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565 Background: Recent prospective clinical trials have demonstrated a differential chemotherapy effect based on age (≤ 50 vs. > 50 years) or menopausal status (pre- vs. post-) in a genomic low risk group. Whether this is a direct anti-tumor effect of chemotherapy or a secondary ovarian function suppression effect caused by chemotherapy is unclear. We aimed to compare the biological characteristics of breast cancer tumors from patients aged ≤ 50 years and from patients aged > 50 years using whole transcriptome analysis to provide insights into this differential chemotherapy response. Methods: The FLEX Registry (NCT03053193) enrolls stage I-III breast cancer patients who receive 70-gene signature (MammaPrint/MP) test with or without 80-gene signature (BluePrint/BP) test and consent to clinically annotated transcriptome data collection. 3868 patients with HR+HER2- tumors were evaluated, of whom 808 were aged ≤ 50 years and 3060 were aged > 50 years. Clinical risk was assessed based on the MINDACT algorithm. MP classified tumors as low risk (LR) or high risk (HR). HR was stratified to H1 or H2; H2 exhibits a greater chemotherapy response. BP and MP classified tumors as luminal A-, luminal B-, HER2-, or basal-type. Differences in MP, BP, and clinical features were assessed by chi-squared or t test. For gene expression analysis, older patients were randomly selected to obtain an equal sample size as younger patients. Differentially expressed genes (DEGs) were detected using limma and considered significant with FDR 50 were post-menopausal. A higher proportion of patients aged ≤ 50 had tumors of high clinical risk (54%) compared to patients aged > 50 (39%) (p < 0.001). Approximately 53% of patients aged ≤ 50 had a HR tumor, of whom 25% classified as H2, while patients aged > 50 had a lower frequency (44%) of HR tumors (p 50, and even fewer DEGs were detected when adjusting for MP risk and BP subtype group. Conclusions: Whole transcriptome analysis identified no substantial differences in gene expression between tumors, including Low Risk Luminal-type tumors, from women aged ≤ 50 (mostly pre or peri-menopausal) and women aged > 50 (mostly post-menopausal). These data support the likely explanation that the observed age-dependent difference in chemotherapy benefit in women ≤ 50 or >50 years of age is not due to intrinsic biological differences in breast cancers due to age, but rather to differences in the effect of chemotherapy on the host. Clinical trial information: NCT03053193.

556 Background: Genomically basal-type breast cancer is a heterogenous subtype that occurs at higher frequencies in non-Caucasian patients. Triple negative breast cancer (TNBC) has been refined into distinct transcriptomic groups including the basal-like immunoactive (BLIA), basal-like immunosuppressed (BLIS), luminal androgen receptor (LAR), and mesenchymal (MES) subtypes. Here we report the distribution of triple negative subtypes in genomically basal cancers from Caucasian (CA), African American (AA), and Latin American (LA) patients and the association of clinical estrogen receptor (ER) status. Methods: The FLEX Registry (NCT03053193) is an ongoing, prospective study evaluating primary tumors from patients with stage I-III breast cancer who receive the 70-gene signature and 80-gene signature (80-GS) molecular testing and consent to clinically annotated full transcriptome data collection. This sub-analysis evaluated 143 80-GS Basal type tumors from patients with self-reported ethnicity (60 CA, 59 AA, 24 LA). TNBC subtypes BLIA, BLIS, LAR, and MES were derived using an adjusted version of the 80-gene centroid signature published by Burstein and colleagues (2015). Differences in clinical ER expression between ethnicities were assessed by Fisher’s exact test. Results: Basal indices from 80-GS were not influenced by patient ethnicity (one-way ANOVA, p = 0.182). The frequency of BLIA, BLIS, LAR, and MES subtypes did not vary significantly by ethnicity (Fisher’s exact test, p = 0.671). The majority of tumors in all ethnic groups were BLIS (67% CA, 75% AA, 63% LA), followed by BLIA (22% CA, 22% AA, 25% LA), with low frequency of LAR (5% CA, 1.7% AA, 8.3% LA) and MES (5% CA, 1.7% AA, 4.2% LA) subtypes. Nearly one third (31%) of Basal type tumors were defined by IHC as ER positive and were present in all TNBC subtypes (39% BLIA, 29% BLIS, 33% LAR, and 20% MES); ER receptor expression ranged from 1-90% and was not associated with specific basal subtype (p = 0.8) nor ethnicity (P = 0.76). Progesterone receptor expression ranged from 1-50%. Conclusions: This analysis demonstrated that genomic Basal type tumor classification by 80-GS encompasses all TNBC subtypes evaluated regardless of ethnicity. Additionally, we show that IHC ER positive tumors occur in all TNBC subtypes assessed. These findings confirm the heterogeneous nature of basal breast tumors in CA, AA, and LA patients and highlight the clinical need to delineate basal biology in the ER+ cohort to advance treatment for basal-like tumors. Clinical trial information: NCT03053193 .