Association Between Changes in Hormone Replacement Therapy and Breast Density—Reply

In Reply: Our study focused on the relatively narrow question of the relationship between HRT and breast density. As Dr Fiorica points out, we cannot exclude the possibility that other unmeasured factors, such as changes in diet, affected changes in breast density.

Fiorica's concerns about breast cancer risk and detection are not directly addressed by our study. Recent studies have shown that increased density is associated with missed cancers¹ and that HRT itself is associated with missed cancers.² The study by Thurfjell et al³ cited by Fiorica may provide biased estimates of the effect of HRT on mammographic screening accuracy because women with high breast density were offered more sensitive 2-view mammography and others were offered 1-view mammography. We concluded that decreases in the sensitivity and specificity of screening mammography associated with HRT results from an increase in breast density. However, before recommending HRT cessation prior to mammography, good estimates are needed of the time from HRT cessation to decreases in density, and the risk associated with cessation and reinitiation of HRT need to be better defined. Fiorica also points out that breast cancer risk increases with age. Thus, our finding that HRT initiation was more strongly associated with increased density among older women is particularly troubling.