EFFECT OF ESTROGEN REPLACEMENT THERAPY ON THE SPECIFICITY AND SENSITIVITY OF SCREENING MAMMOGRAPHY

Background: Previous studies have demonstrated that mammographic breas t density increases following the initiation of estrogen replacement t herapy (ERT). The effect, if any, that this increase in density has on the specificity (related to false-positive readings) and the sensitiv ity (related to false-negative readings) of screening mammography is u nknown, Purpose: Using a retrospective cohort study design, we assesse d the effects of ERT on the specificity and the sensitivity of screeni ng mammography. Methods: Participants (n = 8779) were postmenopausal w omen, aged 50 years or older, who were enrolled in a health maintenanc e organization located in western Washington state and who entered a b reast cancer screening program between January 1988 and June 1993. Two -view mammography was performed as part of a comprehensive breast canc er screening visit. Menopausal status, as well as demographic and risk -factor information, was recorded via self-administered questionnaires . Hormonal replacement therapy type and use were determined from quest ionnaire data and from an automated review of pharmacy records. Indivi duals diagnosed with breast cancer within 12 months of their first scr eening-program mammograms were identified through use of a regional ca ncer registry. Risk ratios (RRs) plus 95% confidence intervals (CIs) o f false-positive as well as false-negative examinations among current and former ERT users (with never users as the reference group) were ca lculated. Reported P values are two-sided. Results: The specificity of mammographic screening was lower for current users of ERT than for ne ver users or former users. Defining a positive mammographic reading as any non-normal reading (either suspicious for cancer or indeterminate ), the adjusted RR (95% CI) of a false-positive reading for current us ers versus never users was 1.33 (1.15-1.54) (P < .001); for former use rs versus never users, the RR (95% CI) was 1.00 (0.87-1.15). The adjus ted mammographic specificities (95% CIs) for never users, former users , and current users of ERT were 86% (84%-88%), 86% (84%-87%), and 82% (80%-84%), respectively. Defining a positive reading more rigorously ( i.e., as suspicious for cancer only), the adjusted RRs (95% CIs) of fa lse-positive readings for current users and former users (versus never users) were 1.71 (1.37-2.14) (P < .001) and 1.16 (0.93-1.45), respect ively. Sensitivity was also lower in women currently receiving ERT. Th e unadjusted RR (95% CI) of a false-negative reading for current users versus never users was 5.23 (1.09-25.02) (P = .04); for former users versus never users, the RR (95% CI) was 1.06 (0.10-10.87). The unadjus ted mammographic sensitivities (95% CI) for never users, former users, and current users of ERT were 94% (80%-99%), 94% (69%-99%), and 69% ( 38%-91%), respectively. Conclusions and Implications: Current use of E RT is associated with lower specificity and lower sensitivity of scree ning mammography. Lower specificity could increase the cost of breast cancer screening, and lower sensitivity may decrease its effectiveness .