u r v i v a l w i t h t r e a t e d cases o f more re c e n t times. They suggested t h e d i f f e r e n c e i n s u r v i v a l curves proves the importance o f not d e l a y i n g . I do not t h i n k t h a t t h i s i s a c c e p t a b l e . The u n t r e a t e d p a t i e n t s c o u l d be q uestioned from the p o i n t o f view o f t h e i r s e l e c t i o n . Grading and s t a g i n g has changed over the decades which makes comparison d i f f i c u l t . F o r the purpose o f t h i s t h e s i s I am not q u e s t i o n i n g the d i f f e r e n c e between t r e a t e d and u n t r e a t e d but q u e s t i o n i n g the d i r e c t r e l a t i o n s h i p between de l a y and s u r v i v a l . Does p a t i e n t d e l a y i n a spectrum o f t r e a t e d p a t i e n t s have any i n f l u e n c e i n outcome? The most thorough and recent review o f delay time has 31 been c a r r i e d out by H.J.G. Bloom under the t i t l e o f "The I n f l u e n c e o f Delay on the N a t u r a l H i s t o r y and Prognosis of B r e a s t Cancer". (14) I t was a study o f cases f o l l o w e d f o r f i v e t o twenty y e a r s . He examined the p r e v i o u s l i t e r a t u r e , some o f which has been examined i n t h i s t h e s i s , and found as I have, two oppos-i n g views. Both views are supported by a wealth o f l i t e r a -t u r e . The f i r s t view which i s g e n e r a l l y the e s t a b l i s h e d t e a c h i n g on the s u b j e c t i s t h a t the g r e a t e r the d e l a y the worse the p r o g n o s i s . The second view i s t h a t p r e v i o u s l y d i s c u s s e d under Park and Lees (1951) (6) , - the s u r v i v a l o f a p a t i e n t does not n e c e s s a r i l y decrease w i t h i n c r e a s i n g de-l a y . Bloom drew our a t t e n t i o n t o a p r e v i o u s r e p o r t (10) o f 470 cases i n which t h e 5-year s u r v i v a l r a t e f o r p a t i e n t s coming w i t h i n 3 months was 51 p e r c e n t , between 3 t o 6 months 47 p e r c e n t , and a f t e r 12 months or more 52 p e r c e n t . With t h i s i n mind Bloom i n v e s t i g a t e d the e f f e c t o f d e l a y on prog-n o s i s o f a s e r i e s o f b r e a s t cancer cases i n which a pro-longed p e r i o d o f f o l l o w up was a v a i l a b l e . The study con-s i s t e d o f 1411 cases seen between 1936 and 1949 at the M i d d l e s e x H o s p i t a l , London. On reviewing the t o t a l cases, 64 percent attended w i t h -i n 6 months o f f i r s t symptom and 82 percent w i t h i n one y e a r . L e s s than h a l f the p a t i e n t s (45 percent) came * v i t h i n 3 months and o n l y 16 percent w i t h i n one month; 18 percent delayed f o r more than one year and 8 p e r c e n t f o r more than 32 2 y e a r s . Bloom compared each group o f 5, 10, 15 and 20 ye a r s u r v i v a l r a t e s a g a i n s t the d e l a y times, demonstrating no c o n s i s t e n t d i f f e r e n c e s w i t h i n c r e a s i n g d e lay. H.J.G. BLOOM (14) TABLE 1 - Delay and Prognosis 5 Year 10 Year Cases S u r v i v a l 0 / Cases Surviv; 0 / 3 months . 571 /a . 53 . 556 % . 36 3-6 . 235 . 44 . 231 . 29 6-12 H . 232 . 45 . 223 . 31 12-18 i i . 58 . 52 . 55 . 29 18-24 i i . 65 . 51 . 61 . 31 2-3 years . 39 . 49 . 38 . 37 3 I I . 63 . 56 . 61 . 38 T o t a l .1263 . 50 .1225 . 33 3 months . 571 . 53 . 556 . 36 3-6 . 235 . 44 . 231 . 29 6-12 . 232 . 45 . 223 . 31 1 year . 225 . 52 . 215 . 33 33 15 Year- 20 Year Cases S u r v i v a l Cases S u r v i v a l % % 3 months . 425 . 24 . 180 . 16 3-6 . 191 . 19 . 83 . 18 6-12 II . 172 . 25 . 79 . 19 12-18 II . 40 . 28 . 19 . 16 18-24 II . 47 . 21 . 20 . 25 2-3 yea r s . 34 . 32 9 . 11 3 II . 42 . 21 9 . 22 T o t a l . 951 . 24 . 399 . 18 3 months . 425 . 24 . 180 . 16 3-6 •I . 191 . 19 . 83 . 18 6-12 ii . 172 . 25 . 79 . 19 1 year . 163 . 25 . 57 . 19 He f e l t t h a t t h i s d i d not g i v e a t r u e p i c t u r e purpose of h i s paper was t o show t h a t i t does not. The q u e s t i o n s which he f e l t needed answering were whether carcinoma o f the b r e a s t advances d u r i n g the d e l a y p e r i o d , and, i s t h i s advancement important t o the outcome? He reviewed i n d i v i d u a l tumour f a c t o r s such as s i z e o f primary growth, lymph node involvement, c l i n i c a l stage and o p e r a b i l -i t y and f e l t they r e f l e c t tumour p o t e n t i a l as regards d e l a y to a l i m i t e d e x t e n t . I f c l i n i c a l stage and h i s t o l o g i c a l grade were used t o show the i n f l u e n c e o f delay, s u r v i v a l was a f f e c t e d by i n c r e a s i n g d e l a y . I n the c o n c l u s i o n Bloom s a i d t h e i n f l u e n c e o f d e l a y on p r o g n o s i s must take i n t o account the i n t r i n s i c b i o l o g i c a l nature o f the tumour. The tumour f a c t o r s , c l i n i c a l stage and h i s t o l o g i c a l grade were s u r e l y j u s t s i g n p o s t s on a " f i x e d s u r v i v a l s c a l e " (a phrase used i n h i s conclusion) and do not r e f l e c t the " i n t r i n s i c b i o l o g i c a l nature" o r MacDonald's (4) term 34 " b i o l o g i c predeterminism" o f the tumour. He admitted t h a t a well-marked d i r e c t c o r r e l a t i o n be-tween d e l a y and s u r v i v a l had not been the experience o f most i n v e s t i g a t o r s . In a more s p e c u l a t i v e frame o f mind he suggested changes i n t h e tumour-host r e l a t i o n s h i p w i t h time might a f f e c t prog-n o s i s . He concluded i n view o f t h i s unanswered q u e s t i o n de-l a y should be continued t o be avoided. He then admitted the o v e r a l l improvement i n s u r v i v a l r e s u l t i n g from e f f o r t s t o reduce d e l a y alone i s l i k e l y t o be l i m i t e d . I t would seem i n t h i s paper a d i r e c t c o r r e l a t i o n between d e l a y and su r -v i v a l has not been demonstrated. S h e r i d a n e t a l (11) (1971) made a n a l y s i s o f 1,840 cases seen at an A u s t r a l i a n t e a c h i n g h o s p i t a l between 1954 and 1965 t o examine the r e l a t i o n s h i p o f d e l a y i n treatment and outcome and a l s o t o e x p l o r e why and where such d e l a y s may occur. He used c l i n i c a l s t a g i n g t o d e f i n e h i s cases and suggested t h a t t h i s was a sa f e assumption because h i s patho-l o g i c a l f i n d i n g s s u b s t a n t i a t e d the c l i n i c a l f i n d i n g s . The a n a l y s i s o f d e l a y used stage 1 t o c a l c u l a t e a d e l a y p a t t e r n t o compare w i t h the a c t u a l o r observed case r a t e i n the o t h e r stages. They compared the s u r v i v a l s o f the ex-pected and observed i n each c l i n i c a l stage l e v e l a g a i n s t d e l a y . The c o n c l u s i o n was made t h a t i n t h i s s e r i e s the more advanced the c l i n i c a l stage, the worse the f a t e o f the p a t i e n t . I do not t h i n k t h a t t h i s i s a reasonable c o n c l u s i o n 35 on the graphic evidence, more that i t shows a " b i o l o g i c a l predeterminism" at each c l i n i c a l stage l e v e l i r r e l e v a n t to delay e s p e c i a l l y i n stage 111 and IV. The following were the f i v e year s u r v i v a l rates of stage 1 and stage 11 for d i f f e r e n t delay periods found i n t h e i r analysis:-Stage 1 Treatment i n l e s s than 4 weeks from f i r s t symptom 74% Treatment i n 5 to 12 weeks from f i r s t symptom 76% Treatment i n 3 to 6 months from f i r s t symptom 85% Treatment i n 6 to 9 months from f i r s t symptom 83% Treatment begun l a t e r than 9 months from f i r s t symptom 73% Stage 11 Treatment i n less than 4 weeks from f i r s t symptom 65.8% Treatment i n 5 to 12 weeks from f i r s t symptom 55.9% Treatment i n 3 to 6 months from f i r s t symptom 59.5% Treatment i n 6 t o 9 months from f i r s t symptom Treatment begun l a t e r than 9 months from f i r s t symptom 46.8% They commented stage 1 percentages d i d not suggest delay was a factor. They suggested that there may be bias because the patients i n the f i r s t few weeks contain a number i n whom the disease was going to develop rapidly, presumably 36 s u g g e s t i n g t h a t the s h o r t delay f i g u r e s would be b e t t e r but t h i s would suggest a success r a t e f o r treatment t h a t does not e x i s t . Stage 11 f i g u r e s were d e s c r i b e d as showing a d e t e r i o r a t i o n through the d e l a y p e r i o d s , and i t would appear c l e a r t h a t the e a r l i e r the p a t i e n t i n stage 11 was operated upon, the b e t t e r chance she would, have o f s u r v i v a l . I f we examine the f i r s t t h r e e l e v e l s o f d e l a y we a c t u a l l y see a r i s e i n the t h i r d f i g u r e and a d i f f e r e n c e o f o n l y 5-10 per-cent as d e s c r i b e d by Park and Lees. (6) There i s no f i g u r e f o r 6-9 months and c e r t a i n l y over 9 months i s a v e r y broad range and c o u l d l e a d t o b i a s t o -wards a poor percentage. I do not t h i n k by any means the d i r e c t r e l a t i o n s h i p o f d e l a y and s u r v i v a l c o u l d be regarded as proven. The paper concluded with an a n a l y s i s of t h e nature o f d e l a y . With age i n r e l a t i o n t o d e l a y the a n a l y s i s suggested the younger the p a t i e n t the s h o r t e r the d e l a y . An a n a l y s i s o f p a t i e n t ' s d e l a y and time brought out the f i n d i n g t h a t t h e r e had been no change i n d e l a y . T h i s i s s u r p r i s i n g and t h e i r c o n c l u d i n g comments are worth r e i t e r a t i n g -" I f the propaganda had been s u c c e s s f u l over the p e r i o d , then the numbers of p a t i e n t s coming f o r a d v i c e e i t h e r because o f s e l f - e x a m i n a t i o n o r because o f d e l i b e r a t e l y s e e k i n g a "cancer check up" should be i n c r e a s i n g " . I t i s a p t l y summarized i n t h e i r t a b l e -37 METHOD OF DISCOVERY OF THE FIRST SYMPTOM P e r i o d Method o f D i s c o v e r y 1954-1957 1958-1961 1961-1965 TOTAL Found by P a t i e n t 97.8% 91.2% 96. 1% 96.7% S e l f -Examination 0.35% 0.54% 0.76% 0.63% M e d i c a l Examination 1.7% 2.1% 3.0% 2.5% 38 3.2 FACTORS INFLUENCING DELAY TIME The l i t e r a t u r e I have reviewed so f a r has looked at the importance of the r e l a t i o n s h i p o f d e l a y and s u r v i v a l . To complete t h e understanding o f d e l a y I f e e l i t i s a l s o necessary to l o o k at f a c t o r s i n f l u e n c i n g and m o t i v a t i n g d e l a y and a l s o some o f the c h a r a c t e r i s t i c s o f d e l a y . Waxman (1959) (16) made a study o f the e f f e c t s o f demo-gr a p h i c and economic f a c t o r s from r e c o r d s o f 740 p a t i e n t s admitted c o n s e c u t i v e l y v/ith cancer o f t h e b r e a s t to the H o s p i t a l o f The U n i v e r s i t y o f P e n n s y l v a n i a . Only t h e r e -cords o f 633 p a t i e n t s were found s a t i s f a c t o r y and adequate i n f o r m a t i o n was o b t a i n e d f o r a l l except 3 p e r c e n t . The r e -cords were f o r the y e a r s 1943 t o 1951. The mean age o f t h i s s e r i e s was 53.7 y e a r s and the authors f e l t at t h a t time t h i s age was c o n s i s t a n t w i t h f i n d -i n g s r e p o r t e d by o t h e r s . (17) An examination o f t h e i r m a r i t a l s t a t u s r e v e a l e d , 67 p e r c e n t married, 16 p e r c e n t x^idowed, 13 p e r c e n t s i n g l e and 3 p e r c e n t d i v o r c e d . They used the p r i c e o f the h o s p i t a l bed t o d e f i n e t h e i r economic s t a t u s . The d i s t r i b u t i o n found was as f o l l o w s : 36 percent ward p a t i e n t s , 46 p e r c e n t occupied s e m i - p r i v a t e and 18 percent were i n p r i v a t e rooms. T h i s would not be a p p l i c a b l e to any study i n Canada. They saw a t r e n d i n t h e i r study o f e a r l i e r r e p o r t i n g o f symptoms w i t h i n c r e a s i n g y e a r s , which they concluded was due t o t h e r e s u l t o f i n c r e a s i n g p u b l i c i t y about cancer. T h i s was not a f i n d i n g i n data o f o t h e r s . (29) (32) T h e i r f i n d -39 i n g s on de l a y suggested the h i g h e r the income the e a r l i e r the p a t i e n t s c o n s u l t t h e i r d o c t o r . N e i t h e r age nor m a r i t a l s t a t u s a f f e c t e d t he chances o f s u r v i v a l i n t h i s s e r i e s . They concluded from t h e i r r e s u l t s the people who have a sh o r t d e l a y have a b e t t e r chance o f s u r v i v a l . G o l d (1964) (18) i n "Causes o f P a t i e n t s * Delay i n Dis e a s e s o f t h e Br e a s t " suggested t h a t c u r r e n t methods o f educ a t i n g the p u b l i c were o f t e n not e f f e c t i v e , i n t e r v i e w s were c a r r i e d out on 150 p a t i e n t s a t t e n d i n g t h e F r a n c i s D e l a f i e l d H o s p i t a l , New York, f o r suspected d i s e a s e s o f t h e b r e a s t , a hundred o f which subsequently were diagnosed as having cancer o f the b r e a s t . V a r i o u s reasons were gi v e n f o r d e l a y and were summa-r i z e d under t h e f o l l o w i n g headings, socio-economic pro-blems, l a c k o f i n f o r m a t i o n and te m p o r i z i n g medical a d v i c e . Seventeen percent o f the women r e p o r t e d t h a t f i n a n c i a l p r o -blems d e f e r r e d them from seeking e a r l y treatment, some o f the p a t i e n t s were working mothers and i n some cases the o n l y wage earner. I n these cases f i n d i n g the time t o at t e n d de-f e r r e d examination. Lack o f i n f o r m a t i o n was a s u r p r i s i n g complaint i n view o f r e c e n t p u b l i c i t y . Some had miscon-c e p t i o n s but one o f t e n women r a t i o n a l i z e d the lump away by a t t r i b u t i n g i t t o trauma. Twenty-three p e r c e n t o f women thought the lump v/as a minor o r temporary c o n d i t i o n and ex-pected i t t o di s a p p e a r . I t i s i n t e r e s t i n g i n the s e r i e s the average s i z e o f b r e a s t cancer tumour was 6 cm. compared t o 40 non-cancerous lumps which were 2.5 cm. That i s not an i n -s i g n i f i c a n t s i z e . N i n e t y - f o u r percent o f the women were not taught the proper technique o f b r e a s t examination. Seventeen pe r c e n t o f the p a t i e n t s had v i s i t e d a doct o r b ut r e c e i v e d t e m p o r i z i n g medical a d v i c e . P s y c h o l o g i c a l f a c t o r s and b e h a v i o u r a l p a t t e r n s were examined i n t h i s paper. Of these the f o l l o w i n g were found t o c o n t r i b u t e t o d e l a