Core Needle Biopsy Specimens Research Articles

The accuracy of core needle biopsy in determining histological type and Scarf-Bloom-Richardson grade in invasive breast cancer

Core needle biopsy provides information not only on the histological diagnosis but also about tumor grade and different prognosis factors for breast cancer. This study was designed to determine the accuracy of percutaneous core needle biopsy (CNB) through comparative analysis of histological diagnosis and SBR tumor grade of invasive breast cancer between CNB and surgical excision specimen (SES). This was a retrospective cross-sectional study from January 2023 to July 2023. All patients with invasive breast cancer diagnosed by CNB and confirmed by surgical excision specimen (SES) examination were included in the study. Patients who received neoadjuvant chemotherapy were excluded. One twenty-three patients were assessed. All patients were female. The median age was 45 years (37 – 54). Invasive ductal carcinoma (IDC) was the major histological type of breast cancer (95.1%) followed by invasive lobular carcinoma (ILC) (4.9%). SBR grade 2 tumors accounted for 78.1% of cases. The majority of patients presented with locally advanced stage breast cancer (65.9%) or a metastatic disease (31.7%). Concordance for histological type was substantial (k= 0.79; p<0,001) whereas it was moderate (k= 0.45; p<0,001) for Scarf-Bloom-Richardson grade. Histological type on CNB correlates almost perfectly with that of the surgical excisional specimen in case of breast cancer. Nevertheless, the agreement of tumor grade between CNB and SES remains moderate, with a significant underestimation and overestimation rates.

Diagnostic accuracy and safety of percutaneous core needle biopsy of retroperitoneal tumours

BackgroundHistologic subtype of cancer guides treatment sequencing and the extent of surgery for retroperitoneal tumours (RPTs) but concerns persist regarding percutaneous core needle biopsy (CNB). ObjectiveEndpoints were the incidence of early complications, needle tract seeding (NTS) after CNB, diagnostic accuracy. MethodsBetween 2015 and 2022, data from patients with RPT who underwent a CNB and who operated on at Institut Curie were collected. We retrospectively reviewed the medical records and microscopic analysis of both CNB and surgical specimens to evaluate the diagnostic accuracy of CNB (quantified using positive and negative predictive values, PPV/NPV). Results313 patients underwent CNB. In 10/326 (3 %) procedures, minor complications were observed. One of 212 (0.47 %) resected RPSs exhibited a local recurrence compatible with NTS. Microscopic analysis of CNB specimens allowed the classification of tumours between groups of cancers and benign/intermediate mesenchymal tumours in 307/313 (98 %) patients. Among the 204 patients with retroperitoneal sarcoma, the overall concordance between CNB and final pathology following resection was 178/204 (87.2 %). The respective PPVs of solitary fibrous tumour, dedifferentiated liposarcoma, leiomyosarcoma and well-differentiated liposarcoma were 100 %, 98 %, 97 % and 68 %, respectively. The diagnosis of a high-grade (G 2-3) sarcoma resulted in a high specificity (97 %) and PPV (98 %) but low sensitivity (76 %). ConclusionsCNB allowed the classification of RPT in the vast majority of patients with a low morbidity rate. Concordance with final diagnosis was high for sarcomas with the exception of well-differentiated liposarcoma. As a result, CNB results should be integrated with imaging/radiomics by multidisciplinary tumour boards.

Concordance Between Core Needle Biopsy and Surgical Specimens in Determining Molecular Biological Subtypes of Breast Cancer by Immunohistochemistry

Background: Breast carcinoma is the most common malignancy among women around the world. Core needle biopsy provides samples that are adequate in size thus allowing a histological diagnosis of breast carcinomas. CNB specimens can also be used for the immunohistochemical (IHC) assays of hormone receptors. Aims: To evaluate the concordance of ER, PR, HER2 Neu and Ki-67 in core needle biopsy and surgical specimens obtained by Modified radical mastectomy (MRM). Methods: A cross-sectional observational study was conducted in the Department of Pathology in association with the Department of Surgery at Murshidabad Medical College and Hospital for a duration of one and a half years. Patients undergoing Core needle biopsy of the breast who have been diagnosed with breast carcinoma on the basis of histopathology report and subsequently planned for MRM who have given consent for the study were included in this study. The samples were classified according to the immunohistochemical staining into four molecular subtypes: Luminal A, Luminal B, HER 2 Neu enriched, and triple-negative subtype depending on the expression of ER, PR, HER 2 Neu, and Ki-67. Result: The most common molecular subtype of breast carcinoma in both CNB and MRM specimens was the Triple-negative subtype. Conclusion: CNB has been found to be a reliable diagnostic tool that can help in determining Histopathological biomarkers for ER, PR positive, and HER2 Neu positive or negative tumors and it has also been found that retesting these markers again on the surgical specimens may not be necessary. Keywords: Core needle biopsy, Breast carcinoma, Molecular subtyping, Immunohistochemistry

Prognostic Value of Immunohistochemistry-based Subtyping Before and After Neoadjuvant Chemotherapy in Patients with Triple-negative Breast Cancer.

