“TILs could change breast cancer treatment”

The presence of tumor-infiltrating T cells (TILs) has a strong prognostic value for patients with early-stage triple-negative breast cancer. This was clearly demonstrated in a study by Verle Geerts and colleagues (Netherlands Cancer Institute, Amsterdam). I gave a presentation on this topic at the recent San Antonio Breast Cancer Symposium. “We hope that we will eventually be able to identify TILs in all early-stage breast cancer patients.”

TILs are playing an increasingly important role in breast cancer treatment. They are seen as a measure of the natural immune response against the tumor. But do TILs also say something about a patient’s prognosis or the chance of treatment success? “Research into this has mainly started in triple-negative breast cancer. Until a few years ago, this subtype of breast cancer was difficult to treat,” says Görtz. “But more and more is being learned about this type of breast cancer. It has been found that triple-negative breast cancer often has TILs. We want to use this property to improve treatment for these patients. TILs may be useful as a prognostic and preventive biomarker.”

stay well

The amount of TILs in tumour tissue was initially investigated in patients who had been treated with chemotherapy. In many cases with TILs, the patients responded well to this treatment and seemed to have a good chance of survival. The value of TILs was also evident in Vincent de Jong’s recent doctoral research on Antoni van Leeuwenhoek, says Goerts. “He studied women under the age of 40 with triple-negative breast cancer who had previously been treated with surgery and radiotherapy but not chemotherapy. In about 20% of them, many immune cells were found around the tumour. They had a good chance of survival without chemotherapy. Perhaps TILs could be used to find out which patients need less chemotherapy or even no chemotherapy at all.”

This research was the starting point for the study conducted by Goertz and colleagues. They also investigated the prognostic value of TILs. Could they be used as a biomarker in stage I triple-negative breast cancer (tumor up to 2 cm, no metastases to lymph nodes)? “International treatment guidelines are not clear about chemotherapy for this group of patients. Previously, Dr. Tessa Steenbruggen at the Netherlands Cancer Institute studied the benefits of chemotherapy for survival. It turned out that in this group of early breast cancer, not all patients benefit from chemotherapy. That is why we looked for a biomarker that could support this treatment decision.

strong immune response

The study was performed using data from the Dutch Cancer Registry and the national pathology database PALGA. The patient group studied was women diagnosed with stage I triple-negative breast cancer between 2005 and 2015 and who underwent immediate surgery without chemotherapy. Tissues were requested from these patients and evaluated by a pathologist for the presence of TILs. This was achieved for 1041 patients. The data were then linked to survival. Gertz: “Patients with more than 30% TILs around the tumor had a better 10-year breast cancer-specific survival than patients with less than 30% TILs. We then divided the entire group into 1a/b and 1c tumors. Patients with a T1c tumor (tumor size between 1 and 2 cm) and more than 50% TILs appeared to have a better 10-year survival than patients with less than 50% TILs. Survival, without chemotherapy, was 95%, and this increased to 98% with more than 75% survival. The 10-year breast cancer-specific survival rate for patients with less than 30% breast cancer is 83%.

Some patients with stage I triple-negative breast cancer therefore have a strong immune response against the tumor, which means that surgery alone may be sufficient. A special finding, says Goertz. “Some of these women have a good life without chemotherapy. This has received attention in the field of breast cancer. Less or no chemotherapy saves the patient many side effects. In our study, the majority of patients had less than 30% TILs, but about 15% had more than 75%. We would like to confirm our results in a future study. The OPTIMAL study will soon start for this purpose, in which several Dutch centers are participating.

work group

TILs are found mainly in triple-negative and HR-2-positive breast cancers, and to a lesser extent in the hormone-sensitive subtype. Görtz knows that the field of research in triple-negative breast cancer is now developing rapidly, but research is also being conducted on other subtypes. “TILs can be clearly seen in biopsy tissue. This is done with the same dye we use to image cancer cells. An international working group has now been set up, the Working Group on TILs in Breast Cancer (www.tilsinbreastcancer.org) which has developed guidelines for identifying TILs. This information can be found on the working group’s website, which also includes videos with explanations. In this way, every pathologist can make the same decision.

Moving

The biopsy with TILs is a snapshot. Not much is known yet about the trajectory of the number of TILs in tumor tissue over time. At what stage do they enter or around the tumor? Does the number change over time or during treatment? Research is also underway on this, says Verli-Görtz. “We now know that it is not only the presence of TILs that matters, but also where they are in relation to the tumor cells. We also see changes in TIL numbers during treatment. This raises new questions. For example, is there a difference in TILs between responders and non-responders and does it matter which treatment is given? The presence of TILs is therefore increasingly becoming a dynamic entity.”