Researchers at Baylor College of Medicine and collaborators have developed and validated a multiparameter molecular classifier test that allows scientists to predict which HER2-positive breast cancer patients could be spared from chemotherapy by receiving anti-HER2 treatment only.
About one in every five breast cancer patients is HER2-positive—meaning that the cancer cells express high levels of a protein called HER2, which helps them grow and spread more quickly. With the introduction of specific anti-HER2 drugs, treating this subtype of breast cancer has become easier. However, chemotherapy is usually still carried out first in order to try and eliminate the cancer completely.
Reporting in Clinical Cancer Research, scientists have now determined that in nearly a third of HER2-positive patients the cancer completely responds to anti-HER2 treatment alone— eliminating the need for expensive and dangerous chemotherapy. In order to identify this subset of patients at the time of diagnosis, the researchers developed a multiparameter molecular test.
“We successfully developed and independently validated a multiparameter molecular test on samples from the tumor that helps us predict at the time of diagnosis the most likely response of a tumor to anti-HER2 therapy alone without chemotherapy, therefore identifying patients who may benefit from chemo-sparing dual HER2-targeted therapy alone,” said Jamunarani Veeraraghavan, assistant professor of the Lester and Sue Smith Breast Center at Baylor and first author of the study.
According to the researchers, the molecular test has three parameters. The first one identifies how much HER2 gene and protein is in the cancer cells and whether the expression is evenly distributed throughout the tumor. This is important because all cells must express high levels of the protein for a complete response to treatment.
The second component of the test analyzes whether the cancer cells express HER2-enriched genes that can reflect the cancer’s growth dependence on the protein. Ultimately, the third parameter looks into a gene called PIK3CA, which—if mutated—allows the the cancer cells to keep proliferating even when the HER2 protein is inhibited, by avoiding HER2-driven pathways.
“We tested our molecular classifier on tumor samples from two of our previous clinical trials,” Veeraraghavan explained. “To be a candidate for HER2 therapy without chemo, a tumor must fulfill all of the above-mentioned characteristics.”
As a next step, the scientists will be evaluating their molecular classifier in a prospective clinical trial to further validate its clinical use in identifying HER2-positive breast cancer patients.
“Traditionally, in an effort to eliminate the tumor we give patients more aggressive treatments, but these also increase the toxicity and affect the patient’s quality of life. But when we provide a personalized treatment, we are giving patients what they need to treat the tumor, not more, minimizing the consequences on their quality of life. This is an important aspect of precision medicine that we do not want to miss,” Veeraraghavan concluded in a press statement.
