Abstract PS2-10-26: Tumor genomic profiling results in breast cancer patients: A comprehensive analysis from a laboratory research registry

Abstract Background: Precision oncology has transformed breast cancer care, with comprehensive genomic profiling (CGP) playing a key role in identifying somatic alterations and biomarkers that guide personalized treatment. Separately, germline testing helps uncover inherited pathogenic variants relevant to therapy and familial risk. Despite the growing use of CGP and germline testing, real-world data on the distribution and clinical relevance of results across diverse breast cancer populations is limited. To better understand the molecular landscape of breast cancer in a real-world setting, we analyzed CGP results from a clinical laboratory research registry, including somatic variant classifications, biomarker profiles, and germline findings. Methods: A retrospective analysis was conducted on 279 breast cancer patients who underwent CGP utilizing a clinical laboratory research registry. Variables assessed included age at diagnosis, sex at birth, histological subtype, ancestry, microsatellite instability (MSI), tumor mutational burden (TMB), PD-L1 expression, tumor variant classifications based on their clinical significance (IA, IB, IIC, IID), and gene-specific alterations. Germline testing rates and pathogenic variant (PV) findings were also assessed. Ordering provider specialties and family history were reviewed to contextualize clinical decision-making. Results: The majority of patients, 253/279 (90.4%), had invasive ductal carcinoma, followed by 22 (7.9%) with invasive lobular carcinoma, 3 (1.1%) with male breast cancer, and 1 (0.36%) with ductal carcinoma in situ (DCIS). The median age at diagnosis was 61 years (range 24-90). Most patients were female (273, 98%). This cohort was predominantly White (156, 53.6%), with Black (32, 11.5%) and Hispanic/Latino (20, 6.9%) individuals comprising smaller proportions. Tumor variant classification showed that 96.8% (270) of patients had at least one classified tumor variant in categories IA, IB, IIC, or IID. IA variants, defined as alterations with an FDA-approved therapy for the patient’s tumor type, were present in 126 patients (45%), where 16 patients harbored 2 variants. The most frequently altered IA genes were PIK3CA (75), ERBB2 (27), ESR1 (10), PTEN (7), AKT1 (6), BRCA1 (5), BRCA2 (4), and gene fusions (4). Microsatellite instability (MSI) was high in only 2 (0.7%) patients. High tumor mutational burden (TMB) was observed in 37 (13.2%) cases. PD-L1 analysis was performed in 204 (73.1%) patients, with 54 (26.5%) having positive PD-L1 expression. Germline testing was conducted in 163 (58%) patients. 14 pathogenic variants were identified, including in MUTYH (5), CHEK2 (2), and one each of BRCA1, BRCA2, RAD51C, TP53, PALB2, APC, and MSH3. Thirteen of these variants (93%) were detected in tumor profiling. Most genomic tests were ordered by medical oncologists (218, 76.8%), followed by genetics providers (51, 18%). There were 499 relatives with reported cancer. 111 (22.2%) had a history of female breast cancer. Half of the patients reported no family history of cancer. Conclusion: This analysis highlights the genomic complexity and heterogeneity of breast cancer. The high prevalence of actionable tumor variants, particularly in PIK3CA and ERBB2, demonstrates the clinical utility of CGP. Importantly, 93% of germline PVs were also detected in tumor profiling; however, one PV was missed, consistent with prior data showing that 8-10% of germline PVs may not be captured by tumor-only testing. Despite guideline recommendations, only 58% of patients underwent germline testing, and just half reported a family history of cancer. These findings underscore the importance of integrating both germline and somatic testing to ensure comprehensive genomic assessment and optimize patient care. Citation Format: G. A. Vidal, S. Benn, A. Martin, K. Hayes, R. Gilmore, R. Fine, L. Brzeskiewicz, T. McKamie, S. Cummings. Tumor genomic profiling results in breast cancer patients: A comprehensive analysis from a laboratory research 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 PS2-10-26.