A multicenter study on efficacy of dual-target neoadjuvant therapy for HER2-positive breast cancer and a consistent analysis of efficacy evaluation of neoadjuvant therapy by Miller-Payne and RCB pathological evaluation systems (CSBrS-026).

Objective: The aim of this study was to investigate the factors influencing pathological complete response (pCR) rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab (H) + pertuzumab (P)] therapy combined with chemotherapy. Additionally, the consistency of the Miller-Payne and residual cancer burden (RCB) systems in evaluating the efficacy of neoadjuvant therapy for early human epidermal growth factor receptor-2 (HER2)+ breast cancer was analyzed. Methods: The clinicopathological data of female patients with early-stage HER2+ breast cancer who received dual-target neoadjuvant therapy at 26 hospitals of the Chinese Society of Breast Surgery (CSBrS) from March 2019 to December 2021 were collected. Patients were allocated to four groups: the HER2 immunohistochemistry (IHC) 3+/hormone receptor (HR)-, IHC3+/HR+, IHC2+ in situ hybridization (ISH)+/HR- and IHC2+ ISH+/HR+ groups. The overall pCR rate for patients, the pCR rate in each group and the factors affecting the pCR rate were analyzed. The consistency between the Miller-Payne and RCB systems in assessing the efficacy of neoadjuvant therapy was analyzed. Results: From March 1, 2019, to December 31, 2021, 77,376 female patients with early-stage breast cancer were treated at 26 hospitals; 18,853 (24.4%) of these patients were HER2+. After exclusion of unqualified patients, 2,395 patients who received neoadjuvant dual-target (H+P) therapy combined with chemotherapy were included in this study. The overall pCR rate was 53.0%, and the patients' HR statuses and different HER2+ statuses were significantly correlated with the pCR rate (P<0.05). The consistency of the pathological efficacy assessed by the Miller-Payne and RCB systems was 88.0% (κ=0.717, P<0.001). Conclusions: Different HER2 expression statuses and HR expression statuses are correlated with the pCR rate after dual-target neoadjuvant therapy in HER2+ breast cancer patients. There is a relatively good consistency between Miller-Payne and RCB systems in evaluating the pathologic efficacy of neoadjuvant therapy for HER2+ breast cancer.

Clinicopathological analysis of early-stage breast cancer patients that meet indications for BRCA1/2 genetic testing.

OBJECTIVE: To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer patients with indications for breast cancer susceptibility genes 1/2 (BRCA1/2) genetic testing in China. METHODS: Based on the indication criteria for BRCA genetic testing specified in the National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology, genetic/familial high-risk assessment: Breast and ovarian (Version 2. 2019), a retrospective analysis was performed on patients with early-stage invasive breast cancer treated at Breast Disease Center, Peking University First Hospital between January 2008 and December 2016. Clinicopathological characteristics of all patients were analyzed, and prognoses were calculated using the Kaplan-Meier method and a Cox proportionate hazards model. RESULTS: A total of 906 early-stage breast cancer patients who had indications for BRCA genetic testing and had complete clinicopathological data and follow-up information were included in the study group, accounting for 34.7% of all breast cancer patients treated in Breast Disease Center, Peking University First Hospital during the study period. Compared with breast cancer patients without indications for BRCA genetic testing, the overall survival (OS) and disease-free survival (DFS) of patients with indications were not significantly different. In the study group, patients with premenopausal status, high T stage, lymph node positive, estrogen receptor (ER) negative, Ki-67>20% and presence of a vascular tumor thrombus had worse prognosis. There were more family histories of gastrointestinal cancer in patients with related indications than in patients without such indications. CONCLUSIONS: Single-center data showed that more than 30% of patients with early-stage breast cancer had indications for BRCA genetic testing. There was no prognostic difference in patients with or without indications for BRCA genetic testing. Premenopausal status, high T stage, lymph node positive, ER negative, Ki-67>20%, and presence of a vascular tumor thrombus were associated with poor prognosis.

Clinical and pathological portraits of axillary presentation breast cancer and effects of preoperative systemic therapy.

