Skip to main content

Advertisement

SpringerLink
Log in

Oral contraceptives and postmenopausal hormones and risk of contralateral breast cancer among BRCA1 and BRCA2 mutation carriers and noncarriers: the WECARE Study

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

OC:

Oral contraceptives

PMH:

Postmenopausal hormones

ER:

Estrogen receptor

DHPLC:

High-performance liquid chromatography

References

  1. Metcalfe K, Lynch HT, Ghadirian P, Tung N, Olivotto I, Warner E, Olopade OI, Eisen A, Weber B, McLennan J et al (2004) Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 22(12):2328–2335

    Article  CAS  PubMed  Google Scholar 

  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)

  3. Narod SA, Dube MP, Klijn J, Lubinski J, Lynch HT, Ghadirian P, Provencher D, Heimdal K, Moller P, Robson M et al (2002) Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 94(23):1773–1779

    CAS  PubMed  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):3831–3836

    Article  PubMed  Google Scholar 

  5. Haile RW, Thomas DC, McGuire V, Felberg A, John EM, Milne RL, Hopper JL, Jenkins MA, Levine AJ, Daly MM et al (2006) BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer before age 50. Cancer Epidemiol Biomarkers Prev 15(10):1863–1870

    Article  CAS  PubMed  Google Scholar 

  6. McLaughlin JR, Risch HA, Lubinski J, Moller P, Ghadirian P, Lynch H, Karlan B, Fishman D, Rosen B, Neuhausen SL et al (2007) Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study. Lancet Oncol 8(1):26–34

    Article  CAS  PubMed  Google 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):7804–7810

    Article  CAS  PubMed  Google 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 26:1411–1418

    Article  PubMed  Google Scholar 

  9. Bernstein JL, Langholz B, Haile RW, Bernstein L, Thomas DC, Stovall M, Malone KE, Lynch CF, Olsen JH, Anton-Culver H et al (2004) Study design: evaluating gene-environment interactions in the etiology of breast cancer–the WECARE study. Breast Cancer Res 6(3):R199–R214

    Article  CAS  PubMed  Google Scholar 

  10. Begg CB, Haile RW, Borg A, Malone KE, Concannon P, Thomas DC, Langholz B, Bernstein L, Olsen JH, Lynch CF, Anton-Culver H, Capanu M, Liang X, Hummer AJ, Sima C, Bernstein JL (2008) Variation of breast cancer risk among BRCA1/2 carriers. JAMA 299(2):194–201

    Article  CAS  PubMed  Google 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):542–550

    Article  CAS  PubMed  Google Scholar 

  12. Langholz B, Borgan O (1995) Counter matching: a stratified nested case-control sampling method. Biometrika 82:69–79

    Article  Google Scholar 

  13. Huberman M, Langholz B (1999) Application of the missing-indicator method in matched case-control studies with incomplete data. Am J Epidemiol 150(12):1340–1345

    CAS  PubMed  Google Scholar 

  14. Horn PL, Thompson WD (1988) Risk of contralateral breast cancer. Associations with histologic, clinical, and therapeutic factors. Cancer 62(2):412–424

    Article  CAS  PubMed  Google Scholar 

  15. Bernstein JL, Thompson WD, Risch N, Holford TR (1992) Risk factors predicting the incidence of second primary breast cancer among women diagnosed with a first primary breast cancer. Am J Epidemiol 136(8):925–936

    CAS  PubMed  Google Scholar 

  16. Trentham-Dietz A, Newcomb PA, Nichols HB, Hampton JM (2006) Breast cancer risk factors and second primary malignancies among women with breast cancer. Breast Cancer Res Treat 105:195–207

    Article  PubMed  Google Scholar 

  17. Li CI, Malone KE, Porter PL, Daling JR (2003) Epidemiologic and molecular risk factors for contralateral breast cancer among young women. Br J Cancer 89(3):513–518

    Article  CAS  PubMed  Google Scholar 

  18. Ursin G, Henderson BE, Haile RW, Pike MC, Zhou N, Diep A, Bernstein L (1997) Does oral contraceptive use increase the risk of breast cancer in women with BRCA1/BRCA2 mutations more than in other women? Cancer Res 57(17):3678–3681

    CAS  PubMed  Google 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):350–356

    Article  CAS  PubMed  Google 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):3170–3178