y : - f e a r and an x i e t y , s i x t y - o n e o f the women i n the study delayed because they f e a r e d t h a t the lump was cancer. Twenty-one f e a r e d t h a t the o p e r a t i o n would a f f e c t t h e i r s e x u a l r e l a t i o n s e s p e c i a l l y i n those whom r e l a t i o n s were good. Other f e a r s were the o p e r a t i o n , the p o s s i b i l i t y o f death and d o c t o r s i n g e n e r a l . F a l s e modesty, shyness and l a c k o f t a c t i l i s m would appear t o p l a y an important p a r t i n i n f l u e n c i n g the d e l a y time. These f a c t o r s were s t r o n g l y a f f e c t e d by f a m i l y h i s -t o r y and u p b r i n g i n g . Women who have never had p l e a s u r a b l e s e n s a t i o n s i n t h e i r b r e a s t s d i s p l a y n e g a t i v i s t i c behaviour. Negative a t t i t u d e s were prominent i n the behaviour o f pa-t i e n t s who dela y e d s e e k i n g treatment. These p a t i e n t s found i t d i f f i c u l t to make the d e c i s i o n t o come f o r examination and f r e q u e n t l y came too l a t e . I n i n o p e r a b l e cancer 56 per-cent l a c k e d p l e a s u r a b l e f e e l i n g s i n the b r e a s t and seemed i n c a p a b l e of even r e c o g n i z i n g changes i n t h e i r b r e a s t s . Gold i n summary suggested f u r t h e r study should be made o f these f a c t o r s i n r e l a t i o n t o d e l a y . T h i s would seem a 41 p r i o r i t y i n view o f the p o s s i b i l i t y o f u s i n g s c r e e n i n g pro-cedures such as mammography on a u n i v e r s a l b a s i s . Those p a t i e n t s who d e l a y f o r the reasons j u s t d i s c u s s e d are' even more u n l i k e l y t o a t t e n d such c l i n i c s . T h e r e f o r e t h e i r prime purpose would be negated. F i s h e r (1967) (19) i n c o n t r a s t to G o l d found d e l a y i n seeking treatment f o r cancer symptoms was l i k e l y t o be g r e a t e s t i n those women \izho were independent, autonomous, possessed o f a c l e a r sense o f i d e n t i t y and r e l a t i v e l y un-concerned. These c o n c l u s i o n s were made on examining o n l y 28 women w i t h b r e a s t tumours and 34 women w i t h cancer o f the c e r v i x . Cameron e t a l (1968) (20) made a study o f 83 women ad-m i t t e d to Middlesex H o s p i t a l , London, England f o r an oper-a t i o n on the b r e a s t . They found the major element o f d e l a y v/as p a t i e n t d e l a y . T h i r t y - e i g h t p e r c e n t r e p o r t e d w i t h i n a week, 61 percent w i t h i n a month, 20 percent had delayed, more than 3 months. F i f t y - s e v e n cases were malignant and 26 were benign. A v e r y i n t e r e s t i n g f i n d i n g - p a t i e n t s w i t h malignant tumours delayed l o n g e r . S i x t y - e i g h t percent o f those w i t h benign tumours came w i t h i n a week i n c o n t r a s t t o 25 p e r c e n t w i t h carcinoma. S i x p a t i e n t s (10%) w i t h cancer d e l a y e d f o r one y e a r o r more. F a c t o r s which might be asso-c i a t e d with d e l a y v/ere examined. Symptoms such as p a i n did. not appear t o shorten d e l a y . Seventy percent presented w i t h a p a i n l e s s lump. P r e v i o u s h o s p i t a l experience d i d not have 42 any e f f e c t on d e l a y . A n x i e t y d i d not d e l a y people s i g -n i f i c a n t l y more than those who were c o n f i d e n t . I f any-t h i n g i t would appear t o encourage them t o see t h e i r d o c t o r e a r l i e r . They found t h a t i f a c l o s e r e l a t i v e o r f r i e n d had b r e a s t cancer they were e q u a l l y d i s t r i b u t e d amongst s h o r t and long d e l a y s . Consciousness o r concern over h e a l t h showed no r e l a t i o n s h i p t o the p a t i e n t ' s de-l a y i n g . Examining t h e reasons i n those who d e l a y e d they f e l l i n t o t h r e e c a t e g o r i e s , f e a r , v a r i o u s domestic reasons and those who f e l t they had l i t t l e reason t o c o n s u l t t h e i r d octor, d i s p l a y i n g ignorance o r a c a p a c i t y t o i g n o r e . Age made no s i g n i f i c a n t d i f f e r e n c e t o d e l a y but the l e n g t h o f formal e d u c a t i o n d i d have a r e l a t i o n s h i p . The more s c h o o l i n g the p a t i e n t r e c e i v e d the s h o r t e r the d e l a y . In summary i n t h i s s e r i e s o f p a t i e n t s w i t h mammary cancer, 54 percent delayed l e s s than a month and twenty-th r e e percent more than 3 months. These f i g u r e s were i n marked c o n t r a s t t o those found by Bloom (14) whose f i n d i n g s were d i s c u s s e d e a r l i e r and t o o t h e r authors. (21) (22.) The s e r i e s i s s m a l l and t h e r e may be some s e l e c t i o n b i a s . I n c o n t r a s t Lynch and Krush (1969) (23) (24) (25) found the o p p o s i t e p i c t u r e at the U n i v e r s i t y o f Nebraska Cancer Chemotherapy C l i n i c . Of e i g h t y - f i v e p a t i e n t s a t t e n d -i n g a m e d i c a l b r e a s t c l i n i c f i f t y - f o u r percent delayed one y e a r or l o n g e r , and o f e i g h t y - f i v e p a t i e n t s seen at a s u r -g i c a l b r e a s t c l i n i c 24 percent delayed one y e a r or l o n g e r . 43 P a t i e n t s i n these groups de l a y e d because o f misconceptions and f a i l u r e t o r e c o g n i z e s e r i o u s symptoms. F e a r d e t e r r e d p a t i e n t s from e a r l y treatment and o t h e r reasons were f a m i l y i l l n e s s and f i n a n c i a l problems. Greer (1974) (26) reviewed a t o t a l o f 160 p a t i e n t s admitted t o Kings C o l l e g e H o s p i t a l f o r b r e a s t tumour b i o p s y , comprising 69 w i t h cancer and 91 with benign tumours o f the b r e a s t . The f o l l o w i n g t a b l e from t h e i r r e p o r t d i s p l a y s p a t i e n t d e l a y time. INTERVAL BETWEEN FIRST SYMPTOM AND FIRST MEDICAL EXAMINATION (MONTHS) DIAGNOSIS <1 1-2 3-12 > 12 TOTAL BENIGN 67(74%) 5(6%) 13(14%) 5(6%) 90 CANCER 33(49%) 12(18%) 18(27%) 4(6%) 67 We see i n t h i s , f i n d i n g s s i m i l a r t o those o f Cameron and H i n t o n (20) who demonstrated s i g n i f i c a n t l y l o n g e r d e l a y times i n p a t i e n t s w i t h a malignant tumour than a benign tumour. I n t h i s s e r i e s Greer f e l t t h a t f e a r o f cancer and d i s f i g u r e m e n t from o p e r a t i o n were prominent reasons f o r d e l a y . Domestic problems were a l s o reasons f o r d e l a y . The s i g n i f i c a n c e o f the lump i n d e l a y e r s was s m a l l , a f i n d i n g i n p r e v i o u s d i s c u s s e d l i t e r a t u r e . T h i s , suggests Greer, i s a d e n i a l r a t h e r than an ignorance; an i n a b i l i t y t o f a c e a p o s s i b l e c r i s i s i n t h e i r l i v e s . I n t h i s paper i t v/as found 44 t h a t medical d e l a y had c o n t r i b u t e d i n as many as 19% o f t h e cancer p a t i e n t s . Rimsten and S t e n k v i s t (1975) (27) found a "docto r s delay" o f 17 percent on examining 115 p a t i e n t s w i t h b r e a s t cancer i n t h e County o f Upp s a l a d u r i n g a 15 month p e r i o d . F i n k (1976) (28) examined d e l a y behaviour i n b r e a s t cancer s c r e e n i n g o f about 31,000 women aged 40-64, u s i n g two s t r a t i f i e d random samples, one de s i g n a t e d as the study group and the othe r as t h e c o n t r o l group. I n a c h i e v i n g a rea s o n a b l y h i g h r a t e o f response f o r the study group v a r i o u s l e v e l s o f l o b b y i n g were used. They were l a b e l l e d a c c o r d i n g t o e f f o r t needed and the r e s u l t s bear a remarkable resem-b l a n c e t o the d e l a y p i c t u r e i n carcinoma o f b r e a s t i n c l i n i -c a l l y p r e s e n t i n g cases. Among a l l the women i n the study sample both examined and not examined, 47% were i n the " m i n o r i t y e f f o r t group", 7% i n the "secondary e f f o r t group", 10 percent i n t h e "repeated e f f o r t group", and 35% were non-p a r t i c i p a n t s . I t would appear t h e r e was c o n s i d e r a b l e s e l f s e l e c t i o n i n mammography s c r e e n i n g . 45 3.3 CHARACTERISTICS OF DELAY IN RECENT YEARS AND FACTORS INFLUENCING THE COURSE AND SURVIVAL OF BREAST CANCER OTHER THAN TREATMENT  Be f o r e c o n c l u d i n g a review o f the l i t e r a t u r e on d e l a y i n carcinoma o f the b r e a s t i t would seem opportune t o loo k at d e l a y c h a r a c t e r i s t i c s i n r e c e n t y e a r s , and f a c t o r s i n -f l u e n c i n g t h e course and s u r v i v a l o f b r e a s t cancer p a t i e n t s . Hackett e t a l (1973) (29) examined p a t i e n t d e l a y i n cancer and f a c t o r s t h a t might c o n t r i b u t e t o d e l a y . T h e i r survey was conducted between 1968 and 1970 at the Massa-c h u s e t t s G e n e r a l H o s p i t a l and co n t a i n e d 563 p a t i e n t s of which 88 were carcinoma o f t h e b r e a s t . The l e n g t h o f d e l a y was not r e l a t e d t o age or sex. T h i r t y - t h r e e p o i n t e i g h t percent came w i t h i n one month and. 61 percent w i t h i n 3 months. F i f t e e n p o i n t s i x percent delayed l o n g e r than one year. U s i n g the index o f s o c i a l p o s i t i o n , d e r i v e d from H o l l i n g s -head t h e i r r e s u l t s suggest a r e l a t i o n s h i p between s o c i a l c l a s s and dela y ; the h i g h e r the c l a s s , the l e s s the delay. The H o l l i n g s h e a d index o f s o c i a l p o s i t i o n i n c l u d e s both o c c u p a t i o n and education, w i t h the former more h e a v i l y weighted. P a t i e n t s w i t h b r e a s t cancer responded most rap-i d l y i n comparison w i t h other cancers. T h i s i s understand-a b l e as 80 percent (30) (31) o f cancers o f b r e a s t present w i t h a lump. A n x i e t y o r f a m i l y h i s t o r y o f cancer d i d not have any a f f e c t on d e l a y . Worry or f e a r c o u l d be counter p r o d u c t i v e and produce a d e n i a l and f a t a l i s m i n p a t i e n t s . Longer, r a t h e r than s h o r t e r d e l a y c o u l d occur w i t h more i n f o r m a t i o n without the assurance t h a t cancer i s c u r a b l e . 46 I t i s n o t a b l e i n t h i s s e r i e s o f p a t i e n t s 8 percent avoided medical h e l p u n t i l they c o u l d no lon g e r operate independent-l y . The authors suggested t h a t i n the g e n e r a l p o p u l a t i o n the f i g u r e may be as h i g h as 10 t o 20 percent. These pa-t i e n t s may never see a d o c t o r and do not respond t o any form o f e d u c a t i o n o r i n f o r m a t i o n program. Delay i n f a c t i s a conscious and d e l i b e r a t e a c t i n s p i t e o f awareness and the i n f o r m a t i o n s u p p l i e d . These are c e r t a i n l y i n t e r e s t i n g con-c l u s i o n s f o r anyone who i s c o n s i d e r i n g embarking on an e d u c a t i o n a l campaign. Dennis et a l (1975) (32) reviewed 237 p a t i e n t s who had undergone r a d i c a l mastectomies f o r carcinoma o f the b r e a s t d u r i n g a f i v e y e a r p e r i o d from January 1965 to December 1970, at t h e S t a t e U n i v e r s i t y H o s p i t a l - Kings County H o s p i t a l Center, New York. The f o l l o w i n g p a t i e n t d e l a y was found:-The average age o f the p a t i e n t s was 52.3 ye a r s and the aver-age p a t i e n t ' s d e l a y was 4.8 months. The 4.8 months i s o f l i t t l e s i g n i f i c a n c e i n comparison wi t h the percentages f o r v a r i o u s d e l a y p e r i o d s (above) which g i v e a complete and comparable p i c t u r e . I t i s i n t e r e s t i n g though, when com-pared w i t h f i g u r e s i n the i n t r o d u c t i o n t o Hackett e t a l (29) <1 month 16.8% 16.4% 9.2% 10.5% 23.2% 16.4% 7.5% 1 month 2 months 3 months 4-8 months 8-12 months >12 months 47 which showed the p a t i e n t s w i t h a tumour at the Massachusetts General H o s p i t a l had the f o l l o w i n g d e l a y : - p a t i e n t s seen between 1917 and 1918 an average d e l a y o f 5.4 months, aver-age o f 4 months 1921 t o 1922 and i n 1930 an average d e l a y o f 4.8 months. The p i c t u r e has not changed over the y e a r s . Dennis e t a l (32) examined d e l a y i n r e l a t i o n to sur-v i v a l and r e c u r r e n c e and found no s i g n i f i c a n t r e l a t i o n s h i p between d e l a y and s u r v i v a l . S u r v i v a l v/as r e l a t e d t o r a t e o f growth, tumour s i z e , lymph node involvement, the number and l o c a t i o n of lymph nodes i n v o l v e d , b l o o d v e s s e l i n v a s i o n and the presence o f systemic metastases. They f e l t though t h a t the l a c k of c o r r e l a t i o n between d e l a y and treatment d i d not n e c e s s a r i l y mean e a r l y treatment was without v a l u e . The c o n c l u s i o n was t h a t the l i f e h i s t o r y o f the tumour was not synonymous wit h the d u r a t i o n o f symptoms and f a c t o r s such as tumour-host r e l a t i o n s h i p p l a y e d a more important p a r t i n the outcome. T h i s was a p o i n t which had been s t r e s s -ed by MacDonald, (5) S u t h e r l a n d (9) and Bloom. (14) P a t i e n t d e l a y had not been w e l l enough d e f i n e d i n terms o f psycho-l o g i c a l f a c t o r s t o develop an e d u c a t i o n a l or i n f o r m a t i o n programme which would i n f l u e n c e delay. Our a t t e n t i o n has been drawn to f a c t o r s i n f l u e n c i n g course and s u r v i v a l o t h e r than t h e treatment g i v e n . Cer-t a i n l y t h e stage o f advancement, r a t e o f growth, l i a b i l i t y t o d i s s e m i n a t i o n may be o f more importance t o the i n d i v i d u a l than delay. There i s no doubt o f the s i g n i f i c a n c e f o r 48 s u r v i v a l , o f s i t e o f o r i g i n o f the tumour w i t h i n the b r e a s t . (12) The l i t e r a t u r e i s e x t e n s i v e on c o n f i r m i n g the impor-tance o f these other f a c t o r s . (34, 35, 36) W i l l i a m s et a l (1976) (30) made a study o f 158 women wi t h p o s s i b l e d i s e a s e o f t h e b r e a s t at t h e U n i v e r s i t y Hos-p i t a l o f Wales B r e a s t C l i n i c . The p r e s e n t i n g symptom i n 81 pe r c e n t was a p a l p a b l e lump. Twenty-five percent o f these lumps were found by r o u t i n e s e l f - e x a m i n a t i o n . They seemed t o re g a r d t h i s as a low f i g u r e but i f one looks again at t h e t a b l e a b s t r a c t e d from S h e r i d a n e t a l (15) i t i s q u i t e a remarkable