The use of longitudinal CT-based radiomics and clinicopathological features predicts the pathological complete response of metastasized axillary lymph nodes in breast cancer.

BACKGROUND: Accurate assessment of axillary status after neoadjuvant therapy for breast cancer patients with axillary lymph node metastasis is important for the selection of appropriate subsequent axillary treatment decisions. Our objectives were to accurately predict whether the breast cancer patients with axillary lymph node metastases could achieve axillary pathological complete response (pCR). METHODS: We collected imaging data to extract longitudinal CT image features before and after neoadjuvant chemotherapy (NAC), analyzed the correlation between radiomics and clinicopathological features, and developed models to predict whether patients with axillary lymph node metastasis can achieve axillary pCR after NAC. The clinical utility of the models was determined via decision curve analysis (DCA). Subgroup analyses were also performed. Then, a nomogram was developed based on the model with the best predictive efficiency and clinical utility and was validated using the calibration plots. RESULTS: A total of 549 breast cancer patients with metastasized axillary lymph nodes were enrolled in this study. 42 independent radiomics features were selected from LASSO regression to construct a logistic regression model with clinicopathological features (LR radiomics-clinical combined model). The AUC of the LR radiomics-clinical combined model prediction performance was 0.861 in the training set and 0.891 in the testing set. For the HR + /HER2 - , HER2 + , and Triple negative subtype, the LR radiomics-clinical combined model yields the best prediction AUCs of 0.756, 0.812, and 0.928 in training sets, and AUCs of 0.757, 0.777 and 0.838 in testing sets, respectively. CONCLUSIONS: The combination of radiomics features and clinicopathological characteristics can effectively predict axillary pCR status in NAC breast cancer patients.

Comparison of the Response to Neoadjuvant Therapy Between Immunohistochemistry HER2 (3+) and HER2 (2+)/ISH+ Early-Stage Breast Cancer: A Retrospective Multicenter Cohort Study.

BACKGROUND: According to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, both immunohistochemical HER2 (3+) and HER2 (2+)/in situ hybridization (ISH) amplified [HER2 (2+)/ISH+] breast cancers (BCs) fall under the HER2-positive BC category. However, there is a lack of studies exploring the difference of neoadjuvant therapeutic response between patients with HER2 (3+) and HER2 (2+)/ISH+ early BC. We aimed to evaluate the neoadjuvant therapeutic response, long-term outcome, and intrinsic subtype heterogeneity between HER2 (3+) and HER2 (2+)/ISH+ BC. METHODS: We examined 2 distinct cohorts. Cohort 1 (C1) encompassed 2648 patients with HER2-positive early BC diagnoses, and they received neoadjuvant therapy (NT) and surgery between January 1, 2009 and December 31, 2022, from the Shanghai Jiao Tong University Breast Cancer Data Base. Cohort 2 (C2) comprised 135 patients with early-stage HER2-positive BC who underwent NT and surgery at Henan Cancer Hospital from January 1, 2021, to December 31, 2022. These patients had available genomic and transcriptomic data at their disposal. C1 and C2 were further categorized into 2 patient cohorts as follows: (1) patients with IHC HER2 (3+) early BC [HER2 (3+) group], (2) patients with HER2 (2+)/ISH+ early BC [HER2 (2+)/ISH+ group]. Among those excluded from the analysis were patients < 18 years or >80 years of age. Clinicopathological parameters, long-term outcomes, and intrinsic subtypes were analyzed. RESULTS: In the C1 population, 83.7% had HER2 (3+) BC, while 16.3% had HER2 (2+)/ISH+ BC. Patients with HER2 (3+) had a significantly higher pathological complete response (PCR) rate (38.9%) than patients with HER2 (2+)/ISH+ (18.1%; P < .001), but the disease-free survival (DFS) was comparable after a median follow-up of 29 months (P = .556). The addition of trastuzumab or trastuzumab plus pertuzumab to neoadjuvant chemotherapy (NAC) improved PCR rates and DFS in HER2 (3+) BC but not in HER2 (2+)/ISH+ BC. In the C2 population, 97.75% HER2 (3+) and 52.17% HER2 (2+)/ISH+ were HER2 enriched (HER2E) subtype (P < .001). HER2E showed increased PCR rates compared to non-HER2E (P = .004). CONCLUSIONS: Compared to HER2 (3+) BC, the limited effectiveness of neoadjuvant trastuzumab and pertuzumab therapy for HER2 (2+)/ISH+ BC is due to subtype heterogeneity. Reassessment of targeted therapy efficacy in patients with HER2 (2+)/ISH+ BC is essential.

Axillary lymph node dissection in triple-negative or HER2-positive breast cancer patients with clinical N2 achieving pathological complete response after neoadjuvant therapy: Is it necessary?

