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Breast‐cancer risk following long‐term oestrogen‐ and oestrogen‐progestin‐replacement therapy

While use of hormone‐replacement therapy (HRT) effectively alleviates menopausal symptoms and prevents osteoporosis and possibly cardiovascular disease, there is concern of a detrimental impact on breast‐cancer risk. There is a particular lack of data regarding the effect of long‐term use of oestrogen‐progestin combinations on breast‐cancer risk. We conducted a large epidemiological study in Sweden, where combined oestrogen‐progestin treatment has been predominant, to examine the influence of different regimens of menopausal hormone therapy on breast‐cancer risk. In this population‐based case‐control study, 3,345 women aged 50 to 74 years with invasive breast cancer (84% of all eligible) and 3,454 controls of similar age (82% of all selected) were included. Mailed questionnaires and telephone interviews were used to collect detailed information on use of hormone replacement and on potential confounding factors. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through multiple logistic regression. There was a trend of increasing breast‐cancer risk with duration of oestrogen/oestrogen‐progestin use (OR for women treated at least 10 years, 2.43; 95% CI, 1.79–3.30, as compared to never‐users), with statistically significant estimates only for women with BMI < 27 kg/m2. Excess risks were observed to current use and use that ceased more than 10 years ago (OR for women treated at least 5 years, OR was 2.68, 95% CI, 2.09–3.42, and OR 2.57, 95% CI, 1.28–5.15, as compared with never‐users, respectively). A positive association which was noted for use of oestrogen combined with testosterone‐derived progestins appeared especially pronounced with continuously combined regimens. Long‐term use of replacement oestrogens with or without progestins may substantially increase the incidence of post‐menopausal breast cancer, particularly among non‐obese women. Int. J. Cancer 81:339–344, 1999. © 1999 Wiley‐Liss, Inc.