response. I t may be the way i n which the ques-t i o n was asked and the s t r e s s t h a t was put on r o u t i n e . They found a s i g n i f i c a n t d i f f e r e n c e i n d e l a y a c c o r d i n g t o age groups. T h i s was not a prominent f i n d i n g i n e a r l i e r reviews o f delay. F o r t y - t h r e e percent o f women under 35 y e a r s attended w i t h i n one week o f onset o f symptoms i n comparison t o 19 pe r c e n t over 35 y e a r s of age. A l s o , o f g r e a t i n t e r e s t was t h a t 30 p e r c e n t o f married women with c h i l d r e n delayed more than 3 months i n comparison w i t h 8 percent i n the r e s t o f the group. Gold, (18) Greer (26) and Cameron (20) have expressed domestic and f i n a n c i a l problems as causes o f de-l a y . T h i s may be t h e reason f o r t h i s d e l a y s t a t i s t i c f o r m arried women with c h i l d r e n . The p o s s i b l e reason f o r d i f -f e r e n t response i n the two age groups i s t h a t these women were p r e s e n t i n g with p o s s i b l e b r e a s t d i s e a s e , not diagnosed carcinoma o f the b r e a s t . As we have seen i n Greer (26) the 49 del a y p a t t e r n between the benign group o f p a t i e n t s and those w i t h carcinoma i s somewhat d i f f e r e n t . The younger age group w i l l c o n t a i n predominantly benign d i s e a s e (see Gold's (18) Ta b l e below). Thus, g i v e n t h a t e a r l y response t o d e l a y we see i n Greer's (26) r e s u l t s w i t h benign d i s e a s e t h a t any c o n c l u s i o n s on change o f d e l a y w i t h age i n carcinoma o f the b r e a s t c o u l d be questioned. AGE DISTRIBUTION OF WOMEN IN STUDY Age Group No. o f P a t i e n t s No. o f P a t i e n t s Without Cancer Ttfith Cancer <30 11 0 30-39 7 7 40-49 18 25 50-59 8 24 60-69 3 20 70> __3 24 TOTAL 50 100 G o l d 1964 (18) The l e v e l of e d u c a t i o n i n t h i s study seemed t o have l i t t l e impact on d e l a y . T h i s i s i n c o n t r a s t t o the s t u d i e s o f Hackett e t a l , (29) and Cameron and H i n t o n . (20) The f o l l o w i n g was the d i s t r i b u t i o n o f d e l a y i n t h i s s e r i e s o f p a t i e n t s % -< 1 week 20% 1 week - 1 month 26% 1- 2 months 15% 2- 3 months 6% > 3 months 23% S i x t y - s e v e n p e r c e n t delayed l e s s than 3 months. 50 A response which i s v e r y i n t e r e s t i n g i s t h a t 77 percent o f p a t i e n t s admitted d e l i b e r a t e l y d e l a y i n g a f t e r n o t i c i n g the lump i n the b r e a s t . There was no undue doct o r d e l a y i n t h i s s e r i e s , 80 percent o f p a t i e n t s b e i n g r e f e r r e d immedi-a t e l y and 92 percent w i t h i n a month. Gold (18) i n r e v i e w i n g p s y c h o l o g i c a l f a c t o r s and be-h a v i o u r a l p a t t e r n s i n d e l a y d i s c u s s e d the p l a c e o f modesty, shyness and l a c k o f t a c t i l i s m i n r e l a t i o n t o d e l a y . I t i s t h e r e f o r e n o t a b l e t h a t i n t h i s paper 30 percent admitted t o embarrassment when examined by a male d o c t o r and 50 percent would have p r e f e r r e d t o have seen a female d o c t o r . I n c o n c l u s i o n they found t h a t e d u c a t i o n so f a r has been l a r g e l y i n e f f e c t i v e . L i k e Lynch and Krush (23) they suggest the p o s s i b i l i t y of e d u c a t i n g g i r l s w h i l e they are s t i l l a t s c h o o l may be the answer. 51 4.0 METHODOLOGY OF RESEARCH 4 .1 OBJECTIVES OF STUDY 4.2 DATA SOURCES 4.3 METHODS OF ANALYSIS 52 4 . 1 OBJECTIVES OF STUDY The methodology w i l l have the o b j e c t i v e o f e x p l o r i n g the r e l a t i o n s h i p betxireen d e l a y and s u r v i v a l . I t i s f e l t t h a t comparing those p a t i e n t s w i t h l o n g and s h o r t d e l a y times and t h e i r r e s p e c t i v e s u r v i v a l s w i l l b e s t enable me t o t e s t the h y p o t h e s i s . The f o l l o w i n g v a r i a b l e s w i l l be examined as they appear i n the r e c o r d s : - age, c l i n i c a l stage, p a t h o l o g i c a l stage, p o s i t i o n of tumour, outcome, h i s t o l o g y , m a r i t a l s t a t u s and socio-economic index as d e f i n e d by B l i s h e n (33). These v a r i a b l e s are chosen because they are l i k e l y t o be a s s o c i -ated both with d e l a y time and w i t h s u r v i v a l . A l s o review-i n g the o t h e r v a r i a b l e s a s s o c i a t e d w i t h d e l a y and s u r v i v a l , I w i l l be more l i k e l y t o show d i f f e r e n c e s t h a t may be o f import t o i n f l u e n c i n g d e l a y i n f u t u r e p l a n n i n g . 53 4.2 DATA SOURCES From the p r e l i m i n a r y review of the data a v a i l a b l e i n the c l i n i c a l records o f the Cancer C o n t r o l Agency, the q u a l i t y o f the data can be judged as good. The review o f delay i n the years 1960, 1961 and 1970 shows that delay has not app r e c i a b l y changed i n a decade. In f a c t i t i s remarkable how c l o s e l y the pat t e r n s of delay f o l l o w each other from year to year. There are changes w i t h the three l e v e l s of age s t r a t i f i c a t i o n but they are minimal and not c o n s i s t e n t . The years 1960 t o 1964 i n c l u s i v e are chosen f o r exam-i n a t i o n . T h i s f i v e years' p e r i o d w i l l produce a l a r g e sample f o r a p e r i o d o f time between then and the present, t o g i v e lengthy f o l l o w up periods f o r comparison. Two groups o f women, those w i t h delay periods l e s s than a month, and 12 months and over, are chosen t o compare w i t h respect t o s u r v i v a l . These two delay periods w i l l give a balanced number o f cases and allows comparison o f two ex-tremes o f delay time. The f o l l o w i n g pages gi v e a data l i s t review w i t h d e f i -n i t i o n s o f the va r i o u s v a r i a b l e s . The column numbers given at the r i g h t of the page i n r e l a t i o n to each v a r i a b l e , repre-sent coding f o r t r a n s c r i p t i o n t o punch cards. Table (XII) shows the data c o l l e c t i o n sheet. Each year i s d e f i n e d and each p a t i e n t i s given an i d e n t i f i c a t i o n number f o r r e c a l l . C l i n i c a l stage i s coded by stage number as d e f i n e d i n Table ( X I I I ) . P a t h o l o g i c a l 54 s t a g i n g i s noted i n a s i m i l a r manner, zero r e c o r d i n g the absence o f the d a t a . The method o f s t a g i n g i s o u t l i n e d i n T a b l e (XIV) . H i s t o l o g y i s d e f i n e d by the f o u r v a r i a b l e s which were found on the p r e l i m i n a r y d a t a review, d i f f e r -e n t i a t i o n , growth, type and d e s c r i p t i v e p a t h o l o g i c a l t e r m i -nology. B l i s h e n ' s Socio-Economic index i s used i n two ways, f i r s t l y t o g i v e a l e v e l u s i n g t h e husband's o c c u p a t i o n and secondly, by u s i n g the p a t i e n t 1 s o c c u p a t i o n . The B l i s h e n Socio-Economic index i s produced u s i n g the v a r i a b l e s , e d u c a t i o n and income. An o c c u p a t i o n i s r a t e d a c c o r d i n g t o the p r e v a i l i n g l e v e l s o f education and income o f i t s incumbents. The d i v i s i o n i n t o c l a s s l e v e l s i s done on an a r b i t r a r y b a s i s and "the p i c t u r e s which emerge u s i n g d i f f e r e n t c u t t i n g p o i n t s do not much d i f f e r from each other." (33) Seven c l a s s e s are d e f i n e d f o r t h i s purpose from one t o seven. C l a s s one being the lowest, s c o r e s from 20.00 t o 29. 99 and the T h i r t i e t h d e c i l e w i l l be d i v i d e d a r b i t r a r i l y a t 35.00 above and 34.99 below i n t o c l a s s e s two and t h r e e . Scores of 40, 50, 60 and 70 and above w i l l be c l a s s e s 4, 5, 6 and 7 r e s p e c t i v e l y . Zero w i l l denote absence o f i n f o r -mation. 55 4.3 METHODS OF ANALYSIS The r e s u l t s w i l l be reviewed i n t a b l e s comparing t h e long and s h o r t d e l a y p e r i o d s w i t h each v a r i a b l e . A c h i -sguare a n a l y s i s a f t e r Armitage (37) w i l l be used t o examine the r e s u l t s . L i f e t a b l e s (38) (39) w i l l be used t o compare s u r v i v a l f o r both d e l a y p e r i o d s . The r e l a t i v e s u r v i v a l r a t e s w i l l be c a l c u l a t e d from these t a b l e s . The r e l a t i v e s u r v i v a l r a t e i s the r a t i o o f the observed t o the expected s u r v i v a l . The expected s u r v i v a l r a t e s w i l l be those o f a group o f women o f the same age, based on the v i t a l s t a t i s t i c s f o r B r i t i s h Columbia, 1968 - 1972. S u r v i v a l graphs w i l l be drawn t o d i s p l a y these f i g u r e s . 56 DATA LIST AND REVIEW 1. YEAR PRIMARY cases are c o n s i d e r e d from each y e a r 1960-1964 i n c l u s i v e . Primary cases are those de-f i n e d as diagnosed and t r e a t -ment i n t h a t y e a r by the cancer c l i n i c or on immediate r e f e r r a l a f t e r treatment o r d i a g n o s i s elsexvhere. C o l s 1-2 2. IDENTIFICATION NUMBER 3. AGE C o l s 3-8 C o l s 9-10 4. CLINICAL STAGE Coded by stage number as i n t a b l e Stage 1, 2, 3, 4 C o l s 11 5. PATHOLOGICAL STAGE Coded by stage number as d e f i n e d i n t a b l e Stage 1, 2, 3, 4 C o l s 12 6. BREAST L e f t or r i g h t Coded L e f t 1 Right 2 C o l s 13 7. SITE L o c a t i o n i n b r e a s t INNER OUTER 4 1 3 2 5 - Whole b r e a s t 6 - N i p p l e area C o l s 14 57 8. BIOPSY DATE c o l s 15 c o l s 16 MONTH c o l s c o l s 17 18 • • • • YEAR C o l s 15-18 DELAY TIME T h i s i s d e f i n e d as the time from the f i r s t symptom the p a t i e n t complains o f , t o the date o f b i o p s y or b i o p s y -s u r g e r y Given i n months. c o l 19 c o l 20 c o l 21 • • • MONTHS C o l s 19-21 10. SURVIVAL I s d e f i n e d as the time from b i o p s y t o death o r l a t e s t date o f f o l l o w up c o l 22 c o l 23 YEARS c o l 24 c o l 25 • • • • MONTHS C o l s 22-25 11. OUTCOME Coded as: 0 - a l i v e 1 - dead from b r e a s t cancer 2 - dead from o t h e r causes 3 - dead from unknown causes 4 - l o s t t o f o l l o w up C o l s 26 58 12. LENGTH OF S i m i l a r l y d e f i n e d as: SURVIVAL OR S u r v i v a l FOLLOW UP C o l C o l C o l C o l 27 28 29 30 • • • • YEARS MONTHS C o l s 27-30 HISTOLOGY IS DEFINED BY FOUR VARIABLES 13. DIFFERENTIATION Coded W e l l = 1 Moderately o r f a i r l y w e l l = 2 Poor = 3 C o l s 31 14. GROWTH I n s i t u = 1 I n f i l t r a t i n g = 2 C o l s 32 15. TYPE D u c t a l = 01 L u b u l a r = 02 C o l s 33-34 16. DESCRIPTIVE M e d u l l a r y = 03 Tub u l a r = 04 P a p i l l a r y = 05 C o l l o i d o r Mucoid = 06 Ad e n o c y s t i c = 07 S c i r r h o u s Carcinoma = 08 Adenocarcinoma = 09 S c i r r h o u s Adenocarcinoma = 10 Carcinoma = 11 59 Comedo Carcinoma = 12 Carcinoma Simplex = 13 Malig n a n t Cystosarcoma P h y l l o d e s = 14 C a r c i n o Sarcoma = 15 Pagets Disease = 16 C o l s 35 17. MARITAL STATUS Coded: M a r r i e d 1 S i n g l e 2 Widowed 3 Separated/ D i v o r c e d 4 C o l s 36 18. SOCIO- B l i s h e n s Socio-Economic Index ECONOMIC as d e f i n e d by husband's o c c u p a t i o n . Coded: 7,6,5,4,3,2,1,0 C o l s 37 19* B l i s h e n s Socio-Economic Index as d e f i n e d by p a t i e n t ' s o c c u p a t i o n . Coded: 7,6,5,4,3,2,1,0 C o l s 38 TABLE XII SHEET FOR COLLECTING DATA YEAR on Cols 1-2 IDENTIFICATION NO, • • • • • • Cols 3-8 AGE • • Cols 9-10 CLINICAL STAGE Stage 1 2 3 4 • Col 11 PATHOLOGICAL Stage 1 2 3 4 • Col 12 SITE Col 13 Col 14 Left 1 Inner 4 1 Outer Right 2 3 2 DATE OF BIOPSY • • • • Cols 15-18 DELAY TIME • • • Cols 19-21 SURVIVAL • • • • Cols 22-25 OUTCOME 0 1 2 3 4 (See Code) • Col 26 LENGTH OF SURVIVAL OR FOLLOW UP • • • • Cols 27-30 HISTOLOGY Differentiation 1 2 3 Insitu/lnfiltrating Type Descriptive (See Code) • • •n Col 31 Col 32 Cols 33-34 Cols 34-35 MARITAL STATUS • Col 36 SOCIO-ECONOMIC STATUS By Husband By Patient •Coding appears in data list review Col 37 Col 38 61 TABLE XIII CLINICAL STAGING OF CARCINOMA BREAST Paterson STAGE 1 STAGE 11 STAGE 111 STAGE 17 NOTE: Stages 1 and 11 conform to Bri t i s h definition of Early The primary tumour i s freely movable on the pectoral muscle (with muscle contracted) or, i f la t e r a l to the pectoral muscle, movable on the chest wall. Skin involvement, including ulceration, may be present, but such involvement must be i n direct continuity with the tumour and there must not be any extension into the skin wide of the tumour i t s e l f . As Stage 1 but there are palpable mobile lymph nodes i n the a x i l l a of the same side. The primary growth i s more extensive than Stage 1 as shown by: (a) The skin invaded or fixed over an area wide of the tumour i t s e l f , but s t i l l limited to the breast. (b) The tumour fixed to underlying muscle but not to chest wall. Axillary lymph nodes may or may not be palpable, but i f lymph nodes are present, they must be mobile. The growth has extended beyond the breast area, as shown by: (a) Fixation of axillary lymph nodes indicating extension outside the capsule. Tumour fixed to the chest wall. Secondary growth i n supraclavicular lymph nodes. Secondary involvement i n skin wide of the breast. Secondary growth i n opposite breast. Distant metastases, e.g. bone, l i v e r , lung, etc. Inflammatory carcinoma i n Stage I? (D) (c) (d) (e) (f) Paget*s Disease of the nipple i s accepted as a primary carcinoma, and Stages 1 unless palpable lymph nodes are present. 62 TABLE XIV PATHOLOGICAL STAGING OF BREAST CARCINOMA STAGE I Disease confined to the breast. STAGE 1-0 Where the disease i s i n s i t u carcinoma only they w i l l be l i s t e d as Stage 1-0. STAGE II As i n one, plus metastatic disease confined to a x i l l a r y lymph nodes below the l e v e l of the apex. II? Level of involvement unknown. STAGE III Direct l o c a l spread from breast primary to: (a) skin wide of tumour (b) underlying f a s c i a (c) underlying muscle STAGE IV (a) Direct extension from breast primary to r i b or c a r t i l a g e of chest wall. (b) Extension of disease beyond the capsule of an a x i l l a r y lymph node. (c) Involvement of apical or i n t e r n a l mammary lymph nodes or tissues. (d) Involvement of an a x i l l a r y lymph node at any l e v e l which i s found p a t h o l o g i c a l l y to be 2.5 cm. i n size or larger. (e) Distant metastases (including supraclavicular lymph nodes). 