Breastfeeding and breast cancer:
a case-control study in Southern Brazil
Amame ntaç ão e c ânc e r d e mama:
e stud o d e c aso -c o ntro le no Sul d o Brasil
1 Dep artam en to M atern o In fa n t il, Fa cu ld a d e d e M ed icin a , U n iv ersid a d e Fed era l d e Pelot a s. Ru a Go n ça lv es Ch a v es 3027, Pelot a s, RS
96015- 560, Bra z il. t essa ro.su l@t erra .com .b r 2 Program a d e Pós-Grad u ação em Ep id em iologia , Fa cu ld a d e d e M ed icin a , U n iv ersid a d e Fed era l d e Pelot a s. Av . Du q u e d e Ca x ia s 250, Pelot a s, RS 96030- 002, Bra z il.
3 Program a d e Pós-Grad u ação em Sa ú d e Colet iv a , U n iv ersid a d e Lu t era n a d o Bra sil.
Ru a M igu el T ost es 101, Ca n oa s, RS 924420- 280, Bra sil. Sérgio T essa ro 1 Jorge U . Béri a 2,3 Ela in e T om a si 2 Cesa r G. Vi ct o ra 2
Abst ract T o i n v est i ga t e t h e rela t i o n sh i p b et w een b rea st f eed i n g a n d b rea st ca n cer i n So u t h ern Bra z il, a ca se- con t rol d esign w a s em p loyed , w it h t w o a ge- m a t ch ed con t rol grou p s. A t ot a l of 250 ca ses o f b rea st ca n cer w ere i d en t i f i ed i n w o m en f ro m 20 t o 60 yea rs o f a ge, w i t h 1,020 h o sp i t a l a n d com m u n i t y con t rols. T h e m a i n st u d y v a ri a b les w ere occu rren ce of b rea st feed i n g a n d d u ra -t i on of b rea s-t feed i n g. A m u l-t i v a ri a -t e con d i -t i on a l logi s-t i c regressi on a n a lysi s w a s em p loyed . Ac-co rd i n g t o t h e resu l t s, b rea st f eed i n g d i d n o t h a v e a p ro t ect i v e ef f ect a ga i n st b rea st ca n cer. Th e od d s ra t io (OR) for w om en w h o b rea st fed w a s 0.9 (95% CI: 0.8- 1.2) com p a red t o w om en w h o d id n ot b rea st feed . For w om en w h o b rea st fed for six m on t h s or less, t h e OR w a s 1.0 (95% CI: 0.6- 1.8). In p re- m en o p a u sa l w o m en w h o b rea st f ed f o r m o re t h a n 2 5 m o n t h s, t h e O R w a s 0 .9 5 (9 5 % CI: 0 .5 - 3 .5 ), a n d i n p o st - m en o p a u sa l w o m en O R w a s 1 .2 7 (9 5 % CI: 0 .5 - 3 .1 ), co m p a red t o w o m en w h o h a d n ot b rea st feed .
Key words Brea st N eop la sm s; Brea st feed in g; Ca se- Con t rol St u d ies
Resumo Pa ra i n v est i ga r est a rela çã o , en t re a m a m en t a çã o e câ n cer d e m a m a n o Su l d o Bra si l, u t i li z o u - se u m d eli n ea m en t o d e ca so - co n t ro le co m d o i s gru p o s d e co n t ro les, em p a relh a d o s p o r i d a d e. Fo ra m i d en t i f i ca d o s 2 5 0 ca so s d e câ n cer d e m a m a em m u l h eres d e 2 0 a 6 0 a n o s e 1 .0 2 0 con t roles h osp it a la res e con t roles d e v iz in h a n ça . As p rin cip a is v a riá v eis est u d a d a s fora m a ocor-rên ci a e o t em p o d a a m a m en t a çã o . A a n á li se m u lt i v a ri a d a f o i rea li z a d a p o r m ei o d e regressã o logíst ica con d icion a l, n ã o en con t ra n d o efeit o p rot et or d a a m a m en t a çã o con t ra o câ n cer d e m a -m a . A ra z ã o d e o d d s( R O ) p a ra q u em a m a m en t o u f o i d e 0 ,9 ( IC9 5 %: 0 ,8 - 1 ,2 ) co m p a ra n d o - se com q u em n ã o a m a m en t ou . Pa ra a s m u lh eres q u e a m a m en t a ra m p or seis m eses ou m en os, a RO foi d e 1,0 (IC95%: 0,6- 1,8). En t re a s m u lh eres n a p ré- m en op a u sa q u e a m a m en t a ra m p or m a is d e 25 m eses, a RO foi d e 0,95 (IC95%: 0,5 3,5) e n a p ós m en op a u sa foi d e 1,27 (IC95%: 0,5 3,1) com -p a ra n d o- se com o gru -p o d a s q u e n ã o a m a m en t a ra m .