To assess the predictive and prognostic value of a subtyping method based on immunohistochemistry in patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC). This study included patients with TNBC treated with anthracycline- and taxane-based NAC and curative surgery. Immunohistochemical (IHC) subtyping was performed using core needle biopsy specimens before NAC (pre-NAC) and residual tumors after NAC (post-NAC). Logistic regression was performed to identify predictive biomarkers of pathological complete response (pCR). Invasive disease-free survival (iDFS), distant disease-free survival (DDFS), and overall survival (OS) were assessed using the log-rank test and Cox proportional hazards regression. A total of 230 patients were followed up for a median of 59 months. Clinical lymph node status and the pre-NAC subtype were independent predictors of pCR (P=0.006 and 0.005, respectively). The pre-NAC subtype was an independent prognostic factor for long-term survival (iDFS: P < 0.001, DDFS: P=0.010, and OS: P=0.044). Among patients with residual disease (RD) after NAC, approximately 45% of tumors changed their IHC subtype. Furthermore, the post-NAC subtype, but not the pre-NAC subtype, was strongly associated with the survival of patients with RD (iDFS: P < 0.001, DDFS: P=0.005, and OS: P=0.006). The IHC subtype predicted response to NAC and long-term survival in patients with early TNBC. In patients with RD, almost 45% of the tumors changed subtype after NAC. The IHC subtype should be considered when planning additional therapies pre- and post-NAC.

Concordance of HER2 Status between Core Needle Biopsy and Surgical Resected Specimens of Breast Cancer: A Narrative Review

Background &amp; Objective: HER2, a molecular biomarker, is routinely evaluated in breast cancer patients to guide therapeutic decisions. However, the concordance of HER2 status between core-needle biopsy (CNB) and surgical specimen (SS) samples is not always high, potentially affecting the accuracy of diagnosis and treatment. This study aims to review recent studies assessing the agreement of HER2 status between CNB and SS samples in breast cancer patients.&#x0D; Materials &amp; Methods: A literature search was conducted in PubMed, Scopus, and Google Scholar databases from January 2018 to August 2023 using the keywords: concordance, core needle biopsy, resection, HER2 status. Ten articles meeting the inclusion criteria were selected for this review.&#x0D; Results: The results demonstrated variable concordance rates of HER2 status between CNB and SS samples, ranging from 83.3% to 99.5%. The primary factors influencing discordance were tumor heterogeneity, preoperative treatment, sampling error, and differing testing methods. Discordance was more prevalent in HER2-negative and HER2-low tumors compared to HER2-positive tumors.&#x0D; Conclusion: The concordance of HER2 status between CNB and SS samples is generally high but not perfect. Therefore, retesting HER2 status on SS samples is recommended to ensure optimal treatment decisions for breast cancer patients.

Use of the Gene Expression Test Prosigna® in Premenopausal Patients with HR+, HER2− Early Breast Cancer: Correlation of the Results with the Proliferation Marker Ki-67

Introduction: In hormone receptor-positive (ER+/PR+) and human epidermal growth factor receptor 2-negative (HER2−) early-stage breast cancer (EBC), gene expression tests such as the Prosigna are increasingly used since classic clinicopathological parameters and the proliferation factor Ki-67 often do not allow a definite therapy decision regarding an adjuvant chemotherapy. While the Prosigna test has been validated for postmenopausal patients, few data are available regarding its use in premenopausal patients. The present study compared the Prosigna test with the Ki-67 index in premenopausal patients. Materials and Methods: Premenopausal patients with HR+ HER2−, pN0-1, G1-2 EBC were retrospectively enrolled (n = 55). The Prosigna assay was performed in formalin-fixed paraffin-embedded tumor samples of surgical resection specimens. Ki-67 was reassessed in original diagnostic core needle biopsy specimens and defined as low, intermediate, or high with the threshold of <10%, 10–24%, ≥25%. Results: According to Ki-67, patients were in the low (LR)-, intermediate (IR)-, and high-risk (HR) groups in 40%, 36%, and 24% of the cases. The Prosigna gene signature assay assessed the risk of recurrence as LR for 45% of the patients, IR for 35%, and HR for 20%. The most frequent intrinsic subtypes were luminal A in 73% and luminal B in 24% of the patients. A moderate correlation was found between Prosigna and Ki-67 scores with a Pearson correlation coefficient of 0.51. In the overall cohort, 47% of the Ki-67-based therapy decision would correspond to those based on the Prosigna score. After exclusion of IR patients, matching of low/low or high/high results was observed in 57% of the cases. Conclusion: According to the present study, there is only limited concordance regarding the risk group stratification between Ki-67 and Prosigna-based risk assessment. The relevance and frequency of premenopausal breast cancer emphasizes the need for further evaluation of gene expression analyses in this setting and the correlation with classic clinicopathological parameters regarding therapy decision-making.

