A prospective prognostic study of the hormonal milieu at the time of surgery in premenopausal breast carcinoma. Menstrual cycle and surgical treatment of breast cancer: findings from the NCCTG N9431 study.
Despite numerous studies, the influence of timing at surgery in relation to the menstrual cycle on the prognosis of breast carcinoma is still controversial. Most studies are retrospective, and the reliability of the menstrual history data is limited by the lack of hormonal assessment at the time of surgery. The authors prospectively studied the influence of the menstrual cycle phase as determined by circulating hormones at the time of surgery on the outcome of breast carcinoma.
                A population of 360 premenopausal women with nonmetastatic breast carcinoma operated on from 1992 to 1995 was analyzed. Serum estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were assayed the day of surgery to define the menstrual cycle phase (follicular, n = 186; ovulatory, n = 24; luteal, n = 150). The mean follow-up was 48 months.
                There were no relations between the menstrual phase at surgery and tumor size, cathepsin D level, Scarff-Bloom-Richardson grade, Pg receptor (PgR), and the number of positive lymph nodes. The mean estrogen receptor level was higher during the follicular phase than in the ovulatory and luteal phases (P < 0.02). Univariate analysis of recurrence free survival (RFS) and overall survival (OS) showed no relations with the menstrual phase or the level of estradiol and progesterone at the time of surgery. High LH or FSH levels (above the medians) were associated with shorter RFS (P = 0.02 and P = 0.04, respectively) or OS (P < or = 0.01 and P = 0.01, respectively). In multivariate analysis, lymph node status, PgR status and LH level were the most significant parameters for predicting OS. There appeared to be no survival differences between menstrual cycle groups after stratification by lymph node status.
                This prospective study showed a lack of prognostic value of timing at surgery in relation to the menstrual period or to estrogen and progesterone levels in premenopausal breast carcinoma. Conversely, high gonadotropin levels could predict OS independently of other prognostic factors.
                Copyright 2001 American Cancer Society. For nearly two decades, multiple retrospective reports, small prospective studies, and meta-analyses have arrived at conflicting results regarding the value of timing surgical intervention for breast cancer on the basis of menstrual cycle phase. We present the results of a multi-cooperative group, prospective, observational trial of menstrual cycle phase and outcome after breast cancer surgery, led by the North Central Cancer Treatment Group (NCCTG) in collaboration with the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the International Breast Cancer Study Group (IBCSG).
                Premenopausal women age 18 to 55 years, who were interviewed for menstrual history and who were surgically treated for stages I to II breast cancer, had serum drawn within 1 day of surgery for estradiol, progesterone, and luteinizing hormone levels. Menstrual history and hormone levels were used to determine menstrual phase: luteal, follicular, and other. Disease-free survival (DFS) and overall survival (OS) rates were determined by Kaplan-Meier method and were compared by using the log-rank test and Cox proportional hazard modeling.
                Of 1,118 women initially enrolled, 834 women comprised the study cohort: 230 (28%) in luteal phase; 363 (44%) in follicular phase; and 241 grouped as other. During a median follow-up of 6.6 years, and in analysis that accounted for nodal disease, estrogen receptor status, adjuvant radiation therapy or chemotherapy, neither DFS nor OS differed with respect to menstrual phase. The 5-year DFS rates were 82.7%, 82.1%, and 79.2% for follicular, luteal, or other phases, respectively. Corresponding OS survival rates were 91.9%, 92.2%, and 91.8%, respectively.
                When menstrual cycle phases were strictly defined, neither DFS nor OS differed between women who underwent surgery during the follicular phase versus the luteal phase. Nearly 30% of the patients did not meet criteria for either follicular- or luteal-phase categories.
In the absence of RCTs, this review provides evidence from large prospective observational studies that timing of surgery does not show a significant effect on survival.