The association of abundant tumor-infiltrating lymphocytes (TILs) in breast cancer tissue with outcomes in patients with early-stage triple-negative breast cancer (TNBC) who do not receive chemotherapy has not been well studied, wrote Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues, in JAMA.
Biomarkers to guide systemic treatment and avoid overtreatment are lacking, and such markers could help identify patients who could achieve increased survival with less intensive therapy, continued the authors of the new study of nearly 2000 individuals.
“TNBC is the most aggressive subtype of breast cancer, and for this reason, current treatment guidelines recommend chemotherapy using multiple drugs either before or after surgery,” Dr. Leon-Ferre said in an interview. “We have learned over the last several years that TNBC is not a single disease, but that there are several subtypes of TNBC that have different risks and different vulnerabilities, and treating all patients similarly may not be optimal.”
What is Known About Tumor-Infiltrating Lymphocytes and Cancer?
Previous studies have shown improved survival in patients with early-stage TNBC and high levels of TILs who were treated with adjuvant and neoadjuvant chemotherapy, compared with those with lower TILs. In a pooled analysis of 2148 patients from nine studies published in the Journal of Clinical Oncology in 2019, a higher percentage of TILs in the stroma surrounding a tumor was significantly associated with improved survival in TNBC patients after adjuvant chemotherapy.
Another study published in the Journal of Clinical Oncology in 2022 showed that elevated TILs were significant predictors of overall survival, but the study included fewer than 500 patients.
The potential mechanisms that drive the association between elevated TILs and improved survival include the ability of TILs to attack cancer cells, Dr. Leon-Ferre said in an interview.
The goal of this study was to evaluate whether TILs could identify a subset of patients with TNBC who had a very low risk of cancer recurrence even if chemotherapy was not given.
“Indeed, we found that patients with stage I TNBC and high TILs had a very low risk of recurrence even when chemotherapy was not administered. These findings will pave the way for future studies aiming to reduce the need for multiple chemotherapy drugs in patients with stage I TNBC and decrease the side effects that patients face,” he said.
What Does the New Study Add?
The current study included 1966 individuals from 13 sites in North America, Europe, and Asia who were diagnosed with TNBC between 1979 and 2017 and were treated with surgery, with or without radiotherapy but with no adjuvant or neoadjuvant chemotherapy. The researchers examined the abundance of TILs in the breast tissue of resected primary tumors; the primary outcome was invasive disease-free survival (iDFS), with recurrence-free survival, distant recurrence-free survival, and overall survival as secondary outcomes.
The median age of the patients was 56 years, 55% had stage I TNBC, and the median TIL level was 15%.
A total of 417 patients had a TIL level of 50% or more, and the 5-year iDFS for these patients was 94%, compared with 78% for those with a TIL level less than 30%. Similarly, 5-year overall survival was 95% in patients with a TIL level of 50% or more, compared with 82% for patients with TIL levels of less than 30%.
Additionally, each 10% increase in TILs was independently associated not only with improved iDFS (hazard ratio[HR], 0.92), but also improved recurrence-free survival (HR, 0.90), distant recurrence-free survival (HR, 0.87), and overall survival (HR, 0.88) over a median follow-up of 18 years.
The current study shows that cancer stage based on tumor size and the number of lymph nodes should not be the only considerations for making treatment decisions and predicting outcomes, Dr. Leon-Ferre said in an interview.
“In fact, our study shows that for tumors of the same stage (particularly for stage I), the risk of recurrence is different depending on the number of TILs seen in the breast cancer tissue. When chemo is not given, those with high TILs have lower risk of recurrence, whereas those with low TILs have a higher risk of recurrence,” he said.