Tumor infiltrating lymphocytes and neutrophil-to-lymphocyte ratio in relation to pathological complete remission to neoadjuvant therapy and prognosis in triple negative breast cancer

ObjectiveTo explore the correlation between the peripheral blood neutrophil-to-lymphocyte ratio (NLR) and tumor infiltrating lymphocyte (TIL) before neoadjuvant therapy (NAT) and the prognosis of patients with triple negative breast cancer. MethodA total of 126 patients with TNBC who received NAT were screened out. TILs, CD8+TIL and FOXP3+TIL were detected by immunohistochemistry in core needle biopsy specimens before treatment, and NLR was calculated. Kaplan-Meier analysis was used to estimate survival rates. Univariate and multivariate analyses were performed using Cox proportional hazards regression. ResultsNLR was negatively correlated with TILs density (p = 0.040) and FOXP3+ TIL was positively correlated with NLR (p = 0.019). Patients with low NLR/high TILs density showed the highest pCR rate (46/48, 95 %), while only 6/22 patients (21 %) with high NLR/low TILs density achieved pCR. Multivariate analysis showed that high NLR was independently associated with pCR ((HR = 5.043, 95 %CI = 1.637–15.535, p = 0.005). High T stage, lymph node involvement, lymphovascular invasion, high NLR, low TILs density and low CD8+ TIL were associated with poor OS and BCSS. Multivariate Cox regression analysis showed that high NLR (HR = 36.182, 95 %CI = 4.120–317.759, p = 0.001), high CD8+ TIL density (HR = 0.182, 95 %CI = 0.044–0.754, p = 0.019) were independently associated with poor OS. Similarly, high NLR (HR = 23.989, 95 %CI = 2.275–252.131, p = 0.008) was independently associated with worse BCSS. ConclusionsNLR may help to screen the high-risk population of TNBC patients after neoadjuvant therapy.

Multi-center study on predicting breast cancer lymph node status from core needle biopsy specimens using multi-modal and multi-instance deep learning

The objective of our study is to develop a deep learning model based on clinicopathological data and digital pathological image of core needle biopsy specimens for predicting breast cancer lymph node metastasis. We collected 3701 patients from the Fourth Hospital of Hebei Medical University and 190 patients from four medical centers in Hebei Province. Integrating clinicopathological data and image features build multi-modal and multi-instance (MMMI) deep learning model to obtain the final prediction. For predicting with or without lymph node metastasis, the AUC was 0.770, 0.709, 0.809 based on the clinicopathological features, WSI and MMMI, respectively. For predicting four classification of lymph node status (no metastasis, isolated tumor cells (ITCs), micrometastasis, and macrometastasis), the prediction based on clinicopathological features, WSI and MMMI were compared. The AUC for no metastasis was 0.770, 0.709, 0.809, respectively; ITCs were 0.619, 0.531, 0.634, respectively; micrometastasis were 0.636, 0.617, 0.691, respectively; and macrometastasis were 0.748, 0.691, 0.758, respectively. The MMMI model achieved the highest prediction accuracy. For prediction of different molecular types of breast cancer, MMMI demonstrated a better prediction accuracy for any type of lymph node status, especially in the molecular type of triple negative breast cancer (TNBC). In the external validation sets, MMMI also showed better prediction accuracy in the four classification, with AUC of 0.725, 0.757, 0.525, and 0.708, respectively. Finally, we developed a breast cancer lymph node metastasis prediction model based on a MMMI model. Through all cases tests, the results showed that the overall prediction ability was high.

The relationship between the change with neoadjuvant chemotherapy in the tumor-infiltrating lymphocyte (TIL) expressions and pathological response in breast cancer patients.

