Abstract 19P
Background
Prognostication in early breast cancer has evolved from use of clinicopathological factors as standalone parameters for recurrence risk prediction to the multi-gene/biomarker tests with or without the inclusion of clinical parameters to predict accurate prognosis. The quantitative gene expression profiles can help derive the biology of the disease, indicating an increased likelihood of rapid growth, metastasis risk. The objective of the current study was to derive a high risk gene classifier for Indian women with early staged breast cancers (ER+, PR+, HER2-ve) predicting risk of recurrence.
Methods
The gene classifier was derived by quantitative gene expression profiling on Nano String nCounter Flex platform using FFPE tissues (n = 160) obtained from Indian women with early BC. Data normalisation and statistical analysis was done using nSolver and Roselind software.
Results
Intrinsic subtype Luminal A and Luminal B was found to be 58.12% (93/160) and 41.8% (67/160) respectively. The risk of recurrence score (ROR-C) was significantly high for luminal B ; 72.9% (27/37) compared to luminal A; 27% (10/37). We identified 54 genes driving the high breast cancer proliferation score (BCP) among the breast cancers in Indian women. The top 10 genes influencing the risk of recurrence with high BCP among the luminal A tumours were PLA2G3, TMPRSS4, ATP10B, BMP7, ATG, GNLY, GRIN1, IL24, SPC25, BLM and FGFR2, CXCL5, CCL7, CCNA1, MYBL2, IL22RA2, CEP55, ATP10B, BMP5, GADD45G among Luminal B. The top genes influencing a poor response to immunotherapy among luminal A was HAPLN1, SLPI, CEACAM5, FGF12, SHC4, CDH2, PAX8, COL4A6, PRKACV, F3, FGF2, and the 7 genes influencing poor response to immunotherapy among luminal B were FGFR2, SOX2, CDCA7L, MDM2, FAM198B, AURKA, TTK.
Conclusions
The salient genes important to drive the breast cancer proliferation increasing the risk of recurrence scores in both luminal A and Luminal B have been derived. The study shows the molecular and immunologic characteristics and its microenvironment in early BC driving treatment response and prognosis. These are being validated as low cost smaller panels for lower middle-income countries such as India.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
R. Vijayalakshmi.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.