TILs A GOOD PROGNOSTIC FACTOR IN TRIPLE NEGATIVE BREAST CANCER

NEW YORK (Reuters Health) - The presence of tumor-infiltrating lymphocytes (TILs) is associated with a reduced risk of death and distant recurrence in women with triple-negative breast cancer (TNBC), according to results from two trials.

As Dr. Sylvia Adams from New York University Cancer Institute told Reuters Health by email, "evaluating lymphocytic infiltration at the time of routine histopathologic assessment improves outcome prediction in patients with triple-negative breast cancer (over the standard TNM staging)."

"More importantly," she added, "the data implicate that TNBC are highly immunogenic with the majority of tumors harboring lymphocytes and that the antitumor host immunity plays a role in the outcome of patients."

Recent studies have confirmed that TILs are most frequently found in highly proliferative tumors and that their presence at diagnosis is associated with a favorable response to neoadjuvant and adjuvant therapy, Dr. Adams and colleagues write in Journal of Clinical Oncology, online July 28.

The team used data from two adjuvant phase 3 trials to evaluate the prognostic utility of TILs within intraepithelial (iTILs) and stromal compartments (sTILs) in 481 women with TNBC treated with adjuvant anthracycline-containing chemotherapy.

Most tumors had lymphocyte infiltration, which was significantly greater in the stromal compartment (80% had at least 10% sTILs) than in the intraepithelial compartment (15% had at least 10% iTILs), according to the report.

Only 4.4% of TNBCs (21/481) had at least 50% TILs, and there were no strong associations between TIL scores and age, menopausal status, or tumor size. The presence of positive lymph nodes, however, increased the likelihood of sTILs being present.

Each 10-point increase in sTIL score was associated with a 14% decrease in the risk of tumor recurrence or death, an 18% decrease in the risk of distant recurrence, and a 19% decrease in the risk of death.

In multivariable analysis, sTILs independently predicted disease-free survival, distant recurrence-free interval, and overall survival.

"TILs at diagnosis therefore likely indicate an ongoing antitumor immune response, which can contribute to improved outcomes (as shown for other solid tumors)," the researchers note, "although underlying mechanisms such as increased response to cytotoxics (suggested by neoadjuvant study) and/or eradication of micrometastatic disease have not yet been fully investigated."

"As all of the patients in our study received adjuvant anthracycline-based chemotherapy, the results do not provide guidance on the choice of treatment regimen and whether patients benefit from treatment or not," Dr. Adams said. "Therefore, TIL assessment should be included in clinical trials to determine its predictive value, which is currently done in several neoadjuvant and adjuvant studies."

"Estimation of the lymphocyte content based on histopathological evaluation of H&E stained tumor sections is a simple method," she explained. "Efforts are ongoing to standardize the TIL evaluation and to establish international guidelines which will provide the basis for incorporation of this biomarker into clinical trials."

Dr. Adams added, "What I am most excited about is that by therapeutically targeting and harnessing the immune system, we have a tremendous opportunity to improve cure rates in patients with TNBC."

In a related editorial, Dr. Sherene Loi from Peter MacCallum Cancer Centre in East Melbourne, Australia, notes that the utility of measuring TILs "will ultimately define the cutoff used to make decisions about therapy."

"We now have evidence from three clinical trial cohorts that immunity is important for the outcomes of primary TNBC, as well as in pre- and postneoadjuvant chemotherapy samples," Dr. Loi concludes. "It would therefore seem that this finding is robust."

"Although at present, the clinical utility of TILs in day-to-day management of primary TNBC is limited, TILs could be useful for stratification in future clinical trials enrolling patients with TNBC once the evaluation method has been standardized," she adds. "The challenge ahead is to determine if TILs per se or a specific immune marker will be predictive for benefit with T-cell checkpoint inhibitors and how to successfully modulate immunity to reduce mortality from TNBC."

SOURCE: http://bit.ly/1o8YoCj and http://bit.ly/1o8YoCj

J Clin Oncol 2014.