Comparative effectiveness of adjuvant chemotherapy on survival in node-positive (N2/N3), stage III ER+/HER2− invasive lobular breast cancer (ILC) versus invasive ductal cancer (IDC).

545 Background: ILC is characterized by loss of E-cadherin expression, with distinct biological and clinical features, and is often perceived to be less sensitive to chemotherapy compared with IDC. Oncologists and pts may face a treatment dilemma regarding the benefits of adjuvant chemotherapy in pts with lower biologic risk but higher anatomic risk (N2/N3), stage III ILC. In this study, we sought to compare the benefit of adjuvant chemotherapy in pN2/N3 ILC compared with IDC. Methods: We used the National Cancer Database (NCDB) to identify adults with primary, non-metastatic, ER-positive/HER2-negative invasive breast cancer diagnosed between 2010 and 2022 who underwent upfront surgery. Patients receiving neoadjuvant systemic therapy were excluded. Analyses were limited to pathologic stage I–III disease with known nodal involvement (N2–N3) and tumor category (T1–4). Propensity score matching (1:3, caliper 0.2; using R 4.5.1) was performed to balance age, sex, race, insurance status, grade, pathologic stage, nodal category, tumor category, Charlson-Deyo comorbidity score, and year of diagnosis. Overall survival (OS) was assessed using Kaplan–Meier methods and Cox proportional hazards models used to estimate hazard ratios (SPSS v28). Results: After propensity matching, we analyzed 28,115 pts with pN2/N3 disease (ILC 9,603 and IDC 18,512). Upstaging from cN0 to pN2/3 was higher for ILC than IDC (20.3% vs 13.3%, p<0.001). ILC pts were more likely to undergo mastectomy compared to IDC (80.2% vs 71.2%, p<0.001). Receipt of adjuvant chemotherapy for pN2/N3 disease was similar between IDC and ILC (78.0% vs 78.4%, p=0.37), as was use of adjuvant radiation and endocrine therapy. Among patients receiving chemotherapy, treatment was associated with a 65% reduction in death in ILC (HR 0.35, 95% CI 0.32–0.38, p<0.001) and a 73% reduction in IDC (HR 0.27, 95% CI 0.26–0.29, p<0.001), compared with no chemotherapy. 5-year OS among chemotherapy-treated patients was lower for ILC compared with IDC (HR 1.4, 95% CI 1.33-1.49; p<0.001, Table 1). In contrast, no OS difference was observed between ILC and IDC among patients who did not receive chemotherapy (HR 1.03, 95% CI 0.96-1.11; p=0.38). Chemotherapy was associated with higher 5-year OS in both IDC (87.7% vs 58.9%) and ILC (84.3% vs 59.2%). Conclusions: Adjuvant chemotherapy was associated with a substantial improvement in 5-year OS among patients with pN2/N3 disease in both IDC and ILC. Pts with ILC and extensive nodal involvement benefit from adjuvant chemotherapy. 5-year survival of IDC and ILC. IDC (18,512) ILC (9,603) No Chemotherapy (4,078) Adjuvant Chemotherapy (14,434) No Chemotherapy (2,071) Adjuvant Chemotherapy (7,532) pN2 (18,669) 62.8% 90.1% 64.4% 87.6% pN3 (9,446) 48.3% 82.2% 51.4% 79.4% pN2/pN3 Combined (28,115) 58.9% 87.7% 59.2% 84.3% P <0.001, log rank.