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According to the results of a study published in Cancer Epidemiology Biomarkers & Prevention, postmenopausal hormone therapy with combined estrogen plus progestin for three years or longer increases the risk of lobular breast cancer.

Postmenopausal hormone therapy with either estrogen alone or estrogen plus progestin effectively manages several common menopausal symptoms. However, large clinical trials conducted as part of the Women’s Health Initiative (WHI) raised concerns about the health risks of these therapies. In 2002, for example, it was reported that combined estrogen plus progestin increases the risk of breast cancer, heart disease, stroke, and blood clots.[1] Women taking estrogen plus progestin had fewer fractures and were less likely to develop colorectal cancer, but these benefits were thought to be outweighed by the risks for most women.

Previous studies have suggested that the link between combined estrogen plus progestin may vary by type of breast cancer, with a greater increase in risk for lobular breast cancer than for ductal breast cancer. Ductal breast cancer is the most common type of breast cancer, accounting for roughly 70% of cases in the United States. Lobular and ductal/lobular breast cancers account for an estimated 16% of cases.

To explore whether the link between postmenopausal hormones and breast cancer varies by type of breast cancer, researchers conducted a study among 524 women with ductal breast cancer, 324 women with lobular breast cancer, 196 women with ductal/lobular breast cancer, and 469 women without breast cancer.[2] All study participants were between the ages of 55 and 74.

The study collected information about use of estrogen alone as well as use of combined estrogen plus progestin. Women who were former or current users of postmenopausal hormone therapy were compared to women who had never used postmenopausal hormones.

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  • Former users of postmenopausal hormones did not have an increased risk of any of the three types of breast cancer.
  • Current users of estrogen alone did not have an increased risk of any of the three types of breast cancer.
  • Current users of combined estrogen plus progestin had a significantly increased risk of lobular and ductal/lobular breast cancer. Current users of estrogen plus progestin were 2.7 times more likely to develop lobular breast cancer and 3.3 times more likely to develop ductal/lobular breast cancer. Risk was only significantly elevated among women had used combined postmenopausal hormones for three years or longer.
  • The link between combined estrogen plus progestin and ductal breast cancer was weaker and only of borderline statistical significance (suggesting that the result could have occurred by chance).

The researchers conclude that current users of combined postmenopausal hormone therapy have an increased risk of lobular breast cancer that becomes apparent after three years of hormone use. A link between combined postmenopausal hormone use and ductal breast cancer-the most common type of breast cancer-was less apparent.


[1]] Rossouw JE, Anderson GL, Prentice RL et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002; 288:321-33

[2] Li CI, Malone KE, Porter PL et al. Relationship between menopausal hormone therapy and risk of ductal, lobular, and ductal-lobular breast carcinomas. Cancer Epidemiology Biomarkers & Prevention. 2008;17:43-50.