Comparing the Gonadotoxicity of Multiple Breast Cancer Regimens: Important Understanding for Managing Breast Cancer in Pre-Menopausal Women

Valentino Martelli,1,2 Maria Maddalena Latocca,1,2 Tommaso Ruelle,1,2 Marta Perachino,1,2 Luca Arecco,1,2 Kristi Beshiri,1,2 Maria Grazia Razeti,1,2 Marco Tagliamento,1,2 Maurizio Cosso,3 Piero Fregatti,4,5 Matteo Lambertini1,2 1Department of Medical Oncology, U.O.C Clinica Di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy; 2Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy; 3Department of Radiology, IRCCS Ospedale Policlinico San Martino, Genova, Italy; 4U.O.C. Clinica Di Chirurgia Senologica, Department of Surgery, IRCCS Ospedale Policlinico San Martino, Genova, Italy; 5Department of Integrated Diagnostic Surgical Sciences, School of Medicine, University of Genova, Genova, ItalyCorrespondence: Matteo LambertiniIRCCS Ospedale Policlinico San Martino, University of Genova, Largo Rosanna Benzi 10, Genova, 16132, ItalyTel +39 010 555 4254Fax + 39 010 555 6536Email matteo.lambertini@unige.itAbstract: Over the last several decades, improvements in breast cancer treatment have contributed to increased cure rates for women diagnosed with this malignancy. Consequently, great importance should be paid to the long-term side effects of systemic therapies. For young women (defined as per guideline ≤ 40 years at diagnosis) who undergo chemotherapy, one of the most impactful side effects on their quality of life is premature ovarian insufficiency (POI) leading to fertility-related problems and the side effects of early menopause. Regimens, type, and doses of chemotherapy, as well as the age of patients and their ovarian reserve at the time of treatment are major risk factors for treatment-induced POI. For these reasons, childbearing desire and preservation of ovarian function and/or fertility should be discussed with all premenopausal patients before planning the treatments. This manuscript summarizes the available fertility preservation techniques in breast cancer patients, the risk of treatment-induced POI with different anticancer treatments, and the possible procedures to prevent it. A special focus is paid to the role of oncofertility counseling, as a central part of the visit in this setting, during which the patient should receive all the information about the potential consequences of the disease and of the proposed treatment on her future life.Keywords: breast cancer, fertility, young patient, oncofertility, premature ovarian insufficiency, anti-Mullerian hormone