63 5.0 RESULTS 5.1 THE DISTRIBUTION OF DELAY TIMES BY YEAR OF DIAGNOSIS, AGE, FIVE YEAR AGE GROUPS, CLINICAL STAGE, PATHOLOGICAL STAGE, BREAST INVOLVED, SITE INVOLVED, HISTOLOGICAL DESCRIPTION, MARITAL STATUS AND SOCIO-ECONOMIC STATUS 5.2 THE ANALYSIS OF THE ASSOCIATION OF DELAY TIME ON SURVIVAL FROM YEAR OF DIAGNOSIS 5.3 THE ANALYSIS OF THE ASSOCIATION OF DELAY TIME ON SURVIVAL FROM DATE OF FIRST SYMPTOM 5.4 THE ANALYSIS OF THE ASSOCIATION BETWEEN DELAY TIME AND SURVIVAL WITH CONTROL FOR OTHER FACTORS 64 5.1 THE DISTRIBUTION OF DELAY TIMES BY YEAR OF. DIAGNOSIS, AGE, FIVE YEAR AGE GROUPS, CLINICAL STAGE, PATHOLOGICAL STAGE, BREAST INVOLVED, SITE INVOLVED, HISTOLOGICAL DESCRIPTION, MARITAL STATUS AND SOCIO-ECONOMIC STATUS The records o f a l l the p a t i e n t s i n both d e l a y groups, d e f i n e d as l e s s than one month and 12 or more months diagno-sed i n 1960, 1961, 1962, 1963 and 1964, were examined. The t o t a l number o f p a t i e n t s was 456. Data was not complete i n every case and the number a v a i l a b l e f o r each v a r i a b l e i s noted w i t h each t a b l e o r s t a t i s t i c a l t e s t . Four hundred and f i f t y - s i x cases were examined f o r t h e i r d i s t r i b u t i o n o f d e l a y by year. There i s an even d i s t r i b u t i o n o f numbers o f cases throughout the y e a r s . T h i s a p p l i e s t o both d e l a y p e r i o d s and i t i s noted t h a t percentage d i s t r i -b u t i o n and numbers of cases v a r i e s l i t t l e from 1960 t o 1964. T h i s confirms the e a r l i e r f i n d i n g i n the P r e l i m i n a r y Data Review t h a t d e l a y has not changed w i t h time. T h i s i s demon-s t r a t e d i n T a b l e XV. T a b l e XVI shows the d i s t r i b u t i o n o f cases i n the d e l a y p e r i o d one year and over by d e l a y time. The t o t a l cases o c c u r r i n g i n the l e s s than one month p e r i o d o f 232 are i n -cluded at the top o f the t a b l e f o r comparison. I t i s i n t e r -e s t i n g t o see t h a t the d e l a y time i n the l o n g d e l a y group i s q u i t e c o n s i d e r a b l e . One hundred, and t h r e e cases have de-l a y e d two y e a r s and over. T h i s i s almost h a l f o f the t o t a l cases (224) i n t h i s group. T a b l e XVII shows the d i s t r i b u t i o n o f d e l a y i n f i v e year age groups. From t h i s t a b l e i t can be seen t h a t cases 65 i n the s h o r t d e l a y group are younger. The t r e n d though i s not a remarkable one. On s t a t i s t i c a l a n a l y s i s i t i s found t o be s i g n i f i c a n t . Delay i n r e l a t i o n t o age i s examined i n T a b l e X V I I I . I n f o r m a t i o n i s a v a i l a b l e i n 456 cases. The f i g u r e s suggest t h a t the young tend t o d e l a y l e s s and t h i s i s confirmed on ° s t a t i s t i c a l a n a l y s i s . T a b l e XIX reviews the d i s t r i b u t i o n o f cases (449) by c l i n i c a l stage i n r e l a t i o n t o s h o r t and l o n g d e l a y times. Almost 50% o f the t o t a l cases were i n c l i n i c a l stage 1 and over 70% i n c l i n i c a l stages 1 and 11. I t i s i n t e r e s t i n g t o see t h a t f o r the d e l a y p e r i o d l e s s than one month almost 90% o f cases f a l l w i t h i n c l i n i c a l stage 1 and 11. While i n the d e l a y p e r i o d 12 months and over o n l y 52% were i n c l i n i -c a l stage 1 and 11. There i s no s u g g e s t i o n i n these f i g u r e s t h a t cases o f a poorer p r o g n o s i s by c l i n i c a l stage would be more prominent i n the e a r l y d e l a y p e r i o d . I n c o n t r a s t we f i n d o n l y 3.8% o f cases i n c l i n i c a l stage IV i n the l e s s than one month d e l a y p e r i o d i n comparison t o 30.4% c l i n i c a l stage IV i n the 12 months and over p e r i o d . These f i g u r e s suggest a marked c o n t r a s t by c l i n i c a l stage i n the two d e l a y p e r i o d s . I t c o u l d be expected t h e r e f o r e , t h a t outcome should be much b e t t e r i n the e a r l y d e l a y group because of the preponderance o f c l i n i c a l stage 1 cases. There i s a c o n s i d e r a b l e s t a t i s -t i c a l d i f f e r e n c e both i n t o t a l X and m t r e n d between shor t and l o n g d e l a y w i t h a n a l y s i s o f T a b l e XIX. 66 U n f o r t u n a t e l y the data a v a i l a b l e f o r d i s t r i b u t i o n o f cases by p a t h o l o g i c a l s t a g i n g i s poor. Only i n f o r m a t i o n on 168 cases i s a v a i l a b l e out o f t h e 456 cases examined. T a b l e XX shows the d i s t r i b u t i o n o f t o t a l cases by p a t h o l o g i c a l s t a g i n g , 23.3% i n p a t h o l o g i c a l stages 1 and 11 but over 13.2% i n p a t h o l o g i c a l stage IV. T h i s i s a t r e n d which i s d i f f e r e n t from T a b l e XIX w i t h the d i s t r i b u t i o n o f cases by c l i n i c a l stage. The t r e n d i s more n o t i c e a b l e when we examine t h e p a t h o l o g i c a l s t a g i n g i n t h e 168 cases i n r e l a t i o n t o de-l a y p e r i o d . I n the l e s s than one month d e l a y p e r i o d more cases were c l a s s i f i e d as p a t h o l o g i c a l stage IV i n c o n t r a s t t o c l i n i c a l s t a g i n g of cases. The d i f f e r e n c e i n the 12 months and over p e r i o d i s not as marked. Thus the short de-l a y cases have more f a v o u r a b l e p a t h o l o g i c a l s t a g i n g , although the d i f f e r e n c e between them and the long d e l a y i s not as marked as f o r c l i n i c a l s t a g i n g . S t a t i s t i c a l a n a l y s i s o f the t a b l e o f p a t h o l o g i c a l s t a g i n g shows no s i g n i f i c a n t d i f f e r e n c e between t h e s h o r t and l o n g d e l a y p e r i o d s i n r e s p e c t t o s t a g i n g by pathology. T a b l e XXI shows the d i s t r i b u t i o n o f cases by b r e a s t . Four hundred and f i f t y - s i x cases were examined, 204 were i n the l e f t b r e a s t and 252 i n the r i g h t b r e a s t . The d i s t r i b u -t i o n by d e l a y demonstrated no s i g n i f i c a n t r e l a t i o n s h i p . The p o s i t i o n o f the tumour i n the b r e a s t w i t h r e s p e c t t o d e l a y p e r i o d s i s shown i n T a b l e XXII. Approximately h a l f o f the tumours i n both d e l a y p e r i o d s are i n the outer upper 67 quadrant of the b r e a s t . The i n n e r upper quadrant c o n t a i n e d 24.1% o f tumours i n the d e l a y p e r i o d l e s s than one month and 17.4% i n the one year and more p e r i o d . A s i g n i f i c a n t d i f f e r e n c e o c c u r r e d w i t h tumours d e s c r i b e d as occupying the whole b r e a s t . F o u r t e e n p o i n t t h r e e percent of tumours i n the one year and more d e l a y p e r i o d were d e s c r i b e d as occupy-i n g the whole b r e a s t . T h i s i s i n marked comparison t o the l e s s than one month d e l a y p e r i o d where we f i n d o n l y 2.6% d e s c r i b e d as occupying the whole b r e a s t . T h i s would i n d i c a t e t h a t tumours i n the one year and over group have much more e x t e n s i v e d i s e a s e and thus p o s s i b l y a worse p r o g n o s i s . G e n e r a l l y f o u r terms were found t o be used i n r e l a t i o n t o h i s t o l o g y i n the p r e l i m i n a r y d a t a review. These are d i f f e r e n t i a t i o n , growth, type and a patho-l o g i c a l d e s c r i p t i v e term. D i f f e r e n t i a t i o n i s d e s c r i b e d as w e l l , moderately or f a i r l y w e l l , and p o o r l y d i f f e r e n t i a t e d . Growth i s r e f e r r e d t o as i n s i t u o r i n f i l t r a t i n g . I n type two terms are used d u c t a l or l o b u l a r . F o u r t e e n p a t h o l o g i c a l d e s c r i p t i v e terms are found t o d e s c r i b e d e t a i l e d h i s t o l o g y . A l i s t o f these are found i n T a b l e XXV. With d i f f e r e n t i a t i o n only, d a t a i n f i v e cases was a v a i l a b l e so t h i s i n f o r m a t i o n has been d i s -carded from f u r t h e r d i s c u s s i o n . With the v a r i a b l e growth, 185 cases were found w i t h t h i s i n f o r m a t i o n . The r e s u l t s are d i s p l a y e d i n T a b l e X X I I I . Only i n one case was the term i n s i t u used. I n f i l t r a t i n g was 68 used i n an equal number of cases i n both delay p e r i o d s . I n type, d u c t a l and l o b u l a r are used e q u a l l y between the two delay p e r i o d s . Information was a v a i l a b l e on 153 cases, over 90% being described as d u c t a l . The f i g u r e s are shown i n Table XXIV. Table XXV d i s p l a y s the p a t h o l o g i c a l d e s c r i p t i v e terms i n r e l a t i o n t o both delay p e r i o d s . Information was a v a i l -able on 453 cases. Three diagnoses are prominent, s c i r r h o u s carcinoma, adenocarcinoma and carcinoma. The suggestion from these f i g u r e s i s t h a t the diagnosis f o r the short delay i s more l i k e l y t o be s c i r r h o u s carcinoma and f o r long delay carcinoma, but the percentage d i f f e r e n c e s are s m a l l . I n adeno carcinoma the d i f f e r e n c e i s very s m a l l . The diagnosis of Paget's disease occurred i n the 1 year or more group, i n four cases but not i n the l e s s than one month group. I n Table XXVI m a r i t a l s t a t u s i s examined w i t h regard t o the two delay p e r i o d s . Information was a v a i l a b l e i n 455 cases. S i x t y - n i n e percent of married women appeared i n the short delay i n comparison to 54.9% i n the long delay group. The s i n g l e and widowed tend more t o the one year or more delay p e r i o d . The d i f f e r e n c e i n the widowed i s over ten percent. The numbers f o r the separated or divorced are s m a l l . Socio-economic s t a t u s and delay are examined i n Tables XXVII and XXVIII by husband's and then the w i f e ' s occupation. Taking i n t o c o n s i d e r a t i o n the l a r g e number of cases v/ithout 69 information, using the husband's occupation there appears to be l i t t l e difference between the delay periods and status levels. The figures suggest the lower income groups tend to delay less. With the patient's occupation the opposite is true though very l i t t l e information i s avail-able (less than 20%). Maybe this trend i s seen because information i s available on single and widowed women, who in Table 31 appear to delay longer. 70 TABLE XV DISTRIBUTION OP DELAY BY YEAR OF DIAGNOSIS YEAR SHORT LONG TOTAL 1960 44 (19%) 49 (21.9%) 93 (20.4°/ 1961 46 (19.8%) 40 (17.9%) 86 (18.9%) 1962 42 (18.1%) 44 (19.6% 86 (18.9%) 1963 56 (24.1%) 47 (21%) 103 (22.6% 1964 43 (18.5%) 44 (19.6% 87 (19.1% U N K N O W N 1 (0.4% 0 (0%) 1 (0.2%) TOTAL 232 (100%) 224 (100%) 456 (100%) %2 TOTAL = 1.42 d f 4 N.S. 71 TABLE XVI TABLE DISTRIBUTION OF CASES IN THE DELAY PERIOD ONE YEAR AND OVER BY DELAY TIME DELAY TIME NUMBER Less than 1 Month 232, -12 Months 8 7 tt 3 15 5 16 k 17 1 18 1 8 19 2 21 1 24 3 3 30 5 36 1 8 42 3 48 9 54 1 60 9 66 1 72 6 84 5 96 k 120 4 132 1 150 1 168 2 180 1 72 TABLE XVII DISTRIBUTION OF DELAY IN FIVE YEAR AGE GROUPS MEAN 54.8 MEAN 59.6 AGE SHORT LONG TOTAL 20-24 1 (0.4%) 0 1 (0.2%) 25-29 3 (1.3%) 0 3 (0.7%) 30-34 9 (3.9%) 1 (.4%) 10 (2.2%) 35-39 14 (6%) 17 (7.6%) 31 (6.8%) 40-44 39 (16.8%) 21 (9.4%) 60 (13.2%) 45-49 35 (15.1%) 33 (14.7%) 68 (14.9%) 50-54 24 (10.3%) 23 (10.3%) 47 (10.3%) 55-59 24 (10.3%) 28 (12.5%) 52 (11.4%) 60-64 23 (9.9%) 22 (9.8%) 45 (9.9%) 65-69 26 (11.2%) 12 (5.4%) 38 (8.3%) 70-74 12 (5.2%) 25 (11.2%) 37 (8.1%) 75-79 12 (5.2%) 23 (10.3%) 35 (7.7%) 80-84 9 (3.9%) 12 (5.4%) 21 (4.6%) 85-89 1 (0.4%) 3 (1.3%) 4 (0.9%) 90-94 0 4 (1.8%) 4 (0.9%) UNKNOWN 0 0 0 TOTAL 232 (100%) 224 (100%) 456 (100%) %2 TOTAL 34.98 cl f 14 P<0.05 *2 TREND 13.08 X2 RESIDUAL 21.90 73 TABLE XVIII AGE DISTRIBUTION OP CASES AND DELAY IN RELATION TO AGE AGE SHORT <44 66 (28.4% 45-64 106 (45.7%) 65-99 60 (25.9%) UNKNOWN 0 TOTAL 232 (100%) X 2 TOTAL 9.40 X 2 TREND 8.99 LONG TOTAL 39 (17.4%) 105 (23%) 106 (47.3%) 212 (46.5%) 79 (35.3%) 139 (30.5%) 0 224 (100%) 456 (100%) a f 2 p <0.01 74 T A B L E X I X C L I N I C A L S T A G I N G I N R E L A T I O N TO D E L A Y T I M E C L I N I C A L S T A G E SHORT LONG T O T A L 149 (64.2%) 70 (31.3%) 219 (48.0%) 56 (24.151 44 (19.6%) 100 (21.9%) 16 (6.9%) 37 (16.5%) 53 (11.6% 9 (3.8%) 68 (30.4% 77 (16.9%) UNKNOWN 2 (0.9%) 5 (2.2%) 7 (1.59 T O T A L 232 (100%) 224 (100%) 456 (100%) X 2 T O T A L X 2 TREND = 83.25 = 81.81 d f 3 d f 1 P <0.001 P <0.001 75 TABLE XX PATHOLOGICAL STAGING IN RELATION TO DELAY TIME PATHOLOGICAL STAGE SHORT LONG 41 (17.7%) 19 (8.5%) 23 (9.9%) 23 (10.3%) 2 (0.9%) 0 (0%) 4 32 (13.8%) 28 (12.5%) UNKNOWN 134 (57.8%) 154 (68.8%) TOTAL 232 (100%) X TOTAL 5.83 224 (100%) d f 3 76 TABLE XXI DISTRIBUTION OF CASES BY BREAST AND DELAY TIME BREAST SHORT LONG TOTAL LEFT 100 104 204 (43.1%) (46.4%) (44.7%) RIGHT 132 120 252 (56.9%) (53.6%) (55.3%) UNKNOWN 0 0 0 TOTAL 232 224 456 (100%) (100%) (100%) % 2 TOTAL 0.51 d f 1 N.S. 77 TABLE XXII DISTRIBUTION OF CASES BY SITE AND DELAY TIME SITE SHORT LONG TOTAL OUTER UPPER 119 (51.3%) 98 (43.8%) 217 (47.6%) OUTER LOWER 19 (8.2%) 17 (7.6%) 36 (7.9%) INNER LOWER 15 (6.5°/ 20 (8.9%) 35 (7.7%) INNER UPPER 56 (24.1%) 39 (17.4%) 95 (20.8%) WHOLE BREAST 6 (2.6%) 32 (14.3%) 38 (8.3%) NIPPLE 17 (7.3%) 18 (8%) 35 (7.7%) UNKNOWN 0 0 TOTAL 232 (100%) 224 (100%) 456 (100%) X 2 TOTAL 23.58 X 2 RESIDUAL 19.12 d f 5 P <0.001 78 TABLE XXIII HISTOLOGICAL DESCRIPTIVE TERM GROWTH IN RELATION TO DELAY GROWTH SHORT INSITU 1 (0.49 INFILTRATING 90 (38.8%) UNKNOWN 141 (60.8%) TOTAL 232 (100%) LONG TOTAL 0 (0%) 1 (0.2%) 94 (42%) 184 (40.4%) 130 (58%) 271 (59.4%) 224 (100%) 456 (100%) 79 TABLE XXIV HISTOLOGICAL DESCRIPTIVE TERM TYPE IN RELATION TO DELAY TYPE SHORT LONG TOTAL DUCTAL 71 69 140 (30.6%) (30.8%) (30.7%) LOBULAR 7 6 13 (3%) (2.8%) (2.9%) UNKNOWN 154 149 303 (66.4%) (66.5%) (66.4%) TOTAL 232 224 456 (100%) (100%) (100%) 80 TABLE XXV PATHOLOGICAL DESCRIPTIVE TERMS IN RELATION TO DELAY DESCRIPTIVE SHORT LONG TOTAL MEDULLARY 11 (4.7%) 3 (1.3%) 14 (3.1%) TUBULAR 0 (0%) 0 (0%) 0 (0%) PAPILLARY 3 (1.3%) 1 (0.4%) 4 (0.9%) COLLOID OR MUCOID 5 (2.2%) 3 (1.3%) 8 (1.8%) ADENOCYSTIC 0 (0%) 0 (0%) 0 (0%) SCIRRHOUS CARCINOMA 90 (38.8%) 71 (31.7%) 161 (35.3%) ADENO CARCINOMA 27 (11.6%) 33 (14.7%) 60 (13.2%) SCIRRHOUS ADENOCARCINOMA 1 (0.4%) 6 (2.7%) 7 (1.5%) CARCINOMA 82 (35.3%) 98 (43.8%) 180 (39.5%) COMEDO CARCINOMA 1 (0.4%) 1 (0.4%) 2 (0.4%) CARCINOMA SIMPLEX 7 (3%) 2 (0.9%) 9 (2.0%) MALIGNANT CYSTOSARCOMA PHYLLODES 1 (0.4%) 1 (0.4%) 2 (0.4%) CARCINO SARCOMA 1 (0.4%) 1 (0.4%) 2 (0.4%) PAGETS DISEASE 0 (0%) 4 (1.8%) 4 (0.9%) UNKNOWN 3 (1.3%) 0 3 (0.7%) TOTAL 232 (100%) 224 (100%) 456 (100%) 8 1 T A B L E X X V I M A R I T A L S T A T U S I N R E L A T I O N T O D E L A Y M A R I T A L S T A T U S S H O R T M A R R I E D 1 6 0 (69%) S I N G L E 1 9 ( 8 . 