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.

Histo- and clinico-pathological analysis of a large series of triple-negative breast cancer in a single center in China: Evidences on necessity of histological subtyping and grading.

OBJECTIVE: To investigate histo-pathological distribution and clinico-pathological significance in a large Chinese triple-negative breast cancer (TNBC) patients serials based on the latest understanding of its clinico-pathological diversity, and to provide more information to clinicians to improve precision of individualized treatment of TNBC. METHODS: A retrospective analysis was performed on patients with TNBC at Breast Disease Center, Peking University First Hospital between January 2010 and December 2019. Histo- and clinico-pathological characteristics were analyzed by Chi-square test and Student's t-test, and prognoses were calculated using Kaplan-Meier method and a Cox proportionate hazards model. Bonferroni correction was used to correct for multiple comparison. RESULTS: Conventional type of TNBC (cTNBC) were identified in 73.7% of 582 TNBC, while special type of TNBC (sTNBC) were 26.3%, including 71 apocrine carcinoma, 20 medullary carcinoma, 31 metaplastic carcinoma, 18 invasive lobular carcinoma, 7 invasive micropapillary carcinoma, 5 adenoid cystic carcinoma and 1 acinic cell carcinoma. Compared to sTNBC, cTNBC was associated with high histologic grade (P<0.001) and lower androgen receptor (AR) expression (P<0.001). TNM stage of low-grade cTNBC was significantly lower than that of high-grade cTNBC (P=0.002). Although no significant difference, there was a trend that the rate of 5-year disease-free survival (DFS) and 5-year overall survival (OS) were longer in high-grade cTNBC than in high-grade sTNBC (P=0.091 and 0.518), and were longer in low-grade sTNBC than in high-grade sTNBC (P=0.051 and 0.350). Metaplastic carcinomas showed larger tumor size (P=0.008) and higher proliferative Ki67 index (P=0.004) than cTNBCs. CONCLUSIONS: Results from our cohort imply that sub-categorization or subtyping and histological grading could be meaningful in pathological evaluation of TNBC, and need to be clarified in more large collections of TNBC.

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.

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.

[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.

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.

Neoadjuvant therapy for early human epidermal growth factor receptor 2 positive breast cancer in China: A multicenter real-world study (CSBrS-015).

BACKGROUND: Pertuzumab has been approved for application in China by the National Medical Products Administration, and both national and international guidelines make recommendations for the use of neoadjuvant treatment with trastuzumab or trastuzumab + pertuzumab plus chemotherapy regimens for patients with indications. The goal of this study was to investigate the short-term clinical efficacy of the neoadjuvant therapies trastuzumab and trastuzumab+pertuzumab for patients with early human epidermal growth factor receptor 2 (HER2)-positive breast cancer in China. METHODS: A real-world study was conducted using the clinicopathological data of patients with early HER2-positive breast cancer who were admitted to the member hospitals of the Chinese Society of Breast Surgery, Chinese Surgical Society of Chinese Medical Association between March 2019 and December 2020. This study analyzed the efficacy and tolerance of trastuzumab+chemotherapy and trastuzumab+pertuzumab+chemotherapy in patients with early HER2-positive breast cancer. The Response Evaluation Criteria in Solid Tumors 1.1 was adopted to evaluate clinical efficacy. The pathological efficacy was evaluated using the MillerPayne grade. The Common Terminology Criteria for Adverse Events (version 5.0) was adopted to evaluate adverse events (AEs). The propensity scores were subjected to propensity score matching using the R language (1:1 matching with a maximum allowable difference of 0.05 between the two groups). Efficacy was compared using the chi-square test, and correlation analysis was performed using linear regression. RESULTS: A total of 1032 patients with early HER2-positive breast cancer met the enrollment criteria and were included in this study. Among these patients, 472 received neoadjuvant trastuzumab+chemotherapy (the trastuzumab group), and 560 received neoadjuvant trastuzumab+pertuzumab+chemotherapy (the trastuzumab+pertuzumab group). The overall pathologic complete response (pCR) rate was 47.2% (487/1032), while the pCR rates of the trastuzumab and trastuzumab+pertuzumab groups were 34.5% (163/472) and 57.9% (324/560), respectively, and the difference was significant (P < 0.001). The incidence of grade 4 AEs was 24/321 (7.5%) in the trastuzumab+pertuzumab group, and there were no cases in which the left ventricular ejection fraction decreased by more than 10%. CONCLUSIONS: Patients in the trastuzumab+pertuzumab group had a higher pCR rate than those in the trastuzumab group, and the toxic side effects were tolerable.