Introduction
Th e o b se r va t io n t h a t e a r ly m o t h e r h o o d p r o -m o t e s a r e d u ct io n in b r e a st ca n ce r r isk in d i-ca t e s t h a t re p ro d u ct ive a n d h o rm o n a l fa ct o rs p lay an im p ortan t role in th e p reven tion of th is n e o p la sm . H o rm o n a l fa cto rs h a ve th e gre a te st effect o n th e m a m m a ry gla n d s d u rin g p u b erty, p re gn a n cy, a n d la ct a t io n , in flu e n cin g ce llu la r alteration s (Ru sso & Ru sso, 1995).
Nu m e ro u s st u d ie s h a ve fo cu se d o n t h e re-la t io n sh ip b e t we e n r e p r o d u ct ive fa ct o r s a n d b r e a st ca n ce r r isk. Th e m a in fa ct o r s st u d ie d h a ve b e e n a ge a t first d e live ry, p a rit y, a ge a t m e n a r ch e , a n d a ge a t m e n o p a u se a ge (H a r r is et al., 1992).
Alth o u gh m u ch is kn o wn a b o u t risk fa cto rs for b reast can cer (Harris et al., 1992), th is kn owl-e d gowl-e h a s n o t rowl-e su lt owl-e d in su ccowl-e ssfu l p rowl-e vowl-e n t ivowl-e m easu res. Preven tion is d ifficu lt b ecau se m an y fa cto rs a re en d o gen o u s, th u s m a kin g in terven -tio n m o re d ifficu lt (Hu lka & Sta rk, 1995).
Breast can cer accou n ts for 24% of all m alig-n a alig-n t alig-n e o p la sm s a alig-n d 49,000 d e a t h s p e r ye a r a m on g wom en in th e Un ited Sta tes (La Vecch ia et a l., 1990). Wo rld wid e, m o re th a n o n e m illio n n e w ca se s we re e st im a t e d fo r t h e ye a r 2000 (Mille r & Bu lb ro o k, 1986). Bre a st ca n ce r is t h e m o st co m m o n n e o p la sm in wo m e n fro m 45 t o 65 yea rs of a ge, with fewer th a n 5% of ca ses oc-cu rrin g a m o n g wo m e n u n d e r 30 ye a rs (Bo rin g et al., 1994). Th e in cid en ce cu rve h as two p eaks, a t 50 a n d 70 ye a rs o f a ge . In Bra zil t h is d ise a se a cco u n t s fo r 15% o f fe m a le d e a t h s (Ch a ga s, 1994), a n d in Rio Gra n d e d o Su l St a t e it is t h e lea d in g ca u se o f fem a le ca n cer d ea th s (Reb elo , 1994).
It h a s b e e n h yp o t h e size d t h a t ch a n ge s o c-cu r r in g d u r in g la ct a t io n p r o t e ct wo m e n fr o m b re a st ca n ce r. Th e se p ro t e ct ive e ffe ct s re su lt fr o m t h e r e le a se o f ce lls t r a n sfo r m e d b y m ilk p rod u ction , wh ich in h ib it b oth cell growth an d t h e a p p e a r a n c e o f p r e - m a lign a n t c lo n e s, a s we ll a s t h e o ccu rre n ce o f se cre t o ry e xch a n ge s an d cell p roliferation (Fen tim an , 1993).
In t h e cit y o f Pe lo t a s, Rio Gr a n d e d o Su l, Bra zil, p reva len ce ra tes fo r b rea stfeed in g a t six m o n th s p o stp a rtu m in 1982 a n d 1993 were a p -p r o xim a t e ly 30 a n d 38% (H o r t a e t a l., 1996; Barros et al., 1986).
Alth o u gh va rio u s stu d ies h a ve d em o n stra ted a p ro tective effect o f p ro lo n gted b rea stfeted in g a ga in st b r e a st ca n ce r , m a in ly in p r e -m e n o p a u se (Bye r s e t a l., 1985; Co lla b o r a t ive Gro u p o n H o rm o n a l Fa ct o rs in Bre a st Ca n ce r, 2002; Marcu s et al., 1999; McTiern an & Th om a s, 1986; Newcom b et al., 1994; Olaya-Con treras et a l., 1999; Tr yggva d o t t ir , 2001), m a n y a u t h o r s
h a ve n o t fo u n d t h e sa m e e ffe ct (Brin t o n e t a l., 1995; Fre u d e n h e im e t a l., 1994; Lo n d o n e t a l., 1990; Mich els et al., 1996, 2001; Th om as & Noo -n a -n , 1993; U K N a t io -n a l Ca se - Co -n t r o l St u d y Gro u p , 1993). In Asia n co u n trie s th e e ffe ct a p -p e a rs t o b e m o re -p ro t e ct ive , b u t in t h e U n it e d St a t e s t h e e ffe ct is n o t a s cle a r (Ke lse y e t a l., 1993). In Am e r in d ia n s in t h e St a t e o f M a t o Grosso d o Su l, Bra zil, m ea n d u ra tion of b rea st-feed in g wa s 84 m o n th s, a n d th is a p p ea rs to ex-e r t a n im p o r t a n t p r o t ex-e ct ivex-e ex-e ffex-e ct a ga in st b rea st ca n cer (Lim a et a l., 2001). In a review o f th e ep id em iological literatu re, th is relation sh ip wa s n o t e vid e n c e d in e it h e r p r e - m e n o p a u sa l o r p o st - m e n o p a u sa l wo m e n (Lip wo r t h e t a l., 2000).
