A new study finds that triple-negative breast cancer tumors with increased immune cells have a lower risk of recurrence after surgery, even when not treated with chemotherapy

ROCHESTER, Minn. — A new multicenter, international study indicates that people who have early-stage triple-negative breast cancer (TNBC) and high levels of immune cells in their tumors may have a lower risk of recurrence and better survival rates, even when not treated with chemotherapy. The study was published in the Journal of American Medical Association (JAMA).

Triple-negative breast cancer is a subtype of breast cancer that does not respond to drugs that target the estrogen receptor or the human epidermal growth factor receptor 2 (HER2) protein. It grows quickly, is more likely to spread beyond the breast before a diagnosis, and is more likely to come back than other types of breast cancer. Triple-negative breast cancer accounts for about 15 percent of all types of breast cancer and is more common in younger people and in women of African American, Hispanic, and Indian descent. Immune cells, also known as tumor-infiltrating lymphocytes (TILs), are naturally occurring immune system cells that can travel from the bloodstream to a tumor and can recognize and destroy cancer cells.

“This is an important finding because it highlights that the abundance of tumor-infiltrating lymphocytes in breast tissue is a prognostic biomarker in people with early-stage triple-negative breast cancer, even when chemotherapy is not administered,” says Dr. Roberto Leon. Ferre, a breast medical oncologist at the Mayo Clinic Comprehensive Cancer Center and first author of the study. “The study findings may inspire future clinical trials to explore whether patients with a favorable prognosis (elevated levels of tumor-infiltrating lymphocytes) can avoid intensive chemotherapy regimens.”

“This meta-analysis strongly confirms the prognostic value of tumor-infiltrating lymphocytes that we previously reported in patients with triple-negative breast cancer who were treated with chemotherapy and extends it to patients who were treated without chemotherapy,” says Dr. Sarah Flora Jonas, statistician. in Gustave Roussy and first co-author of the study. “Future studies could allow the use of this biomarker in conjunction with standard clinicopathological factors to communicate treatment decisions in patients with triple-negative breast cancer.”

“It is interesting to note that the first report that revealed that a higher number of immune cells is related to a better prognosis in patients with breast cancer was described by doctors at Mayo Clinic more than 100 years ago,” says Dr. Roberto Salgado, co-chair of the International Working Group on Immuno-oncological Biomarkers and co-director of the study. “It took a global effort and a subsequent century to re-examine this biomarker and approximate its application in patient healthcare.”

“Currently, tumor-infiltrating lymphocytes are not measured or reported in the routine examination of breast cancer tissue samples,” said co-senior author Dr. Matthew Goetz, a medical oncologist at Mayo Clinic Comprehensive Cancer Center with the Erivan K. Haub Family Professor of Cancer Research Award in Honor of Dr. Richard F. Emslander. “While previous studies focused on measuring tumor-infiltrating lymphocytes in people treated with chemotherapy, this is the largest study that comprehensively demonstrates that the presence of tumor-infiltrating lymphocytes influences the natural behavior of breast cancer in people undergoing chemotherapy.” surgery or radiation without additional medical treatment.”

For this study, researchers at Gustave Roussy and Mayo Clinic, in collaboration with the International Immuno-Oncology Biomarkers Working Group, led 11 additional groups to collect data from 1,966 participants with early-stage triple-negative breast cancer who underwent surgery alone. with or without radiotherapy, but did not receive chemotherapy. Participants were followed for a median of 18 years. The results revealed that higher levels of tumor-infiltrating lymphocytes in breast cancer tissue were associated with lower recurrence rates among participants with early-stage triple-negative breast cancer.

“Five years after surgery, 95 percent of participants with small tumors, stage 1 triple-negative breast cancer, and whose tumors had high levels of tumor-infiltrating lymphocytes were alive, compared with 82 percent of those patients whose tumors had low levels of tumor-infiltrating lymphocytes. Importantly, the rate of breast cancer recurrence was significantly lower among patients whose tumors had high levels of tumor-infiltrating lymphocytes,” says Dr. Stefan Michiels, co-lead author, Oncostat team leader, Gustave Roussy, Inserm U1018, Paris-Saclay University. “With approximately 2,000 study participants, we assembled the largest international cohort of people with triple-negative breast cancer, across three continents, in whom the primary treatment was surgery without chemotherapy.”

“The results of this study could lead to a recommendation to include tumor-infiltrating lymphocytes in pathology reports of early-stage triple-negative breast cancer worldwide, as they have the potential to inform physicians and patients about the right time to choose treatment options,” says Dr. Salgado.

Additionally, this biomarker would only require visual evaluation by a pathologist under microscopic observation, meaning there are no additional costs derived from identifying the presence of immune cells. This could be very beneficial for regions with limited resources, adds Dr. Leon-Ferre.

Most people with early-stage triple-negative breast cancer undergo chemotherapy before or after surgery, including those with stage 1 breast cancer. Most people receive several combination chemotherapy drugs, which can cause significant side effects. Currently, the main factors taken into account in determining the course of each person’s chemotherapy treatment are the size of the tumor and the presence of lymph node metastases. However, the authors identified that the number of tumor-infiltrating lymphocytes further influences the risk of future recurrence.

The investigators plan to evaluate tumor-infiltrating lymphocytes as biomarkers in prospective clinical trials evaluating chemotherapy selection based on tumor-infiltrating lymphocyte levels. At this time, ongoing efforts are underway to conduct additional research with other potential biomarkers.

JOURNALISTS: Dr. Leon-Ferre offers interviews in Spanish and English.

See the study for a full list of authors, disclosures, and funding.

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