In late 2015, Yale Cancer Center launched a clinical trial using an immunotherapy drug for patients with early-stage triple negative breast cancer (TNBC), a less common and aggressive type of breast cancer. In the Q&A below, Principal Investigator, Lajos Pusztai, MD, chief of breast medical oncology, discusses the trial and the potential of immunotherapy for treating breast cancer.
Q. Please explain the study and what makes it unique?
This is among the first clinical trials that include immunotherapy in the treatment of early stage TNBC. Immunotherapies represent a new class of drugs that increase the anti-cancer activity of immune cells residing in cancer tissues. Chemotherapy kills some cancer cells and damages many more, but these damaged cells often survive and cause recurrence of the cancer months or years later.
We hope that unleashing the immune system to clear up these damaged cancer cells will lead to more complete eradication of the cancer and ultimately to higher cure rates.
Q. Who is eligible for the study?
This trial was designed for early stage (clinical stage I-III) TNBC patients.
The immunotherapy, durvalumab, is given with standard-of-care chemotherapy before surgery.
Q. What are the major aims of the study?
The goal of the study is to investigate whether combining immunotherapy and chemotherapy leads to more frequent complete eradication of the cancer versus chemotherapy alone. We know that in 35-40% of TNBC patients, the best chemotherapies, when given before surgery, can lead to complete eradication of the cancer from the breast and lymph nodes.
Patients with this outcome have excellent long term survival prospects. However, this 35-40% complete response rate has not changed in 20 years, and we hope immunotherapy will change that.
Q. What is triple negative breast cancer? Who is most likely to present with it?
Triple negative breast cancer is characterized by the lack of estrogen and progesterone receptors and lack of HER-2 (human epidermal growth factor receptor-2). It is more common in younger women and African American women.
Currently, giving chemotherapy before or after surgery and radiation offers the best option for curing TNBC. By contrast, for estrogen receptor positive- and HER2-positive cancers, several new drugs have become available in the past 20 years that have significantly increased survival rates for these subtypes.
Q. We hear a great deal about the success of immune therapy with some other cancers. How widely is it being explored in any type of breast cancer?
At Yale Cancer Center, we have participated in the first few Phase I trials that explored these drugs in metastatic (stage IV) breast cancer. And preliminary results from five different multicenter trials show anti-cancer activity in 10-20% of patients, with few side effects. Most responses were seen in TNBC.
Based on these results, close to 30 clinical trials are now open nationally and internationally to test immunotherapy drugs more broadly in metastatic breast cancer. However, only few studies test these drugs in early stage (stage I-III) breast cancer.
Q. Yale Cancer Center study is among the first to explore immune therapy for early stage TNBC. Why aren’t there more studies doing this?
Historically, new drugs are extensively tested for efficacy in metastatic cancer before they move into earlier stage cancers. This can take years. Our trial, designed by Yale physicians, builds on our previous research about the role immune cells play in predicting prognosis and response to chemotherapies in TNBC.
There’s a growing body of promising immunotherapy research drawing from trials in a broad range of metastatic cancers, such as lung, melanoma, and bladder. This prompted us to investigate the efficacy of these drugs in early stage breast cancer, and we enrolled the first patient in late 2015. Several similar trials are now also underway in the U.S. and Europe. Yale investigators are excited to bring this new treatment modality to early stage TNBC patients.