What are the Limitations of This Research?
The current study findings are limited by the retrospective design and use of observational data, so the researchers could not make conclusions about causality. Other limitations included lack of data on germline mutations and race or ethnicity, and the potential irrelevance of data from patients treated as long as 45 years ago.
“Because most patients with TNBC receive chemotherapy in the modern times, we needed to work with 13 hospitals around the world to find data on patients with TNBC who never received chemotherapy for various reasons,” Dr. Leon-Ferre said.
To address these limitations, Dr. Leone-Ferre and his colleagues are planning prospective studies where TILs will be used to make treatment decisions.
“Many of the patients in our cohort were treated many years ago, when chemotherapy was not routinely given. Advances in cancer detection, surgical and radiation techniques may lead to different results in patients treated today,” he added.
What Do Oncologists Need to Know?
The current study findings may provide additional information on prognosis that is important to share with patients for decision-making on the risks versus benefits of chemotherapy, Dr. Leon-Ferre said.
“Like any test, TILs should not be used in isolation to make decisions, but should be integrated with other factors including the cancer stage, the overall patient health, patient preferences, and concerns about treatment complications,” he emphasized. “The results of this study allow oncologists to offer a more refined calculation of recurrence risk if patients opt to not receive chemotherapy.”
In the current study, although younger age was associated with higher TIL levels, a finding consistent with previous studies, increased TIL, remained significantly associated with improved survival after adjusting for age, tumor size, nodal status, and histological grade.
Overall, “the findings suggest that for patients with stage I TNBC and TILs greater than 50%, chemotherapy may not be as necessary as it was previously thought,” Dr. Leon-Ferre said.
What Additional Research is Needed?
Prospective studies are needed to validate the findings, including studies in diverse populations, and additional studies may investigate whether early TBNC patients with high TIL levels could achieve high cure rates with less intensive and less toxic chemotherapy regiments than those currently recommended, the researchers wrote in their discussion.
“There are many additional research questions that we need to answer, and look forward to working on,” Dr. Leon-Ferre said, in an interview. These topics include whether TILs can be used to decide on the number of chemotherapy drugs a patient really needs and whether artificial intelligence can be used to evaluate TILs more quickly and effectively than the human eye, he said. Other research topics include identifying which particular type of TILs attack cancer cells most effectively and whether TILs could be increased in patients with low levels in order to improve their prognosis, he added.
The study was supported by the National Research Agency and General Secretariat for Investment, Clinical and Translational Science Awards, the Mayo Clinic Breast Cancer SPORE grant, the Cancer Research Society of Canada, institutional grants from the Dutch Cancer Society, The Netherlands Organization for Health Research, and several foundations. Dr. Leon-Ferre disclosed consulting honoraria to his institution for research activities from AstraZeneca, Gilead Sciences, and Lyell Immunopharma, with no personal fees outside the submitted work.