3114 Background: Many prognostic biomarkers for survival have been studied in the neoadjuvant setting for locally advanced breast cancer (LABC). Our study assessed the correlation between the change in tumour-infiltrating lymphocytes (TIL) before and after neoadjuvant chemotherapy (NAC) in breast tissue and its impact on survival in patients with LABC. Methods: Eighty-four LACB patients were retrospectively analysed in this study. TIL was assessed by means of immunohystochemistry (Eclipse Ni, Nikon, Japan) in paraffin-embedded blocks obtained by core-needle biopsy or surgical specimen with respect to the 'TIL working group' criteria. Results: TIL scores were grouped as 0%, &lt;10%, 10-50%, and &gt;50%, the median TIL percentage was 17.5% before NAC and 5% after NAC, and the difference was statistically significant (p&lt;0.001). Postop-Ki-67 (p=0.005), molecular subtype (p=0.027), pre-NAC TIL score (p=0.006), post-NAC TIL score (p&lt;0.001), postop-Ki-67 (p=0.005) and preoperative residual cancer burden tumour-infiltrating lymphocyte (RCB-TIL) (p&lt;0.001) were significantly correlated with pCR. Higher TIL scores were significantly associated with higher PCR rates. Univariate analysis for disease-free survival (DFS) and overall survival (OS) revealed that postop-Ki-67 level and presence of pCR and postoperative ki-67 score (p=0.031) were significant prognostic factors, respectively. The independent prognostic factor for DFS were postop-Ki-67 score (p=0.012, RR: 6.16, 95% CI: 1.48-9.12), post-NAC TIL score (p=0.041, RR: 0.42, 95% CI: 0.16-1.06) and the presence of pCR (p=0.038, RR: 0.10, 95% CI: 0.01-0.87). Logistic regression analysis showed that a preoperative ki-67 score greater than 14% (p=0.001, OR: 4.55; 95% CI: 0.11-1.49), a postoperative ki-67 score equal to or lower than 14% (p=0.011, OR: 1.10; 95% CI: 0.42-2.29), preop-grade 3 (p=0.01, OR: 2.65; 95% CI: 0.85-3.14), low postop-TIL score (p&lt;0.001, OR: 3.14; 95% CI: 0.79-4.11) were significant predictive factors for pCR. Conclusions: Our study confirms the hypothesis that TIL expressions may be therapeutic targets, especially in specific molecular breast cancer subtypes.

Core needle biopsies alter the amounts of CCR5, Siglec-15, and PD-L1 positivities in breast carcinoma

Core needle biopsies (CNB) are widely used to diagnose breast cancer, but the procedure is invasive and thus, it changes the tumor microenvironment. The purpose of this study is to see how the expression of three potentially anti-inflammatory molecules, namely, programmed death-ligand 1 (PD-L1), sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15), and C-C chemokine receptor-5 (CCR-5), are expressed in CNB and surgical resection specimens (SRS). To do this, we compared the amounts of tumor-infiltrating lymphocytes and the levels of CCR5, Siglec-15, and PD-L1 in tumor cells and inflammatory cells as assessed by immunohistochemistry in CNB and the corresponding SRS of 22 invasive breast carcinomas of no special type and 22 invasive lobular carcinomas. The Siglec-15 H-score was higher in tumor cells in the SRS than in the CNB groups. There was no change in tumor cells CCR5 or PD-L1 between CNB and SRS. The positive inflammatory cell numbers for all markers rose between CNB and SRS, as did the amount of Tils. Furthermore, higher grade tumors and tumors with a high proliferation rate had more inflammatory cells that were positive for the markers and also more PD-L1+ tumor cells. Although changes in inflammatory cells can partly be attributed to the larger sample size of operation specimens, the differences also mirror a true change in the tumor microenvironment. The changes in inflammatory cells could be partly due to the need to restrict excess inflammation at the site of the biopsy.

Novel device for dividing core needle biopsy specimens to provide paired mirror image-like tissues for genetic and pathological tests

In a world that seeks precision medicine, genetic testing is gaining importance in clinical decision making. We previously reported the utility of a novel tool for longitudinally dividing core needle biopsy (CNB) tissues into two filamentous tissues that can provide paired mirror image-like tissues (mirror-tissues) that spatially match each other. In this study, we investigated its application in gene panel testing in patients who underwent prostate CNB. Four hundred and forty-three biopsy cores were obtained from 40 patients. Of them, 361 biopsy cores (81.5%) were judged by a physician to be appropriate for dividing into two pieces using the new device, of which a histopathological diagnosis was successfully reached in 358 biopsy cores (99.2%). Among them, the quality and quantity of nucleic acid in 16 appropriately divided cores were assessed and found to be sufficient for gene panel testing, and histopathological diagnosis was successfully obtained from the remaining divided cores. The novel device for longitudinally-dividing CNB tissue provided mirror image-like paired-tissues for gene panel and pathology testing. The device might be a promising tool for obtaining genetic and molecular biological information, in addition to histopathological diagnosis, helping to advance personalized medicine.

P-score in preoperative biopsies accurately predicts P-score in final pathology at radical prostatectomy in patients with localized prostate cancer.

