Abstract C148: Triple negative breast cancer in Black women: The genomic rearrangement landscape and its relationship to obesity and neoadjuvant treatment outcomes

Abstract Purpose: Obesity affects Black women disproportionately, for multifactorial reasons, 57.2% (Black) vs. 38.2% (White). A higher central body fat as measured by waist-to-hip ratio was associated with a higher risk of all-cause and breast cancer-specific death among Black women who had triple negative breast cancer (TNBC), an aggressive disease which affects Black women at a higher rate and contributes to the 41% worse survival outcomes compared to White women. Obesity is a chronic, inflammatory state which creates a mitogenic microenvironment, promotes tumorigenesis and may drive signaling pathways and genomic alterations associated with TNBC. The relevance of certain genomic alterations in breast cancer and the relationship with treatment has been less well described for TNBC and even less so in Black women. Majority of women with early stage TNBC are treated with neoadjuvant chemotherapy (NAC) given prior to surgery and have excellent survival outcomes if there is no residual breast cancer at the time of surgery, i.e. a pathologic complete response (pCR). The purpose of this pilot study was to investigate the genomic rearrangement and gene expression landscape changes in tumors from Black women with TNBC treated with NAC in a major large health system. Methods: A pilot cohort of 38 Black women with early stage I-III TNBC treated with NAC were identified from the tumor registry of Rutgers Cancer Institute and its affiliates within the RWJBarnabas-Health System, the largest in the state of New Jersey. pCR at time of surgery, pretreatment obesity (BMI ≥30 kg/m2) vs. non-obese (<30 kg/m2) was abstracted from pathology reports and the EMR. Whole genome sequencing and RNA sequencing on archived tissue of pre- and post-treatment tumor specimens and normal tumor-free tissue was performed. Results: Mean age at breast cancer diagnosis was 55, and 65% of women were obese. All patients received standard chemotherapy regimens. 20% achieved a pCR, while 80% had residual disease. Out of those with residual disease, 57% were obese. Preliminary data show differences in tumor genomic alterations between obese and non- obese Black patients treated with NAC and in selected obesity-related genes whose differential expression is known to contribute to aggressive breast cancer. Genes important in tumor promotion, tumor suppression, immunomodulation, drug delivery, and have an impact on survival depending on their expression levels, were differentially expressed. Conclusion: Our findings suggest that among Black women with TNBC, a higher BMI is inversely associated with achieving a pCR. Differences in tumor genomic alterations between obese and non-obese Black patients treated with NAC and in selected obesity-related genes were observed. Differentially expressed genes were also identified. Ongoing work will focus on Black patients with residual disease after NAC, and are thus chemoresistant, and determine whether there are associations with genomic alteration patterns and obesity. Extensive gene expression analysis and signaling pathway analysis will be performed. Citation Format: Coral Omene, Gregory Riedlinger, Anya Litvak, Anupama Nehra, Anita Kinney, Elisa Bandera, Adana AM Llanos, Hao Liu, Mridula George, Deborah Toppmeyer, Shridar Ganesan. Triple negative breast cancer in Black women: The genomic rearrangement landscape and its relationship to obesity and neoadjuvant treatment outcomes [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C148.