AIM: This study aims to identify suitable candidates for axillary sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) among clinical N2 (cN2) triple-negative (TN) or HER2 positive (HER2+）breast cancer patients following neoadjuvant therapy（NAT）. BACKGROUND: Despite the substantial axillary burden in cN2 breast cancer patients, high pathological response rates can be achieved with NAT in TN or HER2+ subtypes, thus enabling potential downstaging of axillary surgery. METHODS: A retrospective analysis was conducted on data from the CSBrS-012 study, screening 709 patients with initial cN2, either HER2+ or TN subtype, from January 1, 2010 to December 31, 2020. The correlation between axillary pathologic complete response (pCR) (yPN0) and breast pCR was examined. RESULTS: Among the 177 cN2 patients who achieved breast pCR through NAT, 138 (78.0 %) also achieved axillary pCR. However, in the 532 initial clinical N2 patients who did not achieve breast pCR, residual axillary lymph node metastasis persisted in 77.4 % (412/532) of cases. The relative risk of residual axillary lymph node metastasis in patients who did not achieve breast pCR was 12.4 (8.1-19.1), compared to those who did achieve breast pCR, P < 0.001. CONCLUSION: For cN2 TN or HER2+ breast cancer patients who achieve breast pCR following NAT, consideration could be given to downstaging and performing an axillary SLNB or TAD.

HER2-Low Status Was Associated With Better Breast Cancer-Specific Survival in Early-Stage Triple-Negative Breast Cancer.

BACKGROUND: Based on the association between the hormone receptor and the status of human epidermal growth factor receptor 2 (HER2)-low, we investigated the clinicopathological and prognostic characteristics of the HER2-low status in early-stage triple-negative breast cancer (TNBC). METHODS: We collected the data of patients with TNBC who received treatment at our hospital and compared the pathological complete response (pCR) rate, overall survival (OS), and breast cancer-specific survival (BCSS) between the HER2-0 and HER2-low subtypes. RESULTS: A total of 1445 patients were included in the study, of which 698 patients (48.3%) showed HER2-low status. A similar pCR rate was observed between HER2-0 and HER2-low patients (34.9% vs. 37.4%; P = .549). T staging, N staging, and HER2 status were associated with BCSS, whereas T staging and N staging were associated with OS. Patients with the HER2-low status showed better BCSS than those with the HER2-0 status (96.6% vs. 93.7%; log-rank P = .027). In patients with non-pCR, the BCSS of the HER2-low subgroup was better than that of the HER2-0 subgroup (log-rank P = .047); however, no similar result was observed in patients with pCR. In patients with stage III, the BCSS and OS of the HER2-low subgroup were better than those of the HER2-0 subgroup (BCSS, log-rank P = .010; OS, log-rank P = .047). No similar results were observed in patients with stages I and II. CONCLUSION: The HER2-low expression was associated with better BCSS in TNBC, especially in the high-risk groups, suggesting that HER2-low breast cancer is a potential independent biological subtype.

Neoadjuvant Efficacy of Three Targeted Therapy Strategies for HER2-Positive Breast Cancer Based on the Same Chemotherapy Regimen.

(1) Background: The objective of our study was to provide evidence for choosing the optimal neoadjuvant therapy strategies for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. Three neoadjuvant targeted therapy strategies (H + Py, trastuzumab plus pyrotinib; H, trastuzumab; HP, trastuzumab plus pertuzumab) based on the same chemotherapy regimen (TC, docetaxel and carboplatin) were included in the present study; (2) Methods: We retrospectively analyzed patients with HER2-positive breast cancer who were treated with neoadjuvant TCH + Py, TCH or TCHP, followed by surgery. The outcome was the pathological complete response (pCR) rate; (3) Results: In total, 545 patients were enrolled. The pCR rate was 55.6% (35/63) in the TCH + Py cohort, 32.7% (93/284) in the TCH cohort, and 56.6% (112/198) in the TCHP cohort. The multivariate analysis showed that patients who received TCH had less possibility to achieve pCR than those who received TCH + Py (odds ratio (OR) = 0.334, 95% confidence interval (CI): 0.181−0.619, p < 0.001), while patients who received TCHP had comparable possibility to those who received TCH + Py (OR = 1.043, 95%CI: 0.554−1.964, p = 0.896); (4) Conclusions: TCH + Py provides a better pCR rate compared with TCH, and a comparable pCR rate with TCHP among patients with HER2-positive breast cancer in the neoadjuvant setting. The present study supports a novel potential treatment option for these patients. Further studies need to be explored in the future.

Impact of Marital Status on Prognosis of Patients With Invasive Breast Cancer: A Population-Based Study Using SEER Database.

