Abstract PD11-07: Use of low-dose tamoxifen to increase screening sensitivity in mammography of premenopausal women
Authors: Eriksson Mikael , Czene Kamila , Hall Per 
Published: February 2021

Abstract
Background. High mammographic density decreases sensitivity of both 2D and 3D mammography. Tamoxifen reduces mammographic density thereby potentially increasing screening sensitivity. We tested if low-dose tamoxifen could be used to increase sensitivity of mammography in premenopausal women.
Methods. Mammography screening sensitivity was calculated using the Swedish KARMA prospective screening cohort including 28,282 premenopausal women. Two models were fitted to estimate screening sensitivity and tumor size based on density level at baseline. BI-RADS dependent sensitivity was estimated in each of the four categories (A, B, C, D). The 2.5 mg tamoxifen arm of the KARISMA tamoxifen trial was used to define the change of mammographic density after exposure to low-dose tamoxifen. The models predicted screening sensitivity and tumor size in the KARMA cohort assuming that all women were exposed to 2.5 mg of tamoxifen. Reduction in interval and advanced cancers were estimated in women with mammographic density decrease of 10%, 20%, 30% and 50%. Mammographic density was measured as percent density and a computerized BI-RADS score was estimated using the STRATUS tool.
Results. During 8 years of follow-up, 287 (56%) screening detected and 230 (44%) interval cancers were diagnosed in the KARMA cohort. The screening sensitivities, before exposure to tamoxifen, were 77%, 69%, 53%, 46% for BI-RADS categories A, B, C and D, respectively. The mean density decrease after exposure to 2.5 mg of tamoxifen was 17.4% and the BI-RADS category dependent change in sensitivity was 0% (p=0.95), 2% (p=0.01), 4% (p&lt;0.001), and 5% (p&lt;0.001), respectively. A density decrease of ≥20% would reduce the number of interval cancers with 24% (p&lt;0.01) and the probability of identifying &gt;20 mm tumors with 4% (p&lt;0.01).
Conclusion. Low-dose tamoxifen has the potential to increase the sensitivity of a screening mammogram and thereby reduce the proportion of interval and advanced cancers.
Table. Number of interval cancers per 100,000 age standardized screened women, change in number of interval cancers after tamoxifen exposure, by percentage mammographic density decrease. Density response is presented using density responder cut-offs and is stratified by computer-generated BI-RADS categories A+B, C, D. The normal (unexposed) group is included as the reference.Number of interval cancers (N)NormalDensity responder cut-off (%)group≥10≥20≥30≥50BI-RADS A+B15510710210088BI-RADS C382356339299253BI-RADS D276197180160129BI-RADS A to D combined813660621559470Difference compared to normal group, N (%)BI-RADS A+Bref.-48 (-31)-53 (-34)-55 (-35)-67 (-43)BI-RADS Cref.-26 (-7)-43 (-11)-83 (-22)-129 (-34)BI-RADS Dref.-79 (-29)-96 (-35)-116 (-42)-147 (-53)BI-RADS A to D combinedref.-153 (-19)-192 (-24)-254 (-31)-343 (-42)Number of interval cancers were significantly reduced in each density decrease group, p&lt;0.01.
Citation Format: Mikael Eriksson, Kamila Czene, Per Hall. Use of low-dose tamoxifen to increase screening sensitivity in mammography of premenopausal women [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD11-07.