番茄社区

Higher levels of tumor infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC) not treated with systemic therapy correlated with significantly better survival, according to a retrospective study of an international patient population.

Five-year distant relapse-free survival (DRFS) for stage I TNBC was 78% among patients with a TIL level less than 30% compared with 94% for those with levels of 50% or greater. Five-year overall survival (OS) was 82% with the low TIL level compared with 95% with the higher level.

After a median follow-up of 18 years, each 10% greater TIL level was associated with incremental 8-13% advantages in invasive disease-free survival (iDFS), relapse-free survival (RFS), DRFS, and OS, reported Roberto Leon-Ferre, MD, of the Mayo Clinic in Rochester, Minnesota, and co-authors in .

"If you look at a tumor at diagnosis, before treatment, and then at the end of the chemotherapy, at the time of surgery, there's a subset of patients that have an increase in TILs, and it appears that those patients that have higher levels of TILs at the end of therapy tend to do better," Leon-Ferre told 番茄社区.

Similar relationships between TILs and outcome have been demonstrated in patients who have received neoadjuvant or adjuvant therapy.

"One of the unique aspects of our study is it's the largest study showing TILs in patients who have never received chemotherapy," he added. "Our focus here has been on whether we can use TILs to identify patients that perhaps do not need chemotherapy. Currently, anybody with triple-negative breast cancer is given combinations of chemotherapy either before or after surgery. Our data suggest that maybe that's not something that should be given to all patients."

Studies also have shown that tumors with higher levels of TILs appear to respond better to chemotherapy and to immunotherapy, said Leon-Ferre.

TNBC is an aggressive form of breast cancer associated with higher recurrence rates and mortality. As such, adjuvant or neoadjuvant chemotherapy is recommended for most patients. Biomarkers to guide optimal use of systemic therapy without overtreatment have yet to be identified.

TIL levels reflect active antitumor immune response, and previous studies showed that patients with early TNBC and high TIL levels in breast tumors have and higher rates of after neoadjuvant chemotherapy. Several small studies had suggested that higher TIL levels correlate with improved survival even in the absence of adjuvant or neoadjuvant chemotherapy.

In an effort to clarify associations between TIL levels and outcomes in early TNBC, investigators at 13 centers in North America, Europe, and Asia pooled data on patients with early TNBC diagnosed from 1979 to 2017 who were not treated with adjuvant or neoadjuvant systemic therapy. Follow-up continued to Sept. 27, 2021.

TIL levels in breast cancer tissue were ascertained by pathologists trained in TIL assessment according to international guidelines. Given the lack of clearly defined optimal TIL thresholds, investigators analyzed TIL levels as a continuous value and according to prespecified thresholds at 30% and 50%. The primary outcome was iDFS; secondary outcomes included RFS, distant disease-free survival (DDFS), DRFS, and OS.

Data analysis included 1,966 patients who had a median age of 56 (41% younger than 50). T1 tumors accounted for 60% of the specimens and T2 for 36%. Additionally, 86% of patients had node-negative disease, and 55% had stage I disease.

The median TIL level was 15%; 34% of patients had TIL levels ≥30%, and 21% had TIL levels ≥50%. Higher TIL levels were associated with younger age and higher tumor grade but not with tumor size or nodal status. Event rates were 55% (1,074) for iDFS, 48% (894) for DDFS, 42% (832) for DRFS, and 41% (803) for OS.

Higher TIL levels had significant associations with the primary and secondary endpoints (P<10^-6). Each 10% increase in TIL level was associated with a significantly lower risk for each outcome:

• 8% for iDFS (HR 0.92, 95% CI 0.89-0.94)
• 10% for RFS (HR 0.90, 95% CI 0.87-0.92)
• 13% for DDFS (HR 0.87, 95% CI 0.85-0.90)
• 13% for DRFS (HR 0.87, 95% CI 0.84-0.90)
• 12% for OS (HR 0.88, 95% CI 0.85-0.91)

Incorporating TIL levels into a clinicopathologic model improved the area under the curve at 5 and 10 years for all outcomes.

Ongoing studies include a focus on the biology of intratumoral immune cells in an effort to understand how immune cells identify cancer cells and eradicate them. Additionally, investigators are examining TILs' potential as a biomarker to select patients for neoadjuvant or adjuvant therapy.

"We are proposing clinical trials to use TILs to select the type of treatment a patient should have," said Leon-Ferre. "Our data would suggest, for example, that a patient with stage I triple-negative breast cancer with high TILs perhaps doesn't need as much chemotherapy, and then we can decrease the side effects and long-term complications."

One advantage of TILs as a biomarker is that it, "unlike many other biomarkers, doesn't require any extra materials or extra test," he added. "It doesn't have additional costs because this is really analyzed looking at the same tissue sample that is used to make the diagnosis. It only requires training of the pathologist. This is a potential biomarker that could be deployed in areas of scarce resources, and that's one of the attractions."

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