title: Temporary ovarian suppression during chemotherapy to preserve ovarian function and fertility in breast cancer patients: A GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology.
abstract: The development of premature ovarian failure and subsequent infertility are possible consequences of chemotherapy use in pre-menopausal women with early-stage breast cancer. Among the available strategies for fertility preservation, pharmacological protection of the ovaries using luteinising hormone-releasing hormone analogues (LHRHa) during chemotherapy has the potential to restore ovarian function and fertility after anticancer treatments; however, the possible efficacy and clinical application of this strategy has been highly debated in the last years. Following the availability of new data on this controversial topic, the Panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guideline on fertility preservation in cancer patients decided to apply the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology around the relevant and current question on the clinical utility of temporary ovarian suppression with LHRHa during chemotherapy as a strategy to preserve ovarian function and fertility in breast cancer patients. To answer this question, preservation of ovarian function and fertility were judged as critical outcomes for the decision-making. Three possible outcomes of harm were identified: LHRHa-associated toxicities, potential antagonism between concurrent LHRHa and chemotherapy, and lack of the prognostic impact of chemotherapy-induced premature ovarian failure. According to the GRADE evaluation conducted, the result was a strong positive recommendation in favour of using this option to preserve ovarian function and fertility in breast cancer patients. The present manuscript aims to update and summarise the evidence for the use of this strategy in light of the new data published up to January 2016, according to the GRADE process.
authors.affiliation: Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino - IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy; Department of Medicine, BrEAST Data Centre, Institut Jules Bordet and l'Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. Electronic address: matteo.lambertini85@gmail.com.
authors.forename: Matteo
authors.initials: M
authors.lastname: Lambertini
authors.affiliation: Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy. Electronic address: michela.cinquini@marionegri.it.
authors.forename: Michela
authors.initials: M
authors.lastname: Cinquini
authors.affiliation: Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy. Electronic address: ivan.moschetti@marionegri.it.
authors.forename: Ivan
authors.initials: I
authors.lastname: Moschetti
authors.affiliation: Fertility and Procreation Unit, Division of Gynecologic Oncology, European Institute of Oncology, Milan, Italy. Electronic address: fedro.peccatori@ieo.it.
authors.forename: Fedro A
authors.initials: FA
authors.lastname: Peccatori
authors.affiliation: Physiopathology of Human Reproduction Unit, IRCCS AOU San Martino - IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. Electronic address: paola.anserini@fastwebnet.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Anserini
authors.affiliation: Department of Gynecology, U.O. di Ginecologia, Università di Genova, IRCCS AOU San Martino - IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. Electronic address: sasmario@unige.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Valenzano Menada
authors.affiliation: Department of Medical Oncology, Ospedale Maggiore Policlinico, Milan, Italy. Electronic address: maurizio.tomirotti@policlinico.mi.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Tomirotti
authors.affiliation: Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, IRCCS AOU San Martino - IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. Electronic address: lucia.delmastro@hsanmartino.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Del Mastro
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D005260:Female; D005298:Fertility / Q000187:drug effects; D059247:Fertility Preservation / Q000379:methods*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives*; D006801:Humans; D016649:Primary Ovarian Insufficiency / Q000517:prevention & control*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D007987:Gonadotropin-Releasing Hormone
keywords: Breast cancer; Fertility preservation; Grades of Recommendation, Assessment, Development, and Evaluation (GRADE); Italian Association of Medical Oncology (AIOM); Luteinising hormone-releasing hormone analogues (LHRHa); Premature ovarian failure