2 % ) W I D O W E D S E P A R A T E D / D I V O R C E D U N K N O W N 4 4 ( 1 9 % ) ( 3 . 9 % ) 0 T O T A L 2 3 2 ( 1 0 0 % ) X 2 T O T A L 1 0 . 2 1 X 2 T R E N D 7 . 0 3 X 2 R E S I D U A L 3 . 1 8 L O N G T O T A L 1 2 3 ( 5 4 . 9 % ) 2 8 3 ( 6 2 . 1 % ) 2 6 ( 1 1 . 6 % 4 5 ( 9 . 9 % ) 6 6 ( 2 9 . 5 % ) 1 1 0 ( 2 4 . 1 % ) 8 ( 3 . 5 ° / 1 7 ( 3 . 7 % ) 1 ( 0 . 4 % 1 ( 0 . 2 % ) 2 2 4 ( 1 0 0 % ) 4 5 6 ( 1 0 0 % ) d f 3 P < 0 . 0 5 82 TABLE XXVII SOCIO-ECONOMIC STATUS AS DEFINED BY HUSBAND'S OCCUPATION IN RELATION TO DELAY STATUS LEVEL SHORT LONG TOTAL 13 (5.6% 6 (2.7%) 19 (4.2%) 17 (7.3%) 26 (5.7%) 13 (5.6%) 13 (5.8%) 26 (5.7%) 29 (12.5% 29 (12.9%) 58 (12.7%) 21 (9.1% 22 (9.8%) 43 (9.5%) 29 (12.5% 23 (10.3%) 52 (11.4% 39 (16.8%) 19 (8.5%) 58 (12.7%) UNKNOWN 71 (30.6% 103 (46%) 174 (38.2%) TOTAL 232 (100%) 224 (100%) 456 (100%) 83 TABLE XXVIII SOCIO-ECONOMIC STATUS AS DEFINED BY PATIENT'S OCCUPATION IN RELATION TO DELAY STATUS LEVEL SHORT LONG TOTAL 4 (1.7%) 4 (1.8%) 8 (1.8%) 1 (0.4%) 0 (0%) 1 (0.2%) 5 (2.2%) 5 (2.2%) 10 (2.2%) 12 (5.2%) 9 (4%) 21 (4.6%) 4 (1.7%) 8 (3.6% 12 (2.6%) 1 (0.4% 7 (3.1% 8 (1.8%) 4 (1.7%) 6 (2.7%) 10 (2.2%) UNKNOWN 201 (86.6°/ 185 (82.6%) 386 (84.6%) TOTAL 232 (100%) 224 (100%) 456 (100%) 84 5.2 THE ANALYSIS OF THE ASSOCIATION OF DELAY TIME ON SURVIVAL FROM YEAR OF DIAGNOSIS The outcome i n the 456 cases as o f June 1977 i s shown i n T a b l e XXIX. One hundred and one p a t i e n t s were s t i l l a l i v e , almost a q u a r t e r o f the cases reviewed. Two hundred and t h i r t y - f i v e p a t i e n t s had d i e d of b r e a s t cancer, over h a l f o f the cases examined. Twelve percent d i e d from o t h e r causes and 3% from unknown causes. Twelve percent o f the cases examined (54) were l o s t t o f o l l o w up. I n r e l a t i o n t o measurement o f s u r v i v a l those cases l o s t t o f o l l o w up were c o n s i d e r e d as o f the date l a s t seen. Sur-v i v a l i n these cases t h e r e f o r e was measured from date o f b i o p s y t o date o f l a s t f o l l o w up. T a b l e XXV examines the outcome i n r e l a t i o n t o the two d e l a y p e r i o d s . Twenty-six percent o f the l e s s than one month group were s t i l l a l i v e as o f June 1977 i n comparison t o 18% o f the one y e a r and over group. The number l o s t t o f o l l o w up was e q u i v a l e n t i n both groups. Four p e r c e n t were dead from unknown causes i n the l o n g d e l a y cases w h i l e o n l y 1.7% o f the s h o r t d e l a y cases f e l l i n t h i s category. T h e r e f o r e , examining outcome we see a d i f f e r e n c e o f 8.4% i n cases a l i v e i n the s h o r t de-l a y group from the l o n g d e l a y group. There was no d i f f e r -ence i n t h e cases when death from o t h e r causes were examined. T h i s would c o n f i r m the s i m i l a r i t i e s i n age d i s t r i b u t i o n we have seen e a r l i e r between the two groups. L i f e t a b l e s are used t o d i s p l a y the s u r v i v a l r a t e o f 85 the s h o r t and l o n g d e l a y groups. T a b l e s XXX and XXXII show the s u r v i v a l r a t e s not i n c l u d i n g cases which d i e d o f competing r i s k . T a b l e s XXXI and XXXIII i n c l u d e cases which d i e d o f competing r i s k and from t h e s e the r e s p e c t i v e ob-served s u r v i v a l r a t e s are c a l c u l a t e d . T a b l e s XXXIV and XXXV show the observed and expected s u r v i v a l r a t e s and the c a l -c u l a t e d r e l a t i v e s u r v i v a l r a t e s f o r s h o r t and l o n g d e l a y . T a b l e XXXVI compares the r e l a t i v e s u r v i v a l r a t e s f o r long and short d e l a y from date o f d i a g n o s i s . We see i n t h i s t a b l e and i n f i g u r e s 3 a c o n s i s t e n t d i f f e r e n c e i n su r -v i v a l o f the short d e l a y over l o n g d e l a y group when su r -v i v a l i s c a l c u l a t e d from the date o f d i a g n o s i s . 86 TABLE XXIX THE OUTCOME IN RELATION TO THE TWO DELAY PERIODS IN 456 CASES EXAMINED AS OF JUNE 1977 OUTCOME SHORT LONG TOTAL ALIVE DEAD FROM BREAST CANCER 61 (26.3%) 110 (47.49 40 (17.9%) 125 (55.8%) 101 (22.1% 235 (51.5% DEAD FROM OTHER CAUSES 27 (11.6%) 26 (11.6°/ 53 (11.6% DEAD FROM UNKNOWN CAUSES 4 (1.7%) 9 (4%) 13 (2.9%) LOST TO FOLLOW UP UNKNOWN TOTAL 30 (12.9%) 232 (100%) 24 (10.7%) 224 (100%) 54 (11.896) Q_ 456 (100%) X2 TOTAL 7.79 X2 TREND 0.32 X2 RESIDUAL 7.47 d f 4, N.S. TABLE XXX LIFE TABLE OF SHORT DELAY FROM YEAR OF DIAGNOSIS NUMBER OF DEATHS NOT INCLUDING CASES WHICH DIED OF COMPETING RISK YEARS AFTER DIAGNOSIS ALIVE AT BEGINNING OF INTERVAL DIE DURING INTERVAL DIE OF WITHDRAWN COMPETING ALIVE RISK DURING INTERVAL EFFECTIVE NBR EXPOSED TO RISK OF DYING PROPORTION DYING PROPORTION SURVIVING SURVIVAL RATE 0-1 235 8 3 0 233.5 0.03 0.966 0.966 1-2 224 19 2 0 223.0 0.09 0.915 0.883 2-3 203 18 4 0 201.0 0.09 0.910 0.804 H 181 11 5 1 178.0 0.06 0.938 0.755 4-5 164 13 0 0 164.0 0.08 0.921 0.695 5-6 151 9 1 5 148.0 0.06 0.939 0.653 6-7 136 4 3 11 129.0 0.03 0.969 0.632 7-8 118 8 3 4 114.5 0.07 0.930 0.588 8-9 103 5 1 5 100.0 0.05 0.950 0.559 9-10 92 4 4 0 90.0 0.04 0.956 0.534 10-11 84 3 1 3 82.0 0.04 0.963 0.514 11-12 77 3 2 6 73.0 0.04 0.959 0.493 12-13 66 0 2 5 62.5 0.0 1.000 0.493 13-14 59 2 0 15 51.5 0.04 0.961 0.474 14-15 42 2 0 16 34.0 0.06 0.941 0.446 15-16 24 1 1 14 16.5 0.06 0.939 0.419 16-17 8 0 0 7 0.0 1.000 0.419 TABLE XXXI LIFE TABLE OF SHORT DELAY FROM YEAR OF DIAGNOSIS NUMBER OF DEATHS INCLUDING CASES WHICH DIED OF COMPETING RISK YEARS AFTER DIAGNOSIS ALIVE AT BEGINNING OF INTERVAL DIE DURING INTERVAL DIE OF COMPETING RISK WITHDRAWN ALIVE DURING INTERVAL EFFECTIVE NBR EXPOSED TO RISK OF DYING PROPORTION DYING PROPORTION SURVIVING OBSERVED SURVIVAL RATE 0-1 235 8 3 0 235.0 0.05 0.953 0.953 1-2 224 19 2 0 224.0 0.09 0.906 0.864 2-3 203 18 4 0 203.0 0.11 0.892 0.770 3-4 181 11 5 1 180.5 0.09 0.911 0.702 4-5 164 13 0 0 164.0 0.08 0.921 0.646 5^ 151 9 1 5 148.5 0.07 0.933 0.603 6-7 136 4 3 11 130.5 0.05 0.946 0.570 7-8 118 8 3 4 116.0 0.09 0.905 0.516 8-9 103 5 1 5 100.5 0.06 0.940 0.486 9-10 92 4 4 0 92.0 0.09 0.913 0.443 10-11 84 3 1 3 82.5 0.05 0.952 0.422 11-12 77 3 2 . 6 74.0 0.07 0.932 0.393 12-13 66 0 2 5 63.5 0.03 0.969 0.381 13-14 59 2 0 15 51.5 0.04 0.961 0.366 14-15 42 2 0 16 34.0 0.06 0.941 0.345 15-16 24 1 1 14 17.0 0.12 0.882 0.304 16-17 8 0 0 7 4.5 0.0 1.000 0.304 TABLE XXXII LIFE TABLE OF LONG DELAY FROM YEAR OF DIAGNOSIS NUMBER OF DEATHS NOT INCLUDING CASES WHICH DIED OF COMPETING RISK YEARS AFTER DIAGNOSIS ALIVE AT DIE BEGINNING DURING OF INTERVAL INTERVAL DIE OF COMPETING . RISK WITHDRAWN ALIVE DURING INTERVAL EFFECTIVE NBR EXPOSED TO RISK OF DYING PROPORTION DYING PROPORTION SURVIVING SURVIVAL RATE 0-1 228 25 3 0 226.5 0.11 0.890 0.890 1-2 200 23 7 1 196.0 0.12 0.883 0.785 2-3 169 12 3 0 167.5 0.07 0.928 0.729 3-4 154 13 6 1 150.5 0.09 0.914 0.666 4-5 134 11 0 0 134.0 0.08 0.918 0.611 5-6 123 6 3 5 119.0 0.05 0.950 0.581 6-7 109 12 3 8 103.5 0.12 0.884 0.513 7-8 86 5 2 0 85.0 0.06 0.941 0.483 8-9 79 7 0 4 77.0 0.09 0.909 0.439 9-10 1 68 1 0 2 67.0 0.01 0.985 0.433 10-11 65 5 2 2 63.0 0.08 0.921 0.398 11-12 56 3 2 3 53.5 0.06 0.944 0.376 12-13 48 0 3 9 42.0 0.0 1.000 0.376 13-14 36 1 0 U 29.0 0.Q3 0.966 0.363 14-15 21 2 1 7 17.0 0.12 0.882 0.320 15-16 11 0 1 6 7.5 0.0 1.000 0.320 16-17 4 0 0 ? 2 t? 0.0 1.000 0.320 TABLE XXXIII LIFE TABLE OF LONG DELAY FROM YEAR OF DIAGNOSIS NUMBER OF DEATHS INCLUDING CASES WHICH DIED OF COMPETING RISK YEARS ALIVE AT DIE DIE OF WITHDRAWN EFFECTIVE PROPORTION PROPORTION OBSERVED AFTER BEGINNING DURING COMPETING ALIVE NBR EXPOSED DYING SURVIVING SURVIVAL DIAGNOSIS OF INTERVAL INTERVAL RISK DURING INTERVAL TO RISK OF DYING RATE 0-1 228 25 3 0 228.0 0.12 0.877 0.877 1-2 200 23 7 1 199.5 0.15 0.850 0.745 2-3 169 12 3 0 169.0 0.09 0.911 0.679 3-k 154 13 6 1 153.5 0.12 0.876 0.595 4-5 134 11 0 0 134.0 0.08 0.918 0.546 5-6 123 6 3 5 120.5 0.07 0.925 0.505 6-7 109 12 3 8 105.0 0.14 0.857 0.433 7-8 86 5 2 0 86.0 0.08 0.919 0.398 8-9 79 7 0 4 77.0 0.09 0.909 0.362 9-10 68 1 0 2 67.0 0.01 0.985 0.356 10-11 65 5 2 2 64.0 0.11 0.891 0.317 11-12 56 3 2 3 54.5 0.09 0.908 0.288 12-13 48 0 3 9 43.5 0.07 0.931 0.268 13-14 36 1 0 14 29.0 0.03 O.966 0.259 14-15 21 2 1 7 17.5 0.17 0.829 0.215 15-16 11 0 1 6 8.0 0.13 0.875 0.188 16-17 4 0 0 ? 2.5 0.0 1.000 0.188 91 TABLE XXXIV SHORT DELAY FROM DATE OF DIAGNOSIS RELATIVE SURVIVAL RATES YEARS OBSERVED AFTER SURVIVAL DIAGNOSIS RATES 1 0.953 2 0.864 3 0.770 4 0.702 5 0.646 6 0.603 7 0.570 8 0.516 9 0.486 10 0.443 11 0.422 12 0.393 13 0.381 14 0.366 15 0.345 16 0.304 17 0.304 EXPECTED RELATIVE SURVIVAL SURVIVAL RATES RATES 0.988 0.964 0.975 0.886 0.961 0.801 0.947 0.741 0.932 0.693 0.916 0.658 0.900 0.633 0.883 0.584 0.866 0.561 0.848 0.522 0.830 0.508 0.811 0.484 0.792 0.481 0.773 0.473 0.753 0.458 0.733 0.414 0.713 0.426 92 TABLE XXXV LONG DELAY FROM DATE OF DIAGNOSIS RELATIVE SURVIVAL RATES YEARS OBSERVED AFTER SURVIVAL DIAGNOSIS RATES 1 0.877 2 0.745 3 0.679 4 0.595 5 0.546 6 0.505 7 0.433 8 0.398 9 0.362 10 0.356 11 0.317 12 0.288 13 0.268 14 0.259 15 0.215 16 0.188 17 0.188 EXPECTED RELATIVE SURVIVAL SURVIVAL RATES RATES 0.980 0.895 0.959 0.777 0.939 0.723 0.918 0.648 0.896 0.609 0.874 0.578 0.852 0.508 0.829 0.480 0.806 0.449 0.783 0.454 0.760 0.417 0.737 0.391 0.713 0.376 0.690 0.375 0.667 0.322 0.644 0.292 0.621 0.303 93 TABLE XXXVI COMPARISON OF RELATIVE SURVIVAL RATES FOR LONG AND SHORT DELAY FROM DATE OF DIAGNOSIS YEARS SHORT LONG AFTER DELAY DELAY DIAGNOSIS  1 0.964 0.895 2 0.886 0.777 3 0.801 0.723 4 0.741 0.648 5 0.693 0.609 6 0.658 0.578 7 0.633 0.508 8 0.584 0.480 9 0.561 0.449 10 0.522 0.454 11 0.508 0.417 12 0.484 0.391 13 0.481 0.376 14 0.473 0.375 15 0.458 0.322 16 0.414 0.292 17 0.426 0.303 94 FIGURE 3 A COMPARISON OF RELATIVE SURVIVAL RATES FOR LONG AND SHORT DELAY FROM DATE OF DIAGNOSIS z i * S 6 r , 1 n 95 5.3 THE ANALYSIS OF THE ASSOCIATION OF DELAY TIME ON SURVIVAL FROM DATE OF FIRST SYMPTOM I n t h i s s e c t i o n s h o r t and l o n g d e l a y are examined from the date o f f i r s t symptom. L i f e t a b l e s are d i s p l a y e d i n Ta b l e s XXXVII, XXXVTII, XXXIX and XXXX. The r e l a t i v e s u r v i v a l r a t e s f o r short and long d e l a y from date o f f i r s t symptom are c a l c u l a t e d i n T a b l e s XXXXI and XXXXII and then compared i n T a b l e XXXXIII and f i g u r e 4. The advantage o f s h o r t d e l a y d i s a p p e a r s and i t would appear t h a t those i n l o n g d e l a y do b e t t e r i n i t i a l l y . I n c a l c u l a t i n g the l i f e t a b l e s f o r l o n g d e l a y the pa-t i e n t s have a l r e a d y s u r v i v e d f o r eigh t e e n months. With t h i s i n mind t h r e e p o s s i b l e c o r r e c t i o n s are made i n the observed s u r v i v a l r a t e s . These are d i s p l a y e d i n T a b l e XXXXIV. The c o r r e c t e d r e l a t i v e s u r v i v a l r a t e s f o r long d e l a y from f i r s t symptom are shown i n T a b l e XXXXV and d i s p l a y e d g r a p h i c a l l y i n f i g u r e s 5. These modify t h e p i c t u r e g i v e n i n f i g u r e 4 and suggest t h a t t h e r e i s v e r y l i t t l e , i f any d i f f e r e n c e between l o n g and s h o r t d e l a y from date o f f i r s t symptom. U s i n g c o r r e c t i o n 2 which g i v e s the poore s t s u r v i v a l f o r l o n g d e l a y suggests an advantage t o short d e l a y o n l y i n the l o n g term. TABLE XXXVII LIFE TABLE OF SHORT DELAY FROM DATE OF FIRST SYMPTOM NUMBER OF DEATHS NOT INCLUDING CASES WHICH DIED OF COMPETING RISK YEARS ALIVE AT DTE DIE OF WITHDRAWN EFFECTIVE PROPORTION PROPORTION SURVIVAL AFTER BEGINNING DURING COMPETING ALIVE NBR EXPOSED DYING SURVIVING RATE FIRST SYMPTOM OF INTERVAL INTERVAL RISK DURING INTERVAL TO RISK OF DYING 0-1 235 8 3 0 233.5 0.03 O.966 O.966 1-2 224 18 1 0 223.5 0.08 0.919 0.888 2-3 205 19 5 0 202.5 0.09 0.906 0.805 3-4 181 11 4 1 178.5 0.06 0.938 0.755 4-5 165 13 1 0 164.5 0.08 0.921 0.695 5-6 151 9 1 5 148.0 0.06 0.939 0.653 6-7 136 3 0 11 130.5 0.02 0.977 0.638 7-8 122 8 6 4 117.0 0.07 0.932 0.594 8-9 104 5 0 5 101.5 0.05 0.951 O.565 9-10 94 5 4 0 92.0 0.05 0.946 0.534 10-11 85 3 1 3 83.0 0.04 0.964 0.515 11-12 78 3 3 6 73.5 0.04 0.959 0.494 12-13 66 0 2 5 62.5 0.0 1.000 0.494 13-14 59 2 0 15 51.5 0.04 0.961 0.475 14-15 42 2 0 16 34.0 0.06 0.941 0,447 15-16 24 1 1 14 16.5 0.06 0.939 0.420 16-17 8 0 0 7 4.5 0.0 1.000 0.420 TABLE XXXVIII LIFE TABLE OF NUMBER OF DEATHS SHORT DELAY FROM DATE OF FIRST SYMPTOM INCLUDING CASES WHICH DIED OF COMPLETING RISK YEARS AbTER FIRST SYMPTOM ALIVE AT BEGINNING OF INTERVAL DIE DURING INTERVAL DIE OF WITHDRAWN COMPETING ALIVE RISK DURING INTERVAL EFFECTIVE NBR EXPOSED TO RISK OF DYING PROPORTION DYING PROPORTION SURVIVING OBSERVED SURVIVAL RATE 0-1 235 8 0 235.0 0.05 0.953 0.953 1-2 224 18 1 0 224.0 0.08 0.915 0.872 2-3 205 19 5 n 205.0 0.12 0.883 0.770 3 ^ 181 11 4 1 180.5 0.08 0.917 0.706 4-5 165 13 1 0 165.0 0.08 0.915 0.646 5-6 151 9 1 5 148.5 0.07 0.933 0.603 6-7 136 3 0 11 130.5 0.02 0.977 0.589 7-8 122 8 6 4 120.0 0.12 0.883 0.520 8-9 104 5 0 5 101.5 0.05 0.951 0.495 9-10 94 5 4 0 94.0 0.10 0.904 0.447 10-11 85 3 1 3 83.5 0.05 0.952 0.426 11-12 78 3 3 6 75.0 0.08 0.920 0.392 12-13 66 0 2 5 63.5 0.03 0.969 0.379 13-14 59 2 0 15 51.5 0.04 0.961 0.365 14-15 42 2 0 16 34.0 0.06 0.941 0.343 15-16 24 1 1 14 17.0 0.12 0.882 0.303 16-17 8 0 0 7 4.5 0.0 1.000 0.303 TABLE XXXIX LIFE TABLE OF LONG DELAY FROM DATE OF FIRST SYMPTOM NUMBER OF DEATHS NOT INCLUDING CASES WHICH DIED OF COMPETING RISK YEARS ALIVE AT DIE DIE OF WITHDRAWN EFFECTIVE PROPORTION PROPORTION SURVIVAL AFTER BEGINNING DURING COMPETING ALIVE NBR EXPOSED DYING SURVIVING RATE FIRST SYMPTOM OF INTERVAL INTERVAL RISK DURING INTERVAL TO RISK OF DYING 0-1 228 0 0 0 228.0 0.0 1.000 1.000 1-2 228 13 2 0 227.0 0.06 0.943 0.943 2-3 213 16 1 0 212.5 0.08 0.925 0.872 3-4 196 13 2 0 195.0 0.07 0.933 0.814 4-5 181 13 5 1 178.0 0.07 0.927 0.754 5-h 162 7 2 0 161.0 0.04 0.957 0.721 6-7 153 9 1 5 150.0 0.06 0.940 0.678 7-8 138 10 6 5 132.5 0.08 0.925 0.627 8-9 117 9 3 1 115.0 0.08 0.922 0.578 9-10 104 11 1 3 102.0 0.11 0.892 0.516 10-11 89 5 1 1 88.0 0.06 0.943 0.486 11-12 82 3 0 2 81.0 0.04 0.963 0.468 12-13 77 7 3 4 73.5 0.10 0.905 0.424 13-14 63 2 3 5 59.0 0.03 0.966 0.409 14-15 53 2 1 10 47.5 0.04 0.958 0.392 15-16 40 1 0 9 35.5 0.03 0.972 0.381 16-17 30 2 1 ? 