ER, PR, and HER2 expression in Ugandan breast cancer patients: An evaluation of in-country RT-PCR compared to IHC.

Abstract

e19009 Background: Breast cancer, the most common cancer in sub-Saharan Africa (SSA), is characterized by poor survival. An accurate assessment of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 receptor (HER2) status, typically via immunohistochemistry (IHC), is considered essential to provide prognostic data and guide therapeutic decision-making. However, due to inaccessible IHC services, these data are often unavailable in many parts of SSA; alternate methods need to be explored. Given the lab infrastructure developed in response to the HIV pandemic, RT-PCR testing is more readily accessible and feasible in SSA. Here we assess the potential of RT-PCR in evaluating the receptor status of women with breast cancer in Uganda. Methods: We enrolled women with a new diagnosis of invasive breast cancer at the Uganda Cancer Institute. Demographic and clinical data were obtained. A formalin-fixed paraffin embedded (FFPE) specimen was utilized for quantitative RT-PCR, using a validated assay for the detection of the ER, PR and HER2. Receptor expression levels were expressed as relative quantity (RQ) compared to housekeeping genes (CALM2). HER2 IHC results were categorized as negative (score 0 or 1+) or positive (3+); 2+ results (n=6) were excluded as FISH testing was not performed. Unstained slides were sent to the Fred Hutchinson Cancer Research Center for IHC. Receiver operating characteristic (ROC) analysis was applied to compare RT-PCR to IHC (gold standard). Results: We analyzed interim data (anticipated N=100 of an ongoing study) from 32 women aged 35 to 56 years. The majority of women (25, 78%) presented with advanced stage disease. Of the 32 cancers, 18 were ER+ (56%), 10 were PR+ (31%), 9 were HER2+ (28%) and 8 were triple negative (25%) by IHC. From ROC analysis, the AUC were 0.94, 0.95, and 0.81 for ER, PR, and HER2 respectively with high sensitivity and specificity (Table). Conclusions: Despite the tremendous need, the ability to detect the ER, PR, and HER2 via IHC in SSA is limited. Here we demonstrate the favorable test characteristics of RT-PCR when compared to IHC. Given the relatively wide accessibility of RT-PCR and endocrine therapy for breast cancer, as well as the recent inclusion of trastuzumab in the WHO’s Essential Medicines List, the results of this study have both direct diagnostic and therapeutic implications. Clinical trial information: NCT03518242 . [Table: see text]