PIK3CA mutations in breast cancer can be accurately detected using ctDNA, according to analysis data presented at the ESMO 2020 Virtual Congress.

Noting PIK3CA is now an established predictive biomarker in breast cancer, “Several studies reported heterogeneous diagnostic accuracy degrees in detecting PIK3CA mutations in ctDNA compared to the gold standard assessment on [tumor tissue] TT,” wrote Claudia De Angelis, MD, Université Libre de Bruxelles, Brussels, Belgium, and co-investigators.

Thus, they conducted a meta-analysis to estimate the overall diagnostic accuracy of PIK3CA mutations evaluated using ctDNA as compared to TT. Studies eligible provided PIK3CA mutation status on TT and matched plasma samples in breast cancer patients.

A total of 1,952 patients were eligible across a total of 34 cohorts in 31 studies. The main factors calculated were pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve. Additional exploratory subgroup analyses were performed by breast cancer stage and subtype, and timing and methods of PIK3CA mutation detection.

The pooled sensitivity and specificity of detecting PIK3CA mutations using ctDNA compared to tumor tissue were 0.74 and 0.95, respectively. Calculating for pooled positive likelihood and negative likelihood ratios, the rates were 6.2 and 0.38, respectively.

The diagnostic odds ratio was calculated to be 23.2 and area under the curve was 0.81.

Significant heterogeneity was observed among the studies analyzed. Higher overall diagnostic accuracy was found, with absence of heterogeneity, for patients with PIK3CA mutations assessed on ctDNA drawn within 60 days of tumor tissue biopsy, or through next-generation sequencing or PCR methods.

Researchers found that high overall diagnostic accuracy of PIK3CA mutation detection on ctDNA observed in this meta-analysis supports the use of this method in clinical practice.

“ctDNA is simple and easily performed and can be assessed at multiple moments of the metastatic disease course,” concluded Dr De Angelis et al.—Kaitlyn Manasterski

De Angelis C, Bruzzone M, Caparica R, Crucitta S. Ceppi M. Accuracy of detecting PIK3CA mutations on circulating tumour (ct) DNA as compared to tumour tissue (TT) in breast cancer (BC) patients (pts): Results from a systematic review and meta-analysis. Presented at: the ESMO Virtual Congress 2020; September 19-21, 2020; virtual. Abstract 101P.