Shorter, safer protocol effectively treats triple-negative breast cancer
Adding radiation at start of treatment regimen produced results similar to current standard of care with fewer toxic side effects
DALLAS – Jan. 30, 2025 – A far shorter, simpler, and less toxic treatment protocol for patients with triple-negative breast cancer produced outcomes similar to the current standard of care, a clinical trial co-led by a UT Southwestern Medical Center researcher shows. The findings, published in the Journal of Clinical Oncology, could lead to new treatment regimens that are significantly safer and less detrimental to patients’ quality of life.
“We think it’s very encouraging to achieve the same results with less chemotherapy, less immunotherapy, and less toxicity by reconfiguring the timing of the radiation that most triple-negative breast cancer patients receive,” said study co-leader Heather McArthur, M.D., M.P.H., Professor of Internal Medicine in the Division of Hematology and Oncology and Clinical Director of the Breast Cancer Program at the Harold C. Simmons Comprehensive Cancer Center.
About 10%-15% of breast cancers are triple negative, meaning that these breast cancer cells don’t have receptors for estrogen or progesterone and make little, if any, of a protein called HER2. Although this high-risk subset of breast cancer has the same signs and symptoms as other common breast cancer subtypes, it tends to affect younger patients and is more common among Black patients. It also often recurs, grows and spreads faster, has fewer treatment options and usually a worse prognosis, Dr. McArthur explained. Patients whose tumors metastasize after initial treatment typically have a life expectancy of just 12 to 18 months.
In a global phase three clinical trial called KEYNOTE-522 that Dr. McArthur co-authored and that published results last year, 1,174 patients at 181 sites with triple-negative breast cancer received the immunotherapy drug pembrolizumab in combination with four chemotherapy drugs before their tumors were surgically removed. They then continued receiving immunotherapy for the next year. In that study, 64% of patients had a pathologic complete response – meaning that no evidence of cancer remained – an unprecedented outcome that made this protocol the new standard of care.
However, Dr. McArthur said, almost all patients who followed this protocol experienced toxicity, causing symptoms such as nausea and vomiting, diarrhea, anemia, and neuropathy. Additionally, the yearlong regimen required numerous medical and follow-up appointments, which affect quality of life.
Hoping to counteract these issues, Dr. McArthur and colleagues devised a new protocol in which 66 breast cancer patients received two doses of pembrolizumab immunotherapy along with radiation before chemotherapy chosen by their doctors, and then followed by surgery. Fifty-four of these study subjects had triple-negative breast cancer, and 12 had hormone-receptor positive breast cancer. The median age of patients was 53 years old. Among participants treated at a single site in California, nearly 73% were white, 12% were Black, 12% were Asian, and 3% were other. The researchers followed these volunteers for an average of 32 months.
Results showed that 59% of patients with triple-negative breast cancer treated on this protocol experienced a total pathologic complete response, a rate close to that in the KEYNOTE-522 trial. However, only 41% of patients in this regimen had serious toxicity, which was about half of that seen in KEYNOTE-522 patients. The significantly shorter treatment timeline also meant that those who responded to the new protocol were finished with cancer therapy far sooner, eliminating a significant number of doctor visits.
Dr. McArthur explained that moving radiation to the beginning of the treatment protocol could help immunotherapy and chemotherapy drugs be more effective, allowing doctors to reduce dosages and durations. Clinical trials ongoing at Simmons Cancer Center are investigating other methods to use radiation in novel ways for cancer therapy.
Dr. McArthur holds the Komen Distinguished Chair in Clinical Breast Cancer Research. She receives personal consulting compensation from Merck.
This study was funded by the National Cancer Institute (NCI) Cancer Center Support Grant (P30CA142543) and grants from the Breast Cancer Research Foundation and the Department of Defense Breast Cancer Program (W81XWH-19-0599 and HT94252310961).
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UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 24 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.