Abstract P4-09-02: Somatic tumor profiles of breast cancer in Latinas
Authors: Neuhausen Susan , Schmolze Daniel , Steele Linda , Tao Shu , Adamson Aaron , Adams Charleen , Hu Donglei , Huntsman Scott , Byun Jung , Gardner Kevin , Perez-Stable Eliseo , Napoles Anna , Weitzel Jeffrey , Ziv Elad 
Published: March 2020

Background: Latinos represent the largest and fastest-growing minority population in the US; breast cancer is the most common cancer and causes the most cancer deaths in this population. Precision medicine is being applied increasingly to guide breast cancer treatment decisions. However, the ability to apply precision medicine for prognosis and targeted treatments for breast cancer in Latinas is limited by insufficient data on somatic mutation and gene expression profiles in available tumor mutation datasets. In The Cancer Genome Atlas (TCGA), one of the largest publicly available tumor mutation datasets, only 31 of ~1100 total breast cancers are Latina. Therefore, we performed whole exome sequencing on matched tumor/normal pairs in 146 tumors from 142 women reporting here on their somatic mutational profile compared to non-Latino women of European ancestry from TCGA. Methods: We enrolled 142 Latinas with invasive breast cancer and obtained blood and tumor tissue (formalin-fixed paraffin embedded). After whole exome sequencing of 146 pairs of tumor (somatic) and normal (germline) samples, high quality data were available for 142 tumor-normal pairs for analysis. Target coverage for normal was ~30X and for tumor was ~100X. Sequence data were aligned using Burrows-Wheeler Aligner, genotype calls were made using GATK and Mutect2 was used to call somatic mutations including base substitutions and small insertions and deletions. We estimated genetic ancestry from the germline genotype data using ADMIXTURE. Results: Age at diagnosis ranged from 31 to 75 years with a median age of 48 years. Histologically, 83% were estrogen-receptor positive, 71 % were progesterone-receptor positive, and 17% were human epidermal growth factor receptor positive; 87% were Stage 1 or 2 at diagnosis. The mean genetic ancestry in our sample was 52.3% European, 41.6% Indigenous American, and 6.2% African. We compared the 30 genes most commonly mutated in breast cancers (e.g., PIK3CA, TP53, MAP3K1, MLL3) in non-Latina Whites in TCGA to our data both overall and by subtype and searched for additional recurrently mutated genes not commonly observed in other populations. Similar to non-Latinos, PIK3CA and TP53 were the most commonly mutated genes; mutations in PIK3CA, GATA3, MAP3K1, and RYR2 were significantly more frequent in Latinas (p-value range from 0.001-0.002). Summary: In general, breast tumors from Latinas have similar rates of somatic mutations in most of the top commonly observed genes in European-ancestry women.

Citation Format: Susan Neuhausen, Daniel Schmolze, Linda Steele, Shu Tao, Aaron Adamson, Charleen Adams, Donglei Hu, Scott Huntsman, Jung Byun, Kevin Gardner, Eliseo Perez-Stable, Anna Napoles, Jeffrey Weitzel, Elad Ziv. Somatic tumor profiles of breast cancer in Latinas [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-09-02.