Postmenopausal women who take combined estrogen/progestin hormone-replacement therapy for three years or more face a fourfold increased risk of developing various forms of lobular breast cancer.
“Previous research indicated that five or more years of combined hormone-therapy use was necessary to increase overall breast-cancer risk,” said Dr. Christopher Li, the lead author of the report, published in the January issue of Cancer Epidemiology, Biomarkers and Prevention. “Our study, the first specifically designed to evaluate the relationship between combined HRT and lobular breast cancers, suggests that a significantly shorter length of exposure to such hormones may confer an increased risk.”
The study, which confirms previous reports of the association between combined hormone-therapy use and increased risk of lobular breast cancers, is the largest study of combined HRT and lobular-cancer risk in the United States. It is also the first such study to take into account the recency and duration of hormone use and the first to include a centralized pathological review of tumor specimens to confirm their histological type: ductal, lobular or mixed ductal-lobular.
Lobular cancer involves the lobules, or chambers, in the breast that contain milk-producing glands. While lobular carcinoma accounts for only about 15 percent of all invasive breast cancers, it is hormonally sensitive and therefore more treatable than the more common ductal variety, which arises in the ducts that carry milk from the lobules to the nipple. However, lobular breast tumors also present a clinical challenge because they are more difficult to detect both by clinical examination and by mammography than ductal cancers, which account for about 70 percent of invasive breast cancers in the United States.
In a study of more than 1,500 postmenopausal, western Washington women, researchers found that current users of combined HRT had a 2.7-fold and 3.3-fold elevated risk of lobular and ductal-lobular cancer, respectively, regardless of tumor stage, size or number of lymph nodes involved. Only women who used combined HRT for three or more years faced an increased risk of lobular cancer. Among mixed ductal-lobular cases, hormone therapy increased the risk of tumors that were predominantly lobular but not tumors that had predominantly ductal characteristics.
The incidence of invasive lobular and ductal-lobular breast cancers has risen rapidly in the United States, increasing 52 percent and 96 percent, respectively, between 1987 and 1999, whereas rates of ductal cancer have increased only 3 percent during this time.
“Our research suggests that the use of postmenopausal hormone-replacement therapy, specifically the use of combined estrogen-plus-progestin preparations, may be contributing to this increase,” said Li, of the Public Health Sciences Division.
The National Cancer Institute funded this research, which also involved researchers from the Human Biology Division.