Abstract P3-07-33: Prediction of the treatment response to neoadjuvant chemotherapy in breast cancer by subtypes using tumor-infiltrating lymphocytes
Authors: Kashiwagi S , Asano Y , Goto W , Morisaki T , Noda S , Takashima T , Onoda N , Hirakawa K 
Published: May 2016

Purpose: Monitoring the host immunological response to cancer in the microenvironment of the interaction between tumor and the body plays an important role in predicting treatment response and outcomes. Recent interest has focused on the morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) and on the evidence showing their clinical relevance. Meanwhile, no consensus has yet been reached on standard methods for pathological evaluation of TILs. Therefore, methods of evaluation have differed in reports to date showing the clinical relevance of TILs. An International Working Group (2014) announced recommendations for evaluating TILs in an effort to improve consistency and reproducibility. In this study, the clinical validity and utility of TILs in NAC were investigated based on this recommendation with a stratified analysis by BC subtypes. Changes in TILs after recurrence, which have seldom been reported to date, are also discussed.

Experimental Design: TILs was evaluated in 177 patients with breast cancer treated with NAC and subsequent curative surgery. All patients received a standardized protocol of NAC consisting of four courses of FEC100 (500 mg/m2 fluorouracil, 100 mg/m2 epirubicin, and 500 mg/m2 cyclophosphamide) every 3 weeks, followed by 12 courses of 80 mg/m2 paclitaxel administered weekly. Forty-five patients had HER2-positive breast cancer and were additionally administered weekly (2 mg/kg) or tri-weekly (6 mg/kg) trastuzumab during paclitaxel treatment. The correlation between TILs evaluated according to the standard method, and prognosis, including the efficacy of NAC, was investigated retrospectively.

Results: In the 96 high-TIL group, compared to the 81 low-TIL group, triple-negative breast cancer (TNBC) (p &lt; 0.001) and HER2-enriched (p = 0.040) were significantly more frequent, and the pathological complete response (pCR) rate were significantly higher (p = 0.003). On multivariate analysis also demonstrated that high-TIL status was an independent factor to indicate significantly more favorable prognosis of the patients compared with low-TIL status (p = 0.036, HR = 0.45). Among the 61 TNBC and the 36 HER2-enriched patients, the pCR rate was significantly higher in the high-TIL group than in the low-TIL group (p = 0.013) (p = 0.014). On multivariate analysis also showed that high-TIL status was an independent factor to predict the favorable prognosis (p = 0.023, HR = 0.24) (p = 0.036, HR = 0.13). Biopsy specimens from local recurrence after successful NAC frequently showed decreased TILs.

Conclusion: TILs may be a biomarker to predict treatment response to NAC in patients with TNBC and HER2-enriched subtypes of BC. A decrease in TILs may also be associated with tumor recurrence.

Citation Format: Kashiwagi S, Asano Y, Goto W, Morisaki T, Noda S, Takashima T, Onoda N, Hirakawa K. Prediction of the treatment response to neoadjuvant chemotherapy in breast cancer by subtypes using tumor-infiltrating lymphocytes. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-33.