Prostate cancer (PCa) is a highly heterogeneous, multifocal disease, and identification of clinically significant lesions is challenging, which complicates the choice of adequate treatment. The Prostatype® score (P-score) is intended to guide treatment decisions for newly diagnosed PCa patients based on a three-gene signature (IGFBP3, F3, and VGLL3) and clinicopathological information obtained at diagnosis. This study evaluated association of the P-score measured in preoperative magnetic resonance imaging/transrectal ultrasound fusion-guided core needle biopsies (CNBs) and the P-score measured in radical prostatectomy (RP) specimens of PCa patients. We also evaluated the P-score association with the pathology of RP specimens. Furthermore, concordance of the P-score in paired CNB and RP specimens, as well as in index versus concomitant nonindex tumor foci from the same RP was investigated. The study included 100 patients with localized PCa. All patients were diagnosed by CNB and underwent RP between 2015 and 2018. Gene expression was assessed with the Prostatype® real-time quantitative polymerase chain reaction kit and the P-score was calculated. Patients were categorized into three P-score risk groups according to previously defined cutoffs. For 71 patients, sufficient CNB tumor material was available for comparison with the RP specimens. The CNB-based P-score was associated with the pathological T-stage in RP specimens (p = 0.02). Moreover, the CNB-based P-score groups were in substantial agreement with the RP-based P-score groups (weighted κ score: 0.76 [95% confidence interval, 95% CI: 0.60-0.92]; Spearman's rank correlation coefficient r = 0.83 [95% CI: 0.74-0.89]; p < 0.0001). Similarly, the P-score groups based on paired index tumor and concomitant nonindex tumor foci (n = 64) were also in substantial agreement (weighted κ score: 0.74 [95% CI: 0.57-0.91]; r = 0.83 [95% CI: 0.73-0.89], p < 0.0001). Our findings suggest that the P-score based on preoperative CNB accurately reflects the pathology of the whole tumor, highlighting its value as a decision support tool for newly diagnosed PCa patients.

Abstract P3-05-15: Clinical significance of breast cancer resistance protein (BCRP) quantified by fluorescence nanoparticle in breast cancer patients undergoing neoadjuvant chemotherapy

Abstract Breast cancer resistance protein (BCRP), also known as ATP-binding cassette transporter G2 (ABCG2), is associated with chemotherapy resistance. BCRP is also implicated in breast cancer stem cells and has been reported as a poor prognostic factor. However, the relationship of BCRP levels in breast cancer tissues with chemotherapy resistance and prognosis has not been clarified to date. Our laboratory recently developed nanoparticles suitable for the quantitative immunohistochemical (IHC) method called phosphor-integrated dots (PIDs). Using PID-based IHC (IHC-PIDs), many biomarker proteins can be visualized and quantitatively analyzed at the single-particle level in paraffine-embedded, formalin-fixed tumor samples. We aimed to evaluate the correlation between quantitatively analyzed BCRP expression and prognosis in breast cancer tissue samples using immunohistochemistry with IHC-PIDs. Thirty-seven Japanese patients diagnosed with invasive ductal carcinoma of the breast who underwent mastectomy and lymph node dissection at Tohoku University Hospital (Sendai, Japan) between 2004 and 2010 were included. All patients had undergone NAC and were pathologically diagnosed with non-pathological complete response or progressive disease and lymph node metastasis postoperatively. The patients were followed up within a median of 10.1 years (range, 1.1–18.2 years). Among the thirty-seven patients, twenty-eight patients had core needle biopsy specimens taken before NAC. BCRP levels in breast cancer tissue and metastatic lymph nodes were quantitatively detected after preoperative chemotherapy and core needle biopsy. Biomarker assay with IHC-PIDs showed high accuracy for quantitative assessment of BCRP with low expression. The optimal PT+LN BCRP cut-off score for predicting survival was 27.4, with a sensitivity of 60.6% and a specificity of 77.3%. BCRP expression in PT+LN samples was dichotomized into high and low groups at this cutoff value, and OS was compared between these group. The results showed that OS was significantly worse in the high BCRP-expression group (log-rank p=0.0089). In conclusion, high BCRP levels are associated with poor prognosis in patients with breast cancer with residual tumors within the primary tumor and lymph nodes after preoperative chemotherapy. These findings provide a basis for further appropriate adjuvant therapy in these patients. Citation Format: Hiroshi Tada, Kohsuke Gonda, Narufumi Kitamura, Minoru Miyashita, Narumi Harada-Shoji, Yohei Hamanaka, Akiko Ebata, Takanori Ishida. Clinical significance of breast cancer resistance protein (BCRP) quantified by fluorescence nanoparticle in breast cancer patients undergoing neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-15.

Cytomorphology of renal angiomyolipoma: performance and accuracy of touch preparation of core needle biopsy.

