Reviewer's□report 
□Oral□contraceptive□use□before□first□birth□and□risk□of□breast□cancer:□A□case□control□study Title: 
Authors: 
Elina□MD,DrPh□Hemminki□( elina.hemminki@stakes.fi )
Tapio□MSc□Luostarinen□( tapio.luostarinen@cancer.fi )
Eero□PhD□Pukkala□( eero.pukkala@cancer.fi )
Dan□MD,PhD□Apter□( dan.apter@vaestoliitto.fi )
Timo□ScD□Hakulinen□( timo.hakulinen@cancer.fi )
□2□ □4□May□2002 Version: Date: 
Reviewer: 
□not□specified Level□of□interest: 
□Unable□to□decide□on□acceptance□or□rejection□until□the□authors□have□responded□ Advice□on□publication: 
to□the□compulsory□revisions 
Oral□contraceptive□use□before□first□birth□and□risk□of□breast□cancer:□A□case□control□study□ 
Comments□for□the□Authors□and□BioMed□Editorial□Board□ 
This□is□a□case-control□study□of□premenopausal□breast□cancer□(age□of□cases□at□diagnosis□must□be□ 
However,□I□have□a□couple□of□major□reservations□that□greatly□diminish□the□value□of□this□study,□and□raise□a□ 
question□on□its□acceptability□for□publication.□ 
1.□The□study□size□(150□cases□and□316□controls)□is□largely□insufficient□to□detect□with□sufficient□precision□ 
the□increase□in□BC□risk□that□is□plausibly□associated□with□OC□use.□Based□on□the□overall□available□ 
evidence,□there□is□little□doubt□that□OCaETMs□are□indeed□associated□with□some□increase□in□BC□risk.□The□ 
two□open□questions□are□a)□the□size□and□duration□of□this□increase;□and□b)□whether□this□is□increase□is□more□ 
marked□(or□limited□to)□some□groups□of□women□identified□on□the□basis□of□time□and□history□of□OC□use,□ 
reproductive□history,□etc.□To□provide□reliable□answers□to□these□questions,□much□larger□studies□are□ 
needed□than□the□present□one.□Comparisons□of□different□types□and□times□of□exposure,□such□as□those□ 
presented□in□tables□3□and□4,□are□based□on□negligible□numbers□of□cases□and□can□be□misleading□To□make□ 
an□example,□the□authors□state□that□aEoeAmong□OC□users,□those□who□had□started□young□did□not□have□a□ 
higher□risk□of□breast□cancer□than□those□who□had□started□older□(25□or□more)□(Table□3)aE.□The□point□ 
estimate□of□the□Odds□Ratio□for□the□age□group□16-19□is□0.5□(i.e□protection□from□the□increased□risk□when□ 
OCaETMs□are□started□early),□but□due□to□the□small□number□of□cases□and□controls□(11□and□36,□ respectively)□it□is□not□possible□to□rule□out□a□50%□increase□in□risk.□ 
2.□As□correctly□acknowledged□and□discussed□by□the□Authors□(pages□7-8)□the□study□design□exposes□it□to□ 
the□possibility□of□a□major□bias:□the□overall□proportion□of□incident□cases□and□sampled□controls□that□were□ included□in□the□study□is□low□( 3.□A□strenght□of□this□study□is□the□objective□assessment□of□exposure,□that,□though□incomplete,□is□definitely 
more□accurate□and□less□biased□than□womenaETMs□memory□of□OC□use.□However,□the□choice□of□such□a□ 
method□is□the□basis□of□the□above□described□selection□that□greatly□weakens□the□study.□ 
In□conclusion,□this□paper□represents□an□example□of□how□epidemiological□papers□should□be□written:□an□ 
exhaustive□description□of□the□methodology,□and□an□objective□presentation□and□discussion□of□the□study□ drawbacks□and□limitations,□without□any□undue□emphasis□on□the□study□results□and□implications.□Its□ reading□may□prove□very□useful□for□those□willing□to□start□a□study□on□this□(or□a□similar)□issue,□even□though□ 
the□results□are□of□limited□interest.□ 
Accordingly,□my□suggestion□is□that□this□paper□could□be□acceptable□for□publication□in□a□revised□version,□ 
more□focussed□on□the□methodological□problems□arising□in□studies□on□the□association□between□ 
OCaETMs□and□BC□(the□discussion□already□includes□many□considerations□on□this□issue).□The□Finnish□ 
study□could□be□used□in□such□a□paper□as□a□case□study.□ 
Minor□points□ 
4.□Analyses□such□as□those□presented□in□table□3□and□4□would□be□better□conducted□without□leaving□out□the□ 
unexposed,□but□using□instead□both□in□univariate□and□multivariate□analyses□the□appropriate□tests□of□ 
heterogeneity□of□the□OR's□and/or□the□specific□interaction□terms□ 
5.□Crude□ORaETMs□in□table□2□are□wrong.□My□calculations□give□(114x57)/(222x15)=1.95□(instead□of□2.1)□ 
and□(21x57)/(37x15)=2.16□-□I□did□not□check□the□other□tables.□ 
Paolo□Bruzzi□MD,□MPH,□PhD□ 
Head,□Unit□of□Clinical□Epidemiology□ 
National□Cancer□Research□Institute□ 
Genoa□-□Italy□ 
Competing□interests: 
None□declared.