- BRCA mutation carriers:
- Are recommended to undergo prophylactic BSO to decrease risk of developing ovarian cancer
- Risk-reducing surgery:
- Should be performed after completion of childbearing and is recommended at:
- Ages of 35 to 40 years for BRCA1 mutation carriers
- Ages of 40 to 45 years for BRCA2 mutation carriers
- Should be performed after completion of childbearing and is recommended at:
- Women who undergo BSO at a young age:
- Are at increased risk of premature menopausal symptoms including:
- Vasomotor symptoms
- Sexual dysfunction
- Vulvo-vaginal atrophy
- In addition, premature menopause:
- May be associated with decreased bone density and cardiovascular disease
- Are at increased risk of premature menopausal symptoms including:
- Short-term hormone replacement therapy (HRT):
- Can be beneficial to alleviate the symptoms of estrogen deprivation:
- A literature review on the use of HRT among BRCA mutation carriers following risk-reducing BSO:
- Summarized data supporting the use of HRT for improvement in menopausal symptoms, quality of life, and sexual function, and suggests an improvement in bone health, cardiovascular health, and cognitive function
- A literature review on the use of HRT among BRCA mutation carriers following risk-reducing BSO:
- Can be beneficial to alleviate the symptoms of estrogen deprivation:
- When assessing breast cancer risk with HRT in this population:
- The summary of available literature does not show an increase in breast cancer risk with short-term HRT use following risk-reducing BSO:
- However, there is notable concern regarding increased breast cancer risk with the use of combination estrogen and progesterone HRT compared to estrogen alone:
- Kotsopoulos and colleagues reported a prospective, longitudinal cohort study of BRCA1 mutation carriers who underwent risk-reducing BSO from 80 centers in 17 countries 1995-2017:
- BRCA1 carriers with a follow-up of 7.6 years following BSO were included
- Of the population, 43% of women used some form of HRT following BSO for a mean duration of 3.9 years
- The authors did not find an associated increase in breast cancer risk with the use of HRT in this population of BRCA1 carriers post-BSO (HR 0.97, p=.89 for any HRT use vs. none)
- In this cohort, most women took estrogen alone (69%) while 18% took combination estrogen plus progesterone and 32% used another formulation of hormone therapy
- While there was no significant difference in the 10-year actuarial risk for any HRT regimen compared to none (p=0.72), there was a difference in women who used estrogen alone, with a reported breast cancer incidence of 12% compared with 22% in those who used estrogen plus progesterone (p=0.04)
- In general, estrogen-alone HRT is recommended for women who have undergone a hysterectomy, while combination estrogen plus progesterone is recommended for women with an intact uterus to reduce the risk of endometrial hyperplasia and cancer (a risk with unopposed estrogen)
- Given these differences in risk, a thoughtful discussion is necessary to balance the risks and benefits of HRT with appropriate gynecologic surgery.
- Kotsopoulos and colleagues reported a prospective, longitudinal cohort study of BRCA1 mutation carriers who underwent risk-reducing BSO from 80 centers in 17 countries 1995-2017:
- However, there is notable concern regarding increased breast cancer risk with the use of combination estrogen and progesterone HRT compared to estrogen alone:
- The summary of available literature does not show an increase in breast cancer risk with short-term HRT use following risk-reducing BSO:
- While premature menopause symptoms are a common concern among young women undergoing risk reducing BSO, few BRCA mutation carriers are currently recommended to consider HRT for symptom management:
- A study reporting on BRCA mutation carriers from the ‘Facing Our Risk of Cancer Empowered’ group found that 81% of the postmenopausal population became menopausal prematurely secondary to surgery or medications
- Of this group, the majority reported concerns of libido /sexuality (78%), cardiovascular disease (78%), and osteoporosis (65%), but HRT use was reported in only 13% of women with no prior cancer history with only 26% of women reporting that this was favored by their healthcare provider
- Continued provider and patient education is needed to educate patients that short-term hormone replacement therapy is safe in BRCA1 mutation carriers following risk reducing bilateral salpingo-oophorectomy
- References
- Gordhandas S, Norquist BM, Pennington KP, Yung RL, Laya MB, Swisher EM. Hormone replacement therapy after risk reducing salpingo-oophorectomy in patients with BRCA1 or BRCA2 mutations; a systematic review of risks and benefits. Gynecol Oncol. 2019;153(1):192-200.
- Kotsopoulos J, Gronwald J, Karlan BY, Huzarski T, Tung N5, Moller P, et al. Hormone replacement therapy after oophorectomy and breast cancer risk among BRCA1 mutation carriers. JAMA Oncol. 2018;4(8):1059-1065.
- Birrer N, Chinchilla C, Del Carmen M, Dizon DS. Is Hormone Replacement Therapy Safe in Women With a BRCA Mutation?: A Systematic Review of the Contemporary Literature. Am J Clin Oncol. 2018 Mar;41(3):313-315.
Rodrigo Arrangoiz MS, MD, FACS, FSSO 