The recognition of renal angiomyolipoma (AML) can be challenging based on cytology preparations such as touch preparation (TP) of core needle biopsy (CNB) and fine needle aspiration. This study evaluated the cytologic features and performance of TP of CNB during rapid onsite evaluation (ROSE) of renal AML. A pathology database search was performed between 2000 and 2021 for renal CNB specimens with ROSE using TP that were primarily favored AML on preliminary impression and/or confirmed AML on CNB or subsequent resection. Twenty confirmed AML were identified (90% female, median age 65.5 years). Sixteen (80%) were deemed adequate for diagnosis at the time of ROSE, and 9 of 16 (56%) had available onsite impression: AML was favored in 4 of 9 cases (44%). Examination of TP slides revealed spindle/epithelioid cells in 20 (100%), adipose tissue in 14 (70%), and blood vessels in 3 (15%). All AML cases were subsequently confirmed by immunohistochemistry. Additionally, 3 other cases with ROSE favoring AML revealed to be "renal parenchyma with fibrosis," clear cell papillary renal cell tumor and clear cell renal cell carcinoma. Onsite evaluation of TP ensures adequate material for diagnosis in most renal AML. Spindle/epithelioid cells were the most common component seen on TP, followed by adipose tissue. Blood vessels were rarely seen. While the recognition of AML at ROSE can be challenging, proper evaluation is important in obtaining adequate diagnostic tissue. Correlation with CNB and utilization of immunohistochemistry are crucial for arriving at the diagnosis.

Abstract P3-04-10: The TILs-US score adding vascularity assessment based on ultrasonography for predicting tumor-infiltrating lymphocytes in human epidermal growth factor receptor 2-positive and triple-negative breast cancer

Abstract Background: Tumor-infiltrating lymphocytes (TILs) are a useful prognostic factor and predictive biomarker of neoadjuvant chemotherapy treatment response for breast cancer, especially in human epidermal growth factor receptor type 2 (HER2)-positive breast cancer and triple-negative breast cancer (TNBC). However, due to heterogeneity of TIL expression and distribution in the tissues, accurately predicting TIL expression, especially using limited core-needle biopsy specimens, is difficult. Therefore, an accurate and simple preoperative evaluation method is needed. We have reported that the TILs-ultrasonography (US) score determined by characteristic US findings has a predictive performance for lymphocyte-predominant breast cancer (LPBC). This study aimed to investigate whether the TILs-US score with added vascularity assessment has a better predictive performance for LPBC. Methods: This multicenter, retrospective study investigated the validation and scoring of the LPBC characteristic imaging findings and applied it for LPBC and non-LPBC prediction. A total of 100 patients with HER2-positive breast cancer (n = 59) and TNBC (n = 41) treated by curative surgery between January 2014 and December 2021 were evaluated. Stromal lymphocytes in surgical pathological specimens were evaluated; the cutoff value for predicting LPBC was defined as ≥50% stromal TILs. Preoperative US was examined for TIL indicators. The US images with characteristic TILs were scored for LPBC prediction. Univariate and multivariate logistic regression analyses were employed for each potential predictor variable of LPBC. Results: A total of 40 patients with ≥50% stromal TILs were defined as having LPBC. The examined characteristic US findings for predicting LPBC, shape (more lobulated), internal echo level (weaker), posterior echoes (stronger), and vascularity assessment (hypervascularity), were significantly associated with LPBC and used to assign the scoring for predicting LPBC. As previously reported, the TILs-US score ranged from 0–7 points based on three ultrasonic tissue characteristics: shape (round, oval, and polygonal or irregular, 0 points; lobulated, 1 point; and small lobulated, 2 points), internal echo level (high or equal, 0 points; low, 1 point; and extremely low, 2 points), and posterior echoes (shadowing or attenuating, 0 points; no change, 1 point; accentuated, 2 points; and extremely accentuated, 3 points). We further added vascularity assessment (avascular or hypovascular, 0 point; moderately vascular, 1 point; and hypervascular, 2 points) to this scoring system. Based on the receiver operating characteristics (ROC) curves (AUC [Area Under the Curve] 0.77), the score cutoff for predicting LPBC was 4 points for TILs-US score (sensitivity, 0.83; specificity, 0.55; and accuracy, 0.66). Multivariate logistic regression analysis revealed that cT (&amp;lt; T2), estrogen receptor (ER) negativity, and a TILs-US score of ≥4 points were significant LPBC predictors (odds ratio [OR] 3.60; p = 0.028; OR 8.68; p = 0.020; OR 5.99; p = 0.005). Conversely, based on the ROC curves (AUC 0.78), the score cutoff for predicting LPBC was 5 points after adding vascularity assessment (sensitivity, 0.93; specificity, 0.57; and accuracy, 0.71). Multivariate logistic regression analysis revealed that cT (&amp;lt; T2), ER negativity, and a TILs-US score adding vascularity assessment of ≥5 points were significant LPBC predictors (OR 5.12; p = 0.010; OR 10.3; p = 0.019; OR 20.1; p &amp;lt; 0.001). Conclusions: Including the vascularity assessment to the TILs-US score, which can be noninvasively obtained using US, is a more accurate preoperative predictor of LPBC. Vascularity assessment may be an auxiliary factor in predicting LPBC. Univariate and multivariate logistic analysis of significant clinicopathological factors predicting lymphocyte-predominant breast cancer. Citation Format: Yuri Kimura, Norio Masumoto, Sadako Akashi-Tanaka, Kayo Fukui, Midori Noma, Aya Nagata, Takashi Nakamura, Hiroaki Shima, Toshitaka Okuno, Akari Murakami, Yoshiaki Kamei, Shogo Nakano, Koji Arihiro. The TILs-US score adding vascularity assessment based on ultrasonography for predicting tumor-infiltrating lymphocytes in human epidermal growth factor receptor 2-positive and triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-04-10.