    Article  CAS  PubMed  Google Scholar 

  21. Armstrong K, Schwartz JS, Randall T, Rubin SC, Weber B (2004) Hormone replacement therapy and life expectancy after prophylactic oophorectomy in women with BRCA1/2 mutations: a decision analysis. J Clin Oncol 22(6):1045–1054

    Article  PubMed  Google Scholar 

  22. Collaborative Group on Hormonal Factors in Breast Cancer (2001) Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58, 209 women with breast cancer and 101, 986 women without the disease. Lancet 358(9291):1389–1399

    Article  Google 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):121–128

    Article  PubMed  Google Scholar 

  24. Foulkes WD, Stefansson IM, Chappuis PO, Begin LR, Goffin JR, Wong N, Trudel M, Akslen LA (2003) Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst 95(19):1482–1485

    CAS  PubMed  Google Scholar 

  25. Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA, Van’t Veer L, Garber JE, Evans G, Isaacs C, Daly MB, Matloff E et al (2002) Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 346(21):1616–1622

    Article  PubMed  Google 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):7491–7496

    Article  PubMed  Google Scholar 

  27. Gronwald J, Tung N, Foulkes WD, Offit K, Gershoni R, Daly M, Kim-Sing C, Olsson H, Ainsworth P, Eisen A et al (2006) Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer 118(9):2281–2284

    Article  CAS  PubMed  Google Scholar 

  28. Fan S, Wang J, Yuan R, Ma Y, Meng Q, Erdos MR, Pestell RG, Yuan F, Auborn KJ, Goldberg ID et al (1999) BRCA1 inhibition of estrogen receptor signaling in transfected cells. Science 284(5418):1354–1356

    Article  CAS  PubMed  Google Scholar 

  29. Fan S, Ma YX, Wang C, Yuan RQ, Meng Q, Wang JA, Erdos M, Goldberg ID, Webb P, Kushner PJ et al (2001) Role of direct interaction in BRCA1 inhibition of estrogen receptor activity. Oncogene 20(1):77–87

    Article  CAS  PubMed  Google Scholar 

  30. Malone JL, Nelson AC, Lieberman R, Anderson S, Holt JT (2009) Oestrogen-mediated phosphorylation and stabilization of BRCA2 protein in breast. J Pathol 217(3):380–388

    Article  CAS  PubMed  Google Scholar 

  31. Poole AJ, Li Y, Kim Y, Lin SC, Lee WH, Lee EY (2006) Prevention of Brca1-mediated mammary tumorigenesis in mice by a progesterone antagonist. Science 314(5804):1467–1470

    Article  CAS  PubMed  Google Scholar 

  32. Walsh T, Casadei S, Coats KH, Swisher E, Stray SM, Higgins J, Roach KC, Mandell J, Lee MK, Ciernikova S et al (2006) Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA 295(12):1379–1388

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

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.

Author information

Authors and Affiliations

  1. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Harlyne J Norris Cancer Research Tower, 1450 Biggy Street, Los Angeles, CA, 90033, USA

    Jane C. Figueiredo, Robert W. Haile, Anh Diep & Shanyan Xue

  2. Division of Cancer Etiology, Department of Population Sciences, City of Hope Comprehensive Cancer Center, National Medical Center, 1500 East Duarte Road, Bldg 173, Duarte, CA, 91010, USA

    Leslie Bernstein

  3. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, M4-C308, P.O. Box 19024, Seattle, WA, USA

    Kathleen E. Malone

  4. Department of Epidemiology, College of Health Sciences, University of California, Irvine, 224 Irvine Hall Suite 100, Irvine, CA, 92697, USA

    Joan Largent

  5. Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1540 Alcazar Street, CHP 220, Los Angeles, CA, 90033-1042, USA

    Bryan Langholz

  6. Department of Epidemiology, University of Iowa, C21-L GH, Iowa City, IA, 52242, USA

    Charles F. Lynch

  7. Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100, Copenhagen, Denmark

    Lisbeth Bertelsen

  8. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 307 East 63rd Street, 3rd Floor, New York, NY, 10065, USA

    Marinela Capanu & Jonine L. Bernstein

  9. Department of Biochemistry & Molecular Genetics, Center for Public Health Genomics, University of Virginia, P.O. Box 800733, Charlottesville, VA, 22908-0733, USA