Th e p r e se n t st u d y wa s d e sign e d t o st u d y t h e r e la t io n sh ip b e t we e n b r e a st fe e d in g a n d b re a st ca n ce r in wo m e n fro m th e so u th e rn re -gion of Rio Gran d e d o Su l, Brazil.
M ethodology
A c a s e - c o n t r o l s t u d y w a s p e r fo r m e d , u s in g t wo co n tro l gro u p s (h o sp ita l- a n d co m m u n ity-b ased ), wh ich were an alyzed join tly to in crease th e stu d y p ower.
Th e re a so n fo r u sin g t wo t yp e s o f co n t ro ls wa s t o re d u ce b ia s. H o sp it a l co n t ro ls m a y n o t b e rep resen tative of th e p op u lation from wh ich ca se s we re re cru ite d , p a rticu la rly if se ve rity o f d isease is n ot com p arab le (Sch lesselm an , 1982); on th e oth er h a n d , com m u n ity con trols m a y b e b ia se d if a cce ss t o h e a lt h ca r e is p r o b le m a t ic (Sch le sse lm a n , 1982). Sim ila r re su lt s fro m t h e c o n t r o l gr o u p s t h u s st r e n gt h e n t h e st u d y’s fin d in gs. Most casecon trol stu d ies em p loy on -ly o n e t yp e o f co n t r o l. Ca se - co n t r o l is t h e d e-sign o f ch o ice fo r slo wly e vo lvin g d ise a se s, a l-lo win g t h e st u d y o f se ve ra l risk fa ct o rs fo r a n y given ou tcom e.
Sample
Sa m p le size wa s c a lc u la t e d wit h a 95% c o n fi-d en ce level (two-tailefi-d test) an fi-d 80% statistical p o wer to d etect a rela tive risk o f 0.6, a ssu m in g a b re a st fe e d in g p re va le n ce ra t e a t six m o n t h s o f 38% (Ho rta et a l., 1996). Th e n u m b er o f n ec-essary cases (in clu d in g allowan ce for losses, re-fu sa ls, a n d a d ju st m e n t fo r c o n fo u n d in g) wa s 233. Th e con trol-to-case ratio was 4:1.
Th e stu d y in clu d ed ca ses fro m Pelo ta s with b o t h h o sp it a l a n d c o m m u n it y c o n t r o ls a n d ca se s fr o m o t h e r n e a r b y cit ie s wit h h o sp it a l con trols from th e sam e cities. Com m u n ity con -tro ls were o n ly o b ta in ed fo r ca ses fro m Pelo ta s d u e to th e logistic d ifficu lty of fin d in g com m u -n ity co-n trols i-n ru ral areas a-n d oth er cities.
Lo sses a n d refu sa ls were d istrib u ted a s fo l-lo ws: a m o n g ca se s, t wo re fu sa ls a n d six l-lo sse s (2.0%); a m o n g co n t r o ls, 32 r e fu sa ls (3.2%), o f wh o m fo u r we r e h o sp it a l b a se d a n d 28 c o m -m u n ity-b a sed (2.4%).
All 132 wo m e n o ve r 60 ye a r s o f a ge wh e n b r e a st c a n c e r wa s d ia gn o se d we r e e xc lu d e d d u r in g d a t a co lle ct io n . Th is d e cisio n wa s d u e t o p o t e n t ia l r e ca ll b ia s, m a in ly in r e la t io n t o d u ration of b reastfeed in g.
Definit ion of exposure
In t e rvie we e s p ro vid e d d a t a o n t h e o ccu rre n ce a n d d u ra t io n o f b re a st fe e d in g (in m o n t h s) fo r e a ch o f t h e ir ch ild r e n , wh ich we r e t o t a le d t o p r o vid e life t im e d u r a t io n o f b r e a st fe e d in g. Ta b le 1 list s t h e st u d y va r ia b le s a n d t h e ir r e-sp ective scales.
Case select ion
All in cid e n t b re a st ca n ce r ca se s (d ia gn o se d in t h e p r e vio u s s ix m o n t h s ) in w o m e n 20 t o 60 ye a rs o f a ge re cru it e d fro m Ma rch 1995 t o Ju -ly 1998 in h o s p it a ls , r a d ia t io n t h e r a p y a n d c h e m o t h e r a p y s e r vic e s , a n d p a t h o lo gy la b o
-ra to ries in th e cities o f Pelo ta s a n d Rio G-ra n d e were in clu d ed .
Select ion of cont rols
Fo r co m m u n it y co n t ro ls, in t e rvie we rs lo ca t e d th e ca se’s h o m e a n d p ro ceed ed leftwa rd s fro m d o o r t o d o o r u n t il t h r e e co r r e sp o n d in g co n -trols were fou n d .
