Steatotic liver disease in metastatic breast cancer treated with endocrine therapy and CDK4/6 inhibitor

Abstract Purpose In early-stage breast cancer, steatotic liver disease (SLD) is associated with increased recurrence, cardiovascular events, and non-cancer death. Endocrine therapy (ET) increases the risk of SLD. The impact of cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) on SLD and prognostic association in metastatic breast cancer is unknown. We characterized the incidence, prevalence, risk factors, and treatment outcomes of SLD in metastatic HR+/HER2- breast cancer receiving CDK4/6i. Methods This single institution, retrospective, cohort study included patients with metastatic HR+/HER2- breast cancer receiving first-line ET and CDK4/6i from January 2018 to June 2022. SLD was defined as a Liver Attenuation Index (LAI) > 25 HU on contrast-enhanced CT scans and/or > 10 HU on plain CT scans. Univariable binary-logistic regression was used to assess associations with SLD. Time to treatment failure (TTF) and overall survival (OS) were analyzed using Cox proportional hazards modeling. Results Among 87 patients with a median age of 58 years and 65.5% postmenopausal, 50 (57.5%) had SLD at anytime (24 at baseline, 26 acquired). SLD at baseline was quantitatively but not statistically associated with age > 65, post-menopausal status, diabetes, smoking, and HER2-low status. SLD at anytime was statistically significantly associated with longer TTF (median 470 vs 830.5 days, HR = 0.38, p < 0.001). No significant differences in OS or grade 3/4 adverse events were observed between groups. Conclusion This study demonstrated a high prevalence of SLD in this population, with SLD presence associated with longer TTF. SLD may be an indicator of better outcomes in metastatic HR+/HER2- breast cancer patients treated with CDK4/6i.