Study: New Biomarker Tool Helps Select Targeted Therapies to Treat Metastatic Breast Cancers

Newswise — Two antibody drug conjugates (ADCs), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), were approved by the FDA to treat metastatic breast cancers. ADCs are a type of targeted therapy that release cancer drugs to specific tumor cells. The efficacy of T-DXd and SG depends on target expression and the best method for measuring that expression is still not known.

A team of researchers led by senior author David Rimm, MD, PhD and first author Charles “Jack” Robbins at Yale Cancer Center evaluated a new “selective” biomarker called Troplex™, which assesses HER2, TROP2, and cytokeratin (CK) using quantitative immunofluorescence (QIF). They propose this new assay to help select which ADC therapy to use first. Rimm and Robbins will present their new findings at the San Antonio Breast Cancer Symposium (SABCS) on December 7.

“It's a new kind of biomarker that we're tentatively calling a selective biomarker, where even though we don't know that it's predictive, it could still help the oncologist select which drug when there are two drugs with two different targets in the same space, and that's a new thing,” said Dr. Rimm, the director of the Yale Cancer Center Tissue Microarray Facility. He’s also an Anthony N. Brady Professor of Pathology and professor of medicine (medical oncology) at Yale School of Medicine.

Dr. Rimm said the poster presentation will reveal the levels of HER2 and TROP2 that they quantitatively determined in hundreds of different breast cancers. Most breast cancers were high for either HER2 or TROP2, providing valuable data to clinicians choosing between the antibody drug conjugate T-DXd and SG, Dr. Rimm said.

“Since the level of target is directly proportional to the likelihood of response, we built an assay that could measure that in a quantitative way,” said Dr. Rimm. “By doing this, we could compare the two and then see which one is higher. If it turns out that TROP-2 is expressed at higher levels than HER2 on average, then oncologists may want to start by treating the patient with SG.”

The Rimm Lab’s next goal is to apply, and evaluate, the same quantitative method with many other pairs of ADC drugs in the hope of finding more selective assays that can be used in clinical settings.