Abstract PR09: Creating a comprehensive patient-derived xenograft (PDX) bank to represent racial disparities in triple-negative breast cancer (TNBC)

Abstract

Abstract Background: Triple negative breast cancer (TNBC) is negative for estrogen receptor (ER), progesterone receptor (PR), and HER2 (human epidermal growth factor receptor 2) and known to be highly aggressive. TNBC carries poor prognosis in all ethnicities but it is especially prevalent in women of African descent, next most prevalent in African American women, and then to a lesser degree in Caucasian women. Cancer cell lines from various ethnicities have been used to study the nature of these tumors, however, PDX models more accurately reflect the characteristics of the original human tumors. To study this aggressive form of breast cancer amongst ethnicities, including up-regulated and down-regulated genes that play major roles across these tumors, we created a multi-ethnic cohort of TNBC PDXs which allows us to model TNBC disease disparities among these populations. Methods: Several trips to Ghana, Africa (Komfo Anoyke Teaching Hospital (KATH)) were made to procure tumors from African women presenting with breast cancer. We created a protocol to successfully freeze and transport tumors back to the University of Michigan, with very limited research supplies available at KATH. Once back at the University of Michigan, tumor pieces were quickly thawed, minced into small fragments and implanted orthotopically into the fat pads of NOD/SCID IL2R gamma null (NSG) mice. For African American and Caucasian PDX development, we collected tumor specimens from lumpectomies performed at the University of Michigan hospital, Baylor College of Medicine, and Van Andel Research Institute and implanted freshly minced tumor pieces into the fat pads of NSG mice. Once the tumors reached at least one centimeter in size, mice were humanely euthanized and their tumors and organs were removed. Samples of each PDX and all organs were formalin-fixed and paraffin-embedded so expression of ER, PR and HER2 receptor status could be confirmed and cancer stem cell populations assessed, and organ metastasis analyzed, by immunohistochemistry. Results: To date we have successfully established (defined by three or more passages) six African, five African American, and five Caucasian TNBC PDXs. We collected TNBC tumors from fifty-six women, of which forty-two tumors were implanted into mice and twenty four PDXs were generated (this total also includes other ethnicities in addition to the three we are looking at in this particular study). Furthermore, we created an inclusive database which indicates those PDXs that grow as tumorspheres to not only study the characteristics and cancer stem cell properties of each of these tumors and compare them based on ethnicity, but also to determine which models are best for investigational drug studies. Conclusions: We developed a method of orthotopic implantation amenable to PDX generation, even for tumor samples collected abroad, which allow us to accurately model TNBC in different ethnicities. These TNBC PDXs afford a more thorough examination of cancer stem cell properties driving aggressiveness of TNBC among different ethnicities and can inform potential drug therapies to treat TNBC and eliminate metastases. This abstract was also presented as Poster A69. Citation Format: Tahra Kaur Luther, Evelyn Jiagge, Michael T. Lewis, David Monsma, Craig Webb, Suling Liu, Hasan Korkaya, Sean McDermott, Shawn G. Clouthier, Lisa Newman, Dafydd Thomas, Max S. Wicha. Creating a comprehensive patient-derived xenograft (PDX) bank to represent racial disparities in triple-negative breast cancer (TNBC). [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr PR09.