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Background: The tumor immune environment not only modulates the effects of immunotherapy, but also the effects of other anticancer drugs and treatment outcomes. These immune responses can be evaluated with tumor-infiltrating lymphocytes (TILs), which has frequently been verified clinically. On the other hand, residual cancer burden (RCB) evaluation has been shown to be a useful predictor of survival after neoadjuvant chemotherapy (NAC). In this study, RCB and TILs evaluations were combined to produce an indicator that we have termed "RCB-TILs", and its clinical application to NAC for breast cancer was verified by subtype-stratified analysis.Methods: A total of 177 patients with breast cancer were treated with NAC. The correlation between RCB and TILs evaluated according to the standard method, and prognosis, including the efficacy of NAC, was investigated retrospectively. The RCB and TILs evaluations were combined to create the "RCB-TILs". Patients who were RCB-positive and had high TILs were considered RCB-TILs-positive, and all other combinations were RCB-TILs-negative.Results: On multivariable analysis, being RCB-TILs-positive was an independent factor for recurrence after NAC in all patients (p < 0.001, hazard ratio = 0.048), triple-negative breast cancer (TNBC) patients (p = 0.018, hazard ratio = 0.041), HER2-positive breast cancer (HER2BC) patients (p = 0.036, hazard ratio = 0.134), and hormone receptor-positive breast cancer (HRBC) patients (p = 0.002, hazard ratio = 0.081).Conclusions: The results of the present study suggest that RCB-TILs is a significant predictor for breast cancer recurrence after NAC and may be a more sensitive indicator than TILs alone. [ABSTRACT FROM AUTHOR]