There is a lack of investigation into the biological characteristics and preoperative systemic therapy (PST) for occult breast cancer (OBC). For this study, departmental records in Breast Disease Center of Peking University First Hospital from January 2008 to December 2015 were retrospectively reviewed to identify cases of OBC. Eleven cases were included, and all patients were female, with a median age of 56 (range: 29-75) years. The sensitivity of magnetic resonance imaging (MRI) was 100%, and the false positive rate was 33.3%. Based on histologic analysis of the axillary node, 9 (81.8%) cases were grade 3, and 2 (18.2%) cases were grade 2; 4 (36.4%) cases were ≥10% estrogen receptor (ER) positive and 6 (54.5%) human epidermal growth receptor 2 (HER2) positive. Nine cases (81.8%) exhibited over 30% Ki67 expression. PST was performed in 5 of the 11 cases. The lymph node response rate was 100% (5/5), but no complete remission was achieved. In conclusion, aggressive subtypes were predominant among the included cases, and PST should be considered for OBC treatment options.

A retrospective prognostic evaluation analysis using the 8th edition of American Joint Committee on Cancer (AJCC) cancer staging system for luminal A breast cancer.

OBJECTIVE: We retrospectively analyzed the clinical prognostic value of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for luminal A breast cancer. METHODS: Using both the anatomic and prognostic staging in the 8th edition of AJCC cancer staging system, we restaged patients with luminal A breast cancer treated at the Breast Disease Center, Peking University First Hospital from 2008 to 2014. Follow-up data including 5-year disease free survival (DFS), overall survival (OS) and other clinic-pathological data were collected to analyze the differences between the two staging subgroups. RESULTS: This study included 421 patients with luminal A breast cancer (median follow-up, 61 months). The 5-year DFS and OS rates were 98.3% and 99.3%, respectively. Significant differences in 5-year DFS but not OS were observed between different anatomic disease stages. Significant differences were observed in both 5-year DFS and OS between different prognostic stages. Application of the prognostic staging system resulted in assignment of 175 of 421 patients (41.6%) to a different group compared to their original anatomic stages. In total, 102 of 103 patients with anatomic stage IIA changed to prognostic stage IB, and 24 of 52 patients with anatomic stage IIB changed to prognostic stage IB, while 1 changed to prognostic stage IIIB. Twenty-two of 33 patients with anatomic stage IIIA were down-staged to IIA when staged by prognostic staging system, and the other 11 patients were down-staged to IIB. Two patients with anatomic stage IIIB were down-staged to IIIA. Among seven patients with anatomic stage IIIC cancer, two were down-staged to IIIA and four were down-staged to stage IIIB. CONCLUSIONS: The 8th edition of AJCC prognostic staging system is an important supplement to the breast cancer staging system. More clinical trials are needed to prove its ability to guide selection of proper systemic therapy and predict prognosis of breast cancer.

Nuclear Gli1 expression is associated with pathological complete response and event-free survival in HER2-positive breast cancer treated with trastuzumab-based neoadjuvant therapy.

Aberrant activation of the hedgehog (Hh) signaling pathway has shown predictive significance for treatment response and prognostic effect for survival in human tumors. However, the associations of the Hh signaling pathway with response to neoadjuvant therapy (NAT) and survival after NAT in breast cancer are unknown. Therefore, we investigated the correlation of pretherapeutic nuclear expression of glioma-associated oncogene homolog 1 (Gli1), a key transcriptional factor of the Hh signaling pathway, with pathological complete response (pCR) and event-free survival (EFS) in HER2-positive breast cancer treated with trastuzumab-based NAT. High nuclear Gli1 expression (OR 0.19; 95 % CI 0.07-0.54; P = 0.002) and positive hormone receptor (HR) status (OR 0.36; 95 % CI 0.14-0.90; P = 0.028) were independent and negative predictors of pCR in multivariate analysis. High nuclear Gli1 expression was significantly associated with lower pCR rates in both HR-positive and HR-negative tumors (P = 0.014 and 0.024, respectively). For survival analyses, multivariate analysis indicated that high nuclear Gli1 expression was the only independent predictor of poorer EFS in both the entire population (hazard ratio 2.97; 95 % CI 1.18-7.44; P = 0.020) and patients with non-pCR (hazard ratio 3.98; 95 % CI 1.35-11.68; P = 0.012). Our study is the first to demonstrate the associations of high nuclear Gli1 expression with resistance to trastuzumab-based NAT and subsequent worse prognosis in HER2-positive disease. These findings suggest that the nuclear Gli1 protein may be a novel target of NAT for HER2-positive breast cancer.

Optimal threshold for stromal tumor-infiltrating lymphocytes: its predictive and prognostic value in HER2-positive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy.

