The Breast Cancer Susceptibility Genes, BRCA1 and BRCA2 are two tumor suppressor genes that play a crucial role in DNA repair processes. [Yoshida 2004]. Inherited mutations in these genes are associated with a higher risk of breast (BC) and ovarian cancer (OC). Risk-reducing salpingo-oophorectomy RRSO (prophylactic removal of both the fallopian tubes and the ovaries without a clinical evident lesion) represents nowadays the main effective prophylactic OC risk measure [Marchetti 2014][NCCN Guidelines 2020] [De Felice 2015], based on evidences of reduced risk by 85% to 95%, [Kauff 2002] [Rebbeck 2002][Gadducci 2010] [Kauff 2007] [Metcalfe 2007]. The current recommendations are for RRSO once childbearing is complete, or anyway at age 35 ¿ 40 years, with an acceptable delay until maximum age 45 years in patients with BRCA2 mutation [De Felice 2017]. Since women undergo this procedure at young age, the result is the premature menopause, negatively impacting several aspects of quality of life (QoL) and health [Madalinska 2005] [Rocca 2006] with occurrence of severe hot flashes, vaginal dryness, sexual dysfunction, sleep disturbances, and cognitive changes [Finch 2011].According to guidelines, hormone replacement therapy (HRT) represents a possible treatment in this setting of patients [NCCN Guidelines 2020] but in clinical practice the administration is a delicate issue due to the potential associated BC risk. However, literature data about the real benefit of HRT in terms of QoL and the risk of BC in BRCA mutated patients are inconsistent. Thus the aim of this prospective study is to evaluate the real impact of systemic HRT on QoL and on short-term BC risk in BRCA mutated patients after RSSO and make a contribute to clarifying these doubts.
BRCA mutation carriers should undergo RRSO in order to reduce their inherited risk for OC and BC. The oncological benefit of this procedure is unquestioned, but short and long-term effects of early menopause may be seriously disabling. HRT represents a possible treatment but must be thoroughly and accurately discussed with patients due to doubts about the real benefit and the possible associated risk of BC. Available data from literature are inconsistent. Thus, the results of our study might represent a starting point for further clinical investigation with longer follow up. The research will provide a help in counselling with patients, clarifying the risk-benefit ratio and defining the better standard of care for the management of BRCA1/2 mutation carriers after prophylactic RSSO according to our experience.