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Breast Cancer: Liquid Biopsies Better Than Tumor Biopsies

Metastatic breast cancer.

Patients with hormone receptor (HR)-positive metastatic breast cancer are typically treated with endocrine therapy. However, patients with mutations in the genes PIK3CA and ESR1 usually develop resistance to endocrine therapy. To discover ways to effectively identify PIK3CA and ESR1 mutations in patients with HR-positive metastatic breast cancer and predict treatment outcomes, researchers at Stanford University evaluated the efficacy of using liquid biopsies compared with solid tumor biopsies to detect these mutations in patients with HR-positive metastatic breast cancer treated with fulvestrant with or without abemaciclib.

For this phase 3 study, which will be presented at the American Association for Cancer Research Annual Meeting on April 2, the researchers collected baseline circulating tumor DNA (ctDNA) plasma samples from 334 patients and formalin-fixed paraffin-embedded (FFPE) tumor samples from 434 patients; all patients had HR-positive metastatic breast cancer. The tumors samples were then assessed for PIK3CA and ESR1 mutations using Droplet Digitalâ„¢ polymerase chain reaction (ddPCR) technology.

The investigators found that 40.3% of the plasma samples and 33.9% of the FFPE samples contained PIK3CA mutations, and ESR1 mutations were found in 64.4% of the plasma samples and 4.4% of the FFPE samples. A correlation was established between the presence of resistance mutations and response to abemaciclib in ctDNA but not in tissue samples. In addition, the researchers found that while abemaciclib was beneficial for all patients, individuals with resistance mutations benefited more.

The researchers concluded from these results that the ctDNA liquid biopsy method could potentially be more successful in identifying PIK3CA and ESR1 mutations and predicting breast cancer therapy response than the FFPE tissue biopsy method.

The lead author of the study, Sara M. Tolaney, MD, MPH, a medical oncologist at the Dana-Farber Cancer Institute, commented, "These findings lend support to the use of ctDNA and liquid biopsies to identify molecular alterations that could help inform treatment choices."

For More Information

Tolaney SM, Toi M, Neven P, et al (2019). Clinical significance of PIK3CA and ESR1 mutations in ctDNA and FFPE samples from the MONARCH 2 study of abemaciclib plus fulvestrant. American Association for Cancer Research Annual Meeting. Abstract 4458. 

Image Courtesy of Ed Uthman

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