The purpose of the present study was to determine the optimal threshold for stromal tumor-infiltrating lymphocytes (TILs) and investigate its predictive and prognostic value in HER2-positive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy (NAC). Levels of stromal TILs were evaluated using hematoxylin and eosin-stained sections of core biopsies from 116 patients. We investigated the correlation between stromal TILs and pathological response to identify its optimal threshold. Using receiver operating characteristic curve analysis, a 30 % threshold best discriminated pathological complete response (pCR) from non-pCR subgroups (P < 0.001). Lymphocyte-rich breast cancer (LRBC) was defined as having ≥30 % stromal TILs level, and was used for analysis. For analyses of predictive factors, multivariate analysis indicated that LRBC was a strong predictor of pCR with an odds ratio of 5.23 (P < 0.001). Negative hormone receptor (HR) status was also significantly associated with pCR (P = 0.028). LRBC significantly predicted pCR in both HR-positive and HR-negative tumors (P = 0.016 and 0.006, respectively). For survival analyses, LRBC was the only independent predictor of improved event-free survival (EFS) among baseline clinicopathological factors in multivariate analysis (P = 0.012). When pathological response was included, both LRBC and pCR were independent predictors of better EFS (P = 0.040 and 0.045, respectively). LRBC significantly predicted longer EFS in the non-pCR subgroup (P = 0.018), whereas LRBC was not significantly associated with EFS in the pCR subgroup (P = 0.825). A 30 % threshold for stromal TILs optimally identified response to trastuzumab-based NAC in HER2-positive breast cancer; its predictive and prognostic value was also validated in our study.

[Clinicopathological features of Luminal B-like breast cancer].

OBJECTIVE: To explored the clinicopathological features of Luminal B-like breast cancer and analyze the value of St. Gallen consensus in its treatment. METHODS: The patients with invasive breast cancer treated at our hospital between January 2010 and December 2012 were recruited and divided into five subtypes according to the criteria of St. Gallen International Expert Consensus report 2013. And their TNM stages, pathological characteristics and Ki-67 status were analyzed for Luminal B-like subtype. RESULTS: The Luminal B-like subtype was found in 390 patients (52.8%), human epidermalgrowth factor receptor 2(HER-2) positive in 89 patients (22.8%) and negative in 301 patients (77.2%).Only 7.3% required chemotherapy based upon the result of gene detection. CONCLUSION: Only those patients for whom the need of chemotherapy is to be determined shall really benefit from gene detection.

[Analysis on clinical and pathological characteristics of 66 patients with stage IV breast cancer].

OBJECTIVES: To explore the clinical and pathological characteristics of stage IV breast cancer and to analyze their relationship with the morbidity and prognosis. METHODS: The records of 66 patients presenting from January 2008 to December 2014 with stage IV breast cancer were reviewed. All of the patients were women and the median age was 57.5 (31 to 80) years, accounted for 3.01% (66/2 189) among the breast cancer patients treated in the same period. Statistical methods were used to analyze the correlation between clinical and pathological characteristics such as T-stage, N-stage, immuno-histo-chemistry and the morbidity and prognosis of stage IV breast cancer. The influence of patients characteristics to metastasis were compared by χ(2) test. Kaplan-Meier curves were reported for overall survival (OS), and the Log-rank test was used to compare the difference in groups. Cox proportional models were fitted for multivariate analysis. RESULTS: The median survival time of stage IV breast cancer was 56.0 months and the 5-year survival rate was 40%. To metastasis, the effects of age, subtypes, histological grade, hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2)had no significant statistics differences. It was concluded that the expression of HER2 (P=0.003) and HR (P=0.001) as well as single metastasis (P=0.029) were the influencing factors of the survival by multivariate Cox regression analysis. Primary tumor R0 surgery group and no surgery group had no significant statistics differences of overall survival and the 5-year survival rate (P=0.102). CONCLUSIONS: Clinical and pathological characteristics have no effect on metastasis. The expression of HER2 and HR as well as single metastasis play important roles in survival.

[Study on clinicopathological classification and clinical and pathological characteristics in breast cancer].