H o sp it a l co n t r o ls we r e o b t a in e d t h r o u gh ra n d o m se le ct io n o f h o sp it a l wa rd s; wh e n t h e n u m b er of h osp ita lized wom en exceed ed th ree o n th e sa m e d a y, th e ro o m n u m b er a n d if n ec-essa ry th e b ed were a lso ra n d om ly selected . All co n tro ls were a ge-m a tch ed with ca ses (p lu s o r m in u s five yea rs).
Diagn oses lead in g to h osp italization of co n -t r o ls we r e a s fo llo ws: a cu -t e clin ica l d ise a se s (19.2%), su r gica l co n d it io n s (12.8%), t r a u m a (9.9%), p n e u m o n ia (9.9%), b r o n c h ia l a st h m a (9.7%), sin u sit is (9.1%), p e p t ic u lce r (8.7%), p ye lo n e p h r it is (8.5%), ga st r o e n t e r it is (8.5%), an d n on -gyn ecological can cers (3.7%).
Dat a collect ion
Ca se s a n d c o n t r o ls a n swe r e d a p r e - c o d e d st a n d a r d ize d q u e st io n n a ir e in c lu d in g so c io -d e m o gr a p h ic , r e p r o -d u c t ive , b r e a st fe e -d in g-h ist o r y, a n d b r e a st d ise a se - g-h ist o r y va r ia b le s. Th e q u e st io n n a ir e a lso in clu d e d in fo r m a t io n o n va r io u s p o t e n t ia l c o n fo u n d in g va r ia b le s (Tab le 1).
Tab le 1
Variab le s and sc ale s e mp lo ye d in the c ase -c o ntro l stud y o f b re ast c anc e r.
Categories Variables Scales
So c io -e c o no mic al Sc ho o ling (ye ars c o mp le te d ) Disc re te De mo g rap hic Ag e (in ye ars) Co ntinuo us
Skin c o lo r (white / no n white ) Dic ho to mo us Marital status (marrie d / sing le ) Dic ho to mo us Family histo ry Bre ast c anc e r Dic ho to mo us Pe rso nal histo ry Bio p sy fo r b e nig n b re ast d ise ase Dic ho to mo us Re p ro d uc tive Ag e at me narc he Dic ho to mo us Ag e o f first c hild Co ntinuo us Numb e r o f c hild re n Disc re te Numb e r o f ab o rtio ns Co ntinuo us O ral c o ntrac e p tive s Dic ho to mo us Me no p ause Co ntinuo us Bre astfe e d ing O c c urre nc e (ye s/ no ) Dic ho to mo us
Logist ics
Th e team con sisted of five in terviewers an d five su p ervisors, on e in each recru itin g site, to id en -t ify ca se s a n d co n -t ro ls a n d re co rd -t h e ir a ge s a n d a d d re sse s. All co n t ro ls we re in t e rvie we d with in th ree m on th s of case id en tification .
Dat a analysis
Th e co lle ct e d d a t a we re in it ia lly cle a n e d t h ro u gh a n a n a lysis o f t h e ra n ge a n d d ist rib u -tion of stu d y variab les an d th eir m u tu al con sis-t e n cy. D issis-t r ib u sis-t io n o f ssis-t u d y fa csis-t o r s wa s sis-t h e n calcu lated for cases an d con trols, as well as th e r e sp e ct ive o d d s r a t io s, 95% co n fid e n ce in t e r-va ls, a n d sign ifica n ce tests. Sta tistica l so ftwa re SPSS In co r p o r a t io n 6.0 fo r Win d o ws a n d Ep i In fo were em p loyed for b oth ap p roach es.
D a t a we r e t h e n su b m it t e d t o m u lt iva r ia t e a n a lyse s, e m p lo yin g co n d it io n a l lo gist ic r e -gression (a ccord in g to th e p roced u re d escrib ed b y Breslow & Day, 1980), wh ich p rovid ed cru d e a n d a d ju st e d va lu e s. Po ssib le in t e ra ct io n s b e-tween va ria b les were a lso in vestiga ted .
Co n t in u o u s va r ia b le s we r e a n a lyze d a s su ch , in clu d in g tests fo r lin ea r tren d , a n d la ter a s ca t e go r ica l va r ia b le s, u sin g t h e like lih o o d ratio test (LRT). Missin g valu es, wh en accou n t-in g fo r le ss th a n 10% o f th e o b se rva tio n s, we re recod ed to th e referen ce ca tegories in th e m u l-tivariate an alyses.
Analysis model
Th e a n a lys is m o d e l in c lu d e d t h e s im u lt a n e -o u s in tro d u ctio n o f a ll p o te n tia l co n fo u n d e rs: sch o o lin g, fa m ily in co m e , skin co lo r , m a r it a l sta tu s, a ge a t m e n a rch e , n u m b e r o f a b o rtio n s, a ge a t first d elivery, n u m b er o f ch ild ren , a ge a t m en o p a u se, u se o f o ra l co n tra cep tives, b en ign b r e a st d ise a se h ist o r y, a n d fa m ily h ist o r y o f b rea st ca n cer. Su b seq u en tly, va ria b les with p < 0.2 we r e ke p t in t h e m o d e l a s c o n fo u n d e r s so th at th e ad ju sted ratios cou ld b e ob tain ed .
