Azam S, et al. - Whether mammographic density (MD) mediates or modifies the link between hormone replacement therapy (HRT) and breast cancer was investigated. MD partially mediated the association between HRT and breast cancer risk. Women with dense breasts exhibited a seemingly stronger link between HRT and breast cancer.

Methods

• MD (mixed/dense or fatty) was evaluated at the first screening after cohort entry for the 4,501 enrollees in the Danish diet, cancer and health cohort (1993–1997) who attended mammographic screening in Copenhagen (1993–2001).
• By questionnaire, HRT use was assessed.
• Using the Danish cancer registry, breast cancer diagnoses until 2012 were obtained.
• Using Cox’s regression, separate analysis of the associations of HRT with MD and with breast cancer was done.
• The proportion (with 95% confidence intervals [CI]) of association between HRT and breast cancer mediated by MD was estimated via mediation analyses.

Results

• At enrollment, mixed/dense breasts were found in 2,444 (54.3%) women, 229 (5.4%) developed breast cancer, and 35.9% were current HRT users.
• Current HRT use was statistically significantly related to having mixed/dense breasts (relative risk and 95% CI 1.24; 1.14–1.35), and higher risk of breast cancer (hazard ratio 1.87; 1.40–2.48), relative to never users.
• MD partially mediated the link between current HRT use and breast cancer risk (percent mediated = 10%; 95% CI 4–22%).
• Compared with fatty (1.37; 0.80–2.35) breasts (p value for interaction = 0.15), women with mixed/dense breasts had a higher current HRT use-related breast cancer risk (1.94; 1.37–3.87).