OBJECTIVE: To explored the relationship of clinicopathological classification and clinical and pathological characteristics of breast cancer and analyze the value in treatment. METHODS: The patients with invasive breast carcinoma had been treated between January 2011 and December 2012. The breast cancer have been divided into luminal A, luminal B, HER2-positive and triple-negative subtypes according to criteria of St. Gallen International Expert Consensus report 2011. The Mann-Whitney test and Kruskal-Wallis test were used to analyze the relationships between four subtypes and TNM staging, histopathological grading. RESULTS: The 530 cases of invasive breast cancer patients were included in this study. The luminal A was 94 cases (17.7%), the luminal B was of 285 cases (53.8%), the HER2-positive was 59 cases (11.1%), and the triple-negative subtype was 92 cases (17.4%). In luminal B subtype, the HER2-positive was 56 (19.6%) and negative was 229 (80.4%). Most of luminal B was later in grade (71.7% of cases were more than II grade) and stage (66.7% were more than stage II). CONCLUSIONS: Clinical pathological classification is important in the individualized treatments of breast cancer, and the Luminal types (A+B) are more than 71.5% of all breast cancer patients, and they should be paid more attention to the endocrine therapy; Luminal B type accounted for 53.8% of all breast cancer and it needs further study to improve the precision of the diagnosis and treatment.

Integrative analysis identifies cancer cell-intrinsic RARRES1 as a predictor of prognosis and immune response in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and limited treatment options. Although immune checkpoint inhibitors (ICIs) have been proven to improve outcomes in TNBC patients, the potential mechanisms and markers that determine the therapeutic response to ICIs remains uncertain. Revealing the relationship and interaction between cancer cells and tumor microenvironment (TME) could be helpful in predicting treatment efficacy and developing novel therapeutic agents. By analyzing single-cell RNA sequencing dataset, we comprehensively profiled cell types and subpopulations as well as identified their signatures in the TME of TNBC. We also proposed a method for quantitatively assessment of the TME immune profile and provided a framework for identifying cancer cell-intrinsic features associated with TME through integrated analysis. Using integrative analyses, RARRES1 was identified as a TME-associated gene, whose expression was positively correlated with prognosis and response to ICIs in TNBC. In conclusion, this study characterized the heterogeneity of cellular components in TME of TNBC patients, and brought new insights into the relationship between cancer cells and TME. In addition, RARRES1 was identified as a potential predictor of prognosis and response to ICIs in TNBC.

[Effects of vinorelbine plus cisplatin as second-line neoadjuvant chemotherapy regimen in the treatment of breast cancer].

OBJECTIVE: To study the value of a combination of vinorelbine and cisplatin (NP) as second-line neoadjuvant chemotherapy regimen for primary breast cancer. METHODS: Primary breast cancer patients on neoadjuvant chemotherapy and non-responsive to anthracyclines plus taxanes received the NP regimen. The clinical objective response was evaluated with dynamic contrast-enhanced magnetic resonance imaging (MRI) according to RECIST 1.1 before operation. The pathological response was evaluated by the Miller-Payne grading system. And the toxicities were observed and evaluated according to National Cancer Institute-Common Terminology Criteria Version 3.0 (NCI-CTC v3.0). RESULTS: A total of 33 breast cancer patients were examined. The outcomes were complete remission (CR, n = 0, 0%), partial remission (PR, n = 16, 48.5%), stable disease (n = 17, 51.5%) and progressive disease (n = 0, 0%). The clinical responsive rate (CR + PR) rate was 48.5%. The pathological response rates were G1 (n = 6, 18.2%), G2 (n = 6, 18.2%), G3 (n = 10, 30.3%), G4 (n = 9, 27.2%) and G5 (n = 2, 6.1%). And the pathological response (G3+G4+G5) was found in 21 cases (63.6%). The most common toxicities included neutropenia and nausea/vomiting. No serious toxicities were observed. CONCLUSION: As a well-tolerated and effective regimen, NP regimen may be recommended as an option of second-line neoadjuvant chemotherapy regimen for primary breast cancer.

[Factors related with pathological complete response of neoadjuvant chemotherapy in primary breast cancer].

OBJECTIVE: To assess the effect of neoadjuvant chemotherapy and the factors related with pathological complete response (pCR) of neoadjuvant chemotherapy in breast cancer. METHODS: The data of 159 primary breast cancer patients who had received neoadjuvant chemotherapy and operation with complete MRI data and histopathology evaluation in this center from January 2009 to December 2011 was analyzed. All the patients were female, aging from 28 to 70 years with a median of 50 years. The neoadjuvant chemotherapy regimens were based on anthracyclines or taxanes, and trastuzumab was used in almost half of the human epidermalgrowth factor receptor 2 positive patients. The response of neoadjuvant chemotherapy was comprehensively evaluated based on RECIST 1.1 and Miller-Payne grading system. SPSS 18.0 was used for statistical analysis. RESULTS: Among the 159 patients, 10.1% patients had achieved complete response according to the MRI evaluation, and the rate of partial response, stable disease, and progressive disease was 65.4%, 24.5%, and 0 respectively. According to the Miller-Payne grading system, 27.7% patients had pathological response evaluated as G5 (pCR), and the response evaluated as G4, G3, G2, and G1 were 28.3%, 18.9%, 12.6%, and 12.6% respectively. The higher histological grade were correlated with pCR statistically (Z = -2.820, P = 0.005). Meanwhile strong expression of Ki67 (Z = -1.989, P = 0.047) and p53 (Z = -2.457, P = 0.014) were related to pCR in a significant statistically way. CONCLUSIONS: The response of neoadjuvant chemotherapy can be predicted. The histological grade and the immunohistochemistry results of Ki67 and p53 are related to pCR of neoadjuvant chemotherapy for primary breast cancer. Basal-like breast cancer had a higher pCR statistically.

