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, represent 5% of all breast cancer cases, yet remains the leading cause of cancer related death in this age group. YWBC is more aggressive and associated with worse outcomes compared to breast cancer diagnosed in women 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 <0.001) and 97% (p<0.001) increase in rate of death from metastatic and initial diagnosis respectively. Additionally, there was a non-significant trend towards increase in rate of death from metastatic diagnosis in patients who had tumor subtype switch and in those with 3 or more metastatic sites. Molecular Profiling. The most common mutations identified were in the PI3K/AKT/PTEN pathway in 50%, ESR1 mutations in 18%, and somatic BRCA mutations in 16% of metastatic samples. Notably, a composite score from WGTA identified 12% of tumors with potential sensitivity to immune checkpoint inhibitor therapy. Compared to non-YWBC, there was a non-significant trend for YWBC tumors to harbor more somatic BRCA mutations, and less alterations in the PI3K/AKT/PTEN pathway. Conclusion. In our cohort, YWBC were characterized by a higher stage at initial breast cancer diagnosis and enriched for TNBC tumors at time of metastatic recurrence. Efforts to characterize matched primary tumors aim to elucidate molecular factors driving metastatic progression in YWBC, and to identify potential therapeutic targets for this high-risk group are ongoing. Citation Format: P. Chapani, N. Pryma, N. LeVasseur, T. Nghiem, M. Marra, J. Laskin, Z. Mitri. Outcomes in Metastatic Young Women Breast Cancer under the Personalized Onco-Genomics Program in British Columbia [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 PS4-02-28.