A nomogram to predict pathologic complete response (pCR) and the value of tumor-infiltrating lymphocytes (TILs) for prediction of response to neoadjuvant chemotherapy (NAC) in breast cancer patients
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The value of tumor-infiltrating lymphocytes (TILs) for prediction of pathologic complete response (pCR) in breast cancer (BC) patients treated with neoadjuvant chemotherapy (NAC) has received increasing attention. In human epidermal growth factor receptor 2 (HER2)-positive BC, advances in HER2-targeted therapy have not yet clarified the clinical implications of pre-NAC TILs. Likewise, the prognostic role of TILs for long-term survival is not well established.
Pre- and post-NAC TIL levels were evaluated in 248 pair-matched pre-NAC biopsy and post-NAC resection samples, and analyzed for predictive and prognostic significance with other clinicopathologic parameters. Additional 60 pre-NAC biopsy samples of HER2-positive BC treated with a TCHP regimen (docetaxel, carboplatin, and a combination of trastuzumab and pertuzumab) were also assessed.
High pre-NAC TILs, clinical nodal stage 0–1 (cN0–1), and negative ER expression were shown to be strong predictive markers for pCR. A nomogram based on these significant clinicopathologic predictors was developed, providing integrated probability of achieving pCR after NAC. The association between high pre-NAC TIL levels and significantly increased pCR rate was also confirmed in HER2-positive BC patients treated with a TCHP regimen. After chemotherapy, increased quantity of post-NAC TILs was shown to have extended BC-specific survival and disease-free survival in univariable and multivariable analyses.
High pre-NAC TIL levels were significantly predictive of pCR in BC, and can act as a surrogate marker for predicting therapeutic effects of a TCHP regimen for HER2-positive BC. Post-NAC TILs in residual disease were a new prognostic marker of risk stratification for long-term survival.
KeywordsTumor-infiltrating lymphocytes Neoadjuvant chemotherapy Pathologic complete response Nomogram TCHP
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.
Informed consent was obtained from all individual participants included in the study.
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