[A study on the predictive and evaluational value of molecular subtypes and dynamic contrast-enhanced magnetic resonance imaging of neoadjuvant chemotherapy for breast cancer].

OBJECTIVE: To investigate the predictive value of molecular subtypes and the evaluational value of dynamic contrast-enhanced MRI of neoadjuvant chemotherapy for breast cancer. METHODS: From January 2010 to December 2011, the 79 patients diagnosed as primary invasive breast cancer, having received 6 cycles of neoadjuvant chemotherapy and finished the mastectomy or the breast conserving surgery entered this study. A total of 79 patients participated in this prospective study. There were 6 (7.6%) luminal A cases, 42 (53.2%) luminal B cases, 14 HER-2 (17.7%) positive cases and 17 (21.5%) triple negative cases. The associations between molecular subtypes and clinical response as well as the pathological response were analyzed. The predictive value of molecular subtypes for the neoadjuvant chemotherapy was studied. RESULTS: Clinical effective rate was 85.3% (66/79). There was no statistical correlation between molecular subtypes and clinical effective rate. Pathologic effective rate was 79.7% (63/79). There was no statistical correlation between molecular subtypes and pathologic effective rate. Twenty-seven case achieved pathologic complete remission (pCR) in all the patients. No case achieved pCR in the patients classified as Luminal A. Twelve cases (28.6%, 12/42) achieved pCR in the luminal B patients.Five cases (5/14) achieved pCR in the HER-2 overexpression patients. Ten cases (10/17) achieved pCR in the triple-negative patients. There was a statistical correlation between the molecular subtypes and the pCR rate (P = 0.039), and between clinical evaluation by dynamic contrast-enhanced MRI and evaluation of pathological response (r = 0.432, P = 0.000). CONCLUSIONS: Molecular subtypes and dynamic contrast-enhanced MRI have a good value of predicting and evaluating the response of neoadjuvant chemotherapy on breast cancer.

Comparison of adverse effects of anti-tumor therapy for breast cancer shortly after COVID-19 diagnosis vs. the control period.

Background: COVID-19 is an acute infectious disease caused by SARS-CoV-2. The best time to restart antitumor therapy in breast cancer patients after SARS-CoV-2 infection is unknown. This study aimed to evaluate treatment-related adverse events in breast cancer patients who received antitumor therapies within a short time after SARS-CoV-2 infection (observation) as well as before (control) and to provide safety data. Methods: We conducted a self-controlled cohort study using the data from the Breast Disease Center of Peking University First Hospital. We identified patients who received antitumor therapy within 28 days after COVID-19 infection between December 20, 2022, and January 20, 2023. The primary outcome was treatment-related adverse events. McNemar's test was used to compare the incidence rate of adverse reactions between periods. Results: We identified 183 patients with breast cancer, of whom 109 were infected with SARS-CoV-2 within 28 days before antitumor treatment and were included. In total, 28 patients (25.7%) received neoadjuvant therapy, 60 (55.0%) received adjuvant therapy, and 21 (19.3%) received advanced rescue therapy. None of patients required hospitalization for severe or critical COVID-19, but 15 patients (13.8%) still had sequelae of COVID-19 while receiving antitumor treatment. The most common adverse events were peripheral neuropathy (n = 32 [29.4%]), pain (n = 29 [26.6%]), fatigue (n = 28 [25.7%]), nausea (n = 23 [21.1%]), and neutropenia (n = 19 [17.4%]). There was no increased risk of overall treatment-related adverse events (n = 87 [79.8%] vs. n = 91 [83.5%]; p = 0.42) or serious adverse events (n = 13 [11.9%] vs. n = 12 [11.0%]; p = 1.00) from receiving antitumor therapy shortly after the diagnosis of COVID-19. We also found no increased risk in subgroup analyses, and no patients discontinued antitumor therapy due to adverse events. Conclusion: Restarting antitumor therapy 2-4 weeks after having mild or moderate COVID-19 is a relatively safe strategy for breast cancer patients that does not increase the risk of treatment-related adverse events.

