Prognostic impact of chemotherapy-induced amenorrhea on premenopausal breast cancer: a meta-analysis of the literature

OBJECTIVE We conducted this meta-analysis of published data to assess the exact prognostic value of adjuvant chemotherapy-induced amenorrhea (CIA) as a prognostic factor for premenopausal breast cancer. METHODS We searched for all relevant studies published before May 2014 in the PubMed, OVID, and EMBASE databases. Relative risks (RRs) were used to estimate the association between CIA and various survival outcomes, including disease-free survival (DFS) and overall survival (OS). RESULTS This meta-analysis identified 13 eligible studies including 5,513 cases and 2,008 controls for DFS and 5 eligible studies including 2,331 cases and 776 controls for OS. Results demonstrated that CIA is associated with improved DFS (RR, 0.67; 95% CI, 0.61-0.74; P < 0.001) and OS (RR, 0.60; 95% CI, 0.50-0.72; P < 0.001). In subgroup analyses, CIA was found to affect DFS (RR, 0.73; 95% CI, 0.61-0.88; P = 0.001) in estrogen receptor (ER)-positive patients; however, similar results were not observed in ER-negative patients (for DFS: RR, 0.97; 95% CI, 0.66-1.41; P = 0.858). Participants with CIA achieved a significantly better prognosis than participants without CIA, irrespective of nodal status, chemotherapy regimen, endocrine therapy, or publication year. CONCLUSIONS This meta-analysis clarifies that CIA contributes to improved prognosis in premenopausal women with ER-positive breast cancer and is at least partially responsible for the benefits of adjuvant chemotherapy in these women, which induce chemical castration.