Abstract PS2-09-22: The Impact of Breast Cancer Histology and Tumor Molecular Subtype on Nodal Positivity

Abstract Introduction: Previous studies have demonstrated higher rates of nodal metastasis in invasive lobular carcinoma (ILC) compared to invasive ductal carcinoma (IDC) of the breast. Although nodal burden also varies by tumor molecular subtype, how this relationship differs by histology (ILC vs IDC) is incompletely understood. The preponderance of ILC tumors are ER+ HER2 non-amplified with poor response to neoadjuvant chemotherapy. Recent data highlighting efficacy of targeted therapy in HER2 low disease provide the opportunity to identify additional patients for whom a neoadjuvant approach might confer eligibility for de-escalation of axillary management. This National Cancer Database (NCDB) analysis characterizes pathological nodal disease (pN+) among patients with clinically node negative (cN0) IDC and ILC hypothesizing that pN+ disease occurs more frequently in ER+ HER2 low ILC compared to IDC. Methods: The NCDB was queried for patients with cN0 invasive breast cancer from 2018-2021 who underwent surgery with axillary staging. ER and HER2 status was defined using College of American Pathologists guidelines with HER2 IHC 1/2+ with FISH non-amplified considered as HER2 low. Multivariable logistic regression was used to identify factors associated with pN+ in the entire cohort and for the cohort with ER+ disease adjusting for age, race, ethnicity, grade and subtype as well as the interaction between histology type and tumor size. Results: Of the 404,132 patients identified, 86.3% had IDC and 13.7% had ILC. Most patients (73.3%) had a tumor size of 2-20mm, well/moderately differentiated tumor grade (79.5%) and ER/PR+ and HER2- tumors (74.7%). Although the majority had pN0 disease (83.8%), lobular histology was associated with greater pN+ (20.4% ILC vs 15.5% IDC; p<0.001). ER+ HER2 low lobular carcinomas had higher pN+ than IDC with similar molecular subtype (21.4% ILC vs 17% IDC; p<0.001). However, on multivariable analysis histology was no longer significantly associated with nodal positivity for the entire cohort or for the cohort with ER+ tumors with no missing data on tumor molecular subtype (N=118,533) (Table 1). Rather, increasing tumor size, age < 51 years, and African American race were associated with increased likelihood of pN+ disease. On assessing the interaction between tumor size and histology it was noted that ILC tumors sized 21-50mm had 7% lower odds of pN+ disease compared to IDC (aOR 0.93, 95% CI 0.87-1.00, p=0.039). However, ILC tumors sized >51 mm had 53% higher odds of pN+ disease compared to IDC patients (aOR 1.53, 95% CI 1.33-1.77). Conclusion: In this study, exploring the relationship of nodal positivity by tumor molecular subtype and breast cancer histology, tumor size was the dominant contributor to pN+ status. As such further investigation is needed to delineate which tumors, particularly as it relates to ILC, may benefit from upfront systemic therapy. Citation Format: S. Myers, Y. Gokun, B. Slover, K. Johnson, A. M. Roy, D. Stover, N. Williams, E. E. Burke. The Impact of Breast Cancer Histology and Tumor Molecular Subtype on Nodal Positivity [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 PS2-09-22.