NOHA: A sensitive, low-cost, and accessible blood-based biomarker to determine breast cancer estrogen receptor status in low-resource settings

Autor: Srinidi Mohan, Augustine Musyoka, Divya Guthikonda, Jamie Saunders, Lora Girata, Alex Mremi, Furaha Serventi, Blandina Mbaga, Elizabeth Patrick, Michael A Jones, Ivette F. Emery, Frances L. Lucas, Susan Miesfeldt
Rok vydání: 2022
Předmět:
Zdroj: Journal of Clinical Oncology. 40:580-580
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2022.40.16_suppl.580
Popis: 580 Background: Significant challenges to breast cancer control in low- and middle-income countries (LMICs) include late-stage disease presentation because of few/no early detection programs, inadequately staffed and equipped pathology laboratories, and constrained treatment options. Estrogen receptor (ER) expression is critical to determining candidacy for cost efficient and accessible hormonal agents in LMICs; however, access to standard immunohistochemistry (IHC)-based ER analysis is grossly limited/nonexistent due to cost and technical requirements. We have identified Nw-hydroxy-L-Arginine (NOHA) as a low cost and accessible blood-based biomarker to distinguish estrogen-receptor negative (ER–) from estrogen-receptor positive (ER+) breast cancer, differentiate ER– high grade versus low grade tumors, and correlate ER– molecular phenotype with ethnic variation. Our studies with US patients suggest the NOHA threshold of – versus ER+ disease (Table 1). Here we examine the clinical utility of NOHA as an alternative to IHC in distinguishing ER– from ER+ breast tumors in Tanzanian patients. Methods: Following informed consent, 70 newly diagnosed breast cancer patients were recruited at Kilimanjaro Christian Medical Center (KCMC; Moshi, Tanzania). Prior to any treatment, a needle prick amount of blood was collected from each patient on a Noviplex plasma card (Shimadsu, U.S.) and stored at -80˚C. Plasma cards and unstained tumor pathology slides were shipped at 2-3 months intervals to US labs for NOHA and immunohistochemistry (IHC) ER testing. Statistical difference was set at p– from ER+ breast cancer in the low-resource setting. Plasma cards stored at -80˚C for up to 3 months retained NOHA stability in assays involving a proprietary antibody-based ELISA, and by LC-MS. Conclusions: This study suggests the clinical utility of NOHA as a cost-effective, accessible replacement for standard IHC testing in determining ER status among breast cancer patients in LMICs, promising to extend access to cost efficient and available hormonal agents and improving outcomes and quality of life. The present study provides foundational knowledge for broader studies of NOHA utility in global breast cancer control, as well as in ongoing development of NOHA rapid-testing technologies. [Table: see text]
Databáze: OpenAIRE