Importance Chemotherapy may result in a detrimental effect on ovarian function and fertility in premenopausal women undergoing curative treatment for early breast cancer (EBC). For this subgroup of patients, a careful consideration for techniques to minimize this risk should be given and the role of gonadotropin-releasing hormone agonists (GnRHa) for protection of ovarian function is not fully resolved. Objective To determine efficacy of GnRHa administered concurrently with chemotherapy for ovarian function preservation. Data sources The search for studies published between 1975 and March/2015 encompassed PubMed, SCOPUS and Cochrane databases, as well as ASCO Annual Meeting and San Antonio Breast Cancer Symposium abstracts. Study selection Prospective, randomized, controlled trials addressing the role of ovarian suppression with GnRHa in preventing early ovarian dysfunction in premenopausal women undergoing treatment for EBC were selected. Data extraction and synthesis Data extraction was performed independently by two authors. The methodology and the risk of bias were assessment based on the description of randomization method, withdrawals and blinding process. Main Outcomes Measures Rate of resumption of regular menses after a minimal follow-up period of 6 months following chemotherapy was used as surrogate to assess the incidence of ovarian dysfunction. Additional secondary outcomes included hormone levels and number of pregnancies. Risk ratio estimates were calculated based on the number of evaluable patients. Analyses were conducted using a random effect model. Results Seven studies were selected, totaling 1047 randomized patients (856 evaluable patients).. The use of GnRHa was associated with a higher rate of recovery of regular menses after 6 months (OR = 2.41; 95% CI 1.40–4.15; p= 0. 002) and at least 12 months (OR 1.85; 95% CI 1.33–2.59; p = 0.0003) following last chemotherapy cycle. The use of GnRHa was also associated with a higher number of pregnancies (OR 1.85; 95% IC 1.02–3.36; p=0.04), although this outcome was not uniformly reported. Conclusions and Relevance GnRHa given with chemotherapy resulted in increased rates of recovery of regular menses and should be considered an option for ovarian function preservation in young women undergoing treatment for EBC. Additional outcomes related to ovarian function and fertility need to be further investigated.

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Compared with first-line continuous chemotherapy administered until disease progression, complete treatment stop did not have a detrimental impact on the overall survival of patients with mCRC. Identification of predictive biomarkers could help clinicians to select the patients who would benefit from continuous cancer-directed therapies.