Androgen Receptor: A New Marker to Predict Pathological Complete Response in HER2-Positive Breast Cancer Patients Treated with Trastuzumab Plus Pertuzumab Neoadjuvant Therapy.

(1) Background: Neoadjuvant therapy is the main therapeutic strategy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients, and the combination of trastuzumab and pertuzumab (HP) has become a routine treatment. How to predict and screen patients who are less likely to respond to neoadjuvant therapy is the focus of research. The androgen receptor (AR) is a biomarker that is widely expressed in all breast cancer subtypes and is probably related to treatment response and prognosis. In this study, we investigated the relationship between AR expression and treatment response in HER2-positive breast cancer patients treated with HP neoadjuvant therapy. (2) Methods: We evaluated early breast cancer patients treated with HP neoadjuvant therapy from Jan. 2019 to Oct. 2020 at Peking University First Hospital Breast Cancer Center. The inclusion criteria were as follows: early HER2-positive breast cancer patients diagnosed by core needle biopsy who underwent both HP neoadjuvant therapy and surgery. We compared the clinical and pathological features between pathological complete response (pCR) and non-pCR patients. (3) Results: We included 44 patients. A total of 90.9% of patients received neoadjuvant therapy of taxanes, carboplatin, trastuzumab and pertuzumab (TCHP), and the total pCR rate was 50%. pCR was negatively related to estrogen receptor (ER) positivity (OR 0.075 [95% confidence interval (CI) 0.008-0.678], p = 0.021) and positively related to high expression levels of AR (OR 33.145 [95% CI 2.803-391.900], p = 0.005). We drew a receiver operating characteristic (ROC) curve to assess the predictive value of AR expression for pCR, and the area under the curve was 0.737 (95% CI 0.585-0.889, p = 0.007). The optimal cutoff of AR for predicting pCR was 85%. (4) Conclusion: AR is a potential marker for the prediction of pCR in HER2-positive breast cancer patients treated with HP neoadjuvant therapy.

Radiomics features based on automatic segmented MRI images: Prognostic biomarkers for triple-negative breast cancer treated with neoadjuvant chemotherapy.

PURPOSE: To establish radiomics prediction models based on automatic segmented magnetic resonance imaging (MRI) for predicting the systemic recurrence of triple-negative breast cancer (TNBC) in patients after neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: A total of 147 patients with TNBC who underwent NAC between January 2009 and December 2018 were enrolled in this study. Clinicopathologic data were collected, and the differences between the recurrent and nonrecurrent patients were analyzed by univariate and multivariate analyses. Patients were randomly divided into training and testing sets. The training set consisted of 104 patients (recurrence: 22, nonrecurrence: 82), and the testing set consisted of 43 patients (recurrence: 9, nonrecurrence: 34). To establish the radiomics prediction model, we used a deep learning segmentation model to automatically segment tumor areas on dynamiccontrast-enhanced-MRI images of pre- and post-NAC magnetic resonance examinations. Radiomics features were then extracted from the tumor areas. Three MRI radiomics models were developed in the training set: a radiomics model based on pre-NAC MRI features (model 1), a radiomics model based on post-NAC MRI features (model 2), and a radiomics model based on both pre- and post-NAC MRI features (model 3). A clinical model for predicting systemic recurrence was built in the training set using independent clinical prediction factors. Receiver operating characteristic curve analysis was used to evaluate the performance of the radiomics and clinical models. RESULTS: The clinical model yielded areas under the curve (AUCs) of 0.747 in the training set and 0.737 in the testing set in terms of predicting systemic recurrence. Models 1, 2, and 3 yielded AUCs of 0.879, 0.91, and 0.963 in the training set and 0.814, 0.802, and 0.933 in the testing set, respectively, in terms of predicting systemic recurrence. All of the radiomics models had achieved higher AUCs than the clinical model in the testing set. DeLong test was used to compare the AUCs between the models and indicated that the predictive performance of model 3 was better than the clinical model, and the difference was statistically significant (p < 0.05). CONCLUSION: The radiomics models built based on the combination of pre- and post-NAC MRI features showed good performance in predicting whether patients with TNBC will have systemic recurrence within 3 years post-NAC. This can help us non-invasively identify which patients are at high risk of recurrence post-NAC, so that we can strengthen follow-up and treatment of these patients. Then the prognosis of these patients might be improved.

