{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T18:01:43Z","timestamp":1779300103356,"version":"3.51.4"},"reference-count":62,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>All cancers develop as a result of mutations in genes. DNA damage induces genomic instability and subsequently increases susceptibility to tumorigenesis. Women who carry mutations of BRCA 1 and BRCA2 genes have an augmented risk of breast and ovarian cancer and a markedly augmented probability of dying because of cancer compared to the general population. As a result, international guidelines recommend that all BRCA1\\2 mutation carriers be offered risk-reducing bilateral salpingo-oophorectomy at an early age to reduce the risk of cancer and decrease the mortality rate of this high-risk population. NCCN guidelines recommend risk-reducing bilateral salpingo-oophorectomy in pre-menopausal women, between 35\u201340 years in BRCA1 mutation carriers and between 40\u201345 years in BRCA2 mutation carriers. Unfortunately, the well-documented reduction of cancer risk is counterbalanced by early sterility and premature ovarian failure with an early onset of secondary menopausal syndromes such as neuromotor, cardiovascular, cognitive and urogenital deficiency. Hormonal replacement therapy significantly compensates for hormonal deprivation and counteracts menopausal syndrome morbidity and mortality; however, some data suggest a possible correlation between hormonal medications and cancer risk, especially in BRCA1\\2 carriers who undergo long-term regimens. Conversely, short-term treatment before the age of natural menopause does not appear to increase the cancer risk in BRCA1 mutation carriers without a personal history of breast cancer after prophylactic surgery. Few data are available on BRCA2 mutation carriers and more well-designed studies are needed. In conclusion, clinicians should propose short-term hormone replacement therapy to BRCA 1 carriers to counteract hormonal deprivation; personalized counselling should be offered to BRCA2 mutation carriers for a balance between the risks and benefits of the treatment.<\/jats:p>","DOI":"10.3390\/ijms24010764","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T04:17:38Z","timestamp":1672633058000},"page":"764","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Role of Hormonal Replacement Therapy in BRCA Mutated Patients: Lights and Shadows"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-6421","authenticated-orcid":false,"given":"Vera","family":"Loizzi","sequence":"first","affiliation":[{"name":"Oncology Unit IRCSS Istituto Tumori \u201cGiovanni Paolo II\u201d, Department of Interdisciplinary Medicine (DIM), University of Bari 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of \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0325-4316","authenticated-orcid":false,"given":"Gerardo","family":"Cazzato","sequence":"additional","affiliation":[{"name":"Section of Pathology, Department of Emergency and organ transplantation (DETO), University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0614-8068","authenticated-orcid":false,"given":"Gianluca Raffaello","family":"Damiani","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Unit, Department of Biomedical Sciences and Human Oncology, University of \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Pinto","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Unit, Department of Biomedical Sciences and Human 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Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1287-4285","authenticated-orcid":false,"given":"Eliano","family":"Cascardi","sequence":"additional","affiliation":[{"name":"Pathology Unit, FPO-IRCCS Candiolo Cancer Institute, 10060 Candiolo, Italy"},{"name":"Department of Medical Sciences, University of Turin, 10124 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5745-372X","authenticated-orcid":false,"given":"Gennaro","family":"Cormio","sequence":"additional","affiliation":[{"name":"Oncology Unit IRCSS Istituto Tumori \u201cGiovanni Paolo II\u201d, Department of Interdisciplinary Medicine (DIM), University of Bari \u201cAldo Moro\u201d, 70124 Bari, 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