Abstract
Cyclic oral contraceptive (OC) use has been associated with increased risk of breast cancer, particularly in African American women, current OC users, and women who begin use early in life. In contrast, the effect of continuous (extended) OC on breast cancer risk is unknown. The purpose of this study was to test the hypothesis that continuous and cyclic OC differ in their effects on mammary gland structure and susceptibility to tumor growth. Starting at day 50 of age, BALB/C mice were fed liquid diets +/- human equivalent doses of ethinyl estradiol and levonorgestrel. After 28 days, 10 mice per group were sacrificed and mammary glands dissected for whole mount and histologic analysis. An additional 20 mice per group were injected orthotopically with 105 syngeneic TM2H mammary epithelial tumor cells, and tracked for tumor latency, growth and tumor burden. The extended OC group showed 65% increase in mammary gland epithelial density compared to control; however, this increased epithelial density was associated with an increased alveolar branching and a decrease in carcinogen-sensitive terminal end buds. These results suggest that short term exposure to continuous OC can induce a more differentiated state in nonparous mouse mammary glands. In mice transplanted with tumor cells, the continuous OC group showed significantly increased tumor latency and decreased tumor burden, compared to controls. These results demonstrate that continuous OC administration, despite the higher levels of hormone exposure, can render mouse mammary gland less susceptible to the growth of transplanted tumor cells.