Results
Of t h e 250 in cid e n t ca se s o f b re a st ca n ce r, 168 (62.7%) we re fro m t h e cit y o f Pe lo t a s a n d 82 (32.8%) were from n eigh b orin g cities. Th e m ean a ge fo r b o t h ca se s a n d co n t ro ls wa s 47 ye a rs (SD = 6.5). Age d istrib u tio n o f ca se s wa s a s fo l-lows: 9.3% ≤ 35 years, 30.8% from 36 to 45 years, a n d 59.9% 45 t o 60 ye a rs. Age d ist rib u t io n o f con trols was: 10.5% ≤ 35 years, 32.9% from 36 to 45 years, an d 56.5% from 45 to 60 years.
Qu a lity co n tro l wa s p e rfo rm e d b y re -in te r-vie win g a p p r o xim a t e ly 5% o f c a se s a n d t h e ir resp ective con trols. For every 15 cases en cou n t e re d , o n e wa s ra n d o m ly se le ct e d t o b e re in t e rvie we d . Ka p p a st a t ist ic (La n d is, 1977; La n d is et al., 1977) was also calcu lated to ch eck in -t e r-o b se rve r a gre e m e n -t . Th e a im wa s -t o ve rify q u a lity o f in te rvie ws a n d se le ctio n . Ka p p a va l-u es fo r b en ign b rea st d isea se h isto ry were 0.82 fo r h o sp it a l- b a se d a n d 0.9 fo r co m m u n it y-b a se d co n t r o ls; fo r y-b r e a st fe e d in g h ist o r y, t h e c o r r e sp o n d in g ka p p a va lu e s we r e 0.76 a n d 0.82, an d 1.0 for cases.
Ta b le 2 sh o ws ch a ra ct e rist ics o f ca se s a n d co n tro l gro u p s. Am o n g p o te n tia l co n fo u n d in g va ria b le s, t h e a d ju st e d o d d s ra t io fo r b re a st can cer in wom en with h igh er sch oolin g was 1.2 (95% CI: 0.6-2.3), with a lin ea r tren d p -va lu e o f 0.28, as com p ared to wom en with n o sch oolin g.
Wo m e n wh o ga ve b ir t h a ft e r a ge 30 p r esen ted a n OR = 1.7 (95% CI: 1.12.4), with a lin -e a r t r -e n d p - va lu -e o f < 0.001, a s c o m p a r -e d t o wo m e n wh o se first d e live ry wa s b e fo re a ge 30. In a d d it io n , fo r w o m e n w it h a h is t o r y o f b e-n ige-n b r e a st d ise a se , t h e o d d s r a t io wa s 1.9 (95% CI: 1.0-3.2), with a lin ea r tren d p -va lu e o f 0.028. In wo m e n with m o re th a n fo u r ch ild re n t h e r e wa s a p r o t e c t ive e ffe c t a ga in st b r e a st c a n c e r , wit h OR = 0.3 (95% CI: 0.2 0.5), c o m -p a r e d t o n u lli-p a r o u s wo m e n . Wo m e n wit h a fa m ily h ist o r y o f b r e a st c a n c e r p r e se n t e d a n OR o f 2.6 (95% CI: 1.8-3.2). Wo m en with a ge a t m e n o p a u se o ve r 50 sh o we d a n OR o f 2.7 (95% CI: 1.6- 4.6) a s c o m p a r e d t o p r e - m e n o p a u s a l wo m e n .
Th e m a jo r it y o f t h e wo m e n h a d b r e a st fe d t h e ir ch ild r e n : 70.0% o f ca se s a n d 80.5% o f c o n t r o ls. Th e p r o p o r t io n o f wo m e n wh o h a d b rea stfed six m o n th s o r less wa s 28.4% fo r ca s-es a n d 24.6% fo r co n tro ls. So m e 19.8% o f ca ss-es a n d 25.4% of con trols h a d b rea stfed for a t lea st two years (Tab le 3).
Th e o d d s ra t io fo r wo m e n wh o h a d b re a st-fed was 0.9 (95% CI: 0.8-1.2). For th ose wh o h ad b reastfed for six m on th s or less as com p ared to t h o se wh o h a d n e ve r b r e a st fe d , OR wa s 1.0 (95% CI: 0.6- 1.8). Th e OR fo r t h o se wh o h a d b re a st fe d fo r 24 m o n t h s o r m o re wa s 1.0 (95% CI: 0.6-1.9).
Tab le 2
Distrib utio n o f c ase s and c o ntro ls and ad juste d o d d s ratio s fo r b re ast c anc e r ac c o rd ing to se le c te d variab le s. So uthe rn re g io n o f Rio G rand e d o Sul, Brazil, 1995-1998.
