Diagnostic performance of TILs-US score and LPBC in biopsy specimens for predicting pathological complete response in patients with breast cancer.

BACKGROUND: Tumor-infiltrating lymphocytes-ultrasonography (TILs-US) score is used to predict lymphocyte-predominant breast cancer (LPBC) in surgical specimens. We aimed to compare diagnostic performance of TILs-US score for predicting pathological complete response (pCR) with that of LPBC in biopsy specimens. METHODS: TILs ≥ 50% in biopsy specimens was defined as biopsy-LPBC, and TILs-US score ≥ 4 was categorized as TILs-US score-high. Basic nomogram for pCR was developed using stepwise logistic regression based on the smallest Akaike Information Criterion, and biopsy-LPBC and TILs-US score nomograms were developed by integrating biopsy-LPBC or TILs-US scores into a basic nomogram. The diagnostic performance of the nomograms for pCR was compared using area under the curve (AUC), categorical net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: This retrospective study evaluated 118 patients with breast cancer, including 33 (28.0%) with biopsy-LPBC, 52 (44.1%) with TILs-US score-high, with 34 (28.8%) achieving pCR. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and AUC for predicting pCR were 0.53, 0.82, 2.96, 0.57, and 0.68, respectively, for biopsy-LPBC, and 0.76, 0.69, 2.47, 0.34, and 0.73, respectively, for TILs-US score. The biopsy-LPBC nomogram showed significant improvements in categorical NRI (p = 0.023) and IDI (p = 0.007) but not in AUC (p = 0.25), compared with the basic nomogram. The TILs-US nomogram exhibited significant improvements in AUC (p = 0.039), categorical NRI (p = 0.010), and IDI (p < 0.001). CONCLUSIONS: The TILs-US score may serve as a novel marker for prediction of pCR in patients with breast cancer. An external validation study is warranted to confirm our findings.

A nomogram to predict the pathological complete response in patients with breast cancer based on the TILs-US score.

BACKGROUND: The tumor-infiltrating lymphocytes-ultrasonography score is a calculation system for predicting lymphocyte-predominant breast cancers in surgical specimens. A nomogram based on the tumor-infiltrating lymphocytes-ultrasonography score was developed to predict the pathological complete response in breast cancer treated with neoadjuvant chemotherapy. METHODS: A retrospective evaluation was conducted on 118 patients with breast cancer treated with neoadjuvant chemotherapy at Hiroshima University Hospital. Tumor-infiltrating lymphocytes-ultrasonography scores ≥4 were classified as high. A nomogram was developed using a stepwise logistic regression model for pathological complete response (ypT0 ypN0), based on the smallest Akaike information criterion. The predictive ability and clinical usefulness of the nomogram were also evaluated. RESULTS: Among 118 patients, 34 (28.8%) achieved a pathological complete response, and 52 (44.1%) exhibited high tumor-infiltrating lymphocytes-ultrasonography. In multivariate logistic regression analysis, high tumor-infiltrating lymphocytes-ultrasonography (odds ratio, 6.01; P < 0.001), clinical complete response (odds ratio, 4.83; P = 0.004) and hormone receptor (odds ratio, 3.48; P = 0.038) were independent predictors of pathological complete response. A nomogram based on tumor-infiltrating lymphocytes-ultrasonography score, clinical complete response, hormone receptor and clinical N status was developed. The nomogram showed an area under the curve of 0.831 and a bias-corrected area under the curve of 0.809. The calibration plot showed a good fit between the expected and actual pathological complete response values. Decision curve analysis also showed the clinical utility of the nomogram for predicting pathological complete responses. CONCLUSIONS: A nomogram based on the tumor-infiltrating lymphocytes-ultrasonography score exhibited a favorable predictive ability for pathological complete response in patients with breast cancer, which can be useful in predicting the residual disease status after neoadjuvant chemotherapy.

The tumor-infiltrating lymphocyte ultrasonography score can provide a diagnostic prediction of lymphocyte-predominant breast cancer preoperatively.

PURPOSE: Tumor-infiltrating lymphocytes (TILs) are known to predict the therapeutic effect in breast cancer. Although a preoperative tissue biopsy can be used to evaluate TILs, TILs that are heterogeneously distributed might require examination of all preoperative tissue biopsy samples. We have recently reported that the TIL ultrasonography (US) score, as determined by characteristic US findings, provides excellent predictive performance for lymphocyte predominant breast cancer (LPBC). We herein aimed to determine whether the preoperative TIL-US score can more accurately predict LPBC than preoperative tissue biopsy. METHODS: We assessed 161 patients with invasive breast cancer that were treated with curative surgery between January 2014 and December 2017. Stromal lymphocytes were examined on preoperative tissue biopsy tissues and surgical pathological specimens. Breast cancer samples with ≥ 50% stromal TILs were defined as pre-LPBC (preoperative tissue biopsy) and LPBC (surgical pathological specimens). Useful factors for predicting LPBC were searched among clinicopathological factors. RESULTS: The TIL-US score cutoff value for predicting LPBC was 4 points based on the receiver operating characteristic curves (area under the curve: 0.88). Several significant predictors for LPBC were revealed by the undertaken multivariate logistic regression analysis (odds ratios: TIL-US score, 26.8; pre-LPBC, 18.6; HER2, 9.2; all, p < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 0.74, 0.89, 0.85, 0.67, and 0.92 for the TIL-US score, respectively, and 0.51, 0.98, 0.87, 0.91, and 0.86 for the pre-LPBC, respectively. CONCLUSION: TIL-US scores can predict LPBC preoperatively and are characterized by a significantly high sensitivity and negative predictive value.

