A prospective observational study that began following more than 50,000 California teachers in 1995 has confirmed reports linking hormone replacement therapy to breast cancer but suggests obesity may offer some protection.
Data from 56,867 women enrolled in the California Teachers Study indicate that women who used estrogen therapy for at least 15 years had a 19% increase in the risk of breast cancer, and women who used combined estrogen-progestin therapy had an 83% increase in breast cancer risk.
The increase in risk was confined to tumors that were positive for both estrogen and progesterone receptors, wrote Tanmei Saxena, an M.D./Ph.D. student at the University of Southern California, Los Angeles, and her coauthors. It was also more pronounced in women with low body mass index (BMI).
“These findings, taken in context of the larger literature on this topic, continue to underscore the need to personalize risk-benefit discussions for women contemplating the use of [hormone therapy],” they wrote (Cancer Epidemiol. Biomarkers Prev. 2010;19:OF1-13).
The California Teachers Study is a prospective cohort study of 133,479 women. For this study, the investigators excluded women who were not California residents, who had a previous or unknown history of breast cancer, who were older than 80 years at baseline, who were premenopausal or of unknown menopausal status, or who had an unknown history of hormone therapy.
Of the remaining 56,867 perimenopausal and postmenopausal teachers, 2,857 (5%) were diagnosed with pathologically confirmed invasive breast cancer. Average age at diagnosis was 67.1 years.
In a multivariate analysis, the investigators adjusted for race/ethnicity, first-degree family history of breast cancer, BMI, smoking history, alcohol consumption during the year prior to baseline, mammographic screening over the prior 2 years, parity and age at first full-term pregnancy, age at menarche, age at menopause, and history of breast biopsy.
Compared with women who never used any hormone therapy, those who did had a statistically significant 40% increase in the risk of breast cancer. The increase in risk was 19% for women who reported at least 15 years of estrogen-alone therapy, and 83% in women who reported at least 15 years of combined estrogen-progestin therapy.
Current use of hormonal therapy was associated with higher risk than past use. The greatest increase in risk—69%—was among women who were using estrogen-progestin therapy currently and had never used any other formulation. The investigators noted that duration of use tended to be shorter among former users.
The longer the women used hormone therapy, the greater the risk. The increase associated with duration of use was statistically significant for all forms of hormone therapy. For example, women using estrogen-progestin therapy for less than 2 years at baseline had a 12% increase in the risk of breast cancer compared with women who never used hormone therapy.
BMI seemed to modify the risk associated with hormonal therapy, the investigators reported. Among women with a BMI of 25 or less, the relative risk of breast cancer was 2.1 in current long-term users of estrogen and progestin, compared with women who had never used hormone therapy. In women with a BMI of 25-30, the relative risk was 1.9 in current long-term users of estrogen and progestin. However, the effect was not statistically significant in women with a BMI higher than 30.
The National Cancer Institute and the California Breast Cancer Research Fund sponsored the study. A coauthor disclosed serving as an expert witness for plaintiffs pursuing Prempro litigation.