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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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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Data availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea

    Hye Won Hwang, Hera Jung, Soo Youn Cho & Eun Yoon Cho

  2. Department of Pathology, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, South Korea

    Jiyeon Hyeon

  3. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Yeon Hee Park, Jin Seok Ahn & Young-Hyuck Im

  4. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Jong-Han Yu & Se Kyung Lee

  5. Division of Forensic Investigation, National Forensic Service Seoul Institute, Seoul, South Korea

    Misun Choi

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  1. Hye Won Hwang
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Correspondence to Soo Youn Cho or Eun Yoon Cho.

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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.

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Informed consent was obtained from all individual participants included in the study.

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Hwang, H.W., Jung, H., Hyeon, J. et al. 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. Breast Cancer Res Treat 173, 255–266 (2019). https://doi.org/10.1007/s10549-018-4981-x

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  • DOI: https://doi.org/10.1007/s10549-018-4981-x

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