Correlation between Androgen Receptor Expression in Luminal B (HER-2 Negative) Breast Cancer and Disease Outcomes.

(1) Background: Hormone receptor positive breast cancer is a subtype of breast cancer with relatively good prognosis, but luminal B (HER−2 negative) breast cancer has a higher risk of recurrence and metastasis. Patients with endocrine therapy resistance and chemotherapy insensitivity have poor prognosis. Androgen receptor (AR) is widely expressed in breast cancer, but there is no clear conclusion about its function and correlation with prognosis in luminal B breast cancer. Further research is needed to reveal the role of AR in luminal B (HER−2 negative) breast cancer. (2) Methods: Retrospectively analyzed patients with early−stage luminal B breast cancer. The correlation between AR and its associated indexes with long−term survival was determined. (3) Results: A total of 985 patients were included with 143 treated by neoadjuvant therapy. Of these, 83.5% of the patients had AR expression ≥65%. High AR expression was associated with good disease−free survival (DFS) and overall survival (OS). In the neoadjuvant population, AR/estrogen receptor (ER) > 1.06 and residual tumor Ki67 > 23% had significantly worse DFS. (4) Conclusion: Low AR (<65%) expression is associated with poor prognosis in luminal B (HER−2 negative) breast cancer patients. High AR/ER and residual tumor Ki67 were associated with poor DFS in neoadjuvant group with a cutoff value of AR/ER > 1.06 and residual tumor Ki67 > 23%.

A nomogram for predicting brain metastasis in patients with de novo stage IV breast cancer.

BACKGROUND: Brain metastasis (BM) is a very serious event in patients with breast cancer. The aim of this study was to establish a nomogram to predict the risk of BM in patients with de novo stage IV breast cancer. METHODS: We gathered female patients diagnosed with de novo stage IV breast cancer between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. After randomly allocating the patients to the training set and verification set, we used univariate and multivariate logistic regression to analyze the relationship between BM and clinicopathological features. Finally, we developed a nomogram which was validated by the analysis of calibration curve and receiver operating characteristic curve. RESULTS: Of 7,154 patients with de novo stage IV breast cancer, 422 developed BM. Age, tumor size, subtype, and the degree of lung involvement were significantly correlated with BM. The nomogram had discriminatory ability with an area under curve (AUC) of 0.640 [95% confidence interval (CI): 0.607 to 0.673] in the training set, and 0.644 (95% CI: 0.595 to 0.693) in the validation set. CONCLUSIONS: Our study developed a nomogram to predict BM for de novo stage IV breast cancer, thus helping clinicians to identify patients at high-risk of BM and implement early preventive interventions to improve their prognoses.

Prognostic value of residual cancer burden and Miller-Payne system after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: To verify the feasibility of using the residual cancer burden (RCB) index to stratify prognosis of patients after neoadjuvant chemotherapy (NAC) and to compare RCB with the Miller-Payne system. METHODS: We retrospectively analyzed clinicopathological data of patients receiving treatment between January 1, 2010 and December 31, 2018. Kaplan-Meier curves were used to compare the survival outcomes and estimate disease-free survival (DFS) and disease-specific survival (DSS). Harrell's concordance index (C-index) was used to evaluate the predictive accuracy of RCB and Miller-Payne system. RESULTS: A total of 423 female patients with complete data were included in the analysis, with a median follow-up time of 58.5 months (range, 7-126 months); 84 patients experienced recurrence, and 48 experienced breast cancer related death. RCB index and the Miller-Payne system were associated with prognosis in the whole cohort. Patients who achieved RCB-I had similar survival outcomes as those with pathological complete response (pCR, RCB-0). In whole cohort, for the RCB index and the Miller-Payne system, respectively, C-indexes for DFS were 0.73 and 0.64, for DSS were 0.74 and 0.64. The average RCB score was different among three subtypes (F=9.335, P<0.001). CONCLUSIONS: The RCB index and the Miller-Payne system can stratify survival outcome of patients after NAC, and RCB had a superior prediction accuracy, especially for triple-negative breast cancer (TNBC). New cut-off value should be sought in order to improve prediction accuracy.

A Clinical-Radiomics Model for Predicting Axillary Pathologic Complete Response in Breast Cancer With Axillary Lymph Node Metastases.