Clinical application of Mycobacterium RT-PCR assay using various specimens for the rapid detection of lymph node tuberculosis: A diagnostic accuracy study.

To evaluate the diagnostic accuracy of the Capital Bio Mycobacterium real-time polymerase chain reaction assay Capital Bio assay for lymph node (LN) tuberculosis (LNTB), and to further compare the effect of different types of LN specimens on the detection capability of the test. We retrospectively analyzed the medical records of LNTB patients who met the inclusion criteria. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve of Capital Bio assay were calculated to evaluate its diagnostic accuracy compared with the final clinical diagnosis as reference standard. Three hundred sixty-four patients were included in the study. The overall sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve of the Capital Bio assay for LNTB were 74.4%, 100.0%, 100.0%, 34.9%, and 0.87, respectively. For the pus specimens, these values for Capital Bio assay were 93.2%, 100.0%, 100.0%, 27.3%, 0.97, respectively. For the core needle biopsy specimens, these values were 65.9%, 100.0%, 100.0%, 33.3%, and 0.83, respectively. For the fine-needle aspiration specimens, these values were 60.0%, 100.0%, 100.0%, 53.9%, and 0.80, respectively. For the tissue, these values were 59.3%, 100.0%, 100.0%, 33.3%, 0.80, respectively. The Capital Bio assay had good effective for the diagnosis of LNTB. Compared to LN fine-needle aspiration and core needle biopsy specimens and tissue specimens, pus specimens were more suitable for molecular testing and had the best diagnostic efficacy.

Nomograms for Predicting Disease-Free Survival Based on Core Needle Biopsy and Surgical Specimens in Female Breast Cancer Patients with Non-Pathological Complete Response to Neoadjuvant Chemotherapy

While a pathologic complete response (pCR) is regarded as a surrogate endpoint for pos-itive outcomes in breast cancer (BC) patients receiving neoadjuvant chemotherapy (NAC), fore-casting the prognosis of non-pCR patients is still an open issue. This study aimed to create and evaluate nomogram models for estimating the likelihood of disease-free survival (DFS) for non-pCR patients. A retrospective analysis of 607 non-pCR BC patients was conducted (2012-2018). After converting continuous variables to categorical variables, variables entering the model were progressively identified by univariate and multivariate Cox regression analyses, and then pre-NAC and post-NAC nomogram models were developed. Regarding their discrimination, ac-curacy, and clinical value, the performance of the models was evaluated by internal and external validation. Two risk assessments were performed for each patient based on two models; patients were separated into different risk groups based on the calculated cut-off values for each model, including low-risk (assessed by the pre-NAC model) to low-risk (assessed by the post-NAC model), high-risk to low-risk, low-risk to high-risk, and high-risk to high-risk groups. The DFS of different groups was assessed using the Kaplan-Meier method. Both pre-NAC and post-NAC nomogram models were built with clinical nodal (cN) status and estrogen receptor (ER), Ki67, and p53 status (all p < 0.05), showing good discrimination and calibration in both internal and external validation. We also assessed the performance of the two models in four subtypes, with the tri-ple-negative subtype showing the best prediction. Patients in the high-risk to high-risk subgroup have significantly poorer survival rates (p < 0.0001). Two robust and effective nomo-grams were developed to personalize the prediction of DFS in non-pCR BC patients treated with NAC.

Comparison of Programmed Cell Death Ligand 1 Status between Core Needle Biopsy and Surgical Specimens of Triple-Negative Breast Cancer.

Pembrolizumab is currently used to treat advanced triple-negative breast cancer (TNBC) and high-risk early TNBC with neoadjuvant chemotherapy (NAC). The tumor-infiltrating lymphocyte (TIL) level and programmed cell death ligand 1 (PD-L1) status are predictors of response to NAC and immune checkpoint inhibitor treatment. We aimed to investigate whether the PD-L1 status in core needle biopsies (CNBs) could represent the whole tumor in TNBC. A total of 49 patients diagnosed with TNBC who received upfront surgery without NAC between January 2018 and March 2021 were included. The PD-L1 expression (SP142 and 22C3 clones) and TIL were evaluated in paired CNBs and resected specimens. The concordance PD-L1 status and TIL levels between CNBs and resected specimens were analyzed. PD-L1 positivity was more frequently observed in resected specimens. The overall reliability of TIL level in the CNB was good [intraclass correlation coefficient (ICC)=0.847, p<0.001]. The agreements of PD-L1 status were good and fair, respectively (SP142, κ=0.503, p<0.001; 22C3, κ=0.380, p=0.010). As the core number of CNB increased, the reliability and agreement also improved, especially from five tumor cores (TIL, ICC=0.911, p<0.001; PD-L1 [22C3], κ=0.750, p=0.028). Regarding PD-L1 (SP142), no further improvement was observed with ≥5 tumor cores (κ=0.600, p=0.058). CNBs with ≥5 tumor cores were sufficient to represent the TIL level and PD-L1 (22C3) status in TNBC.

