Abstract
ABSTRACT Introduction Risk-reducing-salpingo-oophorectomy (RRSO) inevitably leads BRCA mutation carriers to premature menopause. Areas covered To evaluate the existing evidence for use of postmenopausal hormone therapy (HT) in BRCAmc, after RRSO or menopause occurring naturally, for both breast cancer (BC) survivors and those without BC. Expert opinion All BC survivors are excluded from any HT treatment: in other BRCAmc, before 51 years of age the benefits of HT overcome the risks after RRSO and/or premature ovarian insufficiency (POF). After 51 years of age, it is important to treat only women with important vasomotor symptoms, after the failure of alternative therapies. Estrogens-only therapy plays a key role in hysterectomized women (HW). In the case of an intact uterus (UW), associations with the lowest dose of progestins/natural progesterone derivatives have to be preferred, as progestins has been shown to play an important role in BC transformation, especially in BRCA1mc. No studies have been performed in BRCAmc with regard to ‘progestin-free’ HT, in particular the old tibolone (both in HW and UW) and the new tissue-selective estrogen complex (in UW). However, preliminary data obtained from the general population are reassuring about the use of these ‘progestin-free’ preparations and BC safety.
Highlights
Risk-reducing-salpingo-oophorectomy (RRSO) inevitably leads BRCA mutation carriers to premature menopause
Performing risk-reducing-salpingo-oophorectomy (RRSO) for these patients seems to be the best strategy to reduce the risk of ovarian cancer (OC) by up to 96%: it has been shown to reduce the risk of breast cancer (BC) by up to 50% [2], though this protec tive effect has recently been widely questioned [3]
It is important to offer these patients the possibility of postmenopausal hormone therapy (HT), if no contraindi cations exist, to limit the systemic effects related to early estrogen depletion associated with iatrogenic menopause and to protect them from long-term side effects
Summary
Patients carrying germline mutations in BRCA1 or 2 genes present a life-long increased risk of developing ovarian and breast cancer. RRSO inevitably leads patients to premature menopause compared with the average general age of menopause in women (51 years) This involves a num ber of side effects related to estrogen deprivation, being divided into acute and long-term symptoms. Acute symp toms include hot flushes, insomnia, arthralgia, irritability, a decline in libido, and genitourinary syndrome, while longterm symptoms comprehend an increase in cardiovascular risk, dementia, and early-onset osteoporosis [5] For these reasons, it is important to offer these patients the possibility of postmenopausal hormone therapy (HT), if no contraindi cations exist (mainly a previous occurrence of BC), to limit the systemic effects related to early estrogen depletion associated with iatrogenic menopause and to protect them from long-term side effects. Possible postmenopausal HTs can be divided into typical HT formulations [estrogens (E)-only and combined oes tro-progestin (EP) HT] or ‘progestin-free’ HT, with different ways of administration, hormonal components, and regimens (Table 1)
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