Hormone replacement therapy in BRCA mutation carriers: how shall we do no harm?

Women with a BRCA mutation have an increased risk of developing breast and ovarian cancer. Bilateral salpingo-oophorectomy is the only effective strategy to reduce this risk. Risk-reducing bilateral salpingo-oophorectomy (RRSO) is recommended between the ages of 35 and 40 for women carriers of BRCA1 and between the ages of 40 and 45 for women carriers of BRCA1 and BRCA2 mutations. Most women undergo this procedure prior to their natural menopause subsequently developing an anticipated lack of hormones. This condition affects the quality of life and longevity, while it is more pronounced in women carrying a BRCA1 mutation compared to BRCA2 because they are likely to have surgery earlier. Hormone replacement therapy (HRT) is the only strategy able to significantly compensate for the loss of ovarian hormone production and counteract menopausal symptoms. There is strong evidence that short-term HRT use does not increase the risk of breast cancer among women with a BRCA1 mutation. Few data are available on BRCA2 mutation carriers. Therefore, BRCA mutation carriers require careful counseling about the outcomes of their RRSO, including menopausal symptoms and/or the fear associated with HRT use.

Loizzi V ，Dellino M ，Cerbone M ，Arezzo F ，Chiariello G ，Lepera A ，Cazzato G ，Cascardi E ，Damiani GR ，Cicinelli E ，Cormio G ... -  《-》

Risk-Reducing Bilateral Salpingo-Oophorectomy for BRCA Mutation Carriers and Hormonal Replacement Therapy: If It Should Rain, Better a Drizzle than a Storm.

Gasparri ML ，Taghavi K ，Fiacco E ，Zuber V ，Di Micco R ，Gazzetta G ，Valentini A ，Mueller MD ，Papadia A ，Gentilini OD ... -  《-》

The Role of Hormonal Replacement Therapy in BRCA Mutated Patients: Lights and Shadows.

Loizzi V ，Dellino M ，Cerbone M ，Arezzo F ，Cazzato G ，Damiani GR ，Pinto V ，Silvestris E ，Kardhashi A ，Cicinelli E ，Cascardi E ，Cormio G ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Use of total abdominal hysterectomy and hormone replacement therapy in BRCA1 and BRCA2 mutation carriers undergoing risk-reducing salpingo-oophorectomy.

Gabriel CA ，Tigges-Cardwell J ，Stopfer J ，Erlichman J ，Nathanson K ，Domchek SM ... -  《-》

Hormone replacement therapy after risk reducing salpingo-oophorectomy in patients with BRCA1 or BRCA2 mutations; a systematic review of risks and benefits.

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.

Gordhandas S ，Norquist BM ，Pennington KP ，Yung RL ，Laya MB ，Swisher EM ... -  《-》