Creating PDXs from continental African breast tumors: Addressing racial inequity through science

Document Type

Conference Proceeding

Publication Date

7-1-2021

Publication Title

Cancer Res

Abstract

To design interventions to reduce the burden of breast cancer (BC) in women with African ancestry, there is the need to understand the factors - heritable or non-heritable, modifiable or non-modifiable - that are associated with the disease. Patients and tumors from black women have been underrepresented in clinical research which are the main route to identifying new and improved treatments. Triple negative breast cancer (TNBC) is a clinically aggressive form of BC with propensity to metastasize and is enriched in patients with hereditary predisposition to BC. TNBC is most prevalent among black women despite lacking strong links with the known BC. This phenotype prevalence contributes to disparities in BC outcomes between blacks and other populations. There is an urgent need to represent black tumors in clinical research. Here we describe the process we used to transport fresh breast tumors from Ghana, west Africa to the USA to develop PDXs. Considering the shared ancestry between west Africans and diasporan African American, the results of this work will benefit both populations. Through an international collaboration between investigators at University of Michigan (UM) and Komfo Anokye Teaching Hospital (KATH) in Ghana, regular team site visits were initiated to generate surgical specimens for transport to the United States of America (USA). These specimens were used to create in vivo models. With informed consent, excess patient tumor tissue was taken from the operating room, at KATH. The tumors were cut into small pieces, and slow- frozen to -80°C in 10% DMSO/90%FBS. The samples were then transported overnight on dry ice in a commercial flight to UM. At UM, the tumor pieces were rapidly thawed and rinsed off with HBSS or PBS. The tumor sample was cut into smaller fragments (approximately 1-2 mm in diameter), mixed with matrigel (BD), and 25 μl of matrigel per injection site was injected into the mammary fat pad of female NOD/scid/IL2Rgnull (NSG) mice with an 18-gauge needle. From 2012 to 2017, we obtained fresh tumor samples from 49 Ghanaian patients. Of these, 23 (47%) were TNBC and 26 (53%) were other subtypes. Of the 23 TNBC samples, we implanted 18 into NSG mice and developed PDXs from 12. This gave us a success rate of 67%. We have fully characterized these tumors and their corresponding primary tumors. Our results demonstrate a maintenance of the histology and marker expression in the corresponding PDXs. Additionally, we obtained samples and developed PDXs from 17 Caucasian Americans, 13 African Americans, and 2 Asian patients from UM. 20 samples were TNBCs and 13 were non-TNBC. 18 were implanted in mice (12 TNBC, 4 ER+, and 2 Her2+). Of these, 11 developed into PDXs (9 TNBC, 2 ER+). Transporting African tumors to the USA is expensive, challenging, and limits large scale studies. These challenges can be overcome by enhancing African based research resources in order to conduct research in Africa.

Medical Subject Headings

Hematology

PubMed ID

Not assigned.

Volume

81

Issue

13 SUPPL

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