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Background Mammographic breast density (MBD) decline post-tamoxifen initiation is a favorable prognostic factor in estrogen receptor (ER)-positive breast cancer (BC) and has potential utility as a biomarker of tamoxifen response. However, the prognostic value of MBD decline may vary by molecular characteristics among ER-positive patients. Methods We investigated associations between MBD decline (≥10% vs &amp;lt;10%) and breast cancer-specific mortality (BCSM) among ER-positive breast cancer patients aged 36–87 years at diagnosis treated with tamoxifen at Kaiser Permanente Northwest (1990–2008). Patients who died of BC (cases; n = 62) were compared to those who did not (controls; n = 215) overall and by tumor molecular characteristics [immunohistochemistry(IHC)-based subtype (luminal A-like: ER+/PR+/HER2-/low Ki67; luminal B-like: ER+ and one or more of PR-, HER2+, high Ki67) and modified IHC-based recurrence score of ER/PR/Ki67, ie, mIHC3-score]. Percent MBD was measured in the unaffected breast at baseline mammogram (mean=six months before tamoxifen initiation) and follow-up (mean = 12 months post-tamoxifen initiation). Adjusted odds ratios [ORs] and 95% confidence intervals [CIs] were computed from logistic regression models. All statistical tests were 2-sided. Results MBD decline was statistically significantly associated with reduced risk of BCSM overall [OR and 95%CI = 0.38(0.15–0.92)]. This association was, however, stronger among women with aggressive tumor characteristics including luminal B-like [0.17(0.04–0.73)] vs A-like [0.74(0.19–2.92)]; large [0.26(0.08–0.78)] vs small [0.41(0.04–3.79)] tumors; PR– [0.02(0.001–0.37)] vs PR + [0.50(0.18–1.40)] disease; and high [0.25(0.07–0.93)] vs low [0.44(0.10–2.09)] mIHC3-score. Conclusion The findings support MBD decline as a prognostic marker of tamoxifen response among patients with aggressive ER-positive BC phenotypes, for whom understanding treatment effectiveness is critical.

Mammographic Density Decline, Tamoxifen Response, and Prognosis by Molecular Characteristics of Estrogen Receptor–Positive Breast Cancer