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

Expert Opin Drug Saf. 2020 Aug;19(8):1025-1030. doi: 10.1080/14740338.2020.1791818. Epub 2020 Jul 10.

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

Publication types

  • Review

MeSH terms

  • Animals
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Estrogen Replacement Therapy / methods*
  • Female
  • Humans
  • Middle Aged
  • Postmenopause*
  • Salpingo-oophorectomy

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human