Variable Hospit al Communit y O dds rat ios and 95% CI1
Case s (% ) Co ntro ls (% ) Case s (% ) Co ntro ls (% ) Ho sp ital Co mmunity Bo th
Schooling
No ne 14.5 22.7 14.3 10.3 1.0 1.0 1.0
1 to 7 ye ars 50.0 56.2 53.6 65.3 1.3 (0.7-2.3) 0.8 (0.4-1.5) 0.9 (0.5-1.8)
≥ 8 ye ars 35.5 21.1 32.1 24.4 2.3 (1.1-4.6) 1.0 (0.6-1.8) 1.2 (0.6-2.4)
Skin color
No n-white 14.5 18.6 16.1 12.5 1.0 1.0 1.0
White 85.5 81.4 83.9 87.5 1.0 (0.9-1.2) 1.0 (0.8-1.4) 1.0 (0.7-1.6)
M arital status
Marrie d 75.6 84.1 77.4 88.1 1.0 1.0 1.0
Sing le 24.4 15.9 22.6 11.9 1.2 (0.7-1.9) 1.3 (1.0-1.7) 0.9 (0.7-1.3)
Family hist ory of breast cancer
No 76.2 90.1 73.8 85.5 1.0 1.0 1.0
Yes 23.8 9.9 26.2 14.5 3.1 (1.9-5.1) 2.0 (1.3-3.3) 2.6 (1.8-3.7)
Benign breast disease hist ory
No 89.5 94.6 90.5 95.6 1.0 1.0 1.0
Yes 10.5 5.4 9.5 4.4 2.3 (1.0-4.2) 2.8 (1.3-5.9) 1.9 (1.1-3.2)
Age at menarche
< 12 ye ars 41.3 40.7 47.0 44.8 1.0 1.0 1.0
≥ 12 ye ars 58.7 59.3 53.0 55.2 0.9 (0.6-1.3) 1.0 (0.7-1.5) 1.2 (0.9-1.6)
Age of first child
≤ 30 ye ars 70.3 86.0 74.4 79.0 1.0 1.0 1.0
≥ 31 ye ars 29.7 14.0 25.6 21.0 1.4 (0.7-2.8) 1.3 (0.6-2.6) 1.7 (1.1-2.4)
N umber of children
No ne 20.9 8.1 17.9 11.1 1.0 1.0 1.0
O ne 16.9 13.6 16.1 14.9 0.5 (0.2-0.9) 0.8 (0.4-1.6) 0.5 (0.3-0.9) Two 20.9 24.2 22.6 26.2 0.3 (0.1-0.6) 0.6 (0.3-1.4) 0.4 (0.2-0.6) Thre e 20.3 18.0 21.4 19.4 0.4 (0.2-0.8) 0.8 (0.4-1.9) 0.5 (0.3-0.8) Fo ur o r mo re 20.9 36.0 22.0 28.4 0.3 (0.2-0.6) 0.5 (0.2-1.0) 0.3 (0.2-0.5)
N umber of abort ions
No ne 62.8 59.3 62.5 66.2 1.0 1.0 1.0
O ne 19.8 23.4 17.9 19.0 0.8 (0.5-1.3) 1.1 (0.6-1.8) 0.9 (0.6-1.3) Two o r mo re 17.4 17.2 19.6 14.7 0.9 (0.6-1.5) 1.4 (0.8-2.4) 1.1 (0.7-1.7)
Use of oral cont racept ives
No 26.2 27.3 25.0 22.2 1.0 1.0 1.0
Yes 73.8 72.7 75.0 78.8 1.1 (0.7-1.6) 0.9 (0.6-1.6) 0.9 (0.9-1.2)
Age at menopause
Pre -me no p ause 48.3 48.8 40.5 55.8 1.0 1.0 1.0 < 50 ye ars 15.7 23.4 39.3 29.6 0.7 (0.4-1.3) 2.8 (1.6-5.0) 1.6 (1.0-2.3)
≥ 50 ye ars 36.0 27.7 20.2 14.7 1.4 (0.8-2.5) 4.3 (2.2.-8.0) 2.7 (1.6-4.6)
Total 172 516 168 504 250 1.020
1 Ad juste d o d d s ratio amo ng all variab le s simultane o usly.
we re 1.17 (95% CI: 0.6- 3.4) a n d 0.91 (95% CI: 0.3-1.6), re sp e ct ive ly, fo r t h o se wh o b re a st fe d for six m on th s. For th ose wh o b reastfed for over 24 m o n t h s t h e o d d s ra t io s we re 0.95 (95% CI: 0.5- 3.5) a n d 1.27 (95% CI: 0.5- 3.1), in p re - a n d p ost-m en op au se.
Discussion
Th is st u d y’s m e t h o d o lo gica l ch a r a ct e r ist ics m erit a sp ecific d iscu ssion . Two grou p s of con -t ro ls (h o sp i-t a l a n d co m m u n i-t y) we re in clu d e d an d evalu ated join tly, p rovid in g a total of 1,020 co n t ro ls. Th is d e sign h a d t h e a d va n t a ge o f re-d u cin g p o t e n t ia l se le ct io n b ia s, a m a jo r issu e in case-con trol stu d ies. Th e sim ilarity of resu lts b e t we e n t h e t wo t yp e s o f co n t ro ls a llo we d t h e jo in t a n a lysis t o b e m a in t a in e d , t h e r e b y in -creasin g statistical p ower.
