Abstract P3-14-11: Mammaprint and Blueprint identify genomic differences in HR+ HER2- breast cancers from young Black and White women
Authors: Reid Sonya , Pal Tuya , Mayer Ingrid A. , Shu Xiao-Ou , Tezak Ann L. , Hoskins Kent , Sharma Dipali , Robinson Patricia , Wei Jennifer , Ruby Jake , Wang Shiyu , Haan Josien , Menicucci Andrea , Audeh William ,   FLEX Investigators Group
Published: March 2022

Abstract
Introduction: Hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer, the most common immunohistochemical subtype, remains the dominant contributor to annual breast cancer deaths worldwide across all racial and ethnic groups. Black women are 41% more likely to die from breast cancer compared to White women, predominantly among women diagnosed ≤ 50 years of age. Yet, Black women remain underrepresented in clinical trials and population-based studies. Thus, it is critical to better characterize tumor molecular features from young Black women to identify factors contributing to the existing racial survival disparity. In the current study, we compared risk of distant recurrence signature, MammaPrint (MP), molecular subtyping signature, BluePrint (BP), and whole transcriptome differences between young Black women with HR+ HER2- breast cancer compared to matched White controls. Methods: This study included 156 Black women aged ≤ 50 with stage I-III, HR+ HER2- breast cancer of whom, 68 were recruited from 2009-2014 as part of the BEST study (5R01CA204819-04) with follow-up data available (median 114.5 months). The remaining 88 Black women were enrolled in the ongoing FLEX Study (NCT03053193) from 2017. White women (n=156) were randomly selected from FLEX and matched by age, tumor stage, and receptor status. Tumors were classified through MP as Low Risk (MP-LR) versus High Risk (MP-HR), with MP-HR further stratified into HR1 and HR2; HR2 tumors exhibit superior chemosensitivity as demonstrated in a prior large clinical trial of breast cancer patients (ISPY2). All women had MP and BP to classify tumors as Luminal A (MP-LR), Luminal B (MP-HR), HER2, or Basal, and full transcriptomic analyses. Differential gene expression analysis was performed with R package ‘limma’ to compare Black and White women and further compare within each molecular subtype. Differentially expressed genes (DEGs) with a false discovery rate &lt;0.05 were significant. Results: Of 312 young women with localized, HR+ HER2- breast cancer, high grade tumors were more frequent among Black compared to White women (34.6% vs 25.6%; p=0.08). MP-HR tumors were significantly more frequent among Black compared to White women (67.3% vs. 50.0%; p=0.002). Among MP-HR tumors, more HR2 tumors were seen in Black (25.6%) compared to White women (14.1%). Among women with MP-HR tumors and known treatment information, most Black women (94.3%) and all White women received chemotherapy. There were more Luminal B tumors in Black compared to White women (51.9% vs. 41.7%; p=0.07). BP reclassified a larger proportion of ER+ tumors as Basal in Black compared to White women (14.1% vs. 8.3%). Of 68 Black women with available survival data, 7 had death and/or distant recurrence events, of whom 6 (85.7%) had MP-HR tumors (4 Luminal B, 1 HER2, and 1 Basal) and 1 had MP-LR Luminal A tumor. Compared to White women, Black women with: 1) Luminal B tumors had 192 DEGs with upregulation of suspected poor prognosis genes, PSPH and IGHG1; 2) Luminal A tumors had upregulation of PSPH; and 3) Basal tumors had downregulation of POTEH. Conclusion: Among young women with localized HR+ HER2- breast cancer, MP and BP molecular signatures more robustly identified racial disparities in risk and subtype distribution beyond that identified through clinical factors adjusted for age and tumor characteristics. The transcriptomic differences among Black compared to White women across all BP subtypes provide novel insights about tumor biological differences. These findings have tremendous translational potential to identify etiologic underpinnings of racial survival disparities which may guide therapeutic strategies to improve outcomes.
Citation Format: Sonya Reid, Tuya Pal, Ingrid A. Mayer, Xiao-Ou Shu, Ann L. Tezak, Kent Hoskins, Dipali Sharma, Patricia Robinson, Jennifer Wei, Jake Ruby, Shiyu Wang, Josien Haan, Andrea Menicucci, William Audeh, FLEX Investigators Group. Mammaprint and Blueprint identify genomic differences in HR+ HER2- breast cancers from young Black and White women [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-14-11.