Oral contraceptives and postmenopausal hormones and risk of contralateral breast cancer among BRCA1 and BRCA2 mutation carriers and noncarriers: the WECARE Study
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The potential effects of oral contraceptive (OC) and postmenopausal hormone (PMH) use are not well understood among BRCA1 or BRCA2 (BRCA1/2) deleterious mutation carriers with a history of breast cancer. We investigated the association between OC and PMH use and risk of contralateral breast cancer (CBC) in the WECARE (Women’s Environment, Cancer, and Radiation Epidemiology) Study. The WECARE Study is a population-based case-control study of 705 women with asynchronous CBC and 1,398 women with unilateral breast cancer, including 181 BRCA1/2 mutation carriers. Risk-factor information was assessed by telephone interview. Mutation status was measured using denaturing high-performance liquid chromatography followed by direct sequencing in all participants. Outcomes, treatment, and tumor characteristics were abstracted from medical records. Ever use of OCs was not associated with risk among noncarriers (RR = 0.87; 95% CI = 0.66–1.15) or BRCA2 carriers (RR = 0.82; 95% CI = 0.21–3.13). BRCA1 carriers who used OCs had a nonsignificant greater risk than nonusers (RR = 2.38; 95% CI = 0.72–7.83). Total duration of OC use and at least 5 years of use before age 30 were associated with a nonsignificant increased risk among mutation carriers but not among noncarriers. Few women had ever used PMH and we found no significant associations between lifetime use and CBC risk among carriers and noncarriers. In conclusion, the association between OC/PMH use and risk of CBC does not differ significantly between carriers and noncarriers; however, because carriers have a higher baseline risk of second primaries, even a potential small increase in risk as a result of OC use may be clinically relevant.
KeywordsBreast cancer Asynchronous bilateral Contralateral Oral contraceptives Postmenopausal hormones BRCA1 BRCA2
High-performance liquid chromatography
This work was supported by the National Institutes of Health (U01-CA83178, R01-CA97397 and R01-CA42949). J.C.F. is supported in part by a post-PhD Research Fellowship from the National Cancer Institute of Canada (#017602). We thank all the individuals who participated in this study.
Conflict of interest statement
The authors declare that they have no competing interests.
- 2.Malone KE, Begg CB, Haile RW, Borg A, Concannon P, Tellhed L, Xue S, Teraoka S, Bernstein L, Capanu M, Reiner A, Riedel ER, Thomas DC, Mellemkjaer L, Lynch CF, Boice JD, Anton-Culver H, Bernstein JL. A population-based study of the relative and absolute risks of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2 (under review)Google Scholar
- 4.Brohet RM, Goldgar DE, Easton DF, Antoniou AC, Andrieu N, Chang-Claude J, Peock S, Eeles RA, Cook M, Chu C et al (2007) Oral contraceptives and breast cancer risk in the international BRCA1/2 carrier cohort study: a report from EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group. J Clin Oncol 25(25):3831–3836CrossRefPubMedGoogle Scholar
- 7.Rebbeck TR, Friebel T, Wagner T, Lynch HT, Garber JE, Daly MB, Isaacs C, Olopade OI, Neuhausen SL, vanz‘t Veer L et al (2005) Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 23(31):7804–7810CrossRefPubMedGoogle Scholar
- 8.Figueiredo JC, Bernstein L, Capanu M, Malone KE, Lynch CF, Anton-Culver H, Stovall M, Bertelsen L, Haile RW, Bernstein JL (2008) Oral contraceptives, postmenopausal hormones, and risk of asynchronous bilateral breast cancer: the WECARE study group. J Clin Oncol 26:1411–1418CrossRefPubMedGoogle Scholar
- 11.Bernstein JL, Teraoka S, Haile RW, Borresen-Dale AL, Rosenstein BS, Gatti RA, Diep AT, Jansen L, Atencio DP, Olsen JH et al (2003) Designing and implementing quality control for multi-center screening of mutations in the ATM gene among women with breast cancer. Hum Mutat 21(5):542–550CrossRefPubMedGoogle Scholar
- 19.Milne RL, Knight JA, John EM, Dite GS, Balbuena R, Ziogas A, Andrulis IL, West DW, Li FP, Southey MC et al (2005) Oral contraceptive use and risk of early-onset breast cancer in carriers and noncarriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomarkers Prev 14(2):350–356CrossRefPubMedGoogle Scholar
- 20.Lee E, Ma H, McKean-Cowdin R, Van Den Berg D, Bernstein L, Henderson BE, Ursin G (2008) Effect of reproductive factors and oral contraceptives on breast cancer risk in BRCA1/2 mutation carriers and noncarriers: results from a population-based study. Cancer Epidemiol Biomarkers Prev 17(11):3170–3178CrossRefPubMedGoogle Scholar
- 23.Bane AL, Beck JC, Bleiweiss I, Buys SS, Catalano E, Daly MB, Giles G, Godwin AK, Hibshoosh H, Hopper JL et al (2007) BRCA2 mutation-associated breast cancers exhibit a distinguishing phenotype based on morphology and molecular profiles from tissue microarrays. Am J Surg Pathol 31(1):121–128CrossRefPubMedGoogle Scholar
- 26.Eisen A, Lubinski J, Klijn J, Moller P, Lynch HT, Offit K, Weber B, Rebbeck T, Neuhausen SL, Ghadirian P et al (2005) Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. J Clin Oncol 23(30):7491–7496CrossRefPubMedGoogle Scholar