EPIDEMIOLOGY

Risk Factors for InflammatoryBreast Cancer and OtherInvasive Breast Cancers

Schairer C, Li Y, Frawley P, et al (Univ ofMaryland, College Park; Group HealthCooperative, Seattle, WA; Natl Insts ofHealth, Bethesda, MD; et al)

J Natl Cancer Inst 105:1373-1384, 2013

Background.dWe investigated riskfactors for inflammatory breast cancer(IBC), a rare, aggressive, and poorlyunderstood breast cancer that is charac-terized by diffuse breast skin erythemaand edema.

Methods.dWe included 617 IBCcase subjects in a nested case-controlstudy from the Breast Cancer Sur-veillance Consortium database (1994e2009). We also included 1151noninflammatory, locally advanced,invasive breast cancers with chest wall/breast skin involvement (LABC), 7600noninflammatory invasive case subjectswithout chest wall/breast skin involve-ment (BC), and 93 654 control subjectsmatched to case subjects on age andyear at diagnosis and mammographyregistry. We present estimates of rateratios (RRs) and 95% confidence inter-vals (CI) from conditional logisticregression analyses for each casegroup vs control subjects based on mul-tiply imputed datasets.

Results.dFirst-degree family his-tory of breast cancer and high mammo-graphic breast density increased risk ofIBC, LABC, and BC. High body massindex (BMI) increased IBC risk irrespec-tive of menopausal status and estrogenreceptor (ER) expression; rate ratios forBMI 30 and greater vs BMI less than25 were 3.90 (95% CI¼ 1.50 to 10.14)in premenopausal women and 3.70

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(95% CI¼ 1.98 to 6.94) in peri/postmenopausal women not currentlyusing hormones. BMI 30 and greaterslightly increased risk of ER-positiveBC (RR¼ 1.40; 95% CI¼ 1.11 to1.76). Statistically significant reductionsin riskofER-negative IBCwitholder ageat first birth and of ER-positive IBCwithhigher education were not seen forLABC and BC of the same ER status.

Conclusions.dDifferent associa-tionswithBMI, age atfirst birth, andedu-cation between IBC and/or LABC andBC suggest a distinct etiology for IBC.

A rare and aggressive disease, IBCis characterized by a specific clinicalpresentation and is associated with avery high mortality rate. Because IBCaccounts for only 1% to 6% of newlydiagnosed breast cancers each year inthe United States, large national regis-tries and consortia have been the pri-mary sources for investigating theepidemiology of IBC. This study bySchairer and colleagues is the largeststudy to date to evaluate the associationbetween standard risk factors for breastcancer and the development of IBC andincluded a total of 9368 cases in addi-tion to 93 654 controls. Using data fromthe Breast Cancer Surveillance Con-sortium database, the authors com-pared patients with IBC to 3 referencegroups that included patients with non-IBC without chest wall/breastskin involvement (88.4% were stage I/II), patients with locally advanced non-IBC, and control subjects. Moreover,this is the first study to examine theassociation between risk factors andhormone receptor status in IBC.

Although the results showed a sig-nificant association between severalfactors and the risk of developing anytype of breast cancer, obesity emerged

terly

as the strongest risk factor for IBC,irrespective of menopausal status orhormone receptor status. This contrastswith non-IBCs, for which higher BMIwas a risk factor in postmenopausalwomen only. One finding, however, thatwas inconsistent with the increased riskassociated with obesity was the associ-ation between higher mammographicdensity (less breast fat) and the devel-opment of IBC. Overall, these resultsare of great importance for IBC becauseobesity is a modifiable risk factor, andpreventive strategies aimed at reducingobesity may yield the most rewards.

This study also highlights thechallenges in conducting large-scaleepidemiologic studies based on datafrom national registries and consortia.Non-uniform data collection hasresulted in a significant amount ofmissing data and the exclusion ofalmost half of the patients diagnosedwith IBC. As an example, up to 74% ofpatients in this study did not haveinformation on their human epidermalgrowth factor receptor 2 (HER2) status,leading to the exclusion of HER2 fromthe analysis. To overcome these prob-lems, the authors resorted to the use ofcomplex statistical imputations anddummy variables to partially addressthe issue of missing data. Furthermore,national databases and consortia areunable to capture comprehensivedetails on risk factors, such as repro-ductive history, or to complement thisinformation with laboratory studies ofcollected blood and tissue samples.

