Abstract PS4-02-28: Outcomes in Metastatic Young Women Breast Cancer under the Personalized Onco-Genomics Program in British Columbia

Abstract Background. Young women breast cancer (YWBC), defined as diagnosed at age 40 (non-YWBC). Despite this, YWBC is underrepresented and understudied. In this study, we characterize clinical and pathologic features, as well as outcomes of YWBC enrolled in the Personalized Oncogenomics (POG) program at BC Cancer. Methods. Patients with metastatic breast cancer (MBC) enrolled in POG, a personalized oncology platform aimed at characterizing the molecular landscape of advanced cancers, were included and categorized into cohorts as YWBC or non-YWBC. Data collected included patient and tumor characteristics at initial diagnosis and metastatic recurrence, germline mutations, treatments received, and survival outcomes. Clinical tumor subtypes were classified as hormone receptor positive HER2 non-amplified, HER2-amplified, and triple negative breast cancer (TNBC). As all patients enrolled in the POG program undergo whole-genome and transcriptome analysis (WGTA), we evaluated for potential targetable alterations. Results. Patient Characteristics. Between 2012 and 2025, 249 MBC patients were enrolled, with 60 (24%) YWBC and 189 (76%) non-YWBC. Median age at breast cancer diagnosis was 35 (IQR 33 - 38) for YWBC and 52 (IQR 45 - 59) for non-YWBC. In this study population, 7.6% of patients had germline mutations in BRCA, PALB2, or TP53, with no difference between the cohorts. Clinico-Pathologic Features. Compared to non-YWBC, YWBC were more likely to have stage 2-3 disease (76.7% vs 58.7%, p = 0.07), node positive disease (68.3% vs 55%, p = 0.09) and more likely to receive chemotherapy (75% vs 63.5%, p=0.3). De-novo MBC was observed in 20% of YWBC, and 24.9% of non-YWBC. The distribution of tumor subtype at initial diagnosis was similar between the 2 cohorts (p =0.46). Notably, 13% of patients had a tumor subtype switch from initial diagnosis to MBC, partly driven by an increase in TNBC in YWBC, rising from 23.3% to 35%. Treatment and Survival Outcomes. Patients in both cohorts were enrolled to POG after a median of 2 prior lines of therapy for MBC. Compared to stage 1 at initial diagnosis, stages 2 and 3 were associated with shorter time to MBC development (p=0.06 and p=0.01, respectively). There was no significant difference in median overall survival from initial breast cancer diagnosis (7.97 vs 7.53 years, log-rank test p=0.86) or from MBC diagnosis (3.13 vs 2.85 years, log-rank test p=0.47) between YWBC and non-YWBC, respectively. Compared to other subtypes, TNBC was associated with a 79% (p