Link Found Between Immune Activation and Recurrence of HER2+ Breast Cancer

A scientist looking at a DNA sequence as part of the HER2 studyDana-Farber Cancer Institute physician-researcher Ian E. Krop, MD, PhD, has uncovered a promising way to identify patients who will respond well to certain adjuvant therapies for treating HER2+ breast cancer. He presented the findings of his biomarker analysis at the 2019 ASCO Annual Meeting.


Dr. Krop, along with collaborators from academic institutions around the world, conducted a comprehensive genomic analysis of patients enrolled in the APHINITY trial, a large-scale, phase III study investigating the benefit of adjuvant therapy with pertuzumab when added to trastuzumab and chemotherapy in women with HER2+ early-stage breast cancer. This form of breast cancer affects an estimated 50,000 people a year in the United States and is associated with a high rate of recurrence if left untreated or treated with conventional therapy.

“While the APHINITY trial demonstrated a benefit of the combination therapy in reducing breast cancer recurrence, the overall magnitude of the benefit was relatively small,” said Dr. Krop. “We hypothesized that certain biomarkers may help to identify specific subgroups of patients who are most likely to benefit significantly from the addition of pertuzumab to their treatment.”

Instead of analyzing just a few biomarkers, as had been done in previous analyses, Dr. Krop and his team had the resources to conduct a more comprehensive analysis. In addition to looking at DNA mutations, RNA expression and immune biomarkers, they analyzed different ways of measuring HER2 itself.

According to Dr. Krop, one significant but “not unsurprising” finding was that patients with high levels of HER2—the target of pertuzumab—benefit the most from the addition of the adjuvant therapy. Another, more impactful finding was that those cancers with the highest levels of immune activation, as indicated by immune gene signatures and the number of tumor-infiltrating lymphocytes, would particularly benefit.

“Earlier studies of pertuzumab suggested that it worked by blocking HER2 signaling,” he said. “This new analysis suggests that instead, it works in large part by stimulating or modulating the immune response.”

According to Dr. Krop, the genomic analysis had an additional benefit in helping to increase the medical oncology community’s understanding of the biology of HER2+ breast cancer and how immune effects occur. He is following up on his biomarker analysis as the lead investigator in a new study with 15 other large cancer centers that will evaluate other immune-activating agents in combination with chemotherapy and trastuzumab for patients with metastatic HER2+ breast cancer. It is the first trial to study two different immune therapies in this type of breast cancer.

“We hope this new study will continue to enhance treatment approaches to further improve outcomes,” he said. “Taken together, these studies reflect the long-standing role of Dana-Farber/Brigham and Women’s Cancer Center in using the latest generation of RNA and DNA sequencing to enhance patient care.”