Postmenopausal hormone therapy in BRCA gene mutation carriers: to whom and which?

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.

KEYWORDS:

• Hereditary ovarian cancer
• BRCA
• menopause
• postmenopausal hormone therapy
• hormone replacement therapy
• risk-reducing-salpingo-oophorectomy
• estrogens
• progestins
• tibolone
• bazedoxifene
• tissue-selective estrogen complex

Declaration of interest

G Grandi received honoraria for participation in advisory boards and sponsored lectures in international Symposia from Bayer AG, Teva/Theramex, Exeltis Italy, Sandoz/Novartis, Effik Italy and Merck Sharp & Dohme outside the submitted work. L Cortesi served as consultant and/or received speaker honoraria from Astra Zeneca, Merck Sharp & Dohme, Pfizer, Novartis, Tesaro and Clovis outside the submitted work. A Toss served as consultant and/or received speaker honoraria from Eli-Lilly and Roche outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.