Abstract PS7-69: Molecular profiles and clinical-pathological features of Asian early-stage breast cancer patients
Authors: Chen Margaret , Kwong Ava , Hendricks Carolyn , D'Abreo Nina , Lee Laura , Soliman Hatem H. , Cox Charles , Kling Heather M. , Bhaskaran Rajith , Wang Shiyu , Menicucci Andrea , Untch Sarah , Audeh William ,   FLEX Investigators Group
Published: February 2021

Abstract
Background/Objective: Breast cancer incidence in Asian populations has increased in recent years, and variation in prognosis and tumor subtypes indicates that further study is warranted to characterize these differences and identify actionable targets. Patients of Asian ancestry are underrepresented in US registries, and few studies have characterized molecular profiles for these patients. In the current analysis, we assess clinical, pathological, and molecular profiles from self-reported Asian breast cancer patients (AS), in comparison with age-matched Caucasian (CA) and African American patients (AA), to evaluate the influence of Asian ancestry on differential gene expression in breast tumors.
Methods: This meta-analysis included cohorts of self-reported AS, CA, and AA with early-stage, invasive breast cancer (EBC) prospectively enrolled in the US from 2011 to 2020 in FLEX (NCT03053193), MINT (NCT01501487), or IMPACt (NCT02670577) trials. AS were significantly younger (mean, 55 years) than CA (mean, 61 years, p&lt;0.001) or AA (mean, 59 years, p=0.005); thus, an age-matched subset was selected for analyses. 70-gene signature (MammaPrint, MP), 80-gene signature (BluePrint, BP), and clinical-pathological features were compared among age-matched AS (n=103), CA (n=103), and AA (n=100). Whole-genome expression data were quantile normalized using R limma package, and differentially expressed genes (DEGs) were compared among AS (n=90), CA (n=102), and AA (n=96). DEGs with adjusted p-value &lt;0.05 and log2 fold change &gt; ± 0.5 were considered significant.
Results: AS tumors were classified as 59% MP HR, compared with 44% HR in age-matched CA (p=0.08) and 64% HR in age-matched AA (p=0.17). AS had a significantly lower rate of obesity (16%, body mass index ≥30) compared with CA (41%) and AA (67%) (p&lt;0.001). Tumors of AS were predominantly ductal carcinoma (84%), T1 (59%), grade 1 or 2 (70%), lymph-node negative (69%), ER+ (95%), and HER2-negative (89%). Distribution of ER, PR, and HER2 pathology and BP subtypes for AS were similar to CA but significantly different from AA (Table). Histologic tumor type, tumor grade, tumor stage, nodal stage, menopausal status, and frequency of Type 2 diabetes mellitus were not significantly different between AS and CA or AA. Whole-genome expression comparisons revealed 19 significant DEGs between AS and CA, and 45 significant DEGs between AS and AA. Immune-related genes, primarily those involved with B cell responses and signaling, were more highly expressed in AS compared with CA. Expression of genes related to cell-cycle pathways was greater in AS compared with AA.
Conclusions: AS were significantly younger and more often pre/peri-menopausal at diagnosis compared with CA and AA, consistent with the literature. Most clinical-pathological factors were similar between age-matched groups, except for the obesity rate, which was significantly lower in AS than in CA or AA. Although not significant, AS had EBC that was more often MP HR than CA and less often HR than AA; studies with larger patient groups will help confirm these trends. The current analysis revealed different underlying gene expression pathways in AS compared with other ethnic groups, which may result in differential clinical outcomes. As genomic profiling data are not widely available for Asian American EBC patients, further analyses are warranted to elucidate these outcomes and identify appropriate therapeutic strategies.
Pathology and Genomic Results(unknowns excluded)Asian (n=103)Caucasian (n=103)African American (n=100)p-valueAS vs. CAp-value AS vs. AAER status (IHC)ER Positive69 (94.5%)89 (98.9%)73 (80.2%)0.1250.010ER Negative4 (5.5%)1 (1.1%)18 (19.8%)PR status (IHC)PR Positive64 (87.7%)81 (90%)63 (69.2%)0.4110.006PR Negative9 (12.3%)9 (10%)28 (30.8%)HER2 (IHC/FISH)HER2 Positive3 (4.2%)3 (3.4%)13 (14.3%)0.1720.017HER2 Negative64 (88.9%)85 (95.5%)77 (84.6%)Equivocal5 (6.9%)1 (1.1%)1 (1.1%)MP/BP resultsLuminal A39 (40.6%)51 (53.7%)28 (30.4%)0.2320.043Luminal B45 (46.9%)38 (40.0%)42 (45.7%)HER2 (MP HR)7 (7.3%)4 (4.2%)5 (5.4%)Basal (MP HR)5 (5.2%)2 (2.1%)17 (18.5%)
Citation Format: Margaret Chen, Ava Kwong, Carolyn Hendricks, Nina D'Abreo, Laura Lee, Hatem H. Soliman, Charles Cox, Heather M. Kling, Rajith Bhaskaran, Shiyu Wang, Andrea Menicucci, Sarah Untch, William Audeh, FLEX Investigators Group. Molecular profiles and clinical-pathological features of Asian early-stage breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-69.