Liquid Biopsy Finds Actionable Mutations in Metastatic Breast Cancer

Circulating tumor DNA (ctDNA) measured by liquid biopsy was able to identify actionable mutations and provide a real-time molecular assessment of metastatic breast cancer, according to a new study.

“We know that metastatic breast cancer is a clinically and molecularly heterogeneous disease, treated with palliative intent,” said Giovanna Rossi, of the Istituto Oncologico Veneto in Italy. “ctDNA may prove useful for treatment selection, longitudinal monitoring, and a real-time assessment of tumor burden.” She presented the study during a poster discussion session at the San Antonio Breast Cancer Symposium, held December 6–10 in San Antonio, Texas.

The new study was a retrospective analysis of 91 patients with metastatic breast cancer. Most patients (81.3%) had ductal tumors, and 43.9% were estrogen receptor–positive/HER2-negative; 29% of the cohort had triple-negative disease. Sites of metastases included viscera in 42%, bone in 13%, and both in 45% of patients.

Of 277 blood samples analyzed for ctDNA, 84% harbored mutations. The average number of alterations found per sample was 3, and the average ctDNA fraction was 4.5%.

The most common mutations found included TP53 (52%), PIK3CA (40%), ERBB2 (20%), NOTCH1 (15.5%), APC (14%), and MET (13%). The identification of these mutations in ctDNA led to the use of a molecularly targeted therapy in 16 patients (19%).

The median progression-free survival in the full cohort was 5.2 months, and the median overall survival was 21.5 months. Patients with a ctDNA percentage at baseline of < 0.5% had a significantly better progression-free survival than those with a percentage above that mark (P = .003). The same was true for overall survival (P = .012). Patients with fewer than two mutations found at baseline fared better than those with two or more in terms of both progression-free survival-though this did not reach significance (P = .059)-and overall survival (P = .0015).

“Liquid biopsy represents an effective tool in monitoring of patients with metastatic breast cancer,” Rossi said. “Future studies should consider the use of liquid biopsy for molecular and diagnostic stratification.”

Ian E. Krop, MD, of the Dana-Farber Cancer Institute in Boston, was the discussant for the session, and said that “all of us are very excited about the idea of using circulating DNA as a noninvasive approach.” He noted that the increased focus on sequencing and understanding the genomic landscape of metastatic breast cancer is encouraging in general, and that this may help the field understand mechanisms of resistance and improve therapies for this population of patients.