    Patrick Concannon & Sharon Teraoka

  10. Department of Oncology, University Hospital, 221 85, Lund, Sweden

    Ake Borg & Therese Torngren

  11. Faculty of Medicine, University of Oslo, 0310, Montebello, Oslo, Norway

    Anne-Lise Børresen-Dale

  12. Department of Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Rikshospitalet University Hospital, Montebello, 0310, Oslo, Norway

    Anne-Lise Børresen-Dale

Authors
  1. Jane C. Figueiredo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert W. Haile
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leslie Bernstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kathleen E. Malone
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joan Largent
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bryan Langholz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Charles F. Lynch
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lisbeth Bertelsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Marinela Capanu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Patrick Concannon
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ake Borg
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Anne-Lise Børresen-Dale
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Anh Diep
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Sharon Teraoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Therese Torngren
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Shanyan Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Jonine L. Bernstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jane C. Figueiredo.

WECARE Study Collaborative Group

WECARE Study Collaborative Group

Memorial Sloan Kettering Cancer Center (New York, NY): Jonine L. Bernstein Ph.D. (WECARE Study P·I.); Colin Begg. Ph.D.; MarinelaCapanu Ph.D.; Tracy Layne, M.P·H., Xiaolin Liang M.D.; Irene Orlow Ph.D., Anne S. Reiner, MPH.

City of Hope (Duarte, CA) and work performed at the University of Southern California: Leslie Bernstein Ph.D.; Laura Donnelly-Allen.

Danish Cancer Society (Copenhagen, Denmark): Jørgen H. Olsen, M.D. D.M.Sc.; Michael Andersson M.D.; D.M.Sc.; Lisbeth Bertelsen M.D..Ph.D.; Per Guldberg Ph.D.; Lene Mellemkjær Ph.D.

Fred Hutchinson Cancer Research Center (Seattle, WA): Kathleen E. Malone Ph.D. (Sub-contract P·I.); Noemi Epstein.

International Epidemiology Institute (Rockville, MD) and Vanderbilt University (Nashville, TN): John D. Boice Jr. Sc.D.

Lund University (Lund, Sweden): Åke Borg Ph.D.; Therese Törngren M.Sc.; Lina Tellhed B·Sc.

Mount Sinai School of Medicine (New York, NY): Barry S. Rosenstein Ph.D. (Sub-contract P·I.); David P. Atencio Ph.D.

National Cancer Institute (Bethesda, MD): Daniela Seminara, Ph.D. M.P·H.

New York University (New York, NY): Roy E. Shore Ph.D., Dr.P·H.

Norwegian Radium Hospital (Oslo, Norway): Anne-Lise Børresen-Dale Ph.D. (Sub-contract P·I.); Laila Jansen.

Stanford University (Palo Alto, CA): Alice Whittemore Ph.D.

University of California at Irvine (Irvine, CA): Hoda Anton-Culver Ph.D. (Sub-contract P·I.); Joan Largent Ph.D., M.P·H.

University of California at Los Angeles (Los Angeles, CA): Richard A. Gatti Ph.D.

University of Iowa (Iowa City, IA): Charles F. Lynch M.D., Ph.D. (Sub-contract P·I.); Jeanne DeWall M.A.

University of Southern California (Los Angeles, CA): Robert W. Haile Dr.P·H. (Sub-contract P·I.); Bryan M. Langholz Ph.D.; Duncan C. Thomas Ph.D.; Anh T. Diep; Shanyan Xue M.D.; Nianmin Zhou, M.D; Yong Liu M.D.; Evgenia Ter-Karapetova; Andre Hernandez.

University of Southern Maine (Portland, ME): W. Douglas Thompson Ph.D. (Sub-contract P·I.)

University of Texas, M.D. Anderson Cancer Center (Houston, TX): Marilyn Stovall Ph.D. (Sub-contract P·I.); Susan Smith M.P·H.

University of Virginia (Charlottesville, VA) and work performed at Benaroya Research Institute at Virginia Mason (Seattle, WA): Patrick Concannon, Ph.D.; Sharon Teraoka, Ph.D.; Eric R. Olson; Nirasha Ramchurren, Ph.D.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Figueiredo, J.C., Haile, R.W., Bernstein, L. et al. Oral contraceptives and postmenopausal hormones and risk of contralateral breast cancer among BRCA1 and BRCA2 mutation carriers and noncarriers: the WECARE Study. Breast Cancer Res Treat 120, 175–183 (2010). https://doi.org/10.1007/s10549-009-0455-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-009-0455-5

Keywords

Search

Navigation