Dr. Tolaney on Presence of PIK3CA and ESR1 Mutations in MONARCH 2 Trial in Breast Cancer

Sara M. Tolaney, MD, MPH, instructor of medicine, Harvard Medical School, attending physician of medical oncology, Dana-Farber Cancer Institute, discusses the presence of PIK3CA mutations and ESR1 mutations in patients with breast cancer enrolled in the phase III MONARCH 2 trial.

Tolaney and fellow investigators examined the significance of PIK3CA and ESR1 mutations in patients enrolled in the MONARCH 2 trial. The goals of the analysis were to look at the frequency of these mutations as well as to analyze the concordance between their identification in circulating tumor DNA (ctDNA) and formalin-fixed paraffin-embedded (FFPE) tissue. Moreover, investigators wanted to see whether there was a treatment benefit for the patients whose mutations had been identified via ctDNA, adds Tolaney.

In patients who underwent ctDNA testing, about 40% of patients had PIK3CA mutations. In patients whose FFPE tumor tissue was examined, a similar prevalence of mutations was found, says Tolaney. There was approximately a 60% concordance rate between these platforms. Notably, 60% of ESR1 mutations were identified with ctDNA, whereas approximately 4% of patients were found to harbor these mutations within FFPE tissue. Approximately 80% of these samples came from the primary site of disease. In this setting, the use of ctDNA may confer a greater sensitivity advantage as it is known that the rate of ESR1 mutations increases in the metastatic setting—especially in those with prior exposure to aromatase inhibitors, concludes Tolaney.