Abstract

It is unclear whether the phase of the menstrual cycle in which primary surgical treatment occurs influences disease-free survival (DFS) and overall survival (OS) in premenopausal women with breast cancer. We investigated this question in the context of a clinical trial comparing mastectomy alone with mastectomy plus adjuvant oophorectomy and tamoxifen in premenopausal women with operable breast cancer. The date of the first day of the last menstrual period (LMP) was used to estimate the phase of the menstrual cycle when the surgeries were done. Follicular phase was defined as day 1-14 from LMP. Luteal phase was defined as day 15-42 from LMP. DFS and OS statistics were determined and analyzed by Cox proportional hazards ratios and Kaplan-Meier methods. All statistical tests were two-sided. We analyzed results for 565 women who reported an LMP within 42 days before surgery. For women in the mastectomy only arm (n = 289), there were no differences in DFS or OS by menstrual cycle phase. For women in the adjuvant treatment arm (n = 276), those whose surgery occurred during the luteal phase (n = 158) had better DFS (relative risk [RR] = 0.54; 95% confidence interval [CI] = 0.32 to 0.96; P =.02) and OS (RR = 0.53; 95% CI = 0.30 to 0.95; P =.03) than those whose surgery occurred during the follicular phase (n = 118). Moreover, women whose surgery occurred during the luteal phase and who received adjuvant therapy had better 5-year DFS than did women whose surgery occurred during the follicular phase (84%; 95% CI = 78% to 90% versus 67%; 95% CI = 58% to 78%; P =.02); they also had better OS (85%; 95% CI = 78% to 92% versus 75%; 95% CI = 66% to 84%; P =.03). The phase of the menstrual cycle at which surgery was done had no impact on survival for women who received mastectomy only. However, women who received a mastectomy and surgical oophorectomy and tamoxifen during the luteal phase had better outcomes than women who received surgery during the follicular phase.

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