To diagnose primary and secondary squamous cell carcinoma of the thyroid with ultrasound malignancy risk stratification.

Objectives: This study aimed to investigate the clinico-ultrasound features of primary squamous cell carcinoma of the thyroid (PSCCT) and secondary SCCT (SSCCT) and evaluate the accuracy of fine needle aspiration (FNA) recommendation for SCCT with American College of Radiology-Thyroid Imaging and Reporting Data System (ACR-TIRADS) and Chinese-TIRADS (C-TIRADS). Materials and methods: We retrieved 26 SCCT patients (11 PSCCT, 15 SSCCT) from our hospital's pathology database (5,718 patients with thyroid malignancy) over 23 years. Medical records and ultrasound data of the 26 patients with 27 SCCTs were analyzed retrospectively, and each SCCT focus was categorized based on the two TIRADSs. Results: For 26 patients (21 males, 5 females) with an age range of 42-81 years, rapidly enlarging thyroid/neck nodules (18/26, 69.2%), dysphagia (7/26, 26.9%), hoarseness (6/26, 23.1%), dyspnea (5/26, 19.6%), cough (4/26, 15.4%), neck pain (2/26, 7.7%), B symptoms (2/26, 7.7%), and blood in sputum (1/26, 3.8%) were presented at diagnosis. Five asymptomatic patients (5/26, 19.2%) were detected by ultrasound. Hoarseness was more common in PSCCT (5/11, 45.5%) than in SSCCT (1/15, 6.7%) (P=0.032). For 27 SCCTs with a mean size of 3.7 ± 1.3 cm, the ultrasound features consisted of solid (25/27, 92.6%) or almost completely solid composition (2/27, 7.4%), hypoechoic (17/27, 63%) and very hypoechoic echogenicity (10/27, 37%), irregular/lobulated margin with extra-thyroidal extension (27/27, 100%), taller-than-wide shape (13/27, 48.1%), punctate echogenic foci (6/27, 22.2%), hypervascularity (23/27, 85.2%) and involved neck lymph (13/26, 50.0%). A total of 27 SCCTs were evaluated as high malignancy risk stratification (≥TR4 and 4B) by the two TIRADSs and recommended FNA in 96.3-100% (26/27, 27/27). Pathologically, more than half of PSCCTs (7/12, 58.3%) and a quarter of SSCCTs (4/15, 26.7%) were poorly differentiated, while moderately and well-differentiated grades were observed in 5 PSCCTs and 11 SSCCTs (P=0.007). Thirteen patients (50.0%) underwent surgery with radical operation in 5 cases (5/13, 38.5%). Conclusion: SCCT is an extremely rare and aggressive malignancy with a male predominance. PSCCT and SSCCT had similar clinical and ultrasound features except for tumor differentiation and the symptom of hoarseness. SCCT showed a high malignancy risk stratification in ACR-TIRADS and C-TIRADS, with a high rate of FNA recommendation.

Development and external validation of a prediction model for brain metastases in patients with metastatic breast cancer.

