59P - Comprehensive genomic profiling (CGP) unravels druggable targets in breast carcinoma (BC): A single institutional experience

Background

BC is a heterogeneous disease with variable clinical outcomes among patients with the same clinical and pathological characteristics, treated with similar treatment. Despite significant improvement in the outcomes, many of them acquire resistance to multiple anticancer drugs, leading to recurrence and /or metastasis. It remains an unmet need to identify robust molecular defects and novel biomarkers to adopt individualized treatment decisions in BC. CGP using next generation sequencing (NGS) provides more druggable gene aberrations at “one go” that includes somatic BRCA (sBRCA), homologous recombinant repair pathway alteration (HRR) and tumor agnostic markers like tumor mutation burden (TMB) and microsatellite instability (MSI) burden.

Methods

140 BC cases at HCG cancer centre were profiled using Illumina TruSight Oncology 500 assay on a NextSeq2000 in an IRB-approved study. The findings from NGS data were discussed in the molecular tumor board (MTB) and recommendations were documented for change in clinical management and follow-up.

Results

Clinically relevant variants were detected in 133/140 BC patients (95%) with actionable mutations in >80% cases with direct impact on therapy and constituted of 47% Tier 1 and 41% Tier 2 mutations. CGP revealed a multitude of genomic alterations such as PI3KCA/AKT/PTEN signalling pathway (32%) in HR+Her2- mBC and ESR1 mutation (7%) in HR+ mBC predictive of resistance to anti-Her2 and endocrine therapy respectively. 22 patients (16%) with sBRCA and HRR pathways alteration treated either with platinum / PARP inhibitors post platinum treatment were found to have partial-to-complete pathological response (pCR). 23 BC patients with high TMB (16%) were initiated on immunotherapy as a single drug or in combination with chemotherapy and are on follow up. The mutation spectrum, HRR pathway alterations and high TMB of triple- negative BC (TNBC) cases revealed a distinctive mutational profile with clinical utility in >95% cases.

Conclusions

Recommending CGP tests at a more appropriate time helps in modifying BC treatment protocol, clinical decisions and provides patients with greater benefit from targeted treatments based on their specific gene alterations and resistance mechanism.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

B.S. Ajaikumar: Financial Interests, Personal and Institutional, Member of Board of Directors, Executive Chairman: HCG. All other authors have declared no conflicts of interest.