Roberto Leon-Ferre: The role of immune activation on the prognosis of early TNBC if chemotherapy is not given

Roberto Leon-Ferre, Medical Oncologist at Mayo Clinic, shared on their X/Twitter:

”What is the role of immune activation on the prognosis of early TNBC if chemotherapy is not given? We evaluated ~ 2,000 patients with eTNBC from 13 institutions around the globe to answer this. See our results published today in JAMA.

Why is this question important? Currently, most patients with eTNBC are recommended to receive multiagent chemotherapy before/after surgery. This may result in overtreatment and toxicities for some patients who may have a very low risk of recurrence/death to begin with! This is what NCCN says:

However, most trials evaluating the actual benefit of chemotherapy have focused on patients with stage II breast cancer and above, leaving a gap in knowledge for stage I TNBC. In our study, higher TILs were associated with significantly improved survival rates compared to lower TILs.

For stage I TNBC and TILs ≥50%, the 5y OS was 95% (without any chemotherapy!). Contrast that with stage I TNBC and TILs <30%, where 5y OS was 82%. TILs were associated with better survival and recurrence rates independently of other prognostic factors (age, T size, N status, grade).

Even in our modern era of precision medicine and sophisticated molecular profiling, we still rely almost exclusively on tumor size and nodal stage to make treatment recommendations for TNBC! No biomarkers are used to inform the need for or intensity of systemic therapy!

Today, TIL levels are not routinely provided in pathology reports of patients with eTNBC. Our data (and that of previous studies) suggest that TILs provide valuable information for patients and clinicians. TILs Working Group has been hard at work standardize TIL assessment.

TILs only require a microscope, an H and E slide (the same one used to diagnose breast cancer), and a few minutes of a trained pathologist’s time. This means it is cheap and could be used globally without requiring intense financial or tech resources, unlike other biomarkers.

The next frontier is to prospectively evaluate whether eTNBC + high TILs could receive less intensive (and less toxic) chemotherapy regimens (or maybe avoid chemotherapy!) without compromising outcomes. Multiple groups are working on this question through thoughtfully designed clinical trials.

This work would have not been possible without many collaborators. Thank you to all the coauthors and many others that made this effort possible. These days it is not easy to find cohorts of patients with eTNBC who did not receive chemotherapy!”

Source: Roberto Leon-Ferre/X