BACKGROUND: Breast cancer patients with brain metastasis (BM) have a poor prognosis. This study aims to identify the risk factors of BM in patients with metastatic breast cancer (MBC) and establish a competing risk model for predicting the risk of brain metastases at different time points along the course of disease. METHODS: Patients with MBC admitted to the breast disease center of Peking University First Hospital from 2008 to 2019 were selected and retrospectively analyzed to establish a risk prediction model for brain metastases. Patients with MBC admitted to eight breast disease centers from 2015 to 2017 were selected for external validation of the competing risk model. The competing risk approach was used to estimate cumulative incidence. Univariate Fine-Gray competing risk regression, optimal subset regression, and LASSO Cox regression were used to screen potential predictors of brain metastases. Based on the results, a competing risk model for predicting brain metastases was established. The discrimination of the model was evaluated using AUC, Brier score, and C-index. The calibration was evaluated by the calibration curves. The model was assessed for clinical utility by decision curve analysis (DCA), as well as by comparing the cumulative incidence of brain metastases between groups with different predicted risks. RESULTS: From 2008 to 2019, a total of 327 patients with MBC in the breast disease center of Peking University First Hospital were admitted into the training set for this study. Among them, 74 (22.6%) patients developed brain metastases. From 2015 to 2017, a total of 160 patients with MBC in eight breast disease centers were admitted into the validation set for this study. Among them, 26 (16.3%) patients developed brain metastases. BMI, age, histological type, breast cancer subtype, and extracranial metastasis pattern were included in the final competing risk model for BM. The C-index of the prediction model in the validation set was 0.695, and the AUCs for predicting the risk of brain metastases within 1, 3, and 5 years were 0.674, 0.670, and 0.729, respectively. Time-dependent DCA curves demonstrated a net benefit of the prediction model with thresholds of 9-26% and 13-40% when predicting the risk of brain metastases at 1 and 3 years, respectively. Significant differences were observed in the cumulative incidence of brain metastases between groups with different predicted risks (P < 0.05 by Gray's test). CONCLUSIONS: In this study, a competing risk model for BM was innovatively established, with the multicenter data being used as an independent external validation set to confirm the predictive efficiency and universality of the model. The C-index, calibration curves, and DCA of the prediction model indicated good discrimination, calibration, and clinical utility, respectively. Considering the high risk of death in patients with metastatic breast cancer, the competing risk model of this study is more accurate in predicting the risk of brain metastases compared with the traditional Logistic and Cox regression models.

Diagnostic Value of Ultrasound Elastography in the Differentiation of Breast Invasive Ductal Carcinoma and Ductal Carcinoma In situ.

BACKGROUND: Ultrasound elastography (US-E) has been shown superior to the conventional US in diagnosing benign and malignant breast lesions. In contrast, the role of US-E in the differentiation of breast invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) has been poorly described. OBJECTIVE: This study was designed to examine the diagnostic value of US-E in the differentiation of IDC and DCIS. METHODS: Medical records of all patients who underwent preoperative US-E evaluation and were diagnosed with IDC or DCIS at our hospital from April-December 2019 were retrieved and analyzed. Those who had prior surgical treatment, chemotherapy or radiotherapy were excluded. RESULTS: Twenty women with DCIS and 111 women with IDC were included in this study. There were no significant differences in age, maximum lesion diameter and tumor volume between the two groups. While shear wave velocity (SWV) inside the lesion and in the surrounding tissue, strain ratio and tumor area ratio were not substantially different between the two groups, SWV at the edge of the lesion was significantly higher in IDC cases, which had an AUC value of 0.66 with a sensitivity of 65.8% and a specificity of 60.0% for the differential diagnosis of IDC and DCIS. CONCLUSION: Edge SWV is significantly higher in IDC than that in DCIS, which had a moderate diagnostic value for the differentiation of IDC and DCIS, similar to the performance of diffusion-weighted magnetic resonance imaging as reported in the literature. In terms of cost-effectiveness, US-E could be very useful while waiting for further evaluations to determine whether US-E combined with other diagnostic modalities improves the diagnostic performance.

A multicenter study of the clinicopathological characteristics and a risk prediction model of early-stage breast cancer with hormone receptor-positive/human epidermal growth factor receptor 2-low expression.

BACKGROUND: In light of the significant clinical benefits of antibody-drug conjugates in clinical trials, the human epidermal growth factor receptor 2 (HER2)-low category in breast cancers has gained increasing attention. Therefore, we studied the clinicopathological characteristics of Chinese patients with hormone receptor (HR)-positive/HER2-low early-stage breast cancer and developed a recurrence risk prediction model. METHODS: Female patients with HR-positive/HER2-low early-stage breast cancer treated in 29 hospitals of the Chinese Society of Breast Surgery (CSBrS) from Jan 2015 to Dec 2016 were enrolled. Their clinicopathological data and prognostic information were collected, and machine learning methods were used to analyze the prognostic factors. RESULTS: In total, 25,096 patients were diagnosed with breast cancer in 29 hospitals of CSBrS from Jan 2015 to Dec 2016, and clinicopathological data for 6486 patients with HER2-low early-stage breast cancer were collected. Among them, 5629 patients (86.79%) were HR-positive. The median follow-up time was 57 months (4, 76 months); the 5-year disease-free survival (DFS) rate was 92.7%, and the 5-year overall survival (OS) rate was 97.7%. In total, 412 cases (7.31%) of metastasis were observed, and 124 (2.20%) patients died. Multivariate Cox regression analysis revealed that T stage, N stage, lymphovascular thrombosis, Ki-67 index, and prognostic stage were associated with recurrence and metastasis ( P <0.05). A recurrence risk prediction model was established using the random forest method and exhibited a sensitivity of 81.1%, specificity of 71.7%, positive predictive value of 74.1%, and negative predictive value of 79.2%. CONCLUSION: Most of patients with HER2-low early-stage breast cancer were HR-positive, and patients had favorable outcome; tumor N stage, lymphovascular thrombosis, Ki-67 index, and tumor prognostic stage were prognostic factors. The HR-positive/HER2-low early-stage breast cancer recurrence prediction model established based on the random forest method has a good reference value for predicting 5-year recurrence events. REGISTRITATION: ChiCTR.org.cn, ChiCTR2100046766.

