Professor Sherene Loi
Tumour infiltrating lymphocytes (TIL) are an important prognostic biomarker in triple-negative (TNBC) and HER2-positive breast cancer.
Speaking at the San Antonio Breast Cancer Symposium (SABCS), Professor Sherene Loi from the Peter MacCallum Cancer Centre, gave an overview of the evidence for and use of TIL in early-stage and advanced breast cancer.
Professor Loi was speaking as the recipient of the 2020 AACR Outstanding Investigator for Breast Cancer Research which recognises a scientist “whose novel and significant work has had or may have a far-reaching impact on the etiology, detection, diagnosis, treatment, or prevention of breast cancer.”
Professor Loi said more than a decade of work had culminated in TILs being incorporated into documents such as the WHO Classification of Tumours of the Breast, and ESMO and St Gallen International Consensus guidelines for early breast cancer
“And even though many will argue that the clinical relevance of TIL is as yet unclear, in a world where we are rapidly moving towards immunotherapy, this is likely to change in the future. And I will highlight that there are many other prognostic markers that pathologists do in routine day-to-day practice which also do not change clinical practice – such as tumour grading and lymphovascular invasion – but contribute to our understanding of the potential prognosis of that patient.”
The standardised method for evaluating TILs, established by the International TIL Working Group, is available for continuous training purposes on their website.
Professor Loi said robust evidence from about 10,000 patients from clinical trials and institutional cohorts has shown that an increased quantity of TIL is associated with improved rates of pCR in all subtypes and improved prognosis in early TNBC and HER2+ breast cancer.
She presented published data from a meta-analysis in early-stage TNBC which showed higher TIL was prognostic, independent of all clinical or pathological factors including nodal status.
“So even in node negative disease, in 1-3 nodes and with more than three nodes, you can see large absolute differences in recurrence rates and survival by TIL level, suggesting that inducing or improving immunity can improve survival in early-stage TNBC.”
“We don’t fully understand why some patients have low versus high TIL. This is another area of research but it also suggests from a biomarker point of view that some patients who have higher TIL potentially could do just as well with less chemotherapy or no chemotherapy in particular low tumour burden, higher TIL.”
“And it also suggests that potentially some of this chemotherapy could be replaced by agents that can harness this immune response.”
Professor Loi said higher TILs also predict greater magnitude of benefit from PD-(L)-1 inhibitors in advanced breast cancer despite the fact that relapsed or metastatic disease is a low TIL setting.
For example, in the KEYNOTE-119 study, overall survival in metastatic TNBC patients with TILs <5% was poorer in those treated with pembrolizumab rather than chemotherapy in patients.
However in patients with TILs ≥5%, survival was better in those treated with pembrolizumab.
Professor Loi said trials with combinations of treatment such as atezolizumab and trastuzumab (KATE3 study) or tremelimumab, durvalumab and trastuzumab (DIAmOND study) would answer more questions in patients with HER2+ advanced breast cancer.
“At present it is unclear how to generate new immunity and we are exploring a number of different approaches for this, looking at combinations of immunotherapy, looking at dosing and scheduling of different agents, looking at agents that can more effectively break down the tumour microenvironment and relieve immunosuppression such as more potent anti-HER2 agents such as tucatinib,” she said.
Professor Loi’s disclosures include research funding paid to Peter Mac from companies including Novartis, Merck, Roche-Genentech, Seattle Genetics, Pfizer, BMS, Eli Lilly, Nektar Therapeutics and Puma Biotechnology.