Am o n g t h e st u d y’s p o ten tia l lim ita tio n s, in re la t io n t o re ca ll it sh o u ld b e n o t e d t h a t in fo r-m a tio n o n b rea stfeed in g o ften refers to a fa irly d istan t p eriod of tim e p rior to th e ap p earan ce of b reast can cer. As com p ared to con trols, wom en with b reast can cer also ten d to rem em b er m ore facts th at m ay b e related to th e d isease.
Am on g p ositive asp ects, th e d egree of agree-m e n t b e twe e n th e d a ta o b ta in e d b y in te rvie w-ers a n d su p erviso rs is releva n t. Th e h igh ka p p a valu es also in d icate ad eq u ate q u ality con trol in th e d ata collection .
In o r d e r t o a vo id b ia s, in t e r vie ws o f c a se s a n d resp ective co n tro ls were p erfo rm ed b y th e sa m e in t e rvie we r. In a d d it io n , t h e p ro p o rt io n o f wo m e n wh o h a d b r e a s t fe d in t h e t wo c o n -t r o l gr o u p s wa s sim ila r , -t h u s a -t -t e s-t in g -t o -t h e a d e q u a cy o f th e se le ctio n p ro ce d u re : 79.7% in h o s p it a l c o n t r o ls a n d 80.4% in c o m m u n it y con trols.
Accord in g to th e resu lts th ere was n o associ-ation b etween b reastfeed in g an d b reast can cer. Th e se re su lt s a re sim ila r t o t h o se fro m se ve ra l oth er stu d ies, with b oth case-con trol an d coh ort d esign s. However, Hard y et al. (1993) an d Olaya-Co n trera s et a l. (1999) in d ica ted a h igh p ro tec-tive effect again st b reast can cer for wom en wh o b reastfed , in clu d in g a d ose-resp on se tren d . Th e form er stu d y, con d u cted in Brazil, d em on strat-e d m a rkstrat-e d p ro t strat-e ct io n a ga in st b rstrat-e a st ca n cstrat-e r in th e m u ltivariate an alysis.
In t h e p re se n t st u d y, n o o ve ra ll p ro t e ct ive e ffe c t o f b r e a st fe e d in g wa s fo u n d a m o n g wo m e n in p re - m e n o p a u se . Ou r fin d in gs we re sim ila r t o t h o se o f o t h e r st u d ie s in re la t io n t o t h e o ccu rre n ce a n d d u ra t io n o f b re a st fe e d in g a n d m e n o p a u se st a t u s (Br in t o m e t a l., 1995; Lo n d o n e t a l., 1990; Mich e ls e t a l., 1996, 2001; Th om as & Noon an , 1993). However, som e ca se-co n t ro l st u d ie s d e m o n st ra t e d a p ro t e ct ive e f-fe ct in p r e - m e n o p a u sa l wo m e n (Bye r s e t a l., 1985; McTiern a n & Th om a s, 1986; Newcom b et al., 1994; Tryggvad ottir et al., 2001; UK Nation al Ca se -Co n t ro l St u d y Gro u p , 1993), st a t in g t h a t
Tab le 3
O d d s ratio and 95% c o nfid e nc e inte rval fo r b re ast c anc e r c ase s and ho sp ital and c o mmunity c o ntro ls ac c o rd ing to o c c urre nc e and d uratio n o f b re astfe e d ing .
Variable Hospital Community O dds ratios and 95% CI
Case s (% ) Co ntro ls (% ) Case s (% ) Co ntro ls (% ) Ho sp ital Co mmunity Bo th
Ever breastfed
No 32.6 20.3 28.6 18.7 1.0 1.0 1.0
Yes 67.4 79.7 71.4 81.3 0.9 (0.8-1.3) 1.1 (0.8-1.6) 0.9 (0.8-1.2)
Duration breastfeeding
Ne ve r 39.0 30.0 27.4 18.5 1.0 1.0 1.0
≤ 6 mo nths 17.4 16.7 26.2 29.2 0.8 (0.6-1.3) 0.9 (0.6-1.2) 1.0 (0.6-1.8) 7-12 mo nths 14.0 17.1 13.1 15.7 0.9 (0.6-1.3) 0.9 (0.7-1.2) 0.9 (0.4-1.8) 13-24 mo nths 11.0 12.8 12.6 14.7 0.9 (0.5-1.2) 0.8 (0.6-1.1) 0.8 (0.4-1.6)
≥ 25 mo nths 18.0 13.8 20.8 22.0 0.0 (0.6-1.2) 0.9 (0.7-1.2) 1.0 (0.6-1.9)
Total 172 516 168 504 250 1.020
No te : Ad juste d fo r sc ho o ling , skin c o lo r, marital status, family histo ry o f b re ast c anc e r, b e nig n b re ast d ise ase , ag e at me narc he , ag e o f first c hild , p arity, ab o rtio ns, use o f o ral c o ntrac e p tive s, and ag e at me no p ause .
t h is e ffe c t wa s m o r e p r o n o u n c e d in wo m e n wh o b rea stfed a t a n ea rly a ge.
