Postmenopausal Hormone Therapy and Benign Breast Disease
Abstract & Commentary
Synopsis: Postmenopausal hormone therapy does not increase the risk of invasive breast cancer in women with biopsy-proved benign breast disease.
Source: Dupont WD, et al. Cancer 1999;85:1277-1283.
Dupont and associates from vanderbilt university reported a retrospective cohort study of women who underwent breast biopsies that proved to be benign between 1952-1978. The median duration of follow-up was 20 years. During this period of time, there were 444 cases of invasive breast cancer. Women who took estrogen and who had biopsy proven atypical hyperplasia had an increased risk of breast cancer, relative risk 2.87 (CI = 1.3-6.3), but this did not differ significantly from the relative risk in those who did not take postmenopausal estrogen therapy, relative risk 2.53 (CI = 1.0-6.3). Similarly, the relative risk did not differ in women with complex fibroadenoma, comparing users and nonusers. Women who had proliferative disease without atypia did not have a statistically significant increased risk of breast cancer whether they used estrogen or not. Dupont et al concluded that postmenopausal estrogen therapy does not increase the risk of invasive breast cancer in women with true benign breast disease, and that hormone therapy should be contraindicated in these women.
Comment by Leon Speroff, MD
Approximately 5% of breast cancer patients have a history of benign breast disease. Statistical accuracy requires histological characterization and definition. The most important variable in biopsy specimens is the degree and character of epithelial proliferation, and only 4-10% of benign biopsies have atypical hyperplasia. For these reasons, this publication from Vanderbilt is unique and especially helpful. It is the only report with a substantial number (9494 women) followed after a consecutive series of biopsies and analyzed according to histologic types of benign breast disease. The results indicate that estrogen use does not increase the risk of breast cancer in women with surgically proven benign breast disease, even with atypia.
Thus far, there are insufficient data to evaluate the effect of adding a progestin to postmenopausal estrogen regimens. However, it is increasingly apparent that breast tenderness and discomfort are a reflection of the progestational agent, not estrogen (see the data from the PEPI trial).1 Nevertheless, clinicians repeatedly receive complaints of mastalgia from elderly women beginning estrogen therapy for the first time. Although mastalgia by itself is not a risk factor for breast cancer, its presence often creates apprehension and affects compliance with hormone therapy. For these reasons, I recommend trying alternative progestational agents in younger women who report mastalgia, and beginning treatment in elderly women with lower doses of estrogen, either orally or transdermally. Recent studies have indicated that half the usual doses of oral estrogen can maintain bone. However, long-term data are not yet available (the impact on fracture rate and the number of nonresponders are not known). Therefore, after six months to one year, I recommend an increase to standard doses to maximize the bone, cardiovascular, and central nervous system effects.
Reference
1. Greendale GA, et al. Obstet Gynecol 1998;92:982-988.
All of the following are true except:
a. A woman with atypical hyperplasia on a breast biopsy has an increased risk of developing invasive breast cancer.
b. Postmenopausal estrogen therapy does not influence the risk of breast cancer in women with biopsy-proven benign breast disease.
c. Progestins decrease the risk of breast cancer in women with benign breast disease.
d. Mastalgia with postmenopausal hormone therapy is frequently due to the progestin in a combined estrogen-progestin regimen.
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