PURPOSE: To develop a clinical-radiomics model based on radiomics features extracted from MRI and clinicopathologic factors for predicting the axillary pathologic complete response (apCR) in breast cancer (BC) patients with axillary lymph node (ALN) metastases. MATERIALS AND METHODS: The MR images and clinicopathologic data of 248 eligible invasive BC patients at the Peking University First Hospital from January 2013 to December 2020 were included in this study. All patients received neoadjuvant chemotherapy (NAC), and the presence of ALN metastases was confirmed through cytology pre-NAC. The data from January 2013 to December 2018 were randomly divided into the training and validation sets in a ratio of 7:3, and the data from January 2019 to December 2020 served as the independent testing set. The following three types of prediction models were investigated in this study. 1) A clinical model: the model was built by independently predicting clinicopathologic factors through logistic regression. 2) Radiomics models: we used an automatic segmentation model based on deep learning to segment the axillary areas, visible ALNs, and breast tumors on post-NAC dynamic contrast-enhanced MRI. Radiomics features were then extracted from the region of interest (ROI). Radiomics models were built based on different ROIs or their combination. 3) A clinical-radiomics model: it was built by integrating radiomics signature and independent predictive clinical factors by logistic regression. All models were assessed using a receiver operating characteristic curve analysis and by calculating the area under the curve (AUC). RESULTS: The clinical model yielded AUC values of 0.759, 0.787, and 0.771 in the training, validation, and testing sets, respectively. The radiomics model based on the combination of MRI features of breast tumors and visible ALNs yielded the best AUC values of 0.894, 0.811, and 0.806 in the training, validation, and testing sets, respectively. The clinical-radiomics model yielded AUC values of 0.924, 0.851, and 0.878 in the training, validation, and testing sets, respectively, for predicting apCR. CONCLUSION: We developed a clinical-radiomics model by integrating radiomics signature and clinical factors to predict apCR in BC patients with ALN metastases post-NAC. It may help the clinicians to screen out apCR patients to avoid lymph node dissection.

The detection rate of methylene blue combined with another tracer in sentinel lymph node biopsy of early-stage breast cancer: a systematic review and network meta-analysis.

BACKGROUND: Methylene blue (MB) alone or combined with 99mtechnetium-labeled sulphur colloid (Tc99m) or indocyanine green (ICG) is widely used for sentinel lymph node biopsy (SLNB) of early-stage breast cancer in developing countries and regions. However, studies investigating the effectiveness of MB combined with another tracer have produced heterogeneous results. The purpose of this network meta-analysis (NMA) was to evaluate the detection rate of MB alone, MB + Tc99m, and MB + ICG, and to examine the differences between the 3 methods. METHODS: We conducted a comprehensive electronic literature search on the PubMed, Embase, Web of Science, CNKI, and Wanfang Data databases from inception to October 2021. The meta-analysis included 7,498 patients in 49 studies. The risk of bias for each study was independently assessed as low, moderate, or high using criteria adapted from the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Fixed- and random-effects models were used to calculate pooled estimates. Mixed-comparison analysis using random-effects models. We assessed statistical heterogeneity by I2 statistics and evaluated publication bias using Begg's test. RESULTS: The identification rate (IR), false-negative rate (FNR), sensitivity (SEN), and accuracy rate (AR) using MB + Tc99m were 96%, 7%, 93%, and 96%, respectively; the IR, FNR, SEN, and AR using MB + ICG were 97%, 7%, 93%, and 97%, respectively. The NMA found that IR and AR between MB + ICG and MB + Tc99m was OR =1.37 (95% CI: 0.41-4.20) and OR =1.33 (95% CI: 0.56-3.32), respectively. DISCUSSION: Our results are similar to those of most previous studies, and meta-analysis showed that the MB + Tc99m or MB + ICG mapping methods can be used to obtain higher IR and lower FNR than MB alone. Our NMA showed no statistical significance between MB + Tc99m and MB + ICG with IR and AR. Both MB + Tc99m and MB + ICG can be used as effective mapping methods in SLNB of early-stage breast cancer to improve the detection rate.

Case report: Secondary sclerosing cholangitis induced by lapatinib and vinorelbine in a metastasis breast cancer patient.

