Highlights
- •Hormone replacement therapy use improves endocrine symptoms and sexual function after premature surgical menopause.
- •In BRCA mutation carriers, breast cancer risk is not altered by estrogen replacement therapy after oophorectomy.
- •Progestin containing hormonal regimens may have a less favorable breast cancer risk profile for BRCA mutation carriers.
Abstract
Women with germline BRCA1 or BRCA2 (BRCA) mutations, are recommended risk-reducing salpingo-oophorectomy (RRSO) prior to menopause.
Surgical menopause has significant impact on patients' health and well–being. Subsequently,
concerns about surgical menopause influence uptake of RRSO in high risk women. The
role of hormone replacement therapy (HRT) in BRCA mutation carriers undergoing RRSO has been controversial. In the general population,
premature surgical menopause is associated with worse quality of life and cognitive
function, and increased risk of bone and cardiovascular disease; HRT continued until
the natural age of menopause is shown to alleviate a number of these effects. Conflicting
information has been published on HRT and breast cancer risk. For BRCA mutation carriers, potential augmentation of already elevated breast cancer risk
is of great concern. In this article, we provide a review of the literature on HRT
in this high-risk population, including effects on quality of life, cardiovascular,
bone, and brain health. We also review impact of HRT on breast cancer risk, with a
discussion of HRT formulation and surgical approach. Though evidence is limited, HRT
after RRSO has a number of reported benefits and does not appear to impact breast
cancer risk reduction in BRCA mutation carriers. This information is critical when discussing RRSO with patients,
as providers should review risks of early menopause and treatment options. This review
provides information to assist with counseling this specific population.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Gynecologic OncologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.JAMA. 2017; 317: 2402-2416https://doi.org/10.1001/jama.2017.7112
- Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies.Am. J. Hum. Genet. 2003; 72: 1117-1130https://doi.org/10.1086/375033
- NCCN guidelines insights: genetic/familial high-risk assessment: breast and ovarian, version 2.2017.J. Natl. Compr. Cancer Netw. 2017; 15: 9-20https://doi.org/10.6004/jnccn.2017.0003
- Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality.JAMA. 2010; 304: 967-975https://doi.org/10.1001/jama.2010.1237
- Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation.J. Clin. Oncol. 2014; 32: 1547-1553https://doi.org/10.1200/JCO.2013.53.2820
- Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations.N. Engl. J. Med. 2002; 346: 1616-1622https://doi.org/10.1056/NEJMoa012158
- Risk-reducing Salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation.N. Engl. J. Med. 2002; 346: 1609-1615https://doi.org/10.1056/NEJMoa020119
- Chambers, cancer care Ontario's practice guidelines initiative gynecology cancer disease site group, systematic review of management options for women with a hereditary predisposition to ovarian cancer.Gynecol. Oncol. 2004; 93: 280-286https://doi.org/10.1016/j.ygyno.2004.02.013
- Ovarian conservation at the time of hysterectomy and long-term health outcomes in the nurses' health study.Obstet. Gynecol. 2009; 113: 1027-1037https://doi.org/10.1097/AOG.0b013e3181a11c64
- Survival patterns after oophorectomy in premenopausal women: a population-based cohort study.Lancet Oncol. 2006; 7: 821-828https://doi.org/10.1016/S1470
- Long-term health consequences of premature or early menopause and considerations for management HHS public access.Climacteric. 2015; 18: 483-491https://doi.org/10.3109/13697137.2015.1020484
- Obstet. Gynecol. 2017; 129: e134-e141https://doi.org/10.1097/AOG.0000000000002044
