CD204-positive macrophages accumulate in breast cancer tumors with high levels of infiltrating lymphocytes and programmed death ligand-1 expression.

Although immunotherapy has been demonstrated to be promising in triple-negative (TN) breast cancer (BC), most BC cases are classified as non-TN. To enrich the responders for immunotherapy regardless of their subtypes, classification based on tumor-infiltrating lymphocyte (TIL) levels and programmed death ligand-1 (PD-L1) status may be useful. However, this classification has not been fully applied to BC. Furthermore, suppressive subsets in the local tumor microenvironment, such as tumor-associated macrophages (TAMs), which promote tumor progression, cannot be ignored to overcome immunotherapy resistance. The aims of the present study were to classify primary BC cases based on the TIL levels and PD-L1 status, and to identify suppressive immune subsets in each categorized group. A retrospective analysis of 73 patients with invasive BC was performed. The frequency of TILs was evaluated in HE-stained slides (10% cutoff), and PD-L1 levels (SP142; 1% cutoff), as well as immune subsets (CD3+, CD8+, FOXP3+, CD20+, CD68+ and CD204+ cells) were assessed using immunohistochemistry. It was revealed that 22% (16/73) of the tumors were categorized as TIL+PD-L1+, of which 69% (11/16) were TN type. By contrast, 66% (48/73) of the tumors were categorized as TIL-PD-L1-, of which 77% (37/48) were HR+ and HER2- types. The number of CD204+ M2-type macrophages was significantly associated with high histological grade (P=0.0246) and high Ki-67 (P=0.0152), whereas CD68+ macrophages were not associated with these factors. Furthermore, CD204+ macrophages and FOXP3+ Tregs accumulated in 88% (14/16) and 63% (10/16) of TIL+PD-L1+ tumors, respectively, compared with 20.8% (10/48) and 27.1% (13/48) of TIL-PD-L1- tumors. In conclusion, 22% of BC tumors were classified as TIL+PD-L1+ (69% were TN), which were enriched with suppressive immune subsets. These cell types may serve as potential novel immunotherapeutic targets.

Strategy for the accurate preoperative evaluation of the number of metastatic axillary lymph nodes in breast cancer.

BACKGROUND: After the ACOSOG Z0011 trial, it became important to evaluate the number of metastatic axillary lymph nodes (LNs) preoperatively. The purpose of this paper is to confirm whether the number of metastases can be accurately diagnosed by preoperative computed tomography (CT), ultrasound sonography (US), and US-guided fine-needle aspiration cytology (FNAC). METHODS: We retrospectively analyzed the axillary LNs finding of preoperative CT/US of 470 breast cancer patients. Metastasis was suspected based on the following findings: LNs with a long-axis diameter of ≥10 mm or a short-axis diameter of ≥5 mm on CT, and LNs with the absence of a fatty hilum, focal cortical thickness or a cortical thickness ≥2 mm on US. We also examined the results of FNAC making a rapid bedside diagnosis (bedside-FNAC) of 162 LNs that were suspected to metastatic based on the US findings. RESULTS: On CT, all cases with ≥3 LNs with a long-axis diameter of ≥10 mm and a short-axis diameter of ≥5 mm had metastasis. However, there was no relationship between the number of detected LNs and the number of metastases. On US, 75.7% of LNs with the absence of a fatty hilum and all LNs with cortical thickness ≥6 mm had metastasis. The accuracy of bedside-FNAC for suspicious LNs was 100%. CONCLUSIONS: Although we can pick up LNs that are likely to have metastasis on CT/US, it was impossible to accurately predict the number of metastases on CT/US. However, bedside-FNAC of suspicious LNs could accurately predict the number of metastases.

The usefulness of a computer-aided diagnosis scheme for improving the performance of clinicians to diagnose non-mass lesions on breast ultrasonographic images.

PURPOSE: The purpose of this study was to evaluate the usefulness of a computer-aided diagnosis (CAD) scheme for improving the performance of clinicians to diagnose non-mass lesions appearing as hypoechoic areas on breast ultrasonographic images. METHODS: The database included 97 ultrasonographic images with hypoechoic areas: 48 benign cases [benign lesion with benign mammary tissue or fibrocystic disease (n = 20), fibroadenoma (n = 11), and intraductal papilloma (n = 17)] and 49 malignant cases [ductal carcinoma in situ (n = 17) and invasive ductal carcinoma (n = 32)]. Seven clinicians, three expert breast surgeons, and four general surgeons participated in the observer study. They were asked their confidence level concerning the possibility of malignancy in all 97 cases with and without the use of the CAD scheme. Receiver operating characteristic (ROC) analysis was performed to evaluate the usefulness of the CAD scheme. RESULTS: The areas under the ROC curve (AUC) improved for all observers when they used the CAD scheme and increased from 0.649 to 0.783 (P = 0.0167). Notably, the AUC for the general surgeon group increased from 0.625 to 0.793 (P = 0.045). CONCLUSIONS: This study showed that the performance of clinicians to diagnose non-mass lesions appearing as hypoechoic areas on breast ultrasonographic images was improved by the use of a CAD scheme.

Cosmetic evaluation methods adapted to asian patients after breast-conserving surgery and examination of the necessarily elements for cosmetic evaluation.

PURPOSE: Although various strategies have been reported, there are no defined criteria for cosmetic evaluation methods after breast-conserving surgery (BCS). Since Asians tend to have smaller breasts, indistinct inframammary folds, and conspicuous scars, differences in the cosmetic results are expected. So we examined two subjective methods and one objective method to determine the differences, and elements necessary for a cosmetic evaluation after BCS. METHODS: Frontal photographs of 190 Japanese were evaluated using the Harris scale (Harris) and the evaluation method proposed by the Japanese Breast Cancer Society Sawai group (Sawai group) as the subjective methods, and the Breast Cancer Conservation Treatment cosmetic results (BCCT.core) as the objective method, respectively. In order to examine the necessary elements for developing a new ideal method, 100 out of 190 were selected and assessed separately by six raters using both the Harris and modified Sawai group methods in the observer assessment. The correlation between the two methods was examined using the Spearman rank-correlation coefficient. RESULTS: The results of the BCCT.core and the other two methods were clearly different. In the observer assessment, the consensuses of the six raters were evaluated as follows: 27, 27, 26, and 20 cases were evaluated as "excellent," "good," "fair," and "poor," respectively. For the Spearman rank-correlation coefficient, values higher than 0.7 indicated a strong correlation, as seen by the values of 0.909 for the breast shape and 0.345 for the scar. The breast shape accounted for the most significant part of the evaluation, and the scar had very little correlation. CONCLUSION: In this study, we recognized a clear difference between the subjective and objective evaluation methods, and identified the necessary elements for cosmetic evaluation. We would like to continue developing an ideal cosmetic evaluation that is similar to subjective one and is independent from raters.