Is There a Future for Immunotherapy in Breast Cancer?

Lately, immunotherapy—treatment that helps the body’s own immune system fight cancer—has made frequent appearances in news headlines. Indeed, researchers have reported remarkable clinical trial results for a new class of drugs known as ‘immune checkpoint blockade drugs‘ in the treatment of metastatic melanoma, lung, and kidney cancers. Approvals from the U.S. Food and Drug Administration (FDA) for the drugs Keytruda and Opdivo for melanoma and lung cancer have quickly followed. However, it may be that immunotherapies won’t work for all cancers, but only for those considered to be ‘immunogenic’; that is, cancers that trigger activation of the immune system. Researchers are studying different types of breast cancer to determine whether they are immunogenic, and what that might mean for their prognosis and treatments. Continue reading…

A Breast Cancer Tumor's Immune Signature Could Predict Response to Neoadjuvant Therapy

“In a study reported in the Journal of Clinical Oncology, Denkert et al found that increased tumor-infiltrating lymphocytes and the presence of lymphocyte-predominant breast cancer were associated with increased rates of pathologic complete response in patients receiving neoadjuvant anthracycline-taxane treatment with or without carboplatin. Higher rates were observed with carboplatin, with treatment interactions being significant among all patients and among those with HER2-positive disease but not among those with triple-negative disease. mRNA profiles for immune-related genes also distinguished pathologic complete response rates.

“The study involved 580 tumors from patients in the GeparSixto trial, which assessed the effects on pathologic complete response rates of adding carboplatin to neoadjuvant anthracycline plus taxane treatment. The current analysis assessed the effects on pathologic complete response of tumor-infiltrating lymphocyte levels, the presence of lymphocyte–predominant disease, and levels of immune-activating (CXCL9, CCL5, CD8A, CD80, CXCL13, IGKC, CD21) and immunosuppressive genes (IDO1, PD-1, PD-L1, CTLA4, FOXP3).”

Profiling Immune System Genes Could Predict Benefit of Adjuvant Trastuzumab in Early-Stage HER2-Positive Breast Cancer

The gist: Analyzing genes that affect the activity of a patient’s immune system could help doctors predict how well trastuzumab (Herceptin) will work. Researchers recently analyzed immune system genes in 1,282 HER2-positive tumor samples from patients. They found that patients who had more immune system genes “turned on” survived longer without their cancer returning (recurrence) if they received adjuvant (after-surgery) Herceptin instead of chemotherapy. Patients with fewer active immune system genes did equally well whether they were treated with Herceptin or chemotherapy. These results show that immune system gene profiling could potentially be used to make decisions about how to treat early-stage HER2-positive breast cancer.

“In a study reported in the Journal of Clinical Oncology, Perez et al found that an immune function gene profile was associated with significantly improved relapse-free survival among patients with early-stage HER2-positive breast cancer who had trastuzumab (Herceptin) added to adjuvant chemotherapy in the North Central Cancer Treatment Group (NCCTG) N9831 trial…

“The investigators concluded: ‘Increased expression of a subset of immune function genes may provide a means of predicting benefit from adjuvant trastuzumab.’

“They observed: ‘The potential clinical significance of our results, within the context of identification of patients who are likely to benefit (increased [relapse-free survival]) from adjuvant trastuzumab, is considerable. Identification of patients who are unlikely to benefit from trastuzumab on the basis of evaluation of the immune status of the tumor before initiation of therapy may have even greater significance. Patients with low immune function gene expression scores might be enrolled onto trials to test the efficacy of HER2-targeted regimens that combine trastuzumab with some other therapeutic agent. Alternatively, these patients might be the focus of future clinical trials designed to evaluate therapeutic approaches that might enhance the immune activity within HER2-positive tumors and thereby sensitize the tumors to biologic therapies.

“One strategy in this regard cited by the investigators is the inhibition of immune-suppressive signaling pathways—eg, with agents targeting programmed cell death protein (PD-1) or its ligand, PD-L1. Another is to increase immunoreactivity via modification of the immunoglobulin backbone of anti-HER2 antibodies.”

The Future of Precision Immunology

The gist: This Q&A with an immunotherapy expert explores the future of immune system profiling to inform personalized cancer treatments.

“In his State of the Union address, President Obama announced a new precision medicine initiative to work on finding a cure for cancer and other diseases. Howard L. Kaufman, a leading immunotherapy expert from Rutgers Cancer Institute of New Jersey recently shared his thoughts in the Journal of Clinical Oncology on the progress doctors have made in precision immunology – a type of precision medicine that involves creating a profile of a patient’s immune system to fight disease. Kaufman, associate director for clinical science and chief surgical officer at the Cancer Institute, answered some questions from Rutgers Today on the future of the precision medicine field.”