Menopausal Hormone Therapy & Breast Cancer

News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd

Feb. 21, 2006 – Menopausal hormonal therapy is associated with 3 types of breast cancer, according to the results of a population- based case-control study reported in the February issue of Breast Cancer Research.

“Use of menopausal hormone therapy has been shown to increase the risk of breast cancer, and data indicate that combined medium potency estrogen-progestin therapy (mainly estradiol or conjugated estrogens combined with progestin) is associated with a higher risk for breast cancer than medium potency estrogen alone therapy,” write Lena U. Rosenberg, MD, from Karolinska Institute in Stockholm, Sweden, and colleagues. “Studies from the United States have rather consistently found medium potency estrogen-progestin therapy to be more strongly associated with lobular than with ductal breast cancer risk. It is not clear, however, whether use of menopausal hormone therapy also increases the risk of ductal breast cancer, or whether medium potency estrogen alone therapy has differential impacts on lobular and ductal breast cancer risk.”

In this population-based study of women in Sweden aged 50 to 74 years, cases were diagnosed as having invasive ductal (n = 1888), lobular (n = 308), or tubular (n = 93) breast cancer in 1993 to 1995. These cases were compared with 3065 age-frequency matched controls randomly selected from the population.

Risks of both ductal and lobular cancer were increased in women who had used medium-potency estrogen alone. Although medium-potency estrogen-progestin was associated with increased risks for all subtypes, the estimates for lobular and tubular cancer were higher than for ductal cancer. With at least 5 years use of medium-potency estrogen-progestin therapy, odds ratios (ORs) were 5.6 (95% confidence interval [CI], 3.2 – 9.7) for lobular cancer, 6.5 (95% CI, 2.8 – 14.9) for tubular cancer, and 2.3 (95% CI, 1.6 – 3.3) for ductal cancer.

Low-potency oral estrogen (mainly estriol) appeared to be associated with an increased risk for lobular cancer, particularly with short- term use. Reproductive and anthropometric factors, smoking, and past use of oral contraceptives had similar associations with the 3 breast cancer subtypes, but recent alcohol consumption of more than 10 g/day was associated with increased risk only for tubular cancer (OR, 3.1; 95% CI, 1.4 – 6.8).

Study limitations include small number of cases for lobular and tubular cancer; exposure information self-reported and collected retrospectively; retrospective design causing potential recall bias; and histologic classifications by several pathologists at different laboratories.

“Menopausal hormone therapy was associated with increased risks for breast cancer of both ductal and lobular subtype, and medium potency estrogen-progestin therapy was more strongly associated with lobular compared with ductal cancer,” the authors write. “We also found medium potency estrogen-progestin therapy and alcohol to be strongly associated with tubular cancer. With some exceptions, most other risk factors seemed to be similarly associated with the three subtypes of breast cancer.”

The National Institutes of Health and the Swedish Cancer Foundation supported this study. The authors have disclosed no relevant financial relationships.

Breast Canc Res. 2006;8:R11

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