Breast Cancer Research and Treatment

, Volume 155, Issue 2, pp 365–373 | Cite as

Hormone replacement therapy after menopause and risk of breast cancer in BRCA1 mutation carriers: a case–control study

  • Joanne Kotsopoulos
  • Tomasz Huzarski
  • Jacek Gronwald
  • Pal Moller
  • Henry T. Lynch
  • Susan L. Neuhausen
  • Leigha Senter
  • Rochelle Demsky
  • William D. Foulkes
  • Charis Eng
  • Beth Karlan
  • Nadine Tung
  • Christian F. Singer
  • Ping Sun
  • Jan Lubinski
  • Steven A. NarodEmail author


Many BRCA1 mutation carriers undergo elective surgical oophorectomy (often before menopause) to manage their elevated risk of developing ovarian cancer. It is important to clarify whether or not the use of hormone replacement therapy (HRT) to mitigate the symptoms associated with surgical or natural menopause is safe in women with an inherited BRCA1 mutation and no personal history of breast or ovarian cancer. We conducted a case–control analysis of 432 matched pairs of women with a BRCA1 mutation. Detailed information on HRT use after menopause (duration, type, age at first/last use, formulation) was obtained from a research questionnaire administered at the time of study enrollment. Conditional logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI) associated with HRT use. The mean duration of HRT use after menopause was 4.3 years among the cases and 4.4 years among the controls (P = 0.83). The adjusted OR for breast cancer comparing all women who ever used HRT to those who never used HRT was 0.80 (95 % CI 0.55–1.16; P = 0.24). Findings did not differ by type of menopause (natural vs. surgical), by recency of use, by duration of use, and by formulation type. These findings suggest that a short course of HRT should not be contra-indicated for BRCA1 mutation carriers who have undergone menopause and who have no personal history of cancer.


BRCA1 Hormone replacement therapy Breast cancer 



We would also like to thank the study coordinators Marcia Llacuachaqui, Farah Shoukat, and Alejandra Ragone, as well as the students and staff Ellen MacDougall, Zoella Pasta, Nida Mian, Jennifer Ng, Sarah Chin, Hamida Begum, Harmeet Chaudhary, and Yaminee Charavanapavan who helped with the data collection and data entry. Joanne Kotsopoulos is the recipient of a Cancer Care Ontario Research Chair in Population Studies and a Canadian Cancer Society Career Development Award in Prevention. Charis Eng is the recipient of the Sondra J. and Stephen R. Hardis Chair of Cancer Genomic Medicine at the Cleveland Clinic and of the ACS Clinical Research Professorship. Susan L. Neuhausen was partially supported by the Morris and Horowitz Endowed Professorship, and her work was supported by a grant from the National Cancer Institute, National Institutes of Health (R01CA74415). Steven A. Narod is the recipient of a Tier I Canada Research Chair. This study was supported by a Canadian Cancer Society Research Institute grant (703058). Patients were recruited for study from the City of Hope Clinical Cancer Genomics Community Research Network, supported in part by Award Number RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. Siranoush Manoukian is affiliated with the Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.

Compliance with ethical standard

Competing Interests

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Joanne Kotsopoulos
    • 1
  • Tomasz Huzarski
    • 2
  • Jacek Gronwald
    • 2
  • Pal Moller
    • 3
    • 4
  • Henry T. Lynch
    • 5
  • Susan L. Neuhausen
    • 6
  • Leigha Senter
    • 7
  • Rochelle Demsky
    • 8
    • 9
  • William D. Foulkes
    • 10
  • Charis Eng
    • 11
  • Beth Karlan
    • 12
  • Nadine Tung
    • 13
  • Christian F. Singer
    • 14
  • Ping Sun
    • 1
  • Jan Lubinski
    • 2
  • Steven A. Narod
    • 1
    Email author
  1. 1.Women’s College Research InstituteWomen’s College HospitalTorontoCanada
  2. 2.Department of Genetics and Pathology, International Hereditary Cancer CenterPomeranian Medical UniversitySzczecinPoland
  3. 3.Inherited Cancer Research Group, Department for Medical Genetics, The Norwegian Radium HospitalOslo University HospitalOsloNorway
  4. 4.Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium HospitalOslo University HospitalOsloNorway
  5. 5.Department of Preventive Medicine and Public HealthCreighton University School of MedicineOmahaUSA
  6. 6.Department of Population SciencesBeckman Research Institute of City of HopeDuarteUSA
  7. 7.Division of Human GeneticsThe Ohio State University Medical Center, Comprehensive Cancer CenterColumbusUSA
  8. 8.Division of Gynecologic Oncology, Princess Margaret Cancer CentreUniversity Health NetworkTorontoCanada
  9. 9.Department of Molecular GeneticsUniversity of TorontoTorontoCanada
  10. 10.Program in Cancer Genetics, Department of Oncology and Human GeneticsMcGill UniversityMontréalCanada
  11. 11.Genomic Medicine Institute and Center for Personalized Genetic HealthcareCleveland ClinicClevelandUSA
  12. 12.Gynecology OncologyCedars Sinai Medical CenterLos AngelesUSA
  13. 13.Beth Israel Deaconess Medical CenterBostonUSA
  14. 14.Department of Obstetrics and Gynecology and Comprehensive Cancer CenterMedical University of ViennaViennaAustria

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