Abstract PD9-11: The association of breast density with clinicopathological characteristics and survival in patients with early stage ER+ HER2- lobular breast cancer

Abstract Introduction: Breast density (BD), a dynamic radiologist-assessed parameter, is impacted by factors such as - but not limited to - age, parity, hormone therapy, nutrition, family history and obesity. Higher BD is a known breast cancer risk factor, not only due to reduced screening sensitivity but also because of biological processess like increased collagen deposition, potentially promoting tumor growth. While some studies associate high BD with larger tumor size and greater nodal involvement, results remain inconclusive, and the prognostic impact is unclear. Invasive lobular carcinoma (ILC), characterized by distinct clinicopathological and biological features, is understudied in this context. Methods: We conducted a retrospective analysis of patients diagnosed with estrogen receptor (ER) positive, HER2 negative early pure ILC at University Hospitals Leuven (2000-2020). BD was scored using the BIRADS 4th and 5th edition (categories A-D). When feasible, mammograms were independently re-evaluated by radiologists, with the final score based on the majority. If re-evaluation was not possible, the clinical record score was used. Cases lacking a majority consensus were excluded. Survival data were collected until 05/2022. Multinomial logistic regression and Cox regression were employed to evaluate the associations of BD scoring (B/C vs. A, and D vs. A) with clinic-pathological characteristics and survival. The characteristics include age, parity, BMI, tumor grade, tumor size, focality, progesterone receptor, nodal status and treatments (radio- and chemotherapy). Results: We included 968 patients, BD scores were for 628 patients available from clinical records. Two radiologists re-evaluated 325 cases, showing a moderate concordance among themselves and the original score (Fleiss’ kappa = 0.488). For 101 cases with missing data, three radiologists re-assessed BD, showing moderate concordance (Fleiss’ kappa = 0.426). Final BD scores were available for 727 patients (Type A: 6.5%, B: 38.8%, C: 39.6%, D: 15.1%). Multivariable analyses showed significant associations between higher BD and both lower age and BMI. A non-significant trend suggested associations with lower tumor grade and more multifocality. Higher BD was independently associated with both better disease-free survival (DFS) and overall survival (OS) , but not with distant recurrence free survival (DRFS) (median follow-up of 9.94 years). Conclusion: In ER+ HER2- ILC, higher breast density is associated with younger age and lower BMI, and our data suggests a potential link with lower tumor grade and increased multifocality. Higher density was independently associated with better OS and DFS. These results highlight the need for further research into the biological mechanisms underlying these associations. Citation Format: J. Van Cauwenberge, H. Nguyen, R. Prevos, A. Bernaerts, S. Hendrickx, C. Van de Velde, K. Van Baelen, P. Neven, H. Wildiers, G. Floris, A. Smeets, I. Nevelsteen, C. Van Ongeval, C. Desmedt. The association of breast density with clinicopathological characteristics and survival in patients with early stage ER+ HER2- lobular breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD9-11.