27.0 Of°7 0.926 0.353 TABLE XXXX LIFE TABLE OF LONG DELAY FROM DATE OF FIRST SYMPTOM NUMBER OF DEATHS INCLUDING CASES WHICH DIED OF COMPETING RISK YEARS AFTER FIRST SYMPTOM ALIVE AT BEGINNING OF INTERVAL DIE DIE OF DURING COMPETING INTERVAL RISK WITHDRAWN ALIVE DURING INTERVAL EFFECTIVE NBR EXPOSED TO RISK OF DYING PROPORTION DYING PROPORTION SURVIVING OSBSERVED SURVIVAL RATE 0-1 228 0 0 0 228.0 0.0 1.000 1.000 1-2 228 13 2 0 228.0 0.07 0.934 0.934 2-3 213 16 1 0 213.0 0.08 0.920 0.860 M 196 2 0 196.0 0.08 0.923 0.794 181 13 5 1 180.5 0.10 0.900 0.715 5-6 162 7 2 0 162.0 0.06 0.944 0.675 6-7 9 1 5 150.5 0.07 0.934 0.630 7-8 138 10 6 5 135.5 0.12 0.882 0.556 8-9 117 9 3 1 116.5 0.10 0.897 0.498 9-10 104 11 1 3 102.5 0.12 0.883 0.440 10-11 89 5 1 1 88.5 0.07 0.932 0.410 11-12 82 3 0 2 81.0 0.04 0.963 0.395 12-13 77 7 3 4 75.0 0.13 0.867 0.342 13-14 63 2 3 5 60.5 0.08 0.917 0.314 14-15 53 2 1 10 48.0 0.06 0.938 0.294 15-16 40 1 0 9 35.5 0.03 0.972 0.286 16-17 30 2 1 ? 27.5 0.11 0.891 0.255 100 TABLE XXXXI SHORT DELAY PROM DATE OF FIRST SYMPTOM RELATIVE SURVIVAL RATES YEARS OBSERVED AFTER SURVIVAL FIRST SYMPTOM RATES 1 0.953 2 0.872 3 0.770 4 0.706 5 0.646 6 0.603 7 0.589 8 0.520 9 0.495 10 0.447 11 0.426 12 0.392 13 0.379 14 0.365 15 0.343 16 0.303 17 0.303 EXPECTED RELATIVE SURVIVAL SURVIVAL RATES RATES 0.988 0.964 0.975 0.894 0.961 0.801 0.947 0.745 0.932 0.693 0.916 0.658 0.900 0.654 0.883 0.589 0.866 0.571 0.848 0.527 0.830 0.513 0.811 0.483 0.792 0.478 0.773 0.472 0.753 0.455 0.733 0.413 0.713 0.425 101 TABLE XXXXII LONG DELAY FROM DATE OF FIRST SYMPTOM RELATIVE SURVIVAL RATES YEARS OBSERVED EXPECTED RELATIVE AFTER SURVIVAL SURVIVAL SURVIVAL FIRST S Y M P T O M RATES RATES RATES 1 1.000 0.980 1.020 2 0.934 0.959 0.974 3 0.860 0.939 0,916 4 0.794 0.918 0.865 5 0.715 0.896 0.798 6 0.675 0.874 0.772 7 0.630 0.852 0.739 8 0.556 0.829 0.671 9 0.498 0.806 0.618 10 0.440 0.783 0.562 11 0.410 0.760 0.539 12 0.395 0.737 0.536 13 0.342 0.713 0.480 14 0.314 0.690 0.455 15 0.294 0.667 0.441 16 0.286 0. 644 0.444 17 0.255 0.621 0.411 102 TABLE XXXXIII COMPARISON OF RELATIVE SURVIVAL RATES FOR LONG AND SHORT DELAY FROM DATE OF FIRST SYMPTOM YEARS AFTER FIRST SYMPTOM SHORT DELAY LONG DELAY 1 0.964 1.020 2 0.894 0.974 3 0.801 0.916 4 0.745 0.865 5 0.693 0.798 6 0.658 0.772 7 0.654 0.739 8 0.589 0.671 9 0.571 0.618 10 0.527 0.562 11 0.513 0.539 12 0.483 0.536 13 0.478 0.480 14 0.472 0.455 15 0.455 0.441 16 0.413 0.444 17 0.425 0.411 TABLE XXXXIV CORRECTED OBSERVED SURVIVAL RATES FOR LONG DELAY FROM FIRST SYMPTOM YEARS OBSERVED CORRECTION (l) AFTER FIRST SURVIVAL FROM ASSUMING 18 MTHS SYMPTOM FIRST SYMPTOM SURVIVAL = 0.925 YEAR 0 BASED ON SHORT DELAY 1 1.00 0.925 2 0.934 0.864 3 0.860 0.796 4 0.794 0.734 5 0.715 0.661 6 0.675 0.624 7 0.630 0.583 8 0.556 0.514 9 0.498 0.461 10 0.440 0.407 11 0.410 0.379 12 0.395 0.365 13 0.342 0.316 14 0.314 0.290 15 0.294 0.272 16 0.286 0.265 17 0.255 0.236 CORRECTION (2) CORRECTION (3) EXPECTED ASSUMING 18 MTHS ASSUMING 1 YR. SURVIVAL SURVIVAL » 0.830 SURVIVAL =0.980 BASED ON LONG FOR NORMAL DELAY FROM DIAGNOSIS POPULATION 0.830 0.980 0.980 0.775 0.915 0.959 0.714 0.843 0.939 0.659 0.778 0.918 0.593 0.701 O.896 0.560 0.662 0.874 0.523 0.617 0.852 0.461 0.545 0.829 0.413 0.488 0.806 0.365 0.431 0.783 0.340 0.402 0.760 0.328 0.387 0.737 0.284 0.335 0.713 0.261 0.308 0.690 0.244 0.288 0.667 0.237 0.280 0.644 0.212 0.250 0.621 104 TABLE XXXXV CORRECTED RELATIVE SURVIVAL RATES FOR LONG DELAY FROM FIRST SYMPTOM YEARS CORRECTION CORRECTION CORRECTION AFTER FIRST (1) (2) (3) SYMPTOM 1 0. 944 0.847 1.000 2 0.901 0.808 0.954 3 0.847 0.760 0.898 4 0.800 0.718 0.848 5 0.738 0.662 0.782 6 0.714 0.641 0.757 7 0.684 0.614 0.725 8 0.620 0.557 0.657 9 0.572 0.513 0.606 10 0.520 0.466 0.551 11 0.499 0.448 0.529 12 0.496 0.445 0.525 13 0.444 0.398 0.470 14 0.421 0.378 0.446 15 0.408 0.366 0.432 16 0.411 0.369 0.435 17 0.380 0.341 0.402 105 106 107 5 . 4 THE ANALYSIS OF THE ASSOCIATION BETWEEN DELAY TIME AND SURVIVAL WITH CONTROL FOR OTHER FACTORS  I n t h i s s e c t i o n d e l a y and s u r v i v a l a re e x p l o r e d i n r e l a t i o n t o the f o u r c l i n i c a l stages o f the d i s e a s e . L i f e t a b l e s f o r s u r v i v a l i n both s h o r t and lo n g d e l a y f o r each c l i n i c a l stage are used t o c a l c u l a t e r e l a t i v e s u r v i v a l r a t e s . These are compared i n T a b l e s XXXXVI, XXXXVII, XXXXVIII and XXXXIX and d i s p l a y e d g r a p h i c a l l y i n F i g u r e s 6, 7 and 8. The s u r v i v a l o f the long d e l a y group i n c l i n i c a l stages 1 and 11 would appear t o be b e t t e r w h i l e i n c l i n i c a l stages 111 and IV the r e v e r s e i s t r u e . 108 TABLE XXXXVI COMPARISON OF RELATIVE SURVIVAL RATES FOR CLINICAL STAGE I IN SHORT AND LONG DELAY YEARS AFTER RELATIVE SURVIVAL RATE RELATIVE SURVIVAL RATE DIAGNOSIS SHORT DELAY LONG DELAY 0 1.000 1.000 1 0.992 1.000 2 0.916 0.929 3 0.847 0.915 4 0.796 0.841 5 0.751 0.857 6 0.716 0.804 7 0.678 0.766 8 0.629 0.725 9 0.622 0.702 10 0.569 0.718 11 0.562 0.694 12 0.543 0.598 13 0.555 0.559 14 0.535 0.536 15 0.462 0.489 16 0.474 0.502 17 0.488 0.516 109 TABLE XXXXVII COMPARISON OF RELATIVE SURVIVAL RATES FOR CLINICAL STAGE I I IN SHORT AND LONG DELAY YEARS AFTER RELATIVE SURVIVAL RATE RELATIVE SURVIVAL RATE DIAGNOSIS SHORT DELAY LONG DELAY 0 1.000 1.000 1 0.956 0.990 2 0.874 0.980 3 0.737 0.875 4 0.690 0.792 5 0.622 0.730 6 0.591 0.689 7 0.577 0.645 8 0.563 0.598 9 0.472 0.578 10 0.455 0.589 11 0.437 0.568 12 0.388 0.579 13 0.333 0.591 14 0.340 0.603 15 0.347 0.616 16 0.355 0.315 110 TABLE XXXXVTII COMPARISON OF RELATIVE SURVIVAL RATES FOR CLINICAL STAGE I I I IN SHORT AND LONG DELAY YEARS AFTER RELATIVE SURVIVAL RATE RELATIVE SURVIVAL RATE DIAGNOSIS SHORT DELAY LONG DELAY 0 1.000 1.000 1 0.888 0.971 2 0.837 0.798 3 0.783 0.762 4 0.653 0.605 5 0.665 0.562 6 0.604 0.547 7 0.540 0.454 8 0.461 0.430 9 0.472 0.403 10 0.485 0.370 11 0.356 0.208 12 0.367 0.218 13 0.379 0. 228 14 0.196 0.239 I l l TABLE XXXXIX COMPARISON OF RELATIVE SURVIVAL RATES FOR CLINICAL STAGE IV IN SHORT AND LONG DELAY YEARS AFTER RELATIVE SURVIVAL RATES RELATIVE SURVIVAL RATE^ DIAGNOSIS SHORT DELAY LONG DELAY 0 1.000 1.000 1 0.694 0.611 2 0.483 0.399 3 0.380 0.346 4 0.133 0.305 5 0.141 0.262 6 0.150 0.252 7 0.160 0.130 1 1 2 113 114 115 6.0 CONCLUSION 6.1 METHODOLOGICAL ASPECTS OP THE STUDY 6.2 DISTRIBUTION OF DELAY TIME 6.3 ANALYSIS OF SURVIVAL 6.4 INTERPRETATION 6.5 IMPLICATIONS FOR HEALTH PLANNING 6.6 POLICIES AND OBJECTIVES OF HEALTH PLANNING 116 6.1 METHODOLOGICAL ASPECTS OF THE STUDY The o b j e c t i v e o f the c u r r e n t study was t o compare the s u r v i v a l experience o f two groups o f b r e a s t cancer p a t i e n t s , those d e f i n e d as " s h o r t d e l a y " , who came t o c l i n i c a l d i a g n o s i s one month or l e s s a f t e r they n o t i c e d t h e i r f i r s t symptom, and those p a t i e n t s who had " l o n g d e l a y " , d e f i n e d as those who came t o c l i n i c a l d i a g n o s i s a f t e r h a v i n g had symptoms f o r more than one y e a r . I t i s a r e t r o s p e c t i v e study based on the r o u t i n e records of p a t i e n t s admitted t o the Cancer C o n t r o l Agency o f B r i t i s h Columbia. There are some p o s s i b l e l i m i t a t i o n s t o c o n c l u s i o n s based on t h i s a n a l y s i s which may r e s t r i c t the i n t e r p r e t a t i o n o f the r e s u l t s . The q u a l i t y o f the records i n r e s p e c t t o the two major v a r i a b l e s , d e l a y time and s u r v i v a l time, may be so poor t h a t no v a l i d c o n c l u s i o n s are p o s s i b l e . The s u b j e c t i v e i m p r e s s i o n from r e a d i n g the c h a r t s , ab-s t r a c t cards prepared from these and t a l k i n g t o members o f s t a f f at the Cancer C o n t r o l Agency i s t h a t the re c o r d s are o f v e r y h i g h q u a l i t y w i t h r e s p e c t t o these two v a r i a b l e s . The date o f f i r s t symptom n o t i c e d by the p a t i e n t has been an i n t e g r a l p a r t o f the h i s t o r y which i s taken on every new p a t i e n t seen a t the Cancer C o n t r o l Agency s i n c e i t s i n -s t i t u t i o n i n 1938. F o r the purposes o f t h i s study the ab-s t r a c t cards are used. These are a b r i e f summary o f the c l i n i c a l r e c o r d s f o r each p a t i e n t and i n c l u d e s a de s i g n a t e d space f o r the i n t e r v a l between f i r s t symptom and d i a g n o s i s . I n the i n i t i a l d ata survey f o r the study, I examined the 117 a b s t r a c t cards f o r a l l p a t i e n t s w i t h b r e a s t cancer seen at the Cancer C o n t r o l Agency i n the years 1960, 1961 and 1970. T h i s i n v o l v e d the review o f 838 a b s t r a c t cards, and i n o n l y 7 o f these was t h e r e no i n f o r m a t i o n recorded on d e l a y time. Though the i n f o r m a t i o n i s v e r y complete the accuracy might be questioned. These e r r o r s may have been beyond the c o n t r o l o f the r e c o r d i n g p h y s i c i a n and due t o the p a t i e n t 1 s memory or on o c c a s i o n s a d e l i b e r a t e g i v i n g o f m i s i n f o r m a t i o n . G u i l t f e e l i n g s because o f i n c r e a s i n g e d u c a t i o n over r e c e n t years on the need f o r e a r l y d i a g n o s i s i s p o s s i b l y a reason f o r u n d e r e s t i m a t i n g d e l a y . However, i f t h a t has o c c u r r e d d u r i n g the 10 year p e r i o d covered i n the f i r s t p a r t o f the study, i t would show as an i n c r e a s e i n the p r o p o r t i o n o f p a t i e n t s r e p o r t i n g a s h o r t d e l a y time. No t r e n d i n the pro-p o r t i o n o f p a t i e n t s w i t h e i t h e r s h o r t or long d e l a y times was seen between 1960, 1961 and 1970. T h e r e f o r e , such a b i a s would not be l i k e l y . S i m i l a r l y the i n f o r m a t i o n on s u r v i v a l times can be used w i t h c o n f i d e n c e . A l l b r e a s t cancer p a t i e n t s seen at the Cancer C o n t r o l Agency are maintained on an a c t i v e f o l l o w - u p system. F o r the m a j o r i t y o f p a t i e n t s , t h i s i s because they are f o l l o w e d by c l i n i c a l examinations on r e c a l l t o the c l i n i c . F o r the p a t i e n t s whose follo w - u p care i s handled e n t i r e l y by t h e i r f a m i l y d o c t o r or s p e c i a l i s t o r who move o u t s i d e the p r o v i n c e , f o l l o w - u p i s maintained by l e t t e r or phone c a l l c o n t a c t w i t h the p h y s i c i a n or even d i r e c t l y w i t h the p a t i e n t 118 on at l e a s t an annual basis. This follow-up system has dated from the e a r l i e s t days of the c l i n i c , and thus the proportion of cases who were l o s t to follow-up was not high. In the major part of the study, related to the 456 cases of breast cancer seen i n the c l i n i c between 1960 and 1964, only 12% (54) of these were l o s t to follow-up before the end point of the study i n June 1977. The rest were eithe r s t i l l on active follow-up within a year at that time, or have been followed up u n t i l death. This 12% loss i s reassuringly small, although i t i s s t i l l s u f f i c i e n t to cause some error i f the method of analysis d i d not take account of i t . However i n the su r v i v a l analysis performed, an a c t u a r i a l method was used i n which a patient l o s t to follow-up only contributes to the analysis for that period during which t h e i r status i s known. The d i s t r i b u t i o n of loss of follow-up i s 30 patients (12.9%) i n short delay, and 24 (10.7%) i n long delay, and i t i s therefore very un-l i k e l y that any bias i n the res u l t s would thus occur. The data was incomplete f o r some of the variables which are possibly associated with delay and s u r v i v a l . The missing information has resulted i n some l i m i t a t i o n of the analyses which could be done. For example, the pathological grade of the tumour v/as not available i n most cases, information being only available i n 168 (37%). In fact the medical records do contain t h i s information for most patients, but i t v/as not routinely put on to the abstract cards. To extract t h i s one 119 piece of information would therefore have required a very-large increase i n the time needed for data extraction, and i t v/as not thought e s s e n t i a l to do t h i s . The most important factor which has been shown i n other work (14) to be related to the s u r v i v a l of breast cancer i s the c l i n i c a l stage of the disease. Information oh t h i s v/as available for a l l but 7 of the cases. In socio-economic status heavy reliance i s placed on the husband's occupation for c l a s s i f i c a t i o n and data i s missing i n 174 (38%) cases. Only i n 15% (70) i s the patient's occupation taiown. During the period studied, approximately 70% of the t o t a l number of breast cancer cases seen i n the Province of B r i t i s h Columbia were seen by the Cancer Control Agency. The number seen at the Cancer Control Agency v / i l l not be representative i n a l l respects to the t o t a l scene i n the province. For example, amongst the group not seen at the Cancer Control Agency would be a number of cases diagnosed only on autopsy, a number of lesions perhaps i n e l d e r l y or otherwise d e b i l i t a t e d patients which would not receive any treatment, and possibly a group of very early l o c a l i z e d tumours which would be treated by surgery alone, and because radiotherapy or other treatment was not advised, would not necessarily be referred to the Cancer Control Agency. How-ever, there i s l i t t l e ground to conclude that the r e s t r i c t i o n of the study to the cases seen at the Cancer Control Agency should change the r e l a t i o n s h i p between s u r v i v a l time and 120 d e l a y time. A l l p o s s i b l y a s s o c i a t e d v a r i a b l e s have been c o n s i d e r e d except f o r the s i z e o f tumour and i t would appear from the l i t e r a t u r e (10) (17) t h a t t h i s v a r i a b l e i n i t s e l f i s not p a r t i c u l a r l y important. 