Indian triple-negative breast cancers (TNBC) make up a substantially higher proportion of breast cancers than in developed countries (approximately 30% vs. 15-20%, respectively). Hence, effective management of TNBC requires identification of molecular factors that drive the heterogeneity including immune genes. Our goal was to perform a comprehensive analysis of the molecular and immune landscapes of TNBCs in India and compare it with the Western population.
A well-characterised cohort of 42 Indian breast cancer patient samples were used for this study. Unsupervised consensus clustering of gene expression profiles was performed to identify TNBC subtypes and was compared with that of the METABRIC data. Later, the subtypes were associated with mutations, immune cell enrichment and other clinical outcomes.
Our results showed at least three immune-related subtypes (2 immune-enriched and 1 immune-dormant) of Indian TNBC. We arrived at a signature of 25 genes of which certain genes expressed in immune-enriched groups were related to cells from B, CD4 T, natural killer, macrophage and monocytes. Interestingly, 57% of the dense infiltrated tumors overlapped with the one of the immune-enriched subtype which showed a better survival. We validated these subtypes using METABRIC data and observed significant differences in overall survival (p = 0.01). Interestingly, proportion of better prognosis tumors is lower in our series as compared to METABRIC (23% Vs 58%) indicating greater proportion of more aggressive phenotype of Indian TNBCs.
Overall, this is the first study, to our knowledge, to profile large-scale Indian TNBCs and identify heterogeneity associated with disease prognosis and immune response. Future study warrants the validation and clinical utility of this classification to guide the subtype-specific therapy in Indian patients with TNBC.
Anguraj Sadanandam
None
A. Sadanandam: • Entitled to a share of royalty received by the licensor for a patent entitled “Colorectal cancer classification with different prognosis and therapeutic responses” – Patent number PCT/IB2013/060416 filed 26-Nov-2013, EPFL, Lausanne, Switzerland. • Molecular predictors of therapeutical response to specific anti-cancer agents -13/401,780, 21-Feb-2012, LBNL, Berkeley, CA, USA.
All other authors have declared no conflicts of interest.