To understand triple-negative breast cancer, we first have to understand how breast cancer is classified. Breast tumors are broadly classified into three major subtypes: estrogen receptor (ER)- and/or progesterone receptor (PR)-positive, HER2 receptor positive, or triple-negative.
Triple-negative breast cancer (TNBC) is defined by what it’s not. The tumor cells do not express either of the hormone receptors, or the HER2 receptor. About 10-15 percent of breast cancers are triple-negative, including many hereditary breast cancers that are driven by mutations in the BRCA1 or BCRA2 genes.
TNBC is a devastating disease, and this is compounded by a lack of targeted therapies. Triple-negative breast cancer research is a major focus for BCRF. This past year, BCRF is supporting more than $15 million research in triple-negative metastatic breast cancer.
This research has led scientists to discover that TNBC is more likely to respond to immunotherapy than other types of breast cancer, but response rates are still low. Being able to predict which patients are likely to respond is key to the success of immunotherapy.
On Triple-Negative Breast Cancer Day, we highlight promising results from a recent study and how it may impact those with metastatic triple-negative breast cancer.
Immunotherapy shows promise for patients with triple-negative breast cancer.
The study, led by BCRF investigator, Dr. Leisha Emens, may change the standard of care for some patients with metastatic triple-negative breast cancer.
As reported in the New England Journal of Medicine, adding the immunotherapy drug, atezolizumab, to chemotherapy improved survival of patients with advanced triple-negative breast cancer compared to chemotherapy alone, specifically in patients whose tumors had high amounts of the immune checkpoint protein PD-L1.
“Immunotherapy is revolutionizing cancer therapy across multiple tumor types,” Dr. Emens said at the 2018 San Antonio Breast Cancer Symposium where she presented new data from the IMpassion 130 trial.
“The breakthrough came with the discovery of the PD1 pathway.”
What is PD-1?
The PD1 receptor forms a bond with a partner protein called PD-L1, thereby shutting down the immune response. Tumors may hijack this system by increasing PD-L1 production in the tumor microenvironment, effectively shutting down the immune response.
Anti-PD-L1 therapy, like that used in the IMpassion130 study, prevents PD-L1 and PD1 from forming a bond and allows the T-cells, the smart bombs of the immune system, to seek out tumor cells and kill them.
The Study
IMpassion130 was the first international, randomized, placebo-controlled, double-blind Phase III trial that demonstrated clear benefit of immunotherapy in selected patients with metastatic triple-negative breast cancer. In addition, it identified a marker to identify those patients most likely to benefit.
The trial, which included BCRF researchers Dr. Hope Rugo, Dr. Eric Winer and Dr. Sherene Loi in addition to Dr. Emens, enrolled 902 patients with advanced triple-negative breast cancer who had not received prior treatment for their metastatic disease. All patients received Abraxane® (nab-paclitaxel) as standard chemotherapy; half received the PD-L1 drug atezolizumab in addition to chemotherapy while the other received chemotherapy plus a placebo.
The trial investigators compared progression-free survival–PFS (the time between start of therapy and when the tumor growth increases or spreads) –between the group that received atezolizumab plus chemotherapy and the group that received chemotherapy plus placebo. In both the overall population and in patients with high PD-L1 tumors, adding anti-PD-L1 therapy to chemotherapy had a significant improvement in PFS. In patients with high levels of PD-L1 in the immune cells around the tumor, PFS was increased from 5.0 months to 7.5 months.
In the first interim analysis of overall survival (OS), the trial investigators found that the addition of anti-PD-L1 therapy to chemotherapy increased OS from 15.5 months to 25 months, also specifically in those patients with high PD-L1 levels. Together, these findings identify PD-L1 as a predictive biomarker that should be used to select patients most likely to benefit from this combination therapy, as the PD-L1 negative subgroup did not benefit from the addition of immunotherapy to chemotherapy.
“This is a significant improvement in this subgroup of patients,” noted Dr. Emens. “We believe this trial has identified a new standard of care for first-line therapy for metastatic triple-negative breast cancer patients with PD-L1+ disease,” she said.
Challenges ahead
While there is much excitement about the results of IMpassion130, there are still many challenges to making immunotherapy effective in a wider range of breast cancer patients.
Dr. Emens explained that IMpassion 130 involved patients who had not received prior therapy for metastatic or locally advanced TNBC. Efforts are ongoing to develop approaches for effective immunotherapy later in the course of therapy as well as in the neoadjuvant (pre-surgical) setting for early-stage breast cancer.
Efforts are also ongoing by Dr. Emens and others to develop alternative strategies for PD-L1-negative breast cancer patients that may include vaccine or other approaches in addition to anti-PD-L1 therapy.
Watch the full interview with Dr. Emens below.
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