121 6.2 THE DISTRIBUTION OF DELAY TIME I n the f i r s t p a r t o f the study, the delay times on a l l p a t i e n t s seen at the Cancer C o n t r o l Agency i n the years 1960, 1961 and 1970 were s t u d i e d . This demonstrated t h a t 26% of the p a t i e n t s seen i n those years showed a short delay time, defi n e d as l e s s than one month, whereas 20% of them showed a long delay time, d e f i n e d as one year or over. The patterns of delay time have not changed f o r p a t i e n t s w i t h b r e a s t cancer i n B r i t i s h Columbia i n the decade from 1960 t o 1970. T h i s i s s u r p r i s i n g when one considers the h e a l t h i n f o r m a t i o n t h a t has been a v a i l a b l e and the changes t h a t have occurred i n a t t i t u d e s i n those t e n y e a r s . I t would have been a n t i c i p a t e d t h a t during t h i s decade there would be a s h i f t toward e a r l i e r diagnosis which would be showed by an increase i n the p r o p o r t i o n i n the short delay group and a decrease i n the p r o p o r t i o n i n the long delay group when com-pa r i n g 1970 t o 1960 data. The s t a b i l i t y of these patterns has been a l s o shown by Hackett et a l (29) i n a study of 563 p a t i e n t s w i t h d i f f e r e n t types o f cancer and by Dennis et a l i n 237 p a t i e n t s w i t h r a d i c a l mastectomies. I t would be i n t e r -e s t i n g t o explore a more recent year t o determine i f the s t a -b i l i t y i n delay p a t t e r n s has continued. C e r t a i n l y , s i n c e 1970 there has been an i n c r e a s i n g amount of i n f o r m a t i o n from Cancer S o c i e t i e s , popular magazines and news media and the occurrence of b r e a s t cancer i n well-known North American women has drawn a t t e n t i o n t o a personal r e s p o n s i b i l i t y f o r e a r l y d i a g n o s i s . However, the present r e s u l t s suggest t h a t 122 i t i s v e r y l i k e l y t h a t the p a t t e r n s o f d e l a y time i n a popu-l a t i o n are remarkably s t a b l e and have not responded t o such i n f l u e n c e s . T h i s v/ould have important i m p l i c a t i o n s f o r h e a l t h programs and p l a n n i n g f o r both now and i n the f u t u r e . The 456 cases examined were d i s t r i b u t e d e v e n l y between the two d e l a y p e r i o d s examined. The d e l a y time i n the long d e l a y group was q u i t e c o n s i d e r a b l e . One hundred and t h r e e cases out o f 224 d e l a y e d two years and over. There was a s t a t i s t i c a l l y s i g n i f i c a n t r e l a t i o n s h i p be-tween age and d e l a y . The younger p a t i e n t tended to d e l a y l e s s . T h i s confirmed the f i n d i n g o f S h e r i d a n e t a l (15) who suggested i t may be due t o f a c t o r s "such as g r e a t e r ignorance i n the o l d e r group, a g r e a t e r sense of f a m i l y needs i n the younger, and perhaps a more p h i l o s o p h i c a t t i t u d e i n the o l d e r age groups". There i s c o n s i d e r a b l e l i t e r a t u r e (18) (19) (21) (23) c o n c e r n i n g the p s y c h o l o g i c a l aspects o f d e l a y but no f i r m c o n c l u s i o n s were found t o c o n f i r m the above. Cameron and H i n t o n (20) summarized the l i t e r a t u r e a p t l y by s a y i n g "the i n t e r r e l a t i o n s h i p between knowledge and d e n i a l , a n x i e t y and p r o f e s s e d i n d i f f e r e n c e t o cancer i s complex and these v a r i o u s s t u d i e s r e v e a l no c e r t a i n way o f p r e d i c t i n g people's r e a d i n e s s t o r e p o r t w i t h cancer symptoms". There v/as a s t a t i s t i c a l l y s i g n i f i c a n t d i f f e r e n c e between the two d e l a y p e r i o d s v/ith r e g a r d t o c l i n i c a l s t a g i n g . The s h o r t d e l a y group were more l i k e l y t o be c l a s s i f i e d as c l i n i c a l stage 1. N i n e t y percent of cases i n the s h o r t d e l a y 123 were i n c l i n i c a l stage 1 and 11 compared t o 52% i n the long d e l a y group. C o n v e r s e l y o n l y 3.8% o f the s h o r t d e l a y ap-peared i n grade IV a g a i n s t 30.4% o f the l o n g d e l a y . T h i s would suggest t h a t t h e s h o r t d e l a y group should have a b e t t e r p r o g n o s i s . There i s no d i f f e r e n c e seen i n the patho-l o g i c a l s t a g i n g . There was a r e l a t i o n s h i p t o m a r i t a l s t a t u s . Those ma r r i e d tended t o d e l a y l e s s w h i l e s i n g l e and widowed were found more i n the one y e a r or over d e l a y group. The support and concern w i t h i n a f a m i l y group may account f o r t h i s d i f f e r e n c e . No d i f f e r e n c e v/as found i n socio-economic s t a t u s be-tween the d e l a y groups, assessed by the B l i s h e n Socio-Economic Index (33) v/hich i s based on e d u c a t i o n and income. A i t k e n -Sv/an and Paterson (21) a l s o showed no a s s o c i a t i o n i n t h e i r study. Hacket e t a l (29) found ( u s i n g H o l l i n g s h e a d ' s Index) t h a t the h i g h e r the c l a s s , the l e s s the d e l a y . However t h i s study reviewed d e l a y i n a l l types of cancer which have many v a r i e d p r e s e n t a t i o n s so i t s s i g n i f i c a n c e i n b r e a s t cancer i s l i m i t e d . The p r e s e n t r e s u l t s suggest t h a t socio-economic s t a t u s i s not a f a c t o r i n d e l a y i n B r i t i s h Columbia, although f u r t h e r study u s i n g a more r e f i n e d index v/ould be u s e f u l . 124 6.3 ANALYSIS OF SURVIVAL Of the 456 cases s t u d i e d , by June 1977, 235 had d i e d ; of b r e a s t cancer, 53 d i e d o f o t h e r causes, 101 p a t i e n t s were s t i l l a l i v e , and 54 were l o s t t o f o l l o w - u p . The a n a l y s i s was c a r r i e d out by computing a c t u a r i a l s u r v i v a l r a t e s and a l s o r e l a t i v e s u r v i v a l r a t e s ( t h a t i s , the r a t i o o f t h e observed s u r v i v a l t o t h e expected s u r v i v a l , based on B r i t i s h Columbia l i f e t a b l e s , which thus a d j u s t s f o r the age d i s t r i b u t i o n o f the p a t i e n t s ) . Comparison o f the s u r v i v a l experience o f l o n g and s h o r t d e l a y p a t i e n t s i s not n e c e s s a r i l y simple t o i n t e r p r e t . I compared s u r v i v a l i n t h r e e ways: (1) Based on s u r v i v a l time from the date o f d i a g n o s i s . (2) Based on t h e s u r v i v a l time from the date o f f i r s t symptom. (3) Based on the s u r v i v a l time from the date o f d i a g n o s i s , w i t h i n c l i n i c a l stage. (1) S u r v i v a l Time From Date o f D i a g n o s i s . The r e l a -t i v e s u r v i v a l r a t e s e s timated from date of d i a g n o s i s (Table XXXVI) show t h a t the p a t i e n t s w i t h s h o r t d e l a y have a b e t t e r s u r v i v a l r a t e . T h i s d i f f e r e n c e i s shown by a 8.4% d i f f e r -ence shown i n the f i v e y e a r s u r v i v a l r a t e s (69.3% s h o r t de-l a y compared t o 60.9% long d e l a y p a t i e n t s ) , the d i f f e r e n c e i n 10 and 15 y e a r s u r v i v a l s b e i n g r e s p e c t i v e l y 6.8% and 13.6%. These r e s u l t s are c o n s i s t e n t w i t h those o f Park and Lees ( 6 ) . We can conclude from t h i s , t h a t a group o f pa-t i e n t s w i t h s h o r t d e l a y time do have a b e t t e r p r o g n o s i s , as 125 estimated from the date o f d i a g n o s i s , than those w i t h a long delay time. (2) S u r v i v a l Time From Date o f Diagnosis. I n terms of the s u r v i v a l time as seen from the p a t i e n t ' s p o i n t of view r a t h e r than from the p h y s i c i a n ' s p o i n t of view, i t i s more l o g i c a l t o estimate s u r v i v a l from the time of f i r s t symptom. A n a l y s i s (Figure 4) us i n g s u r v i v a l from the date of f i r s t symptom d i d not show b e t t e r s u r v i v a l r a t e f o r the short delay group, and i n f a c t the p a t i e n t s who delay f o r a long time i n i t i a l l y appear t o do b e t t e r . A f t e r f i f t e e n years, there would appear to be no advantage t o e i t h e r group. Using the long delay group and e s t i m a t i n g s u r v i v a l from date of f i r s t symptom, I am i g n o r i n g any m o r t a l i t y which has occurred i n the f i r s t months a f t e r the symptom developed. I n examining these p a t i e n t s i n t h i s way I may have produced a b i a s i n favour of the long delay group. These p o s s i b l e c o r r e c t i o n s f o r t h i s b i a s are considered v a l i d f o r f u r t h e r comparison. The f i r s t , which would be the one g i v i n g the lowest reasonable estimate of the m o r t a l i t y during t h a t p e r i o d , would be t o assume t h a t from the date of f i r s t symptom t o the date o f diagnosis these women experience the same mor-t a l i t y r a t e as a l l women i n t h e i r age group i n the province. Thus we take the expected number of deaths f o r women of tha t age group over an 18 month p e r i o d and adjust the s u r v i v a l r a t e s a c c o r d i n g l y (Tables XXXXIV and XXXXV) . The second 126 approach would be t o assume t h a t the r a t e o f death i n the f i r s t 18 months a f t e r symptoms f o r the long d e l a y group i s the same as t h a t r a t e o f death f o r t h i s group i n t h e 18 months a f t e r d i a g n o s i s , which i s the e a r l i e s t p e r i o d on which we have i n f o r m a t i o n . I n f a c t the r a t e o f death i n t h i s group o f women i n the f i r s t 18 months a f t e r d i a g n o s i s i s q u i t e h i g h , and i s c o n s i d e r a b l y h i g h e r than t h a t o f the short d e l a y p a t i e n t s . I t seems c l e a r t h a t the use o f t h i s approximation w i l l g i v e a p e s s i m i s t i c l i m i t . A t h i r d ap-proach, which g i v e s an i n t e r m e d i a t e r e s u l t i s t o assume t h a t the s u r v i v a l r a t e o f the lo n g d e l a y p a t i e n t s i s the same as t h a t o f the sh o r t d e l a y women i n t h e i r f i r s t 18 months a f t e r treatment. U s i n g these c o r r e c t i o n s ( F i g u r e 5) i t would seem i n t he f i r s t nine t o t e n ye a r s those w i t h long d e l a y do s l i g h t l y b e t t e r or t h e r e i s no d i f f e r e n c e . I n the long term though, the p a t t e r n r e v e r s e s and s h o r t d e l a y p a t i e n t s from date o f f i r s t symptom have a lon g e r s u r v i v a l . The advantage though i s no more than 5 - 10%. I n a r e t r o s p e c t i v e study such as t h i s no d e f i n i t e answer can be produced. The most reasonable i n t e r p r e t a t i o n would be t h a t the advantage i s somewhat l e s s than t h a t , as based on the i n t e r m e d i a t e c o r -r e c t i o n d e s c r i b e d above, although t h e r e i s an i n d i c a t i o n ' t h a t the improvement i s b e g i n n i n g t o be n o t i c e a b l e at around 15 y e a r s a f t e r t h e f i r s t symptom. E x t e n s i o n o f the study t o c o n s i d e r perhaps 20 years follow-up would t h e r e f o r e be u s e f u l , as any t r e n d may become more obvious. 127 T h e r e f o r e , p a t i e n t s i n B r i t i s h Columbia w i t h carcinoma o f the b r e a s t i n my s h o r t d e l a y group appear t o g a i n l i t t l e over the long d e l a y group i n the way o f s u r v i v a l . T h i s i s a c o n c l u s i o n which confirms Bloom's (14) e a r l i e r f i n d i n g s and i s a l s o a c o n c l u s i o n confirmed i n r e c e n t l i t e r a t u r e (40). I t h i n k though l o o k i n g back on the r e s u l t s we now know, I may have been v e r y s e l e c t i v e i n the two d e l a y groups chosen. S u t h e r l a n d (9) i n h i s reviexv o f d e l a y suggests the worst p r o g n o s i s i s i n an i n t e r m e d i a t e group who are essen-t i a l l y "tumour determined". I have i n f a c t chosen i n t h i s r e s e a r c h p o s s i b l y the two groups t h a t w i l l do e q u a l l y w e l l . T h i s i s e s p e c i a l l y t r u e o f my one year and over group who c o u l d be d e s c r i b e d as ha v i n g "tumour determined" d e l a y . They have a l r e a d y s u r v i v e d f o r one year o r i n some cases much l o n g e r as a l r e a d y d i s c u s s e d e a r l i e r . T h e r e f o r e , Suther-land's o b s e r v a t i o n may w e l l apply t o t h i s r e s e a r c h . "Thus, by a pro c e s s o f " n a t u r a l s e l e c t i o n " (MacDonald, 1942), those who d e l a y more than a yea r o r two w i l l i n c l u d e a d i s p r o p o r -t i o n a t e number w i t h tumours o f low, or comparatively low, malignancy. Consequently, the m o r t a l i t y r a t e s o f the l o n g -d e l a y group w i l l be weighted f a v o u r a b l y ; those o f the s h o r t and i n t e r m e d i a t e - d e l a y groups, unfavourably." (3) S u r v i v a l Time From Date o f D i a g n o s i s W i t h i n C l i n i c a l  Stage. The r o l e o f d e l a y time as a p r o g n o s t i c f a c t o r which can be used by the c l i n i c i a n at the time o f d i a g n o s i s t o p r e d i c t p r o g n o s i s , might be deduced from t h i s a n a l y s i s . 128 These r e s u l t s ( F i g u r e s 6 and 7) shew t h a t f o r p a t i e n t s i n Stage I or Stage I I , those w i t h a l o n g d e l a y time do b e t t e r than those w i t h a s h o r t d e l a y time. The p r o g n o s i s f o r the long d e l a y group i n Stage I and I I i s s u r p r i s i n g l y much b e t -t e r than the p h y s i c i a n may suspect. S u t h e r l a n d (9) has de-s c r i b e d d e l a y groups as " p e r s o n a l i t y determined" and "tumour determined" and i n t h i s d e s c r i p t i o n may l i e the reason f o r t h e above r e s u l t s . Stage I tumours o f e a r l y d e l a y have y e t to show t h e i r t r u e c o l o u r s w h i l e the l o n g d e l a y group which are "tumour determined" are s t i l l i n Stages I and I I a f t e r at l e a s t a year, i n d i c a t i n g they have e i t h e r an i n t r i n s i c a l l y l e s s a g g r e s s i v e tumour, o r more e f f i c i e n t tumour growth i n h i -b i t i o n mechanisms. T h i s p o s s i b l y g i v e s support t o Mac-Donald's (4) c o n t e n t i o n o f " B i o l o g i c a l Predeterminism". However, i n Stages I I I and IV, the l o n g d e l a y p a t i e n t s do worse. P a t i e n t s i n these stages have e i t h e r a v e r y ex-t e n s i v e l o c a l d i s e a s e or have d i s t a n t metastases. One c o u l d h y p o t h e s i z e t h a t p a t i e n t s who reach t h i s stage i n e i t h e r 1 month or 18 months a f t e r symptoms both have a g g r e s s i v e d i s -ease, and t h e r e f o r e the argument which may apply t o the e a r l i e r stages does not h o l d . I t should be remembered though a p a t i e n t i s c l a s s e d f o r example i n Stage IV whether they have one i s o l a t e d m e t a s t a t i c l e s i o n , which may be t r e a t a b l e , o r have l a r g e e x t e n s i v e and m u l t i p l e metastases, which would be r e s i s t a n t t o any treatment. 