Investigators analyzed cells within triple-negative breast cancers before and after radiation therapy combined with pembrolizumab and identified three patient groups with different responses to the treatment. Their study, published by Shiao et al in Cancer Cell, found that for some patients with this difficult-to-treat cancer, radiation therapy plus immunotherapy could yield the best tumor-fighting immune response prior to surgery.
“Our most important finding was identifying these three different patient groups,” said Simon Knott, PhD, Co-Director of the Applied Genomics Shared Resource at Cedars-Sinai Cancer and senior author of the study. One group, Dr. Knott said, didn’t respond at all to therapy; one responded well to immunotherapy; and one responded only to immunotherapy plus radiation therapy. “This could help us employ our most aggressive treatment options only when needed most,” Dr. Knott said.
More on Triple-Negative Breast Cancer
Triple-negative breast cancer cells test negative for receptors to the hormones estrogen and progesterone and for the HER2 protein. These tumors—which account for 10% to 15% of breast cancer cases—grow and spread faster than other breast cancer subtypes and in general have fewer treatment options.
Patients with triple-negative breast cancer generally receive treatment to shrink their tumors before having surgery. Immunotherapy is part of that presurgical treatment regimen.
“Triple-negative breast cancer is the only type of breast cancer we treat with immunotherapy,” said Stephen Shiao, MD, PhD, Co-Director of the Cancer Therapeutics Program at Cedars-Sinai Cancer and first author of the study. “Unfortunately, only 20% to 30% of patients respond to immunotherapy on its own. Combining it with chemotherapy boosts response to 60% but exposes patients to significant toxicity.”
Trial Details
To determine whether a combination of radiation therapy and immunotherapy would improve patient response, investigators launched a clinical trial in which they examined tumors from 34 patients with triple-negative breast cancer. Patients underwent biopsies before treatment, after one course of the PD-1 inhibitor pembrolizumab, and after a second course of pembrolizumab plus radiation therapy. Investigators then analyzed the biopsied tissues.
The investigators used single-cell genetic profiling to identify the cancer cells and different types of immune cells making up each tumor. They also looked at proteins expressed by cells, mapping their positions and permitting a better understanding of how the different cells interact. The analysis yielded profiles for three types of treatment responders, Dr. Knott said.
“We saw that tumors of patients who didn’t respond at all to presurgical therapy had no immune cells in them, and tumors of patients who responded right away to immunotherapy were packed with certain types of immune cells,” Dr. Knott said. “That wasn’t surprising. But we found another group of patients with tumors that looked quite similar to the tumors of nonresponders and didn’t respond to the initial round of immunotherapy. However, they did respond after the combination of immunotherapy and radiotherapy. After the combination therapy, immune cells invaded the tumors, and the tumors shrank.”
Dan Theodorescu, MD, PhD, Director of Cedars-Sinai Cancer and the PHASE ONE Distinguished Chair, said that the study’s findings suggest radiotherapy may positively impact immune response in these tumors.
“This study will guide investigators toward the next generation of clinical trials,” Dr. Theodorescu said. “The investigators also describe a new framework for mapping the distribution of immune cells within tumors, and that could help us identify new precision medicine approaches for patients with breast cancer [as well as] other cancers.”
The investigators’ next task is to find practical ways to identify these responder groups in a clinical setting, via blood samples or other means, to better tailor treatments. They will also explore the possibility of combining radiotherapy with other types of immunotherapy prior to surgery as a way to improve response for high-risk patients, Dr. Shiao said.
Disclosure: For full disclosures of the study authors, visit cell.com/cancer-cell.
