Hormone replacement therapy in BRCA mutation carriers and risk of ovarian, endometrial, and breast cancer: a systematic review

J Cancer Res Clin Oncol. 2021 Jul;147(7):2035-2045. doi: 10.1007/s00432-021-03629-z. Epub 2021 Apr 22.


Purpose: BRCA mutation carriers have an increased risk of developing breast or ovarian cancer. Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is associated with a decrease in risk for tubal and ovarian cancer. Hormone replacement therapy (HRT) may increase breast, ovarian, and endometrial cancer risk in the general population. This review analyses the published data on HRT and risk of cancer in BRCA mutation carriers with and without RRBSO.

Methods: We included all relevant articles published in English from 1995 to October 2020. Sources were identified through a search on PubMed and Cochrane Library.

Results: We included one case-control and one retrospective cohort study on ovarian and one case-control study on endometrial cancer risk and HRT in BRCA mutation carriers. Regarding breast cancer risk, one case-control study on BRCA mutation carriers with and without RRBSO and one case-control study, one Markov chain decision model, two prospective cohort studies, and one metaanalysis on carriers after RRBSO were included. For ovarian cancer, results were ambiguous. For breast cancer, most studies did not find an adverse effect associated with HRT. However, some of the studies found a risk modification associated with different formulations and duration of use.

Conclusion: Although data are limited, HRT does not seem to have a relevant effect on cancer risk in BRCA mutation carriers. RRBSO should not be postponed to avoid subsequent HRT in this population. Adequate HRT after RRBSO should be offered to avoid chronic diseases resulting from low estrogen levels. However, further data on the safety of different formulations are needed.

Keywords: BRCA1; BRCA2; Breast cancer; Hormone replacement therapy; Ovarian cancer.

Publication types

  • Systematic Review

MeSH terms

  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Breast Neoplasms / etiology*
  • Breast Neoplasms / pathology
  • Endometrial Neoplasms / etiology*
  • Endometrial Neoplasms / pathology
  • Female
  • Genetic Predisposition to Disease
  • Heterozygote
  • Hormone Replacement Therapy / adverse effects*
  • Humans
  • Mutation*
  • Ovarian Neoplasms / etiology*
  • Ovarian Neoplasms / pathology


  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human