- The 2017 hormone therapy position statement of The North American Menopause Society.Menopause. 2017; 24: 728-753https://doi.org/10.1097/GME.0000000000000921
- Hormone replacement therapy in young women with surgical primary ovarian insufficiency.Fertil. Steril. 2016; 106: 1580-1587https://doi.org/10.1016/j.fertnstert.2016.09.018
- Early menopause: primary ovarian insufficiency and surgical menopause.Semin. Reprod. Med. 2010; 28: 360-369https://doi.org/10.1055/s-0030-1262895
- Writing group for the women's health initiative investigators, risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women's health initiative randomized controlled trial.JAMA, J. Am. Med. Assoc. 2002; 288: 321-333https://doi.org/10.1001/jama.288.3.321
- Use of hormone replacement therapy after risk-reducing salpingo-oophorectomy.Acta Obstet. Gynecol. Scand. 2017; 96: 547-555https://doi.org/10.1111/aogs.13120
- Impact of hormone therapy on quality of life after menopause.Menopause. 2013; 20: 1098-1105https://doi.org/10.1097/GME.0b013e318298debe
- Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes.Cochrane Database Syst. Rev. 2004; https://doi.org/10.1002/14651858.CD002978.pub2
- Management of symptomatic vulvovaginal atrophy: 2013 position statement of the North American menopause society.Menopause. 2013; 20: 888-902https://doi.org/10.1097/GME.0b013e3182a122c2
- The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic Salpingo-oophorectomy.J. Clin. Oncol. 2006; 24: 3576-3582https://doi.org/10.1200/JCO.2005.05.1896
- Sexual activity and functioning after risk-reducing salpingo-oophorectomy: impact of hormone replacement therapy.Gynecol. Oncol. 2016; 140: 101-106https://doi.org/10.1016/j.ygyno.2015.11.016
- The impact of prophylactic salpingo-oophorectomy on menopausal symptoms and sexual function in women who carry a BRCA mutation.Gynecol. Oncol. 2011; 121: 163-168https://doi.org/10.1016/j.ygyno.2010.12.326
- Hormone replacement therapy after risk-reducing salpingo-oophorectomy minimises endocrine and sexual problems: a prospective study.Eur. J. Cancer. 2017; 84: 159-167https://doi.org/10.1016/j.ejca.2017.07.018
- The effects of pre-operative menopausal status and hormone replacement therapy (HRT) on sexuality and quality of life after risk-reducing salpingo-oophorectomy.Maturitas. 2016; 85: 42-48https://doi.org/10.1016/j.maturitas.2015.12.004
- Osteoporosis risk and management in BRCA1 and BRCA2 carriers who undergo risk-reducing salpingo-oophorectomy.Gynecol. Oncol. 2015; 138: 723-726https://doi.org/10.1016/j.ygyno.2015.06.020
- Menopausal symptoms and bone health in women undertaking risk reducing bilateral salpingo-oophorectomy: significant bone health issues in those not taking HRT.Br. J. Cancer. 2011; 105: 22-27https://doi.org/10.1038/bjc.2011.202
- Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis.Menopause. 2006; 13: 265-279https://doi.org/10.1097/01.gme.0000218683.97338.ea
- Increased cardiovascular mortality following early bilateral oophorectomy.Menopause. 2009; 16: 15-23https://doi.org/10.1097/gme.0b013e31818888f7
- Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause.Neurology. 2007; 69: 1074-1083https://doi.org/10.1212/01.wnl.0000276984.19542.e6
- Non-cancer endpoints in BRCA1/2 carriers after risk-reducing salpingo-oophorectomy.Familial Cancer. 2012; 11: 69-75https://doi.org/10.1007/s10689-011-9480-8
- Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials.JAMA. 2013; 310: 1353https://doi.org/10.1001/jama.2013.278040
- Clinical and pathologic characteristics of patients with BRCA -positive and BRCA -negative breast cancer.J. Clin. Oncol. 2008; 26: 4282-4288https://doi.org/10.1200/JCO.2008.16.6231
- The pathology of familial breast Cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2.J. Clin. Oncol. 2002; 20: 2310-2318https://doi.org/10.1200/JCO.2002.09.023
- PROSE study group, 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. 2005; 23: 7804-7810https://doi.org/10.1200/JCO.2004.00.8151
