Memorial Sloan Kettering Cancer Center, New York, NY
Rodrigo Ramella Munhoz , Allan Andresson Lima Pereira , Andre Deeke Sasse , Paulo Marcelo Hoff , Tiffany A. Traina , Clifford A. Hudis , Ricardo Jose Marques
Background: The risks of chemotherapy-induced ovarian dysfunction and fertility impairment remain a clinical challenge in the management of premenopausal women diagnosed with early breast cancer (EBC). For this subgroup of patients (pts) undergoing treatment with curative intent, careful consideration of techniques to minimize these risks should be given. In this setting, the role of gonadotropin-releasing hormone agonists (GnRHa) for protection of ovarian function is not fully resolved. Methods: We searchedPubMed, SCOPUS and Cochrane Central Register of Controlled Trials databases, as well as ASCO Annual Meeting and San Antonio Breast Cancer Symposium abstracts. Prospective, randomized trials investigating the effect of GnRHa administered concurrently with chemotherapy (CT) for ovarian function preservation were selected for data extraction. Results: Six placebo-controlled studies were included in the analysis, totaling 827 randomized pts (673 evaluable pts). GnRHa used for ovarian suppression included either goserelin or triptorelin. Anthracycline and cyclophosphamide-based regimens were administered to over 90% of the pts in the neo- or adjuvant setting; a smaller proportion received taxanes. The use of GnRHa was associated with statistically significant improvement in the rate of recovery of regular menses after 6 months (OR = 2.53; 95% CI 1.23-5.22; p = 0, 01) and at least 12 months (OR 1.76; 95% CI 1.17-2.64; p = 0,007) following last CT cycle among evaluable pts. A higher number of pregnancies occurred among pts treated with GnRHa in comparison to the control arms, however, the total number of attempted pregnancies was not uniformly reported and this was not statistically significant (OR 1.79; 95% IC 0.97-3.31). Additional analyzes addressing mean time to recovery of menses and changes in hormonal levels were hampered by incomplete data. Conclusions: This meta-analysis provides evidence to support the use of GnRHa as a tool to prevent chemotherapy-induced amenorrhea in young women undergoing treatment for EBC. Additional outcomes related to ovarian function and fertility need to be further investigated.
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