The benefits of estrogen replacement therapy (ERT) in women have been well established. Some concern remains that estrogen may increase the risk of breast cancer, and it has been shown that unopposed estrogen use may lead to endometrial carcinoma. Whether ERT increases the risk of breast cancer in women who have had previous biopsies that revealed benign breast tissue has been unknown. On the contrary, before data were released in 1985, it was believed that these women had a two- to threefold elevation in breast cancer risk. Using data collected from the Nashville Breast Cohort, Dupont and colleagues assessed the risk of breast cancer in women who had histologically defined benign breast biopsies and had received ERT.

The women in the study included those who had undergone a breast biopsy that revealed benign breast parenchyma or fibroadenoma. Any woman who later was found to have breast cancer or carcinoma in situ treated by mastectomy was excluded from analysis. The use of ERT was defined as the use of non-contraceptive estrogens for at least one month at or after menopause or after 40 years of age. The age of menopause was considered to be the age at which a woman's menses had completely stopped, assuming this to be the case if a woman was given ERT after age 40. The actual age of menopause could not be determined in 20 percent of the women. Follow-up was terminated if the patients developed breast cancer (4.7 percent), underwent bilateral mastectomy for reasons other than breast cancer (3.8 percent), were lost to follow-up (2.9 percent), died from other causes (10.6 percent) or completed the study questionnaire (78.1 percent). The histologic slides of all patients, those with and without breast cancer, were reviewed by pathologists who had no knowledge of patient outcomes.

A total of 9,494 patients were in the original cohort and, after exclusion criteria were applied, 5,813 women were included in the analysis. More than 96 percent of the study subjects were white. The median follow-up was 20 years, which accounted for 190,845 woman-years of follow-up.

It was found that ERT users were younger at menopause (46 compared with 48 years of age), less likely to have had a natural menopause and more likely to have had children than the women who did not use ERT. There was a total of 444 confirmed cases of breast cancer in the entire cohort of women. However, there was no difference in the relative risk of invasive breast cancer in patients with proliferative breast disease identified on biopsy regardless of whether they received ERT. In women with an original diagnosis of complex fibroadenoma, the relative risk was 1.57 if they received ERT and 1.46 if they did not. In women who had neither a diagnosis of atypical hyperplasia nor fibroadenoma, these risks were 1.0 for the women in the ERT group and 1.27 for those who did not receive hormone therapy. The differences were not statistically significant. In addition, it was also found that a family history of breast cancer (a mother, sister or daughter) did not affect the risk in users versus nonusers of ERT.

The authors conclude that there is no increased risk of breast cancer associated with use of ERT in women who have undergone previous biopsies revealing benign breast tissue. Consequently, ERT is not contraindicated in this subgroup of patients once they become menopausal.