The Effect of Withdrawal of Combined Hormone Replacement Therapy (HRT) on the Proliferation of Breast Cancers in Postmenopausal Women
R Mathew, C Laronga, G Acs. University of South Florida College of Medicine, Tampa, FL; Moffitt Cancer Center, Tampa, FL
Background: Postmenopausal combined HRT has been shown to be associated with a slightly increased risk of breast carcinoma (BC). Recent registry data showed a decrease in the incidence of BC corresponding in time to the decreased used of HRT following the 2002 publication of the results of the Women's Health Initiative trial. Based on the proliferative effect of estrogen and progesterone on benign mammary epithelial cells, it was hypothesized that the observed drop in BC incidence may be due to decreased proliferation of BC following HRT withdrawal. However, apart from one small study, there is very limited information available regarding the effect of HRT on the proliferation of human BC in clinical material.
Design: We selected 404 invasive BC diagnosed in postmenopausal women with available core needle biopsy (CNB) and subsequent surgical excision for the study. Among these 312 patients never used HRT, while 92 patients were current users of combined HRT at the time of CNB (median duration of use: 10 years). Immunohistochemical assays for Ki67 were performed on 5m thick paraffin sections. Slides were digitized using an Aperio ScanScope XT. The percentage of Ki67 positive tumor cells (proliferation index, PI) was determined in at least 10 separate tumor areas in corresponding CNB and excisions. Mean PI values were compared using the Wilcoxon signed rank test.
Results: All current users stopped HRT after diagnosis of BC on CNB, the median time between CNB and excision was 41 days. We found no significant difference between never and current users with regard to age, tumor size, histologic type, grade, presence of lymphatic invasion and nodal metastasis, and hormone receptor and HER2 status. The number of mitoses per 10 high power fields was significantly higher in excisional compared to CNB material in both current and never users. The PI of BC was significantly higher in never users compared to current users in both CNB and excision. We found no significant difference in PI determined in CNB and subsequent excison either in never or current HRT users.
Conclusions: Our results do not support the hypothesis that withdrawal of HRT results in decreased proliferation of BC contributing to the observed recent drop in BC incidence. These findings are in contrast to prior data obtained in benign mammary epithelial cells and likely reflect important differences in the regulation of cell proliferation in benign and malignant cells.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 22, Tuesday Afternoon