Hormone replacement therapy, percent mammographic density, and sensitivity of mammography.

Objective: We examine to what extent the lower mammographic sensitivity found in hormone replacement therapy (HRT) users can be explained by any association of HRT use with higher mammographic density and more difficult to detect cancers.

Methods: We used logistic regression to estimate the odds of a false-negative screen (a breast cancer diagnosed in the 24 months after a negative screening examination) for HRT users and to estimate, and adjust for, mammographic density (measured on a continuous scale, blinded, using a reliable, computer-assisted method), tumor characteristics (size, grade, and morphology), and potential confounders (age, symptom status, family history, and prior screening) among women ages > or =55 years who attended BreastScreen Victoria for first round screening mammography in 1994 and 1995 (1,086 breast cancers) and for subsequent round screening (471 breast cancers) in 1995 and 1996.

Results: After adjusting for confounders, HRT users were more likely to have a false-negative screen [first round: odds ratio (OR), 1.99; 95% confidence interval (95% CI), 1.4-2.9; subsequent round: OR, 2.29; 95% CI, 1.4-3.8]. This effect was modestly attenuated by adjusting for mammographic density (first round: OR, 1.54; 95% CI, 1.0-2.3; subsequent round: OR, 1.97; 95% CI, 1.2-3.3). Adjusting for tumor characteristics resulted in a modest increase in the odds of a false negative at first round but had no effect at subsequent round.

Conclusions: Mammographic density only partly explains the effect of HRT on sensitivity. Further research needs to clarify whether hyperemic breast tissue changes affect cancer detectability in HRT users as well as the possibility that the quality of mammography may be poor in some HRT users.