Erythropoietin receptor expression and its relationship with trastuzumab response and resistance in HER2-positive breast cancer cells.

Resistance to trastuzumab is a major issue in the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Several potential resistance mechanisms have been investigated, but the results are controversial and no conclusion has been reached. Erythropoietin receptor (EPOR) may function in cell growth, and expressed in various cancer cells. Because the downstream signaling pathways for EPOR and HER2 partially overlapped, we hypothesized that EPOR may play a role in the inhibition effect of trastuzumab and resistance to trastuzumab. Here, we detected the expression of EPOR mRNA and protein in HER2-positive breast cancer cell lines and tissues. EPOR expressed in SKBR3, MDA-MB-453, and UACC-812 cell lines, but not in BT474. Of the 55 HER2-positive cancer tissues, EPOR was positive in 42 samples and highly expressed (H-score ≥ 25) in 24 by immunohistochemistry. The difference between EPOR expression and Ki67 index was significant (P = 0.033), and EPOR expression also positively correlated with higher pathological stage (Spearman correlation coefficient = 0.359; P = 0.007). Exogenous EPO antagonized trastuzumab-induced inhibition of cell proliferation in HER2/EPOR dual-positive breast cancer cells. We then exposed SKBR3 cells to trastuzumab for 4 months to obtain trastuzumab-resistant SKBR3 cell line, which demonstrated higher phosphorylated EPOR level, higher EPO expression and more extracellular secretion than non-resistant parental SKBR3 cells. Downregulation EPOR expression using short hairpin RNA resensitized trastuzumab-resistant cells to this drug, and SKBR3 cells with EPOR downregulation demonstrated attenuated trastuzumab resistance after the same resistance induction. EPOR downregulation plus trastuzumab produced a synergetic action in the inhibition of cell proliferation and invasion in SKBR3 and MDA-MB-453 cell lines. Therefore, EPOR expression may be involved in tumor progression and proliferation in HER2-positive breast cancer. EPO/EPOR contributes to the mechanism of trastuzumab resistance in SKBR3 cell lines, and EPOR downregulation can reverse the resistance to trastuzumab and increase the inhibition effect of this drug.

Regulation of piglet T-cell immune responses by thioredoxin peroxidase from Cysticercus cellulosae excretory-secretory antigens.

Taenia solium (T. solium) cysticercosis is a serious threat to human health and animal husbandry. During parasitization, Cysticercus cellulosae (C. cellulosae) can excrete and secrete antigens that modulate the host's T-cell immune responses. However, the composition of C. cellulosae excretory-secretory antigens (ESAs) is complex. This study sought to identify the key molecules in C. cellulosae ESAs involved in regulating T-cell immune responses. Thus, we screened for thioredoxin peroxidase (TPx), with the highest differential expression, as the key target by label-free quantification proteomics of C. cellulosae and its ESAs. In addition, we verified whether TPx protein mainly exists in C. cellulosae ESAs. The TPx recombinant protein was prepared by eukaryotic expression, and ESAs were used as the experimental group to further investigate the effect of TPx protein on the immune response of piglet T cells in vitro. TPx protein induced an increase in CD4+ T cells in piglet peripheral blood mononuclear cells (PBMCs), while CD8+ T cells did not change significantly. This resulted in an imbalance in the CD4+/CD8+ T-cell ratio and an increase in CD4+CD25+Foxp3+ Treg cells in the PBMCs. In addition, TPx protein initiated T helper 2 (Th2)-type immune responses by secreting IL-4 and IL-10 and suppressed Th1/Th17-type immune responses. The results showed that ESAs were involved in regulating piglet T-cell immune responses cells. This suggests that TPx protein found in ESAs plays an essential role to help the parasite evade host immune attack. Moreover, this lays a foundation for the subsequent exploration of the mechanism through which TPx protein regulates signaling molecules to influence T-cell differentiation.