Abstract Background /Purpose: The clinical benefit of accessing comprehensive genomic profiling (CGP)-guided recommended therapies in invasive lobular carcinoma (ILC) remains poorly defined.This study aimed to evaluate the impact of achieving CGP-guided recommended therapy on overall survival (OS) among breast cancer patients enrolled in the nationwide C-CAT registry. Methods: We retrospectively analyzed 7,363 breast cancer cases (IDC: 6,902; ILC: 461) registered in the C-CAT database between June 2019 and June 2025 who underwent CGP testing and provided consent for secondary use. Patients were stratified according to receipt of CGP-guided recommended therapy. Kaplan-Meier curves were generated and survival differences were tested by log-rank analysis. Results: In ILC, frequent alterations included CDH1 (309 cases), PIK3CA (278), and TP53 (182). Subtype distribution comprised HER2-positive (0.3%), luminal (73.7%), luminal/HER2 (2.2%), and triple-negative (17.7%). A total of 55 ILC patients (12%) achieved recommended therapy, most commonly with pembrolizumab monotherapy (n = 11) or capivasertib-based regimens (n = 10). These patients demonstrated significantly longer median OS compared with those not receiving recommended therapy (35 vs. 16 months; P = 0.019). Conclusions: This large nationwide registry analysis demonstrates that access to CGP-guided recommended therapy is associated with a significant improvement in OS in ILC. Notably, despite limited availability of targetable alterations and trial opportunities in ILC, meaningful survival benefit was observed. These findings underscore the clinical importance of expanding access to CGP-driven recommended therapies for all breast cancer patients, and highlight the value of large-scale real-world evidence in rare subtypes such as ILC. Citation Format: M. Makita. Impact of Access to CGP-Guided Recommended Therapies on Overall Survival in Invasive Lobular and Ductal Carcinomas: Insights from theC-CAT Registry 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 PS1-13-19.
Mitsuro Makita (Tue,) studied this question.