Novel Next-Generation Sequencing Assay Proves Accurate in Detecting Mutations Among Patients Advanced HR-Positive, HER2-Negative Breast Cancer

A new liquid biopsy analysis using Plasma-SeqSensei IVD Software to detect mutations among patients with hormone receptor (HR)-positive, HER2-negative breast cancer undergoing hormonal therapy and CDK4/6 inhibitor treatment was found to be feasible and accurate. Secondary exploratory analyses also found an association between the presence of PIK3CA mutations and worse treatment response.

This assay is a multi-gene, next-generation sequencing (NGS) target panel on circulating tumor DNA (ctDNA) to detect molecular alterations of AKT1, HER2, ESR1, KRAS, PIK3CA, and TP53. According to Alessandra Virga, MD, IRCCS Instituto Romagnolo per lo Studio dei Tumori, and coauthors, “Research has shown that the presence of mutations involved in resistance pathways can result in reduced sensitivity to [CDK4/6 inhibitors]” results in a “need for the identification of molecular biomarkers that may be able to select responsive patients.”

In this study enrolled 16 patients with advanced HR-positive, HER2-negative breast cancer undergoing hormonal therapy with CDK4/6 inhibitor treatment. Plasma samples were collected at 2 points: baseline and 3 months following CDK4/6 inhibitor treatment. From the samples, ctDNA was isolated and analyzed using the Plasma-SeqSensei IVD Software. The primary objective was to assess the accuracy and feasibility of this assay. Secondary exploratory objectives were evaluating the relationship between genomic profiling and clinical outcomes.

This test achieved a sensitivity of 95.2% and an optimal percentage of specificity. There were 5 patients who presented with progressive disease, 3 of which had PIK3CA mutations and 1 with ESR1 genes in the baseline sample. Of the 3 patients with PIK3CA mutations, 2 patients showed a higher mutant allele frequency at 3 months following CDK4/6 inhibition. There were additionally 3 patients with stable disease and 8 patients with a partial response. Of those 11 total patients, the mutant allele frequency of detect alterations had either decreased significantly or disappeared during CDK4/6 inhibition. Patients with alterations in PIK3CA were significantly associated with worse progression-free survival.

Source:

Virga A, Gianni C, Palleschi M, et al. A novel AKT1, ERBB2, ESR1, KRAS, PIK3CA, and TP53 NGS assay: A non-invasive tool to monitor resistance mechanisms to hormonal therapy and CDK4/6 inhibitors. Biomedicines. 2024; 12(10):2183. doi:10.3390/biomedicines12102183