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ESTROGEN REPLACEMENT THERAPY: RELATIVE RISK OF BREAST CANCER

Executive Summary

ESTROGEN REPLACEMENT THERAPY: RELATIVE RISK OF BREAST CANCER increased 10% in 23,244 women who were taking estrogens prescribed for symptoms of menopause, a study published in the Aug. 3 edition of the New England Journal of Medicine concludes. "There was a tendency for this risk to increase with increasing duration of treatment, to an excess risk of 70% in women with more than nine years of use," Leif Bergkvist, MD/PhD, et al., reported. The study cohort was developed from Swedish women aged 35 or older, who had estrogen prescriptions filled in the Uppsala region, an area of about 1.3 mil. inhabitants. The incidence of breast cancer was determined by linking each woman's national registration number with newly diagnosed cases reported to the Swedish Cancer Registry. Of the 23,244 women in the study cohort, 253 developed breast cancer during a mean follow-up period of 5.7 years. The median age of women in the cohort was 53.7 years. Researchers were also able to evaluate breast cancer risk according to the type of estrogen used and the presence of progestin. The analysis of estradiol use showed higher estimates of risk than of total estrogens, and approximately a doubling of the relative risk following six years of treatment. Bergkvist, et al., found no association between weaker estrogens, primarily estriols, and breast cancer, nor did they find evidence of an increased risk of breast cancer after the use of conjugated estrogens. However, "the discrepancy between our negative findings and the American results with conjugated estrogens could be due to a lack of power in our data, since conjugated estrogens were involved in only approximately 20% of the treatment periods, and few of these periods exceeded five years," the researchers explained. "There was also a difference in the doses used; in the U.S. studies, a conjugated-estrogen dose of 1.25 mg or more was the most common, whereas in our cohort most women used only 0.625 mg." The study also found that the addition of progestin offered no protection against the development of breast cancer. "This observation raises concern about the long-term treatment with a combination of estrogens and progestins that has been proposed for widespread use prophylaxis against osteoporosis in menopausal women," the article states. "Estrogen in combination with progesterone may actually increase the risk of breast cancer over that associated with exposure to estrogen alone." An editorial appearing in the same issue of the New England Journal of Medicine calls the fourfold risk increase after more than four years' use of estrogen plus a progestin "the most provocative finding" of the Swedish study. Noting that the estrogen/progestin combination has been most widely used in the U.S. since the 1980s, Elizabeth Barrett-Connor, MD, University of California/San Diego, remarked: "Now a possibly increased risk of breast cancer in women receiving postmenopausal hormone replacement must be considered in the risk-benefit equation of such treatment." She noted that it has been expressed that adding a progestin may negate the suspected benefit of estrogen in cardiovascular disease. "In my opinion, the data are not conclusive enough to warrant any immediate change in the way we approach hormone replacement, but they do show the need for additional research," Barrett-Connor concluded. "Biologic and epidemiologic studies are needed to define the cause of breast cancer and to determine the safest form of estrogen replacement."
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