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

Mikael Eriksson,Per Hall,Kamila Czene,Emily F Conant

doi:10.3390/cancers13020302

Abstract

Simple SummaryThis 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.

Highlights

Percent mammographic density was higher in women with interval cancers (39.1%) compared to women with screen-detected cancers
We have previously shown that after exposure to 2.5 mg of tamoxifen for six months, the average relative density decrease was 15.4% in the KARISMA trial, a density change non-inferior to the density change seen after exposure to 20 mg standard dose of tamoxifen
A ≥20% relative decrease in density was seen in 55% of the population. In this group of women, we estimated that mammographic sensitivity would increase by 7% and the number of interval cancers would decrease by 24%, and the number of large screen-detected breast cancers would decrease by 4%

Summary

Introduction

Breast cancer is the most common cancer in women and mammographic screening has been shown to decrease breast cancer specific mortality [1,2]. As the amount of radiographically “white” or “dense” tissue increases, the sensitivity of mammography decreases due to “masking” of cancers by dense breast tissue [3]. The use of hormonal replacement therapy is known to increase mammographic density and lower screening sensitivity [5]. More than half of all premenopausal women attending mammography screening have high breast density corresponding to BI-RADS categories C and D [6]. Women with mammographically dense breasts are more likely to be diagnosed with interval cancers than are women with less dense breasts [7]

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