Longer duration of hormone therapy use associated with invasive breast cancer risk

Saxena T. Cancer Epidem Bio Prev. 2010;19:OF1-13.

Women who used estrogen therapy for more than 15 years had a 19% greater risk for developing invasive breast cancer compared with women who had never used hormone therapy, a new study found.

The increased risk was also reported in women who used estrogen-progestin therapy for at least 15 years, who had an 83% greater risk for breast cancer. Breast cancer risk was highest among women who reported continuous use of combination estrogen-progestin therapy, according to the researchers.

“The benefits of HT for relief of postmenopausal symptoms among women are clear, but the risks are more complicated than we had previously thought,” Tanmai Saxena, MD, PhD student at Keck School of Medicine at the University of Southern California, said in a press release.

Saxena and researchers for the California Teachers Study studied the association between HT use and breast cancer risk in a prospective cohort of women who were current, recent or retired public school teachers and administrators participating in the California State Teachers Retirement System.

The study included 2,857 women with invasive breast cancer (mean age, 67.1 years). Mean follow-up was 9.8 years.

Characteristics of women who reported any HT use vs. never-users included:

Younger age.
White.
No family history of breast cancer.
Parous.
Younger age at menarche.
Previous/current smoking or alcohol consumption.
Screening mammogram within 2 years before study entry.
Younger age at menopause.
History of breast biopsy.
Lower BMI at baseline.

According to the results, the duration of estrogen-progestin therapy and estrogen therapy use among women with a BMI less than 29.9 also increased the risk for breast cancer. Conversely, breast cancer risk was decreased among women with BMI of 30 or greater. The increased risk associated with HT was limited to tumors that were positive for both estrogen and progesterone receptors and those that were HER2-positive tumors; risk was slightly decreased for HER2-negative tumors.

“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 HT,” the researchers concluded.

The conclusions are not surprising. Estrogen alone has been shown not to cause increased breast cancer risk over up to 7 years of use, based upon results of the Women's Health Initiative. These are very reassuring data for women, as most will not require hormones for such a long duration of time. However, for women with prolonged symptoms or an indication for ongoing use of estrogen alone, this study indicates that if you use it long enough after menopause, estrogen may increase breast cancer risk. The risk is substantially lower than it is for estrogen plus progestin and is, overall, small. The findings highlight the need for individualization of therapy and annual assessments of risks and benefits for women taking hormones.

– Nanette Santoro, MD

Professor and E. Stewart Chair of Obstetrics and Gynecology,
University of Colorado at Denver School of Medicine

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