Risks of breast and endometrial cancer after estrogen and estrogen-progestin replacement

Objective: We studied the risk of breast and endometrial cancer in a cohort of 11,231 Swedish women prescribed different replacement hormone regimens. Methods: All 10,472 women at risk of developing breast cancer and 8,438 wom en at risk of endometrial cancer were followed up from the time of the ques tionnaire in 1987-88 through 1993, by record-linkages to the National Swedi sh Cancer Registry. Using data from a questionnaire we analyzed the relatio nships between hormone exposures and cancer risk, with non-compliers and us ers of less than 1 year as a reference group. Results: For breast cancer, women reporting use of estrogens combined with progestins had evidence of an increased risk relative to women denying inta ke or taking hormones for less than 1 year; relative risk (RR) = 1.4 (95% c onfidence interval 0.9-2.3) after 1-6 years of intake, and RR=1.7 (95% CI 1 .1-2.6) after more than 6 years. This excess risk seemed confined to recent exposure. We found no association with intake of estrogens alone using non -compliers and short-term takers as the reference group. The risk of invasi ve endometrial cancer was increased four-fold in women using medium-potency estrogens alone for 6 years or longer, RR = 4.2 (95% CI 2.5-8.4). Women on such long-term progestin-combined treatment had a lower, non-significant, excess risk (RR = 1.4; 95% CI 0.6-3.3). Conclusions: We conclude that long-term recent use of estrogen-progestin co mbined replacement therapy may increase the risk of breast cancer. Exposure to estrogen alone substantially elevates the risk of endometrial cancer, a n increase that can be reduced or perhaps avoided by adding progestins.