New molecular classification of breast cancer predicts response to chemotherapy

Different molecular subtypes of breast cancer respond differently to chemotherapy, a research team from The University of Texas M. D. Anderson Cancer Center reported at the annual San Antonio Breast Cancer Symposium meeting.

The findings reinforce the emerging notion that breast cancer should be classified according to its gene expression profile, in order to make accurate predictions about the outcome of the disease and select the optimal treatment for patients, says the senior investigator, Lajos Pusztai, M.D., Ph.D., an associate professor in the Department of Breast Medical Oncology.

Four major molecular subgroups of breast cancer ? normal-like, luminal (ER-positive), basal-like (mostly ER-negative), or erbb2+ (mostly HER-2 amplified) ? have been previously defined, based on expression of 424 genes involved in cancer development. Scientists have already shown that each subgroup has a different prognosis. In this recent study Pusztai and his group looked at whether these molecular subgroups also respond differently to chemotherapy that is delivered before surgery.

The research team obtained tumor tissue biopsies from 82 patients with newly diagnosed breast cancer before they were given a commonly used chemotherapy (Taxol/FAC). Patients with basal-like and erbb2+ subgroups were found to have the highest rates (45 percent each) of a pathological complete response, while only 6 percent of luminal tumors had a complete response. Among the normal-like cancers, no response was seen.

They then looked at the genes associated with response in basal-like and erbb2+ patients and found that they were different, “suggesting that the mechanisms of chemotherapy sensitivity may be unique to a subgroup,” Pusztai says.

“This is of great interest because it suggests that stratification of patients into molecular subgroups may be needed in order to develop the most accurate predictors of treatment response,” he says. “Different sets of genes present in different molecular subgroups may determine the response to a particular regimen of chemotherapy.”