Clinical-genomic Discordance and Chemotherapy (CT) Outcomes in Early-Stage HR+/HER2-invasive Lobular Carcinoma.

e12531 Background: Invasive lobular cancer (ILC) is biologically and clinically distinct from invasive ductal carcinoma (IDC). Prior studies evaluating CT benefit across these histologic subtypes yielded conflicting results, highlighting a knowledge gap. We studied the impact of adjuvant CT on overall survival (OS) and identified factors associated with CT receipt in patients (pts) with early-stage HR+/HER2– ILC and IDC. Methods: Data was obtained from the National Cancer Database for pts who had surgical resection of ILC or IDC of the breast between 2010 and 2021. Subgroup analyses were conducted by CT receipt, Oncotype DX Recurrence Score (RS) (low (L) 0–15, intermediate (I)16–25, high (H) ≥26) and menopausal status, with age (< 50 vs ≥50 years) used as a proxy. Overlap propensity score weighting (OPSW) balanced confounding factors (race, ethnicity, T and N stage, grade (G), and use of radiation and hormone therapies), and OPSW Cox proportional hazard models assessed the association between ILC vs IDC and OS. Results: Of the total 954,934 pts, 15% had ILC. ILC cohort had more G2 tumors (63.5 vs 49.1%), postmenopausal pts (88.4 vs 84.5%), higher clinical T stage (T2: 25.3 vs 18.7%, T3: 5.7 vs 1.2%), and node-positive disease (N1-3: 6.9 vs 6.1%). RS testing was available in 38% of pts: ILC had higher rates of L (19.4 vs 19.2) and I (16.3 vs 13.0) RS, whereas IDC had more H RS (6.0 vs 2.9), all p < 0.001. Among pts who received CT (n = 196,829), 14.2% had ILC. In this cohort, ILC pts had more G1 (23.1 vs 14.2%) and G2 (68.2 vs 47.7%) tumors, higher T stage (T2: 39.4 vs 36.3%; T3: 14.9 vs 3.0%), and nodal involvement (N1-3: 21.9 vs 18.0%) and more were postmenopausal pts (78.2 vs 69.5%). ILC pts who received CT had higher rates of L (4.3 vs 2.9), I (11.1 vs 10.3), and unknown (75.4 vs 65.6) RS, while IDC pts had higher rates of H RS (21.2 vs 9.2), all p < 0.001. ILC pts who received CT had higher mortality compared to IDC (aHR 1.20, 1.16–1.25). Univariate 10-year OS was higher for ILC (Table 1). However, ILC pts with I (aHR 1.23, 1.06–1.43) and unknown RS (aHR 1.22, 1.17–1.27) had higher mortality compared to IDC. No OS difference was observed in low (p = 0.76) or high (p = 0.92) RS groups. Among postmenopausal pts, OS differences were observed in I (aHR 1.21, 1.03–1.42) and unknown RS (aHR 1.22, 1.17–1.27). Among premenopausal pts, the difference was observed only in unknown RS (aHR 1.28, 1.15–1.43). Conclusions: We observed a discordance between clinical and genomic risk in ILC, with ILC pts presenting with higher clinical risk but low or unknown RS. CT decisions appeared driven more by clinicopathologic factors than RS suggesting that existing recurrence prediction models may not reliably predict outcomes in ILC, highlighting the need for new individualized treatment strategies. 10-year OS of ILC vs IDC pts who received adjuvant CT. RS groups ILC OS (%) IDC OS (%) p-value Overall cohort 76.2 81.8 <0.01 L 88.3 88.8 0.76 I 87.0 89.3 0.01 H 80.8 80.6 0.92