Impact of Hormone Replacement Therapy on Breast Cancer Risk Varies by Race, Weight, and Breast Density

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The impact of hormone replacement therapy on breast cancer risk varies according to the patient’s to race/ethnicity, body mass index, and breast density. An analysis of 1,642,824 screening mammograms with 9,300 breast cancer cases in postmenopausal women aged 45 years or older found that hormone replacement therapy was more strongly associated with breast cancer in leaner women with dense breasts. 

“Black women, obese women, and women with breast tissue composed largely of fat may benefit from [hormone replacement therapy] use with minimal excess breast cancer risk,” Ningqi Hou, MD, PhD, of the University of Chicago, reported in the Journal of the National Cancer Institute.

Key Findings

Data for the study was from the Breast Cancer Surveillance Consortium, a longitudinal registry of mammography screening in the United States, and “multiple imputation methods were used to accommodate missing data for [hormone replacement therapy] use (14%) and other covariables,” the researchers reported. 

Use of hormone replacement therapy was associated with more than a 20% increased risk in white women (odds ratio [OR] = 1.21; 95% CI = 1.14–1.28), Asian women (OR = 1.58; 95% CI = 1.18–2.11), and Hispanic women (OR = 1.35; 95% CI = 1.09–1.67) but not black women (OR = 0.91; 95% CI = 0.72–1.14; Pinteraction = .04). “In women with low/normal [body mass index] and extremely dense breasts, [hormone replacement therapy] use was associated with the highest breast cancer risk (OR = 1.49; 95% CI = 1.21–1.83), compared with nonusers. In overweight/obese women with less-dense breasts, no excess risk was associated with [hormone replacement therapy] use (adjusted ORs = 0.96–1.03),” the investigators wrote. 

About 55% of the study population had an increased risk of breast cancer due to hormone replacement therapy use, the researchers found. For the 20% of the study population that was overweight and obese with less-dense breasts, “the association between [hormone replacement therapy] use and breast cancer risk was essentially absent (adjusted ORs = 0.96–1.03). The remaining 25% of the study population had an elevated risk of breast cancer due to [hormone replacement therapy] use, but statistical significance was not reached.”

The study did not include information on the type of hormone replacement therapy used and the duration of use. The authors concluded that if their findings are confirmed in other studies with more detailed information about these and other risk factors, hormone replacement therapy use “may be reasonable for some women.” 

Cautious Interpretation

In an accompanying editorial, Mary Beth Terry, PhD, and Parisa Tehrnifar, DrPH, of Columbia University, Mailman School of Public Health, in New York, commented, “Results from studies such as that by Hou et al that lack details of [hormone replacement therapy] use, including type and duration, should be interpreted cautiously before drawing conclusions about risk stratification by race/ethnicity…. Beyond single stratifications by [body mass index] and race, however, the Hou et al study advances the literature by examining breast density in combination with these factors. Even this large study, though, is underpowered for examining race/ethnicity interactions with both [body mass index] and breast density,” the editorialists wrote.

“Ultimately, efforts that improve risk stratification, whether made through improved risk models or through measuring valid intermediate biomarkers such as breast density, will inform appropriate use of not only [hormone replacement therapy], but also other medications including chemopreventive drugs,” they added. ■

Hou N, et al: J Natl Cancer Inst 105:1365–1372, 2013.
Terry MB, Tehranifar P: J Natl Cancer Inst 105:1342–1343, 2013.