The TILs-US score on ultrasonography can predict the pathological response to neoadjuvant chemotherapy for human epidermal growth factor receptor 2-positive and triple-negative breast cancer.

BACKGROUND: The tumor-infiltrating lymphocyte (TIL)-ultrasonography (US) score determined through characteristic US findings has predictive performance of lymphocyte-predominant breast cancer (LPBC). This study aimed to investigate whether the TIL-US score before neoadjuvant chemotherapy (NAC) can predict the pathological complete response (pCR). METHODS: We evaluated patients with human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (n = 55) and triple-negative breast cancer (TNBC) (n = 24) who underwent surgery after NAC from November 2012 to April 2019. Pre-NAC biopsy examination was performed to examine stromal TILs; the cutoff value for predicting pCR was defined as ≥50% stromal TILs. The TILs-US score was calculated from the pre-NAC US findings. Based on previous data, the cutoff value for predicting pCR was set at ≥4 points. RESULTS: Forty-six patients achieved pCR. The TIL-US score was significantly associated with the pCR rate (p = 0.003) but not the pre-NAC biopsy findings (p = 0.055). Multivariate logistic regression analysis revealed that a TILs-US score ≥4 and HER2 positivity were significant pCR predictors (odds ratio [OR] 3.69; p = 0.031; OR 8.74; p = 0.025). CONCLUSIONS: TILs-US scores can be used to evaluate the therapeutic effect of NAC, and may be used as a non-invasive, convenient, and an alternative method to assess stromal TILs in pre-treatment biopsies.

Ultrasonography Combined With Contrast-enhanced Ultrasonography Can Predict Lymphocyte-predominant Breast Cancer.

Background: We investigated whether contrast-enhanced ultrasonography (CEUS) scores can predict lymphocyte-predominant breast cancer (LPBC). Patients and Methods: We evaluated 75 patients who underwent US and CEUS. LPBC was defined as tissues with ≥50% stromal tumour-infiltrating lymphocytes (TILs) preoperatively. Characteristic US images predicting LPBC were evaluated using TIL-US scores via three ultrasonic tissue characteristics: Shape, internal echo level, and posterior echoes. TIL-CEUS was evaluated based on TIL-US plus CEUS. Results: TIL-US and TIL-CEUS cut-offs for predicting LPBC were 4 and 6 (area under the curve=0.93 and 0.96, respectively) points based on receiver operating characteristics curves. Sensitivity, specificity, and accuracy values (95% confidence intervaI) were 0.94 (0.77-0.99), 0.75 (0.70-0.77), and 0.80 (0.72-0.82); and 0.94 (0.78-0.99), 0.86 (0.81-0.87), and 0.88 (0.80-0.90) for TIL-US and TIL-CEUS, respectively. TIL-CEUS score was a significant single predictor for LPBC in multivariate logistic regression (p=0.001). Conclusion: TIL-CEUS can be used for preoperative LPBC prediction and detection.

Novel tumor-infiltrating lymphocytes ultrasonography score based on ultrasonic tissue findings predicts tumor-infiltrating lymphocytes in breast cancer.

BACKGROUND: The presence of tumor-infiltrating lymphocytes (TILs) is a prognostic factor for breast cancer. However, because of tumor tissue heterogeneity, an accurate and simple evaluation method is needed. We determined if preoperative characteristic ultrasonography (US) image findings are predictive of lymphocyte-predominant breast cancer (LPBC). METHODS: We evaluated 191 patients with invasive breast cancer treated by curative surgery between January 2014 and December 2017. Stromal lymphocytes in surgical pathological specimens were evaluated. Fifty-two patients with ≥ 50% stromal TILs were defined as having LPBC. Preoperative US images were examined for indicators of TILs. The US images with characteristic TILs were scored for prediction of LPBC. RESULTS: Shape (more lobulated), internal echo level (weaker), and posterior echoes (stronger) were predictors of LPBC and used to assign the TILs-US scores (0-7 points); the score cutoff for predicting LPBC was 4 points (sensitivity, 0.73; specificity, 0.87; accuracy, 0.83) based on the receiver operating characteristics (ROC) curves (AUC 0.88). Multivariate logistic regression analysis identified nuclear grade (NG), OR 3.4; estrogen receptor (ER), OR 5.7; human epidermal growth factor receptor type-2 (HER2), OR 4.1; and TILs-US score, OR 14.9 as LPBC predictors (all, p < 0.05). The sensitivity, specificity, and accuracy for predicting LPBC were 0.75, 0.69, and 0.71 for NG and 0.33, 0.96, and 0.79 for ER and HER2, respectively. ROC analysis showed that the diagnostic abilities of NG, ER, and HER2 were lower than that of the TILs-US score. CONCLUSIONS: LPBC showed characteristic US imaging findings. The TILs-US score was an accurate preoperative predictor of LPBC.