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. 2025 Apr;210(2):405-416.
doi: 10.1007/s10549-024-07578-2. Epub 2024 Dec 25.

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

Diego Malon  1   2 , Consolacion Molto  3   4   5 , Shopnil Prasla  6 , Danielle Cuthbert  7   8 , Neha Pathak  7   8 , Yael Berner-Wygoda  7   8 , Massimo Di Lorio  7   8 , Meredith Li  7   8 , Jacqueline Savill  7   8 , Abhenil Mittal  9   10 , Eitan Amir  7   8 , Kartik Jhaveri  6 , Michelle B Nadler  7   8
Affiliations

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

Diego Malon et al. Breast Cancer Res Treat. 2025 Apr.

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 presence of SLD, 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 statistically associated with post-menopausal status. It was quantitatively but not statistically associated with age > 65, diabetes, smoking, and HER2-low. 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 correlated with longer TTF. SLD may be an indicator of better outcomes in metastatic HR+/HER2- breast cancer patients treated with CDK4/6i.

Keywords: CDK 4/6 inhibitors; Computed tomography; Endocrine therapy; MASLD; Metastatic breast cancer; NAFLD; SLD.

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Conflict of interest statement

Declarations. Conflict of interest: Dr. Diego Malon reports honoraria/speaking fee from Bristol Meyers Squibb. Dr. Consolacion Molto reports honoraria/speaking fees from AstraZeneca and Merck. Dr. Eitan Amir reports honoraria/consulting or Advisory role fees from Seagen, Gilead, AstraZeneca and Novartis. Dr. Nadler reports speaker honorarium and consulting fees from Novartis and Exact Sciences. All of them outside of the scope of this submitted work. No Conflict of Interest for Shopnil Prasla, Danielle Cuthbert, Neha Pathak, Yael Berner-Wygoda, Massimo Di lorio, Meredith Li, Jacqueline Savill, Abhenil Mittal and Kartik Jhaveri. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki and The University Health Network Research Ethics Board approval was obtained (Approval Number 22-5856). Consent to participate: Due to the characteristics of the study written informed consent of the participants is not required. A waiver of consent will not adversely affect the rights and welfare of the subjects. This research will not affect clinical care of the individuals.

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