Safety of menopausal hormone therapy in breast cancer survivors older than fifty at diagnosis: A systematic review and meta-analysis.

Due to the higher incidence of hormone responsive tumours in women >50, the safety of hormone replacement therapy (HRT) in older breast cancer survivors may differ from younger age groups. The primary outcome in this review was the risk of tumour recurrence and secondary outcome the relationship with breast cancer-related mortality. Medline, CINAHL, Cochrane, Google Scholar and EMBASE databases were searched through August 2018 for studies reporting exposure to HRT in survivors ≥50 at primary diagnosis. Random effects models were used to estimate the combined relative risk (RR) of tumour recurrence and breast cancer-related mortality using the Mantel-Haenszel method and the quality of evidence determined for the primary outcome. Overall, nine studies (four cohort, one case-control, four RCTs; n = 16,002) were included. Very low quality evidence from observational studies demonstrated no adverse effect on tumour recurrence with HRT use (RR 0.80, 95% CI 0.53 to 1.19; I2 = 66%; n = 11,984), while moderate quality evidence from RCTS demonstrated an adverse effect (RR 1.46, 95% CI 1.20 to 1.77; I2 = 17%; n = 4108). Similarly, observational studies demonstrated no adverse effect on breast cancer-related mortality (RR 0.32, 95% CI 0.21 to 1.49; I2 = 0%, n = 2182), while RCTs demonstrated a non-significant higher risk (RR 1.07, 95% CI 0.77 to 1.49; I2 = 0%; n = 3918). Ultimately, despite conflicting findings, evidence of sufficient quality suggests that HRT may increase the risk of tumour recurrence in older survivors. However, adverse effect on mortality is unlikely. Caution with HRT use in survivors is further advised.