To address these issues, our teamat the Morgan Welch InflammatoryBreast Cancer Research Program andClinic at The University of Texas MDAnderson Cancer Center has spear-headed the development of an inter-national registry specifically focused

on IBC. The IBC Registry was estab-lished in 2007 with the objective ofprospectively collecting tissue, serum,plasma, whole blood, imaging, andclinical and epidemiologic data frompatients with IBC. This multidiscipli-nary approach will allow us to

conduct molecular epidemiologicstudies to determine the underlyingmechanisms associated with thedevelopment and outcomes of this rareand lethal disease.

(The authors receive support fromthe State of Texas Rare and Aggressive

Breast D

Breast Cancer Research ProgramGrant.)

T. M. Fouad, MDR. El-Zein, MD, PhDN. T. Ueno, MD, PhD

Prospective Analysis ofAssociation between Statin Useand Breast Cancer Risk in theWomen’s Health Initiative

Desai P, Chlebowski R, Cauley JA, et al(Weill Cornell Med College, NY; Univ ofCalifornia, Los Angeles; Stony Brook UnivMed Ctr, NY; et al)

Cancer Epidemiol Biomarkers Prev 22:1868-1876, 2013

Background.dStatins are a classof cholesterol-lowering drugs thataffect many intracellular pathwaysthat may have implications for chemo-prevention against cancer. Epidemio-logic data on statins and breast cancerare conflicting. We analyzed updateddata from the Women’s Health Initia-tive (WHI) to assess the relationshipbetween statins and breast cancer risk.

Methods.dThe population in-cluded 154,587 postmenopausal womenages 50 to 79 years, with 7,430 patholog-ically confirmed cases of breast canceridentified over an average of 10.8 (SD,3.3) years. Information on statins wascollected at baseline and years one,three, six, and nine. Self- and inter-viewer-administered questionnaireswere used to collect information on riskfactors. Cox proportional hazards regres-sion was used to calculate HRs with 95%confidence intervals (CI) to evaluate the

relationship between statin use and can-cer risk. Statistical tests were two-sided.

Results.dStatins were used by11,584 (7.5%) women at baseline.The annualized rate of breast cancerwas 0.42% among statin users and0.42% among nonusers. The multivari-able adjusted HR of breast cancer forusers versus nonusers was 0.94 (95%CI, 0.83e1.06). In the multivariable-adjusted, time-dependent model, theHR for simvastatin was 0.87 (95% CI,0.71e1.07). There was no significanttrend by overall duration of use (Pvalue for trend 0.68). There was noeffect of tumor stage, grade, or hor-mone receptor status.

Conclusion.dOverall, statins werenot associated with breast cancer risk.

Impact.dOur study is one of thelargest prospective observational stud-ies on this topic, and substantiallyadds to the literature suggesting norelationship between statins and breastcancer risk.

In this article, Desai and col-leagues updated data from more than150 000women enrolled in theWomen’sHealth Initiative to evaluate the asso-ciation of statin use with the risk ofbreast cancer. They found that the useof a statin was not associated withbreast cancer risk. Undertaking multi-ple analyses, they also found that less

than 1 year of statin use was signifi-cantly protective, but numerous otheranalyses by statin type and potencyrevealed no relationship, and theauthors noted that there is no clearbiological explanation for this result.These findings contradict the priorreport from this cohort1 showing an18% reduction in invasive breast cancerrisk with the use of lipophilic statins.The main difference in this report is4 years of additional follow-up and over3000 more breast cancer cases. Follow-up for the prior study was through 2004,whereas this report extends data col-lection through 2010. In total, the pre-vention data for statin use remainmixed, with numerous limitations notedin the discussion. The possibility that theinitial finding is real but was mitigatedby changes in other factors specific tothe late 2000s cannot be assessed.

W. A. Woodward, MD, PhD

Reference1. Cauley JA, McTiernan A,

Rodabough RJ, et al; Women’sHealth Initiative Research Group.Statin use and breast cancer:prospective results from theWomen’s Health Initiative. J NatlCancer Inst. 2006;98:700-707.

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