Risk of Breast Cancer by Type of Menopausal Hormone Therapy: a Case-Control Study among Post-Menopausal Women in France

Background: There is extensive epidemiological evidence that menopausal hormone therapy (MHT) increases breast cancer risk, particularly combinations of estrogen and progestagen (EP). We investigated the effects of the specific formulations and types of therapies used by French women. Progestagen constituents, regimen (continuous or sequential treatment by the progestagen), and time interval between onset of menopause and start of MHT were examined. Methods: We conducted a population-based case-control study in France in 1555 menopausal women (739 cases and 816 controls). Detailed information on MHT use was obtained during in-person interviews. Odds ratios and 95% confidence interval adjusted for breast cancer risk factors were calculated. Results: We found that breast cancer risk differed by type of progestagen among current users of EP therapies. No increased risk was apparent among EP therapy users treated with natural micronized progesterone. Among users of EP therapy containing a synthetic progestin, the odds ratio was 1.57 (0.99-2.49) for progesterone-derived and 3.35 (1.07-10.4) for testosterone-derived progestagen. Women with continuous regimen were at greater risk than women treated sequentially, but regimen and type of progestagen could not be investigated independently, as almost all EP combinations containing a testosterone-derivative were administered continuously and vice-versa. Tibolone was also associated with an increased risk of breast cancer. Early users of MHT after onset of menopause were at greater risk than users who delayed treatment. Conclusion: This study confirms differential effects on breast cancer risk of progestagens and regimens specifically used in France. Formulation of EP therapies containing natural progesterone, frequently prescribed in France, was not associated with increased risk of breast cancer but may poorly protect against endometrial cancer.