Association of CD10 and VEGF Expression with Tumour Characteristics and Treatment Response in Patients of Carcinoma BreastA Prospective Cohort Study

Introduction: Majority of breast cancer patients receive systemic therapy. This has led to an extensive search for effective factors to predict the outcome. Two such markers for breast cancer are Cluster of Differentiation 10 (CD10) and Vascular Endothelial Growth Factor (VEGF). There is limited data available in the literature to support these parameters in breast cancer patients, especially from the Indian subcontinent. Aim: To ascertain the association of pre-chemotherapy levels of CD10 and VEGF with tumour load in breast cancer and treatment response. Materials and Methods: A prospective cohort study was conducted in the Department of Surgery in collaboration with the Department of Pathology at Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, New Delhi, India, from November 2015 to February 2017. A total of 39 patients with Locally Advanced Breast Cancer (LABC) were included in the study. Preoperative levels of CD10 and VEGF were estimated in large needle core biopsy specimens. Standard anthracycline based chemotherapy was given to all patients as a 21 days cycle for three cycles. All patients underwent modified radical mastectomy after Neoadjuvant Chemotherapy (NACT). Levels of CD10 and VEGF were estimated again in the mastectomy specimen. Increase/decrease or no change in VEGF and CD10 expression percentage was ascertained for each patient after systemic therapy. Variables that were studied in the present study were Tumour, Nodes, and Metastasis (TNM) staging of patient, expression of VEGF and CD10 in large needle core biopsy specimens and its association with tumour load, response to NACT and its association with CD10 and VEGF and histopathological characteristics like presence or absence of lymphovascular invasion oestrogen, progesterone and Human Epidermal Growth factor Receptor 2 (HER2)/neu receptor status. Statistical analysis was done using the Statistical Package for Social Sciences (SPSS) version 22.0. Association between two ordinal variables was established using Kruskal-Wallis test. A comparison of ordinal paired data was done using Wilcoxon signed-rank sum test. The p-value &lt;0.05 was taken as significant. Results: The mean age of study participants was 42.0±11.4 years. Increase in TNM staging lead to higher CD10 and VEGF expression (p-value&lt;0.05 and &lt;0.029, respectively). There was a significant reduction in CD10 and VEGF expression postchemotherapy (p-value&lt;0.05). CD10 expression was found higher in subjects with ER-negative status (22 patients) with p-value=0.014 and HER2/neu positive status (19 patients) with p-value=0.028. Subjects with HER2/neu positive status had higher VEGF expression (20 patients) with p-value=0.032. Conclusion: CD10 and VEGF can be used as independent markers for indicating poor prognosis and can be used as target for development of novel therapies in carcinoma breast.

HER2-Low Status Is Not Accurate in Breast Cancer Core Needle Biopsy Samples: An Analysis of 5610 Consecutive Patients.

HER2-Low status is found in approximately half of breast cancer patients and shows potential benefits from novel antibody-drug conjugates (ADCs). Data on the accuracy of HER2-Low status between core needle biopsy (CNB) and surgical excision specimen (SES) samples are lacking. We aimed to investigate the accuracy of HER2-Low status diagnosis between CNB and SES samples. Consecutive early-stage breast cancer patients who underwent surgery from January 2009 to March 2022 with paired CNB and SES samples were retrospectively reviewed. HER2-Low was defined as IHC 1+ or IHC2+ and FISH-negative. Concordance rates were analyzed by the Kappa test. Further clinicopathological characteristics were compared among different HER2 status and their changes. A total of 5610 patients were included, of whom 3209 (57.2%) and 3320 (59.2%) had HER2-Low status in CNB and SES samples, respectively. The concordance rate of HER2 status in the whole population was 82.37% (Kappa = 0.684, p &lt; 0.001), and was 76.87% in the HER2-Negative patients (Kappa = 0.372, p &lt; 0.001). Among 1066 HER2-0 cases by CNB, 530 patients were classified as HER2-Low tumors. On the contrary, in 3209 patients with HER2-Low tumor by CNB, 387 were scored as HER2-0 on the SES samples. ER-negative or Ki67 high expression tumor by CNB had a high concordance rate of HER2-Low status. A relatively low concordance rate was found when evaluating HER2-Low status between CNB and SES samples in HER2-Negative breast cancer patients, indicating the necessity of retesting HER2 low status at surgery, which may guide further therapy in the era of anti-HER2 ADCs.