129 6.4 INTERPRETATION I t appears f a c t o r s which i n f l u e n c e p a t i e n t s f a l l i n t o two l a r g e groups when determining how e a r l y they w i l l r e -spond t o t h e i r d i s e a s e . F i r s t l y , t h e r e are f a c t o r s which are r e l a t e d t o t h e tumour. The most important o f which i s speed o f growth, which may be r e f l e c t e d by i t s degree o f d i f f e r e n t i a t i o n o r o t h e r p a t h o l o g i c a l c h a r a c t e r i s t i c s . Secondly, t h e r e are f a c t o r s r e l a t e d t o the p a t i e n t , p a r t i c -u l a r l y p e r s o n a l i t y f a c t o r s which determine h e r response t o the d i s e a s e . I t i s the i n t e r a c t i o n o f these two groups o f f a c t o r s which l e a d s t o the p a t t e r n s o f d e l a y i n carcinoma o f the b r e a s t . The i n t e r p r e t a t i o n o f my r e s u l t s with r e -spect t o s u r v i v a l i s t h e r e f o r e d i f f i c u l t as the d i f f e r e n c e i n s u r v i v a l between long d e l a y and s h o r t d e l a y p a t i e n t s w i l l r e f l e c t both c h a r a c t e r i s t i c s o f the tumour and c h a r a c t e r i s -t i c s o f t h e p a t i e n t s . There are s e v e r a l approaches t o the f i n d i n g s o f t h i s study. C h a r a c t e r i s t i c s o f p a t i e n t s such as age and m a r i t a l s t a t u s i n the two d e l a y groups can be i n t e r p r e t e d . I have shown t h a t women who are married tend t o have s h o r t e r d e l a y times than those who are e i t h e r s i n g l e o r widowed. T h i s might suggest t h a t women who have a spouse t o whom they can r e l a t e on p e r s o n a l matters and i n whom they can c o n f i d e t h e i r w o r r i e s , are more l i k e l y t o r e c e i v e support and encour-agement t o seek e a r l y treatment. I t c o u l d be because these women have a husband and pr o b a b l y dependents, t h a t they are more concerned t o r e c e i v e optimum treatment, whereas women 130 without such r e s p o n s i b i l i t i e s may be able to j u s t i f y delay more e a s i l y . A much less l i k e l y alternative i s that the type of tumour which occurs i n married women i s d i f f e r e n t i n terms of i t s speed of growth or i t s symptomatology from that occurring i n single or widowed women. With respect to age, the younger the patient the les s l i k e l y they are to delay. This could be due to personality factors e s p e c i a l l y those associated with attitude to the body i t s e l f , as we have seen great changes i n t h i s area i n the l a s t decade. Increase i n education by schools and news media may also play a part. C e r t a i n l y , we may be seeing possible early changes i n the pattern of delay and a review of l a t e r years as stated e a r l i e r might be of value. With respect to tumour c h a r a c t e r i s t i c s there i s no support for the view that tumours of younger women, apart from those associated with pregnancy and l a c t a t i o n are more ra p i d l y growing. A second type of int e r p r e t a t i o n i s to review delay time as a prognostic factor, looking at the disease from the physician's rather than from the patient's point of view. This would be using the accepted c l i n i c a l d e f i n i t i o n that disease i s measured from the date of c l i n i c a l diagnosis. My re s u l t s suggest that the short delay group i n the long term did better and therefore there i s some substantiation i n shortening delay. Again my res u l t s agreed with Suther-land' s (9) conclusion that the benefit i s s t a t i s t i c a l l y moderate and claims should be modest. As a prognostic 1 3 1 f a c t o r my analyses of d e l a y time w i t h i n groups c l a s s i f i e d by c l i n i c a l stage i s the most i n t e r e s t i n g . I have i d e n -t i f i e d a group o f p a t i e n t s , those who have l o n g d e l a y and are c l a s s i f i e d i n c l i n i c a l Stages I and I I whose pro g n o s i s i s good and would p o s s i b l y b e n e f i t from s h o r t e n i n g d e l a y . C e r t a i n l y the treatment g i v e n these p a t i e n t s should be based on t h i s c o n s i d e r a t i o n . I t would appear those w i t h l o n g de-l a y times have a l e s s a g g r e s s i v e tumour. A r e l a t i o n s h i p o f b i o l o g y o f the tumour, d e l a y and outcome are suggested i n these r e s u l t s , "the b i o l o g i c predeterminism" suggested by MacDonald (4) ( 5 ) . I t would be h e l p f u l i n f u r t h e r s t u d i e s t o see i f d e l a y time i s a u s e f u l p r o g n o s t i c a t o r i f i n f o r -mation on not o n l y c l i n i c a l stage, but more d e t a i l e d i n f o r -mation on the extent o f the d i s e a s e (such as number o f lymph nodes i n v o l v e d , or the number and s i t e s o f d i s t a n t metasta-ses) , and another c h a r a c t e r i s t i c such as p a t h o l o g i c a l grade are i n c l u d e d . The t h i r d approach t o i n t e r p r e t i n g the d a t a i s the most d i f f i c u l t . There i s no doubt w i t h r e s p e c t t o p u b l i c h e a l t h programs, comparisons o f l o n g and s h o r t d e l a y p a t i e n t s are u s e f u l . I have taken a time p e r i o d i n which we can r e g a r d the p u b l i c e d u c a t i o n measures as b e i n g f a i r l y modest. Twenty-s i x p ercent o f p a t i e n t s p r e s e n t e d promptly and w i l l not bene-f i t by any e d u c a t i o n a l programs wi t h r e s p e c t t o d e l a y . Where-as 20% showed a very l o n g d e l a y and the r a t i o n a l e o f any h e a l t h e d u c a t i o n program t h e r e f o r e would be t o encourage 132 these patients to present with their symptoms much ear l ier . The question i s , "does a benefit in terms of the outcome from the disease occur"? The present study cannot direct ly answer that question, although the findings demonstrated here v/ould suggest that the possible improvement which could result from ear l ier diagnosis would be very small. The optimum method of va l id ly assessing the impact of educational programs on early diagnosis would be a prospective randomized t r i a l , in which a large number of women in the breast cancer r isk age groups for example from 40 to 65, were randomized into one group who would receive efforts aimed at early diagnosis and another group who would not receive such efforts. 133 6.5 DUPLICATIONS FOR HEALTH PLANNING H e a l t h p l a n n i n g i n the l a s t twenty years has been d i r e c t e d a t e a r l y i d e n t i f i c a t i o n o f d i s e a s e and prompt treatment. I n cancer, d e l a y has been something t o be avoided, and carcinoma o f the b r e a s t has been no e x c e p t i o n . V a r i o u s methods of s c r e e n i n g , mammography, thermography and b r e a s t s e l f - e x a m i n a t i o n , have been propagated t o o b t a i n the e a r l i -e s t diagnosis, and encourage people t o a v o i d d e l a y . Y e t as we have seen i n the l i t e r a t u r e review t h e r e i s no f i r m e v i -dence to show t h a t d e l a y i s r e l a t e d t o s u r v i v a l . I t was w i t h t h i s i n mind t h a t d e l a y v/as e x p l o r e d i n p a t i e n t s w i t h c a r c i n -oma o f the b r e a s t i n B r i t i s h Columbia. We see t h a t d e l a y has not changed w i t h present educa-t i o n a l methods. We must conclude t h a t e i t h e r the wrong methods have been used or d e l a y i s u n a l t e r a b l e , a psycho-l o g i c a l t r a i t t h a t i s r e s i s t a n t t o any form o f propaganda. C e r t a i n l y a r e - e v a l u a t i o n o f e d u c a t i o n a l methods i s - i n d i c a t e d . The p a t t e r n we see would c o n f i r m what "the Walton Report" (41) has p o i n t e d out. The problem i s t h a t program a t t e n d e r s are s e l f - s e l e c t e d and they come from the segment o f the pop-u l a t i o n t h a t i s most h e a l t h c o n s c i o u s . From the r e s u l t s v/e see the long d e l a y group, d e f i n e d as c l i n i c a l stage 1 and 11, had a b e t t e r s u r v i v a l r a t e . Would t h a t s u r v i v a l r a t e be markedly improved i f t h i s group o f one year and over p a t i e n t s changed t o the s h o r t d e l a y group? T h i s v/ould i n v o l v e an i n t e n s i f i c a t i o n o f r e s e a r c h i n t o the m o t i v a t i o n s o f t h i s 134 group. P r e v i o u s r e s e a r c h has i n v o l v e d s m a l l numbers, d e a l t w i t h i n d i v i d u a l e x p e r iences, i n s u f f i c i e n t t o g i v e an i n -depth understanding o f m o t i v a t i o n s o r s t a t i s t i c a l l y s i g n i f -i c a n t f i g u r e s on which t o a c t . T h i s group i n i t s b e t t e r s u r v i v a l r a t e i n c l i n i c a l stage I and I I cases than the sh o r t d e l a y group c e r t a i n l y shows a p o s s i b l e p o t e n t i a l t o improve s u r v i v a l i n carcinoma o f the b r e a s t i f d e l a y c o u l d be improved. C e r t a i n l y f o r h e a l t h p l a n n i n g t o l e n d support to v a r i o u s e d u c a t i o n a l programs and s c r e e n i n g procedures a g r e a t e r understanding o f d e l a y and s u r v i v a l and a s s o c i a t e d v a r i a b l e s i s e s s e n t i a l . More d e f i n i t i v e s t u d i e s should be made o f the psycho-l o g i c a l c h a r a c t e r i s t i c s o f d e l a y . V a r i o u s d e l a y p e r i o d s should be s t u d i e d along w i t h d e t a i l e d pathology t o d e f i n e those who might b e n e f i t from s h o r t e n i n g the d e l a y p e r i o d . A r e - e v a l u a t i o n o f e d u c a t i o n a l methods i n the l i g h t o f un-changing d e l a y p a t t e r n s i s necessary. S t u d i e s o f mammography and p h y s i c a l examination i n women l e s s than f i f t y and a t r i a l o f b r e a s t s e l f - e x a m i n a t i o n are c a l l e d f o r . I n the f u t u r e , h e a l t h p l a n n i n g must t r a v e l more d e f i n e d paths so t h a t programs are more e f f e c t i v e . I n the past t h e r e has been p o s s i b l y a wastage o f funds due t o programs and p o l i c i e s i n which the o r i g i n a l t h e s i s was p o o r l y supported or ongoing e v a l u a t i o n was absent. I n f u t u r e , h e a l t h p l a n n i n g must answer Cochrane's and Hol l a n d ' s (42) q u e s t i o n : " I s the t e s t ( v a r i o u s b r e a s t 135 s c r e e n i n g programs) j u s t i f i e d , s c i e n t i f i c a l l y and f i n a n -c i a l l y , by the r e s u l t i n g b e n e f i t t o the Community?". 136 6.6 POLICIES AND OBJECTIVES OF HEALTH PLANNING I n t h e p a s t h e a l t h p l a n n i n g programs have been con-cerned w i t h d i s t r i b u t i o n o f r e s o u r c e s , access t o treatment and u n i v e r s a l i t y o f s e r v i c e . These g o a l s have e s s e n t i a l l y been accomplished i n B r i t i s h Columbia. New d i r e c t i o n s are b e i n g formulated and the p o l i c y o f p r e v e n t i o n i s prominent. Y e t the b a s i c s c i e n c e of p r e v e n t i o n i s p o o r l y understood, s c r e e n i n g procedures, psychology o f d e l a y and p a t i e n t m o t i -v a t i o n are p o o r l y researched. I f these parameters are not w e l l d e f i n e d , e v a l u a t i o n i s w o r t h l e s s o r i n a p p r o p r i a t e . The o b j e c t i v e f o r the p o l i c y o f p r e v e n t i o n and i n t e r i m o b j e c -t i v e s cannot be formulated. E v a l u a t i o n o f t e n i s a process o f c o u n t i n g numbers and not a re-examination o f b a s i c p r i n c i p l e s . I n the r e s e a r c h I have c a r r i e d out we see the l a c k o f d e l a y i n one p a r t i c -u l a r d i s e a s e i s not as advantageous as f i r s t b e l i e v e d . There-f o r e any p l a n n i n g o r program based on t h i s i n f o r m a t i o n needs c o n t i n u a l review and should never be regarded as e s t a b l i s h e d . I t should be p o s s i b l y on t r i a l throughout i t s a p p l i c a t i o n and a l t e r e d , m o d i f i e d or c a n c e l l e d as i t i s e v a l u a t e d . There should be a process o f d i s c o v e r y b e f o r e a s t a t e -ment o f p o l i c y and broad g o a l s i s made. The process o f d i s c o v e r y may take the form o f a p r e l i m i n a r y p l a n and must c o n t a i n a statement o f i n f o r m a t i o n a v a i l a b l e and r e q u i r e d . The q u a l i t y of i n f o r m a t i o n should be c l o s e l y s t u d i e d . The l i m i t a t i o n s o f any g i v e n procedure should be known. T h i s i s e s p e c i a l l y t r u e o f any program proceeded w i t h and whose 137 e x p e c t a t i o n s may be s e t too h i g h . U n t i l we know more about the m o t i v a t i o n o f delay, f o r example i n r e l a t i o n t o b r e a s t cancer an i n c r e a s e i n the marginal b e n e f i t s o f s h o r t e n i n g d e l a y w i l l not be made. Such o t h e r r e l a t e d programs as h e a l t h e d u c a t i o n may be v e r y w a s t e f u l and i n e f f e c t u a l . T h e r e f o r e withotit b a s i c r e s e a r c h as a p r e l i m i n a r y t o the p l a n n i n g process and a f i r m knowledge o f the r e s u l t i n g l i m i -t a t i o n s o f t h a t r e s e a r c h , popular programs may become esta b -l i s h e d which g i v e r i s e t o l i t t l e g a i n t o s o c i e t y but p o l i t -i c a l l y may be d i f f i c u l t t o remove. I n view o f t h i s p l a n n i n g has a l s o now to l o o k at the economic aspect o f any g i v e n program b e f o r e i t i s embarked upon. An e x p l o r a t i o n o f a l t e r -n a t i v e s i s necessary. The r e s p o n s i b i l i t y o f d e c i s i o n r e s t s more h e a v i l y now than ever b e f o r e on p l a n n e r s . I n the p a s t b a s i c h e a l t h care was the g o a l and needs were e a s i l y d e f i n e d . We now depend more on the understanding o f the n a t u r a l h i s -t o r y o f a d i s e a s e and a t e c h n i c a l knowledge i s necessary t o d i s c r i m i n a t e between the v a r i o u s p r i o r i t i e s . There i s no doubt more r e s o u r c e s must be spent on r e -s e a r c h and c o l l e c t i o n o f i n f o r m a t i o n b e f o r e p l a n s and p o l -i c i e s can be formulated. Any p r o s p e c t i v e h e a l t h care p l a n i n f u t u r e w i l l be expensive and we must ensure t h a t the m a r g i n a l b e n e f i t a t l e a s t equals the marginal c o s t . Only r e s e a r c h can d e f i n e those b e n e f i t s f o r us. I n c o n c l u s i o n t h i s t h e s i s has p o i n t e d out t o the p l a n n e r the importance o f adequate r e s e a r c h i n t o the n a t u r a l 138 h i s t o r y o f a d i s e a s e b e f o r e any programs are embarked on. 139 7.0 BIBLIOGRAPHY 1. SHAPIRO, S., St r a x , P., Venet, L. 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