Abstract 6215: Metabolic risk is an important determinant of adipocyte hypertrophy beyond age, BMI and breast density in patients with ductal carcinoma <i>in situ</i>
Authors: Charlotta V. Mulder, Mathilde Almekinders, Renaud Tissier, Lennart Mulder, Petra Kristel, Esther Lips, Marjanka Schmidt, Jelle Wesseling
Journal: Cancer Research (2025)

Background: Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive breast cancer, but distinguishing patients with harmless from potentially hazardous DCIS remains a challenge. Consequently, a cornerstone of DCIS research is finding prognostic biomarkers. One such recent biomarker is adipocyte hypertrophy, which has been shown to be prognostic of ipsilateral invasive breast cancer (iIBC) in post-menopausal women with primary DCIS. However, little is known about the correlation between adipocyte size, clinical factors and mammographic density. Methods: Archival hematoxylin and eosin- stained breast biopsy and excision specimens were retrieved from 669 women diagnosed with primary DCIS between 2000 and 2020 treated at the Netherlands Cancer Institute. These slides were digitized whereafter a machine-learning algorithm using HALO®, was applied to retrieve adipocyte size. Radiology reports were obtained to extract mammographic BI-RADS density. Age at diagnosis, body mass index (BMI), menopausal status and information on comorbidities were extracted from electronic patient records. Associations between adipocyte size and clinical factors and mammographic density were investigated using univariable and multivariable linear regression models. Using a clinically relevant cutoff point for adipocyte size, multivariable logistic regression was performed. Results: The median age at primary DCIS diagnosis was 55 years (interquartile range (IQR): 49.0 -63.0) and most DCIS lesions were grade 3 (40.9%). The median BMI was 24.1 (IQR: 21.9 - 27.1). The majority of women were post-menopausal (47.8%) and had dense breasts (53.8%). Significant positive correlations were found between adipocyte size and age, BMI and all metabolic comorbidities with the exception of smoking. Strong negative correlations were found between adipocyte size and mammographic density categories C and D. In univariable linear models with age and BMI, metabolic risk was able to further differentiate between patients with and without adipocyte hypertrophy beyond age and BMI. This was confirmed using multivariable logistic regression comparing models adjusted and unadjusted for metabolic risk. Conclusion: BMI is the strongest predictor of adipocyte hypertrophy in DCIS patients, however metabolic risk further differentiates between patients with and without adipocyte hypertrophy. Future work should be done on collecting long term follow-up and ascertaining subsequent breast cancer in these patients. If successful, BMI and metabolic risk can potentially be incorporated into risk prediction models for subsequent invasive breast cancer. Citation Format: Charlotta V. Mulder, Mathilde Almekinders, Renaud Tissier, Lennart Mulder, Petra Kristel, Esther Lips, Marjanka Schmidt, Jelle Wesseling. Metabolic risk is an important determinant of adipocyte hypertrophy beyond age, BMI and breast density in patients with ductal carcinoma in situ [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6215.