In se ve r a l e p id e m io lo gica l in ve st iga t io n s, a n d p a r t ic u la r ly in a r e c e n t m e t a - a n a lys is o f 53 st u d ie s (Co lla b o ra t ive Gro u p o n H o rm o n a l Fa c t o r s in Br e a s t Ca n c e r , 2002), b r e a s t fe e d -in g h a s b e e n id e n t ifie d a s a p r o t e c t ive fa c t o r again st b reast can cer. Th e association b etween lactation an d th e red u ction in b reast can cer in -c id e n -c e h a s b e e n lim it e d a n d in -c o n sist e n t . Ch a n ge s in b re a st fe e d in g b e h a vio r wo rld wid e a ffect n o t o n ly in fa n t feed in g p a ttern s (n a tu ra l vs. a rt ificia l m ilk), b u t b re a st fe e d in g d u ra t io n a n d in t e n sit y a s we ll. Th is d ive r sit y co u ld e x-p lain th e d ifferen t resu lts ob tain ed b y d ifferen t stu d ies.
Th e e ffe ct o f la ct a t io n a p p e a r s t o b e sm a ll (if a n y) a n d lim it e d t o a m in o rit y o f wo m e n a t risk o f b rea st ca n cer. It is n o t clea r wh y b rea st-feed in g wou ld red u ce b reast can cer risk. A b io-logical b asis for an in verse association b etween b r e a st fe e d in g a n d b r e a st ca n ce r r isk h a s n o t b e e n a d e q u a t e ly e lu cid a t e d , a lt h o u gh se ve ra l m e c h a n ism s h a ve b e e n p o st u la t e d . On e h yp o th esis is th a t la cta tio n ca u ses lo n gterm en -d ogen ou s h orm on a l ch a n ges, p ossib ly re-d u ce-d e stro ge n , a n d in cre a se d p ro la ctin p ro d u ctio n , wh ich m a y d ecrea se a wo m a n ’s cu m u lative ex-p osu re to estrogen , th ereb y in h ib itin g th e in itiation or growth of b reast can cer cells (Freu d en -h e im e t a l., 1997). It -h a s a lso b e e n su gge st e d t h a t a p r o t e ct ive e ffe ct o f b r e a st fe e d in g o n b re a st ca n ce r risk m a y b e a ttrib u te d to th e e
x-Tab le 4
Distrib utio n o f c ase s and c o ntro ls in p re- and p o st-me no p ausal wo me n, ac c o rd ing to the o c c urre nc e o f b re astfe e d ing .
Pre-menopause Post -menopause
Case s Co ntro l Case s Co ntro ls n = 110 n = 533 n = 140 n = 487
Variab le n % n % AO R 95% CI n % n % AO R 95% CI
Ever breastfed p = 0.89 p = 0.19
No 28 25.5 1 0 0 18.8 1.00 – 42 30.0 100 20.3 1.00 – Yes 82 74.5 4 3 3 81.2 0.91 0.4-2.2 98 70.0 387 79.7 0.92 0.4-1.5
Duration P* = 0.92 p * = 0.63
of breast feeding
Ne ve r 28 25.5 1 0 0 18.8 1.00 – 42 30.0 100 20.3 1.00 –
≥ 6 mo nths 36 32.7 1 6 9 31.7 1.17 0.6-3.4 36 25.7 131 26.7 0.91 0.3-1.6 7-12 mo nths 14 12.7 85 15.9 1.11 0.4-3.2 17 12.1 66 13.5 1.00 0.5-3.0 13-24 mo nths 13 11.8 75 14.1 1.12 0.5-4.0 16 11.4 65 13.5 1.00 0.4-2.8
≤ 25 mo nths 21 19.1 1 0 4 19.5 0.95 0.5-3.5 29 20.7 125 25.9 1.27 0.5-3.1
AO R = Ad juste d fo r sc ho o ling , skin c o lo r, marital status, family histo ry o f b re ast c anc e r, b e nig n b re ast d ise ase , ag e o f me narc he , ag e o f first so n, p arity, ab o rtio ns, use o f o ral c o ntrac e p tive s and ag e o f me no p ause .
p = p -value ; p * = p -value fo r line ar tre nd ; 95% CI = 95% c o nfid e nc e inte rval
cretion of carcin ogen ic agen ts from b reast d u c-tal tissu e th rou gh b reastfeed in g (Titu s-Ern stoff e t a l., 1998). Acco rd in g to a n o th e r b io lo gica lly p la u sib le h yp o t h e sis, wo m e n wit h o n ly o n e c h ild a n d wh o ga ve b ir t h b e fo r e t h e a ge o f 30 co u ld b e a t le sse r r isk o f b r e a st ca n ce r (Gr u -en ke et al., 1987).
Th e im p o rta n ce o f a ge a t first ge sta tio n fo r th e m o d u la tio n o f b rea st ca n cer risk is d erived fro m exp erim en ts o n a n im a ls p a rticu la rly su s-cep tib le to carcin ogen esis (Brin ton et al., 1983). However, in a rat m od el, Ru sso et al. (1982) ob -se r ve d n o p r o t e ct io n a ga in st b r e a st ca n ce r from eith er b reastfeed in g or p regn an cy.
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