Abstract B091: Molecular alterations in black and Hispanic women with early breast cancer
Authors: Prasad Preethi , Montagna Cristina , Mesias Jesus D. Anampa , Oktay Maja , Sparano Joseph A. 
Published: September 2020

Abstract
Background: Black race is associated with inferior outcomes in early breast cancer, including hormone-receptor (HR) positive and HER2-negative disease, even when receiving comparable adjuvant systemic chemotherapy and endocrine therapy (Sparano et al. JNCI 2012; Albain et al. AACR SABCS 2018, abstract GS4-07). Hispanic ethnicity is associated with lower breast cancer incidence but higher mortality rates than non-Hispanic whites. Molecular differences in breast cancer could account for these disparities. A prior report based on Whole Exome Sequencing (WES) from the Cancer Genome Atlas (TCGA) in 105 African-American women showed higher rates of TP53 mutations and lower frequency of PIK3CA mutations (Keenan et al. JCO 2017), whereas data in Hispanics is limited. We use a custom sequencing panel called the Einstein Comprehensive Cancer Panel (ECCP) of ~150 genes commonly mutated in malignancies (Miller et al. Oncotarget 2017) in a cohort of 20 non-Hispanic black (NHB) and 24 Hispanic (H) women with early breast cancer. Methods: Ion AmpliSeq targeted libraries were prepared from genomic DNA isolated from breast tumor and adjacent non-tumor tissues and sequenced on the Ion Proton platform. Sequencing reads were analyzed using the Ion Torrent Suite’s Torrent Variant Caller followed by the Ion Reporter Software for variant calling and annotation. Results: Samples for 20 NHB and 24 H women were analyzed. The characteristics of the NHB/H cohorts were similar in age (median 55/59 years), stage (61%/73% with Stage II-III), and HR+/HER2-negative subtype (70%/77%). In NHB women, the most frequent pathogenic mutations were in TP53 (20%), PIK3CA (15%), BRCA1 (10%), CDH1 (10%), and KM2TC (10%). Of the NHB patients who recurred, 33% had a pathogenic mutation in TP53 and 16% in KRAS. Of NHB women with HR+ HER2- disease, the most common pathogenic mutations were in PIK3CA (21%) followed by CDH1, TP53, KM2TC, and BRCA1 (all 14%). In H women, the most frequent pathogenic mutations were in PIK3CA (50%) and TP53 (21%) followed by CDH1, FAT4, ATM, and KM2TC (all 8%). Of NHB women with HR+ HER2- disease, the most common pathogenic mutations were in PIK3CA (55%), TP53 (11%), and FAT4 (11%). Of the H patients who recurred, one had a deleterious mutation in TP53, BRCA1, and PIK3CA while the other had a deleterious mutation in GATA3. Conclusions: We found that the NHB and H patients had different molecular profiles despite similar clinical presentations with regard to age, stage, and subtype. The most notable finding was the very high rate of PIK3CA/PIK3R1 (50%) in breast cancers occurring in Hispanic women, which has implications for screening H women with metastatic breast cancer for PIK3CA-directed therapies such as alpelisib. The cohort has variants of unknown significance with mutations in genes that are not described in the literature as well as some hypermutated patients. This study indicates the importance of expanding molecular testing in diverse populations.
Citation Format: Preethi Prasad, Cristina Montagna, Jesus D. Anampa Mesias, Maja Oktay, Joseph A. Sparano. Molecular alterations in black and Hispanic women with early breast cancer [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B091.