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Blood-Based Test Identifies which MBC Patients May Respond to mTOR Targeted Therapy

By BCRF | February 24, 2016

A blood-based test, measuring what is called cell-free DNA in blood plasma, identified mutations in the estrogen receptor gene, called ESR1, in 30 percent of patients from the BOLERO-2 clinical trial of everolimus plus exemestane. The identified mutations correlated with response to therapy and survival.

 “Using a simple blood test, we found that mutations in the estrogen receptor are more common in patients with advanced, estrogen receptor-positive (ER+) breast cancer than previously appreciated,” explained Dr. Sarat Chandarlapaty, lead author on the study and BCRF Investigator.

Hormone receptor–positive breast cancer is typically managed with endocrine therapies. However, resistance to endocrine therapy leading to disease recurrence and progression is a persistent challenge this type of breast cancer. Scientists have identified other pathways that when targeted in combination with endocrine therapies may overcome resistance. The BOLERO-2 trial is studying the addition of a new targeted therapy, an mTOR inhibitor called everolimus, to endocrine therapy with an aromatase inhibitor called exemestane. The study included 724 patients with metastatic breast cancer that was hormone receptor-positive but did not overexpress HER2.

Dr. Chandarlapaty emphasized that the results are preliminary and additional studies are needed to confirm the findings. If confirmed, measuring ESR1 mutations in the blood may prove to be predictive as to which patients are more likely to respond to the combination therapy.

Blood-based technology – so-called “liquid biopsy” – is an exciting field pursued by several BCRF Investigators including Drs. Chandarlapaty, James Hicks, Peter Kuhn and others. The hope is to reduce the need for surgical biopsies throughout treatment with simple blood tests that can monitor response to therapy or disease progression while there is still time to change the treatment.