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TILs Emerge as Robust Biomarker, Shed Light on Immunotherapy Potential in TNBC

Laura Panjwani
Published: Wednesday, Oct 14, 2015

Sylvia Adams, MD

Sylvia Adams, MD

Tumor-infiltrating lymphocytes (TILs) have emerged as a strong prognostic biomarker in triple-negative breast cancer (TNBC).

A recent study, which evaluated over 500 tumors from the Eastern Cooperative Oncology Group (ECOG) trials E2197 and E1199 for density of TILs, found that for each 10% increase in stromal TILs, there was a 14% reduction of recurrence risk or death (P = .02), 18% reduction of risk of distant recurrence (P = .04), and a 19% reduction of risk of death (P = .01).

With a median follow-up of 10.6 years, higher stromal TIL scores were associated with better prognosis, according to study results.

Understanding the impact of TILS on TNBC prognosis could lead to a better understanding of which patients will respond positively to immunotherapy, said lead study author Sylvia Adams, MD, associate professor, Department of Medicine, New York University Langone Medical Center.

In an interview with OncLive, Adams explains the potential of TILs, as well as other biomarkers, including PD-1/PD-L1, in TNBC and other breast cancer types.

OncLive: What is the role of TILs as a prognostic biomarker for triple-negative breast cancer?

Dr Adams: It is now well established that TILs are a robust biomarker in early TNBC, independent of any other known prognostic factor. In our study, which used archived samples from patients in E1199 and E2197, and looked at the tumorsfrom 500 women who underwent adjuvant chemotherapy for TBNC. It showed that the presence of TILS in their tumors at diagnosis so, really, in the untreated patient, predicted better survival. It was a continuous marker, so any increase in TILs was predictive. This is very strong data, which have been confirmed by studies in Europe that showed almost identical data. We are fairly confident in these findings.

What are potential impacts of these findings?

Basically, TILS represent the patient’s own immune reaction against the tumor. They are found in the tumor and, when they are looked at in more detail, it is clear that they contain tumor antigen-specific T cells. That means that the patient has generated an immune response against the tumor, and this helps with lowering cancer recurrence after adjuvant chemotherapy and improving survival in TNBC. That is the major excitement, because it means that, maybe, by improving the immune response against the tumor we can further impact survival. It is already naturally shown to be significant.

Is there any possibility that this biomarker could be effective in other breast cancer types beside TNBC?

It has been studied extensively in other breast cancer types. In some hormone receptor [HR]–positive tumors TILS are found at diagnosis, however, they do not predict outcomes. In HER2-positive breast cancer, there are also TILs present in some tumors. Some studies show that they predict outcome for patients that receive adjuvant chemotherapy with trastuzumab (Herceptin), while other studies did not confirm this. This remains controversial. We are focused on TNBC, which is the area with the most promise for TILs as a predictive biomarker and the area in most need of novel therapies.

What are the next steps in this research?

The next steps will be to test immunotherapies in different settings of TNBC. We would like to test them in the advanced disease setting of just a single agent, but also in combination with certain chemotherapies, which may stimulate immune response, and see how it clinically works out. Certainly, it is also important that we look at TILs in pretreatment biopsies to further refine this and other biomarkers. Excitingly, there are going to be FDA registration trials planned for TNBC, which are randomizing patients to standard initial chemotherapy with or without the added immunotherapy or use immunotherapy as single agent after chemotherapy has failed.

Could PD-1 and PD-L1 have a role as a biomarker for immunotherapies in breast cancer?

It looks like PD-1 and PD-L1 in many other cancers are good predictors of response. Currently ongoing trials are looking at what biomarkers can be used in breast cancer, but it is not yet known.

What is on the horizon for immunotherapy in breast cancer?

The fact that we have a targetable subset of breast cancers, which is the TNBC subgroup, is the major accomplishment of the past few years. The potential success that immunotherapies hold in TNBC includes durable responses in patients who have metastatic disease, which typically has a very poor prognosis. It is very exciting to be in the immunotherapy space and be able to find treatments for women who have very limited treatment options. Chemotherapy is the main treatment for this subtype of metastatic TNBC, and outcomes have remained very poor despite chemotherapy, with a median survival of less than 1 year.

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