Does the risk of breast cancer vary with different combinations of hormone replacement therapy?

August 22, 2010

Study Design:  Prospective observational study

Study Eligibility: Healthy perimenopausal and postmenopausal women who were current, recent, or retired public school teachers and administrators participating in the California State Teachers Retirement System

Enrollment: 56,867

Research Question: What is the effect of using different hormone therapy combinations: estrogen therapy (ET) alone versus estrogen-progestin therapy (EPT) on breast cancer risk?

Previous results, from the Women's Health Initiative, have shown that hormone replacement therapy with estrogen plus progestin is associated with an increased risk of breast cancer.

In the California's Teachers Study, investigators wanted to see if the risk of breast cancer was different with different hormone therapy (HT) combinations, and if the risk varied by cancer subtype.  The study evaluated estrogen therapy (ET) alone versus estrogen-progestin therapy (EPT) on breast cancer risk in healthy perimenopausal and postmenopausal women.

In 1995, study participants were mailed a baseline questionnaire detailing information on personal medical history, family history of breast cancer, reproductive factors, HT use, and lifestyle factors. Incident invasive breast cancer diagnoses were identified through the California Cancer Registry (CCR). The primary endpoint was overall risk of breast cancer associated with (ET) and (EPT) regimens. Secondary endpoints included; risk associated with duration of HT use, effect modification of HT use on Body Mass Index (BMI), and HT use and specific breast cancer subtypes.

Incidence of breast cancer was recorded through December 31, 2006. At the time, women who had ever used HT were at a 40% elevated risk of developing breast cancer compared with women with no history of HT use. Women who reported 15 or more years of estrogen therapy (ET) use had a 19% greater risk of breast cancer compared with women who had never used HT. Whereas women using EPT for 15 or more years had an 83% greater risk than women who did not use HT.  Risks associated with EPT and ET use were increased with duration of HT use for women with a body mass index (BMI) of <29.9 kg/m2 but not for women with BMI of ≥30 kg/m2. Greater risks associated with EPT and ET use and breast cancer incidence were limited to tumors that were ER positive, PR positive and HER2+ positive.  There was slightly less risk of developing HER2− negative tumors in those with a history of EPT or ET use. 

Some of the limitations of the study included the self-reported measure of HT. There was also a limited number of women with complete data for some subtype analyses.

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