Breakthrough Insights from IISER Pune on EGFR and AR in Indian TNBC

A groundbreaking study from the Indian Institute of Science Education and Research (IISER) Pune has shed new light on the molecular landscape of triple-negative breast cancer (TNBC) in Indian patients. Published in the prestigious Scientific Reports, the research reveals significant co-expression of Epidermal Growth Factor Receptor (EGFR) and Androgen Receptor (AR) in a substantial subset of tumors, offering potential avenues for targeted therapies tailored to the Indian population.

TNBC, characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), accounts for 22-31% of breast cancers in India—far higher than the 10-15% seen in Western countries. This aggressive subtype presents unique challenges due to its heterogeneity and lack of approved targeted treatments until recent immunotherapy advances like pembrolizumab.

The Rising Burden of TNBC in India

Breast cancer is the most common cancer among Indian women, with over 200,000 new cases annually. TNBC strikes younger women, often at advanced stages, leading to poorer outcomes. Indian studies consistently report higher TNBC prevalence, linked to genetic, environmental, and socioeconomic factors. For instance, a meta-analysis pooled prevalence at around 31%, underscoring the urgent need for India-specific research.

• Higher incidence in premenopausal women under 40.
• Limited access to screening exacerbates late diagnoses.
• Five-year survival rates lag behind global averages at ~60-70%.

IISER Pune's work addresses this gap through the Centre for Translational Cancer Research, a collaboration with Prashanti Cancer Care Mission, emphasizing basic science translation to clinical impact.

Methodology: Profiling an Indian TNBC Cohort

The study analyzed 93 formalin-fixed paraffin-embedded (FFPE) tumor samples from Indian TNBC patients treated at Sahyadri Hospitals, Pune. Researchers employed immunohistochemistry (IHC) to assess EGFR, cytokeratin 5/6 (CK5/6—a basal marker), and AR expression. Multiplex immunofluorescence confirmed cellular co-localization, while survival data correlated markers with disease-free survival (DFS) and overall survival (OS). Public single-cell RNA-sequencing (scRNA-seq) datasets validated findings.

Led by Madhura Kulkarni and collaborators including L.S. Shashidhara from IISER Pune's Biology Department, the cohort reflected real-world Indian demographics: median age ~45, predominantly advanced stages.

Prevalence of EGFR and AR Expression

EGFR overexpression, a hallmark of basal-like TNBC, was found in 65% of tumors—higher than some global reports (40-60%). These tumors were higher grade (G3) and vimentin-positive, indicating mesenchymal features linked to invasion.

AR positivity stood at 38%, associated with lower vimentin, suggesting a luminal androgen receptor (LAR) subtype less mesenchymal but paradoxically trending toward worse outcomes. Both markers correlated with shorter DFS/OS, though not statistically significant due to sample size.

Novel Discovery: Cellular Co-Expression of EGFR and AR

The study's novelty lies in identifying 25% tissue-level co-expression and 15% cellular co-expression—EGFR+ AR+ double-positive tumor cells in the same tissue regions. Multiplex IHC visualized these rare cells (~0.8-5% in scRNA-seq validation).

Patients with double-positive cells trended toward worse DFS, hinting at aggressive biology. This subset may evade single-agent therapies, explaining resistance patterns.

Patient Outcomes and Prognostic Insights

EGFR+ tumors linked to recurrence risk; AR+ to metastasis. Co-expressing cases amplified this, urging subtype-specific monitoring. While not reaching significance, trends align with global data where EGFR/AR drive stemness and therapy resistance.

In India, where TNBC dominates young patients, these markers could stratify risk for intensified surveillance or trials.

Implications for Targeted Therapies

EGFR inhibitors (e.g., cetuximab) and AR antagonists (e.g., enzalutamide) show promise in TNBC subsets globally. Dual blockade may overcome co-expression-driven resistance. Ongoing trials (e.g., NCT05404334) explore AR in TNBC; India-specific arms needed.

• Potential for precision medicine in resource-limited settings.
• Combination with immunotherapy (PD-L1 inhibitors).
• Need for Indian clinical trials to validate.

IISER Pune's Pivotal Role in Cancer Research

IISER Pune, under the Department of Science and Technology, excels in interdisciplinary research. The Centre for Translational Cancer Research bridges academia-clinic gaps, building a biobank for future studies. Collaborations with Sahyadri Hospitals enable prospective cohorts.Explore research jobs at IISER Pune

This publication exemplifies India's growing research prowess, with IISERs contributing to global knowledge on population-specific cancers.

Broader Context: India's Cancer Research Landscape

India's TNBC burden demands localized profiling. ICMR initiatives like ICMR-NICPR and Bharat Cancer Genome Atlas complement IISER efforts. Challenges include funding, infrastructure; solutions via public-private partnerships.

Stakeholders: Patients gain hope; researchers, new hypotheses; policymakers, targeted funding.

Photo by vaishnavi pawar on Unsplash

Future Outlook and Actionable Steps

Prospective validation, larger cohorts, functional studies on co-expressing cells ahead. Dual EGFR/AR trials could transform TNBC management in India.

Researchers: Leverage IISER biobanks. Students: Pursue oncology at premier institutes like IISER Pune.Build your academic CV for cancer research Find university positions in India Browse higher ed jobs Rate professors and courses

For collaboration, visit IISER Pune.