- Hereditary breast cancer clinical study group, hormone therapy and the risk of breast cancer in BRCA1 mutation carriers.J. Natl. Cancer Inst. 2008; 100: 1361-1367https://doi.org/10.1093/jnci/djn313
- Hormone replacement therapy after menopause and risk of breast cancer in BRCA1 mutation carriers: a case-control study.Breast Cancer Res. Treat. 2016; 155: 365-373https://doi.org/10.1007/s10549-016-3685-3
- Hormone replacement therapy after oophorectomy and breast cancer risk among brca1 mutation carriers.JAMA Oncol. 2018; https://doi.org/10.1001/jamaoncol.2018.0211
- Breast cancer after use of estrogen plus progestin in postmenopausal women.N. Engl. J. Med. 2009; 360: 573-587https://doi.org/10.1056/NEJMoa0807684
- Effects of conjugated equine estrogen in postmenopausal women with hysterectomy.JAMA. 2004; 291: 1701https://doi.org/10.1001/jama.291.14.1701
- Adverse endometrial effects of long-cycle estrogen and progestogen replacement therapy.N. Engl. J. Med. 1996; 334: 668-669https://doi.org/10.1056/NEJM199603073341018
- Can progestin be limited to every third month only in postmenopausal women taking estrogen?.Maturitas. 1995; 21 (accessed October 7, 2018): 39-44
- Cyclic hormone replacement therapy using quarterly progestin.Obstet. Gynecol. 1994; 83 (accessed October 7, 2018): 693-700
- Intrauterine release of levonorgestrel–a new way of adding progestogen in hormone replacement therapy.Obstet. Gynecol. 1992; 79 (accessed October 7, 2018): 963-967
- Intrauterine application of progestins in hormone replacement therapy: a review.Climacteric. 2000; 3 (accessed October 7, 2018): 199-211
- The levonorgestrel intrauterine system in menopausal hormone replacement therapy: five-year experience.Fertil. Steril. 1999; 72: 161-163https://doi.org/10.1016/S0015-0282(99)00162-4
- Effects of the levonorgestrel-releasing intrauterine system plus estrogen therapy in perimenopausal and postmenopausal women: systematic review and meta-analysis.Menopause. 2011; 18: 1060-1066https://doi.org/10.1097/gme.0b013e31821606c5
- Risk of endometrial carcinoma associated with BRCA mutation.Gynecol. Oncol. 2001; 80: 395-398https://doi.org/10.1006/gyno.2000.6082
- BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma.Cancer. 2013; 119: 332-338https://doi.org/10.1002/cncr.27720
- Uterine Cancer after risk-reducing salpingo-oophorectomy without hysterectomy in women with BRCA mutations.JAMA Oncol. 2016; 2: 1434-1440https://doi.org/10.1001/jamaoncol.2016.1820
- Kathleen cuningham foundation consortium for research into familial breast cancer (kConFab), risk of uterine cancer for BRCA1 and BRCA2 mutation carriers.Eur. J. Cancer. 2017; 84: 114-120https://doi.org/10.1016/j.ejca.2017.07.004
- BRCA germline mutations in Jewish women with uterine serous papillary carcinoma.Gynecol. Oncol. 2004; 92: 521-524https://doi.org/10.1016/j.ygyno.2003.11.009
- Hereditary breast cancer study group, the incidence of endometrial cancer in women with BRCA1 and BRCA2 mutations: an international prospective cohort study.Gynecol. Oncol. 2013; 130: 127-131https://doi.org/10.1016/j.ygyno.2013.03.027
- Use of Total Abdominal Hysterectomy and Hormone Replacement Therapy in BRCA1 and BRCA2 Mutation Carriers Undergoing Risk-reducing Salpingo-oophorectomy.2008https://doi.org/10.1007/s10689-008-9208-6
- Prophylactic salpingectomy and delayed oophorectomy as an alternative for BRCA mutation carriers.Obstet. Gynecol. 2013; 121: 14-24https://doi.org/10.1097/AOG.0b013e3182783c2f
- Bilateral Salpingectomy With Delayed Oophorectomy For Ovarian Cancer Risk Reduction: A Pilot Study in Women With BRCA1/2 Mutations.2018https://doi.org/10.1016/j.ygyno.2018.04.564
Article info
Publication history
Published online: January 17, 2019
Accepted:
December 13,
2018
Received in revised form:
December 12,
2018
Received:
November 15,
2018
Identification
Copyright
© 2018 Elsevier Inc. All rights reserved.
