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Birrer and colleagues recently reviewed the available literature on the safety of hormone replacement therapy (HRT) in BRCA carriers [1]. Four publications were considered relevant for the purpose of this review. Studies were done to evaluate the impact of HRT on menopausal symptoms (n = 2) or breast cancer risk (n = 2) after bilateral salpingo-oophorectomy (BSO) in BRCA mutation carriers. The concern of an elevated breast cancer risk among mBRCA carriers on HRT does not appear to be a significant issue based on the limited data available, which indicate that HRT appears to be safe in young mBRCA carriers who have undergone BSO. This was demonstrated best in the Prevention and Observation of Surgical Endpoints study that included 462 female mBRCA carriers, all of whom were followed from time to BSO (note, patients were censored at the time of prophylactic mastectomy) [2]. Within this population, 114 women took HRT, 93 of 155 who had a BSO, and 21 of 307 who did not have a BSO. Compared with the entire cohort, there was no impact on breast cancer risk with HRT among those who underwent a BSO (hazard ratio (HR) 0.37; 95% confidence interval (CI) 0.14-0.96). It is also interesting to note that, although in a limited sample size, among the 93 patients who had a BSO, 54 patients took estrogen alone and 34 took progesterone with or without estrogen (five did not specify). There was no significant difference in breast cancer risk reduction between the two groups. An additional analysis concentrated on those women who underwent a BSO before 50 years; the authors reported that HRT had no significant impact on the subsequent risk of breast cancer. In a matched case–control study by Eisen and colleagues [3], a subset of 472 postmenopausal women with BRCA1 mutations were examined to compare an increased risk of breast cancer in patients treated with estrogen alone (n = 28) or combination estrogen and progesterone (n = 19). An inverse association between estrogen use alone (odds ratio (OR) 0.51; 95% CI 0.27-0.98) and breast cancer risk was observed, whereas no significant association was seen in combination therapy and risk of breast cancer (OR 0.66; 95% CI 0.34-1.27).

In a study by Armstrong and colleagues [4], the use of HRT (both progesterone and estrogen) after risk-reducing surgery (BSO and prophylactic mastectomy) until age 50 translated into a gain in life expectancy for these patients, which varied by age: there was a gain of 0.78, 0.79, and 0.79 years for a 30-, 35-, and 40-year-old women, respectively. Interestingly, the gains in life expectancy were less pronounced if women used HRT for life, with added 0.39, 0.39, and 0.37 years calculated.


  • Frits Riphagen
    Brussels, Belgium


  1. Birrer N, Chinchilla C, Del Carmen M, Dizon DS. Is hormone therapy safe in women with a BRCA mutation? A systematic review of the contemporary literature. Am J Clin Oncol 2016 Feb 2. Epub ahead of print
  2. Rebbeck TR, Friebel T, Wagner T, et al. Effect of short-term hormone replacement therapy on breast cancer reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 2005;23:7804-10
  3. Eisen A, Lubinski J, Gronwald J, et al. Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers. J Natl Cancer Inst 2008;100:1361-7
  4. Armstrong K, Schwartz JS, Randall T, et al. Hormone replacement therapy and life expectancy after prophylactic oophorectomy in women with BRCA1/2 mutation: a decision analysis. J Clin Oncol 2004;22:1045-54
  5. Anglian Breast Cancer Study Group. Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Br J Cancer 2000;83:1301-8
  6. Peto J, Collins N, Barfoot R, et al. Prevalence of BRCA1 and BRCA2 mutations in patients with early-onset breast cancer. J Natl Cancer Inst 1999;91:943-9
  7. Malone KE, Daling JR, Doody D, et al. Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women aged 35 to 64.Cancer Res 2006;66:8297-308
  8. Chlebowski RT, Hendrix S, Langer R, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative randomized trial. JAMA 2003;289:3243-53
  9. Madalinska JB, van Beurden M, Bleiker EM, et al. The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy. J Clin Oncol 2006;24:3576-82
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