Evaluation of Tumor-Infiltrating Lymphocytes as Predictors of Response to Neoadjuvant Chemotherapy in Patients With Locally Advanced Breast Cancer

评估肿瘤浸润淋巴细胞作为局部晚期乳腺癌患者新辅助化疗疗效预测指标的价值

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Abstract

Background This study aimed to evaluate tumor-infiltrating lymphocytes (TILs) as predictors of response to neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer (LABC). Methods Overall, 35 patients with LABC were included in the study. Information on demographic profile, medical history, and signs and symptoms was collected for each patient, and a complete clinical evaluation was conducted, which involved physical examination, imaging studies (mammogram/ultrasound imaging), biopsy of each patient, and a metastatic workup. Patient consent was obtained for core-needle biopsy under local anesthesia, followed by a pathologic assessment of the type of breast cancer, before NACT and after mastectomy. Patients treated with NACT were followed up for response using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and were scheduled for modified radical mastectomy (MRM) on completion of NACT. MRM specimens were sent for immunohistopathologic analysis for CD3 and CD5, and for grading. Subsequently, correlations between TILs and grading with NACT response and type of cancer were analyzed. Results Of the 35 patients, 24 were positive for CD3. A correlation was identified between NACT in LABC patients and CD3 TILs, as 68.6% of patients were CD3-positive, with 54.3% showing stromal CD3 variants and 14.3% showing intramural CD3 variants. This result indicates that CD3 TILs can be an indicator of response to NACT in LABC patients. In the sample, 48.6% of patients showed CD5 positivity, with stromal predominance. Overall, 17 patients (48.6%) had a RECIST complete response to NACT, 16 (45.7%) had a partial response, and 1 (2.9%) had progressive disease. Therefore, the study showed a significant response to NACT in LABC patients (p-value < 0.0001), and reductions in tumor size could be evaluated using RECIST criteria. Conclusions NACT had a significant effect on tumors, as shown by RECIST assessments in patients with LABC. TILs can be used as promising prognostic markers to evaluate and predict patients' responses to NACT. Evaluating TILs is expensive but may be useful for the diagnosis and prediction of immunologic responses in breast cancer and other types of carcinomas following chemotherapy.

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