Risk predictors as companion diagnostics for ER positive, HER2 negative early staged breast cancers from India.
Authors: Vijayalakshmi Ramshankar, Aravinda lochan Gopalakrishnan, Arvind Krishnamurthy, Venkatraman Radhakrishnan, Priya Iyer
Journal: Journal of Clinical Oncology (2024)

e13049 Background: Gene expression profiling tests can identify women with breast cancer most likely to benefit from chemotherapy providing accurate prognostic information than other non-genetic clinicopathological parameters. These derive specific molecular features of a tumour indicating an increased likelihood of rapid growth, metastasis risk, and response to chemotherapy. The tests are typically performed after surgery, in conjunction with other available information such as tumour size and grade. The objective of the current study was to evaluate the risk prediction as a companion diagnostic assay for women with early staged breast cancers (ER+,HER2-ve). Methods: The risk prediction was done evaluating quantitative gene expression profiling on Nanostring nCounter Flex platform using total RNA extracted from FFPE tissues (n = 81) obtained from trucut biopsy tissues and post MRM specimens after ensuring the tumour representation. The gene quantitations were derived after normalisation and using nSolver and Roselind software based statistical analysis. Results: We found 55.5% (45/81) and 44.5% (36/81) to be of intrinsic subtype Luminal A and Luminal B among our breast tumours respectively. The risk of recurrence score was high for luminal B (36.1% ; 13/36) compared to luminal A (13.4% ; 6/45). There was no difference pertaining to the Tumour Inflammation score (TIS score) among the luminal A and B that depicted good response to immunotherapy with 80% (36/45) among the luminal A and 72.3% (26/36) among the luminal B. We have identified top 38 differentially expressed genes that drive the high breast cancer proliferation score among the breast cancers in Indian women. The top 5 genes influencing the risk of recurrence with high BCP among the luminal A tumours were GNLY, CHRNA5, CDC20, MELK, RRM2 and among luminal B we got FGFR2, AURKA, MYBL2, CCNE2 and UBE2C. The top genes combining both types influencing the genomic risk of recurrence were FGFR2, MYBL2, AURKA, TTK, UBE2c and ORC6. The genomic risk of recurrence is based only on the gene expression unlike the risk of recurrence which includes the tumour size and nodal involvement. The top genes influencing a poor response to immunotherapy among luminal A was CNTFR, HAPLN1, FGF12, COL4A6 and CDH2 and the top genes influencing poor response to immunotherapy among luminal B was FGFR2, MYCN, AURKA and FAM198B. Conclusions: This is the first study from India using risk prediction test as a companion diagnostics assay for ER+ HER2-ve early staged breast cancer. The salient genes important to drive the breast cancer proliferation increasing the risk of recurrence scores in both luminal A and Luminal B intrinsic subtypes have been derived. We can validate these gene signatures as smaller panels of tests that can be low cost and more suitable for LMIC like India. The BCP panel of genes were relevant driving the recurrence.