Abstract 3603: Metabolic profiles distinguish breast cancer progression in African American women

Breast cancer (BCa) is one of the most common malignancies in women and the incidence, distribution, clinical outcome and mortality rates vary widely among women of different ethnic backgrounds. Because tissue from African American (AA) women is difficult to obtain for biomarker studies, new population-relevant biomarkers that enable earlier detection and novel therapeutic intervention development are critical. To identify new biomarkers and targets that have the potential to be leveraged for earlier detection, classification of disease progression and development of improved therapeutics for AA patients, plasma and tissue samples were selected from two AA BCa case and control cohorts at the Tissue, Plasma and Clinical Bank at the Howard University Cancer Center (HUCC). Samples were from women either diagnosed with BCa, screened for potential BCa lesions or undergoing reduction mammoplasty surgery at both Howard University and Providence Hospitals. Samples were analyzed by untargeted metabolomics using 1 H nuclear magnetic resonance (NMR) spectroscopy. Multivariate and statistical analyses determined bins important to differentiating BCa by progressive stage and grade from control reduction mammoplasty tissues and fibrocystic fibroadenoma. Significant bins were library-matched to identify corresponding metabolites and distinguish common and unique metabolites between tissue groups and compare tissue profiles to plasma samples. Metabolites from each study group were also correlated with other known clinicopathologic BCa risk factors, including age, BMI, and smoking status, to determine their influence on disease progression. Several metabolites were found to distinguish nonmalignant reduction mammoplasty tissues from fibrocystic fibroadenomas, and from Grade (G) I-II estrogen receptor (ER)-positive or GI-II ER-negative tumors and GIII ER-positive or GIII ER-negative tumors. For example, in three comparisons using orthogonal partial least squares discriminant analyses (OPLS-DA) between reduction mammoplasty, fibrocystic fibroadenomas and the malignant tissues, we found 8 unique metabolites when comparing reduction mammoplasty versus fibrocystic fibroadenomas (4-hydroxybenzoate, dimethylamine, formate, glutamine, glutathione, histidine, methionine and UDP-N-acetylglucosamine); 2 unique metabolites comparing reduction mammoplasty versus GI-II (ER-positive and -negative) tumors (2-phenylpropionate and succinate); and 6 unique metabolites comparing reduction mammoplasty versus GIII (ethanolamine, glycine, hypoxanthine, maltose, sucrose and uridine). Our results demonstrate the continued usefulness of metabolomics-based research and the potential for these findings to identify early detection or disease staging biomarkers in a population that experiences a disparate burden of this disease. Citation Format: Delisha A. Stewart, Wimal W. Pathmasiri, Susan L. McRitchie, Lance Buckley, Tammey J. Naab, Robert L. DeWitty, Vikisha T. Fripp, Estelle Cooke-Sampson, Desta A. Beyene, Luisel Ricks-Santi, Robert L. Copeland, Susan J. Sumner, Yasmine M. Kanaan. Metabolic profiles distinguish breast cancer progression in African American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3603.