Secondary sclerosing cholangitis (SSC) is a rare cholestatic liver disease that may have a severe clinical course. A 61-year-old woman with a history of metastasis breast cancer was admitted to our hospital for the second cycle of chemotherapy with lapatinib and vinorelbine. The patient had no reports of elevated liver function tests (LFTs) in the previous multiple chemotherapies or history of liver disease. However, the admission laboratory results showed severe cholestatic liver injury with the possibility of SSC by magnetic resonance cholangiopancreatography. Although chemotherapy was discontinued and patient was treated with hepatoprotective drugs, the LFTs did not improve and liver biopsy indicated mild injury of intrahepatic bile duct epithelium and hepatocyte. We added ursodeoxycholic acid and prednisolone to protect the liver, and laboratory data showed a response. To prevent the progression, lapatinib and vinorelbine were reintroduced and transient increases in alanine aminotransferase and γ-glutamyl transpeptidase were observed. With no evidence of viral or autoimmune liver disease, SSC induced by lapatinib and vinorelbine was diagnosed. This is the first case report of tyrosine kinase inhibitors and vinorelbine induced SSC and clinicians should be aware of the possibility of it. More case reports about this adverse drug reaction are needed to delineate optimal management.

Retrospective analysis of sentinel lymph node biopsy using methylene blue dye for early breast cancer.

BACKGROUND: Methylene blue is the most commonly used tracer for sentinel lymph node (SLN) biopsy (SLNB) in China. This study aimed to investigate the feasibility of clinical application of SLNB using methylene blue dye (MBD) for early breast cancer and the prognosis of patients with different SLN and non-SLN statuses. METHODS: We retrospectively analyzed the clinicopathological data of patients with early breast cancer treated at the Peking University First Hospital between 2013 and 2018. We calculated the SLN identification rate (IR) in SLNB with MBD and the false-negative rate (FNR), and analyzed the prognosis of patients with different SLN and non-SLN statuses using Kaplan-Meier curves. RESULTS: Between January 2013 and December 2018, 1603 patients with early breast cancer underwent SLNB with MBD. The SLN IR was 95.8% (1536/1603). Two SLNs (median) were detected per patient. There were significant differences in FNR between patients with SLN micrometastasis and macrometastasis (19.0% vs. 4.5%, χ2 = 12.771, P < 0.001). Chi-square test showed that there were significant differences in SLN successful detection rates among patients with different vascular tumor embolism status (96.3% vs. 90.8%, χ2 = 9.013, P = 0.003) and tumor (T) stages (96.6% vs. 94.1%, χ2 = 5.189, P = 0.023). Multivariate analysis showed that vascular tumor embolism was the only independent factor for SLN successful detection (odds ratio: 0.440, 95% confidence interval: 0.224-0.862, P = 0.017). Survival analysis showed a significant difference in disease-free survival (DFS) between patients with non-SLN metastasis and patients without non-SLN metastasis (P = 0.006). CONCLUSION: Our single-center data show that, as a commonly used tracer in SLNB in China, MBD has an acceptable SLN IR and a low FNR in frozen sections. This finding is consistent with reports of dual tracer-guided SLNB. Positive SLNs with non-SLN metastasis are associated with DFS.

Validation of the CPS+EG and Neo-Bioscore staging systems after preoperative systemic therapy for breast cancer in a single center in China.

BACKGROUND: Prognostic assessment after preoperative systemic therapy (PST) plays a vital role in determining treatment in breast cancer patients. Many researchers have sought to develop a system to quantitate residual tumor and its correlation with prognosis after PST. This retrospective study validated the CPS + EG staging system and Neo-Bioscore in a single center in China. METHODS: Data from patients with non-metastatic primary breast cancer who were treated with PST and surgery from Jan. 2008 to Dec. 2014 at the Breast Disease Center of Peking University First Hospital, China, were reviewed. DFS, DSS and OS were calculated using the K-M curve and AUC. Multivariate analysis was used for a Cox proportional hazards model. All calculations were performed with SAS 9.4. RESULTS: A total of 403 patients were enrolled in this study. The median follow-up period was 45 (range 11-107) months. The five-year DFS, DSS and OS rates were 86.4%, 91.2% and 90.5%, respectively. The CS, PS, CPS + EG staging system and Neo-Bioscore stratified patients according to DFS, DSS, and OS after PST, with all P values < 0.0001. The CPS + EG staging system and Neo-Bioscore stratified prognosis after PST better than CS. HER2-positive patients without trastuzumab treatment had obviously worse DFS and OS than other subgroups with different HER2 statuses that scored a 3 in the Neo-Bioscore system. CONCLUSIONS: The CPS + EG staging system and Neo-Bioscore can improve prognostic prediction in non-pCR breast cancer patients after PST and, provided unfavorable prognostic factors such as insufficient treatment are incorporated, will have broader clinical applicability.