DoD Breakthrough Award to Target Triple-Negative Breast Cancer

The Department of Defense has awarded a three-year $1.2 million Breakthrough Award grant to help researchers at the University of Kansas Cancer Center identify tailored treatments for people with triple-negative breast cancer.

Priyanka Sharma, MD, breast medical oncologist, and Shane Stecklein, MD, PhD, radiation oncologist, will lead the project. The intent of the Breakthrough Award program is to support research that has the potential to lead to or make breakthroughs in breast cancer. The Breakthrough Award is a coveted and highly competitive grant. Out of all breast cancers, triple-negative breast cancer is often more aggressive, difficult to treat and more likely to come back. About 15% of breast cancers diagnosed in American women are triple-negative. Unlike hormone-driven breast cancers and breast cancers driven by the HER2 gene, there are no targeted treatments for triple-negative breast cancer.

Recent clinical trials demonstrate that a combination of chemotherapy and immunotherapy is more effective compared to chemotherapy alone in triple-negative breast cancer. Immunotherapy harnesses the patient’s own immune system and equips it to better fight cancer. Although immunotherapy improves the effectiveness of chemotherapy, it also comes with risks. The patient’s immune system may attack its own tissues. This rare side effect can be severe and even deadly, and many patients with triple-negative breast cancer are cured with chemotherapy alone.

Drs. Sharma and Stecklein will look at two molecular markers:

• DDIR, a marker of immune system activation, and
• HRD, a marker that indicates defects in DNA repair that are associated with sensitivity to chemotherapy.

According to Dr. Sharma, these markers can predict how a patient will respond to treatment.

“People with triple-negative breast cancer have fewer options when it comes to personalized cancer treatment,” Dr. Sharma said. “By using DDIR and HRD together, we hope we can predict who will have good outcomes with chemotherapy alone and who will benefit from a combination of chemotherapy and immunotherapy.”

Dr. Stecklein added that by using this biology-driven classification scheme, they hope to define groups of patients who will benefit from specific treatment approaches. This will maximize the effectiveness of treatment and minimize or eliminate unnecessary or ineffective treatments that carry significant risks.

“We have known for years that triple-negative breast cancers are a biologically diverse group of tumors. Despite this knowledge, we approach treatment the same way for nearly all patients,” Dr. Stecklein said. “Our DDIR/HRD classification scheme gives us insight into how sensitive an individual triple-negative breast cancer patient’s tumor is to chemotherapy, and how primed her immune system is to help fight the tumor.”

The team will lean on their findings from two clinical trials. The NeoSTOP trial demonstrated that a less intense course of chemotherapy using two drugs led to similar outcomes compared to the standard four-drug chemotherapy regimen. The second study, NeoPACT, tested the less-intense course of chemotherapy with immunotherapy. Participants in both studies contributed tumor samples. The team has already measured DDIR in the NeoSTOP and NeoPACT tumor samples, and the grant will fund measuring HRD. They will then classify tumors based on whether they had one, both or neither of the markers and evaluate outcomes in patients who got chemotherapy alone or chemotherapy with immunotherapy. The grant will also support testing the DDIR/HRD classification scheme in a prospective cohort of triple-negative breast cancer patients to confirm their findings.

“The goal is to look at an individual’s tumor profile and customize treatment based on their unique cancer subtype,” Dr. Sharma said. “These findings may help us get closer to making precision medicine a reality for those with triple-negative breast cancer.”