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

We examined the extent to which the lower mammographic sensitivity found in hormone replacement therapy (HRT) users could be explained by any association of HRT use with higher density and more difficult to detect cancers (e.g. lobular cancers). Eligible women included women aged 55 years and older who attended BreastScreen Victoria for first-round screening mammography in 1994 and 1995 (1086 breast cancers) and for subsequent-round screening (471 breast cancers) in 1995 and 1996. Percent density was measured on a continuous scale, blinded, using a reliable, computer-assisted method.

True positive cancers were invasive breast cancers diagnosed at screening and false negative cancers were cancer diagnosed within 24 months of a negative screening examination. After adjusting for age, symptom status, family history, past history of mammography (at first round) and time since screen (at subsequent round), HRT users had higher risk of having a false negative (first round: odds ratio [OR], 1.99; 95% confidence interval [CI], 1.4–2.9 and subsequent round: OR, 2.29; 95% CI, 1.4–3.8). This effect was attentuated by adjusting for mammographic density (first round: OR, 1.54; 95% CI, 1.0–2.3 and subsequent round: OR, 1.97; 95% CI, 1.2–3.3), indicating the density only partly explains the effect of HRT on sensitivity.