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Use of Low-Dose Tamoxifen to Increase Mammographic Screening Sensitivity in Premenopausal Women

Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden
Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Department of Oncology, Södersjukhuset University Hospital, Karolinska Institutet, 118 83 Stockholm, Sweden
Author to whom correspondence should be addressed.
Cancers 2021, 13(2), 302;
Received: 22 December 2020 / Revised: 10 January 2021 / Accepted: 12 January 2021 / Published: 15 January 2021
(This article belongs to the Special Issue Risk Assessment for Breast Cancer)
This is the first study to model the effects of tamoxifen on mammographic density and screening sensitivity. Low-dose tamoxifen reduces mammographic density in premenopausal women by, on average, 20%. Potential outcome analyses suggest that a reduction in mammographic density improves mammography screening sensitivity, reduces the proportion of large tumors, and subsequent interval cancers.
Increased breast density decreases mammographic sensitivity due to masking of cancers by dense tissue. Tamoxifen exposure reduces mammographic density and, therefore, should improve screening sensitivity. We modelled how low-dose tamoxifen exposure could be used to increase mammographic sensitivity. Mammographic sensitivity was calculated using the KARMA prospective screening cohort. Two models were fitted to estimate screening sensitivity and detected tumor size based on baseline mammographic density. BI-RADS-dependent sensitivity was estimated. The results of the 2.5 mg tamoxifen arm of the KARISMA trial were used to define expected changes in mammographic density after six months exposure and to predict changes in mammographic screening sensitivity and detected tumor size. Rates of interval cancers and detection of invasive tumors were estimated for women with mammographic density relative decreases by 10–50%. In all, 517 cancers in premenopausal women were diagnosed in KARMA: 287 (56%) screen-detected and 230 (44%) interval cancers. Screening sensitivities prior to tamoxifen, were 76%, 69%, 53%, and 46% for BI-RADS density categories A, B, C, and D, respectively. After exposure to tamoxifen, modelled screening sensitivities were estimated to increase by 0% (p = 0.35), 2% (p < 0.01), 5% (p < 0.01), and 5% (p < 0.01), respectively. An estimated relative density decrease by ≥20% resulted in an estimated reduction of interval cancers by 24% (p < 0.01) and reduction in tumors >20 mm at detection by 4% (p < 0.01). Low-dose tamoxifen has the potential to increase mammographic screening sensitivity and thereby reduce the proportion of interval cancers and larger screen-detected cancers. View Full-Text
Keywords: breast cancer; low dose tamoxifen; mammography screening breast cancer; low dose tamoxifen; mammography screening
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MDPI and ACS Style

Eriksson, M.; Czene, K.; Conant, E.F.; Hall, P. Use of Low-Dose Tamoxifen to Increase Mammographic Screening Sensitivity in Premenopausal Women. Cancers 2021, 13, 302.

AMA Style

Eriksson M, Czene K, Conant EF, Hall P. Use of Low-Dose Tamoxifen to Increase Mammographic Screening Sensitivity in Premenopausal Women. Cancers. 2021; 13(2):302.

Chicago/Turabian Style

Eriksson, Mikael, Kamila Czene, Emily F. Conant, and Per Hall. 2021. "Use of Low-Dose Tamoxifen to Increase Mammographic Screening Sensitivity in Premenopausal Women" Cancers 13, no. 2: 302.

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