EGFR and AR expression and co-expression in Indian triple-negative breast cancer with patient outcome association

Abstract

Triple negative breast cancer (TNBC) is a highly heterogeneous disease lacking established molecular targets. Its incidence is notably higher in Indian women compared to Western populations. To characterize molecular diversity within Indian TNBCs, we analyzed 93 tumor samples for the expression of EGFR, CK5/6, and androgen receptor (AR) and examined their association with clinicopathological parameters and patient outcomes. EGFR expression was detected in 65% of tumors and AR in 38%. EGFR-positive tumors were of higher grade and had a significant association with vimentin positivity and were associated with a trend toward shorter disease-free survival (DFS). AR-positive tumors exhibited lower vimentin expression, suggesting a less mesenchymal phenotype, but paradoxically showed a trend toward poorer survival. Approximately 25% of the tumors displayed co-expression of EGFR and AR at the tissue level, and 15% contained EGFR-positive, AR-positive, double-positive tumor cells, as detected by multiplex immunofluorescence. Patients harboring such double-positive cells showed a trend towards poorer DFS. Single-cell RNA-sequencing data from independent TNBC cohorts confirmed the presence of EGFR + AR+ tumor cells at lower frequencies (0.8-5%). These findings suggest that EGFR-AR co-expression in TNBC tumors is defined as an exploratory group with potential therapeutic implications to combat the increased risk of recurrence. Our results underscore the importance of population-specific molecular profiling in TNBC and suggest that dual targeting of the EGFR and AR pathways may be a promising direction for clinical research in Indian breast cancer patients.