Predicting Breast Cancer Response Improves Treatment

Predicting Breast Cancer Response Improves Treatment
Biomarker may lead patients with hard-to-treat cancers to better outcomes.

Vanderbilt-Ingram Cancer Center Associate Professor of Cancer Research Justin Balko, Pharm.D., Ph.D., was one of the first investigators to suspect that a biomarker used to predict melanoma’s response to immunotherapy might do the same for individuals with breast cancer.

His past research has demonstrated how major histocompatibility complex class II (MHC-II) expression can be used to predict immunotherapy-specific benefit in patients with breast cancer, opening the door to new pathways in addressing triple-negative breast cancer and other hard-to-treat forms of the disease.

In Balko’s recent research, MHC-II on the tumor cells was predictive of response to durvalumab, a monoclonal antibody targeting PD-L1, in combination with neoadjuvant chemotherapy (NAC) and pembrolizumab, targeting PD-1 in combination with NAC. The findings did not reflect the efficacy of NAC alone.

Balko and other Vanderbilt University Medical Center investigators are now working to expand these inquiries in a phase 3 clinical trial of the immunotherapy response, still in the planning stages.

A growing sense of opportunity has spurred interest in the potential of MHC-II as a biomarker predictor of benefit to breast cancer patients who are treated with the anti-PD-1 and anti-PD-L1 immunotherapies originally developed for advanced melanoma. Triple-negative cancers are defined by lack of expression of the estrogen receptor, progesterone receptor and human epidermal growth factor-2 (HER2) protein that characterize other forms of the disease. Triple-negative cancers also tend to be more aggressive and to come back more often than other types of breast cancer.

In previous studies, NAC has been found to elicit pathological complete response in about 30 percent of triple-negative breast cancer patients, thus improving recurrence-free and overall survival rates, while the addition of immunotherapy increases this by about 15 percent. In patients with melanoma, just over 50 percent of treated patients respond.

Balko said his team remains committed to a translational approach to their research, including data integration from genomic and molecular profiling studies, molecular biology and signal-transduction methodologies. These efforts also encompass publicly available databases, in vitro and in vivo studies and histologic methods.

“Translational studies are important, as they give us an opportunity to better understand breast cancer in the laboratory, while making sure that those discoveries are directed at achieving an impact to patients diagnosed and living with breast cancer,” the researcher said.

The methods and findings of the Balko Research Lab at Vanderbilt will be among those featured in a series of program sessions at the San Antonio Breast Cancer Symposium December 7-10. Research being presented by Balko and colleagues will examine immune checkpoint inhibitors, biomarkers that identify immunotherapy response, progesterone receptors and therapeutic vulnerabilities in triple negative breast cancer.

The San Antonio Breast Cancer Symposium is an international symposium for academic and private physicians and researchers, as well as patient advocates and other appropriate health care professionals. Attendance is expected to reach 8,000 researchers (combining in-person and virtual) from more than 80 countries.

The program highlights discoveries in breast cancer in medical, surgical and radiation oncology. The event promises to offer valuable feedback to breast cancer researchers and offer opportunities to integrate data from various lines of research, potentially enabling yet more discoveries, Balko said.