Objective: This study aimed to investigate the prognostic roles of marital status in patients with invasive breast cancer. Method: We extracted the data of patients with invasive breast cancer who were diagnosed during 2010-2015 and had complete staging and molecular typing from the Surveillance, Epidemiology, and End Results (SEER)-18 database. Kaplan-Meier curve method and Cox regression analysis were performed to investigate the differences in breast cancer-specific survival (BCSS) and overall survival (OS) in the total population and various subgroups with different marital statuses. Results: Among the 324,062 patients with breast cancer in this study, 55.0%, 40.0%, and 5.0% were married, unmarried, and unknown, respectively; 51.8%, 32.2%, 10.5%, and 5.5% were patients with Stages I, II, III, and IV breast cancer, respectively. The 5-year BCSS and OS of married patients were 92.6% and 88.1%, respectively, higher than those of unmarried patients (88.3% and 78.1%, P < 0.001). After adjustment for sex, age, T and N stages, histological grade, insurance status, race, year of diagnosis, and molecular subtypes, married status was an independent predictor of better BCSS [hazard ratio (HR) = 0.775, 95% confidence interval (CI) = 0.753-0.797, P < 0.001) and OS (HR = 0.667, 95% CI = 0.653-0.681, P < 0.001). After multivariate analysis of various subgroups of sex, age, stage, histological grade, insurance status, race, and molecular subtype, married status was an independent predictor of better BCSS in all subgroups except for Grade IV, age < 35 years, and uninsured subgroups. Marital status was an independent predictor of better OS in all subgroups except the subgroup with age <35 years. Conclusions: In conclusion, marital status was an independent prognostic factor for breast cancer. The unmarried patients with breast cancer had a worse prognosis, except for the subgroup with age <35 years. Hence, unmarried patients with breast cancer and age ≥35 years may need additional psychosocial and emotional support to achieve more prolonged survival, besides active treatment of primary disease.

Efficacy and Safety of Mitoxantrone Hydrochloride Injection for Tracing Axillary Sentinel Nodes in Breast Cancer: A Self-Controlled Clinical Trial.

Background: Mitoxantrone hydrochloride injection for tracing (MHI), a new strategy to identify lymph nodes, has not been tested for axillary node staging in breast cancer. This multicenter, self-controlled, non-inferiority trial aimed to evaluate MHI's efficacy and safety in sentinel lymph node biopsy (SLNB). Methods: The trial was conducted across seven hospitals from December 2019 to December 2020. Patients with early-stage breast cancer received MHI and technetium-99m (99mTc) during the surgery. Sentinel node detection rates were compared between MHI and 99mTc to evaluate non-inferiority and concordance. Non-inferiority was valid if the lower limit of the 95% CI of sentinel node relative detection rate difference was ≥-5%. Results: SLN relative detection rate of MHI was 97.31% (362/372). Of the SLNs, 79.69% (871/1093) were co-detected by both tracers. Of the patients, 4.13% (16/387) had adverse events and recovered during the follow-up. Conclusions: MHI is a lymphatic tracer with comparable efficacy to radionuclides and can be used alone or in combination with radioactive substances for SLNB. Clinical Trial Registration: http://www.chinadrugtrials.org.cn, CTR20192435.

Analysis of the expression profile of serum exosomal lncRNA in breast cancer patients.

BACKGROUND: Breast cancer (BC) is a common tumor that seriously affects women's physical/mental health and even life. BC invasion and metastasis are still the main causes of mortality in BC patients. Exosomal long non-coding RNAs (exo-lncRNA) play an important role in cell communication and can help to understand better the physiological and pathological conditions that result from BC. This study investigates new potential targets and functions of the expression profiles of exo-lncRNAs in BC patients through high-throughput screening and bioinformatics. METHODS: Samples were collected from two BC patients and one healthy subject. The serum exosomal RNAs were subsequently purified, and a library was established for quality inspection and sequencing. The resultant data was compared with the reference data to obtain the differential expression of exo-lncRNAs, and predict the target genes. To obtain the final results, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to annotate the function and pathway of the differentially expressed genes. RESULTS: After a comprehensive comparison of the BC patients and healthy subjects, we discovered five up-regulated exo-lncRNAs and six down-regulated exo-lncRNAs of interest. Combining our results with a literature review and screening, we found that VIM-AS1, SNHG8, and ELDR play a role in the progression of BC, with VIM-AS1 predicting 35 target miRNAs; SNHG8 predicting 12 target miRNAs, and ELDR predicting 24 target miRNAs. Target prediction considered that the target gene of VIM-AS1 was VIM and that the target gene of SNHG8 was PRSS12. GO enrichment analysis showed that VIM mainly played a role in cell processes, biological regulation, metabolic regulation, and molecular adhesion, while PRSS12 was enriched through cell metabolism, catalytic activity, and hydrolase activity. KEGG pathway enrichment results also indicated how the VIM protein functions in cancer development through the viral infection signaling pathway and miRNA signaling pathway. CONCLUSIONS: There is a significant difference in the expression profiles of serum exo-lncRNAs between BC patients and healthy individuals. This may be closely related to BC's occurrence, development, and metastasis, and therefore provides a theoretical basis for more in-depth studies into exo-lncRNA.

Essential amino acid metabolism-related molecular classification in triple-negative breast cancer.

Aim: To develop an approach to characterize and classify triple-negative breast cancer (TNBC) tumors based upon their essential amino acid (EAA) metabolic activity. Methods: We performed bioinformatic analyses of genomic, transcriptomic and clinical data in an integrated cohort of 740 TNBC patients from public databases. Results: Based on EAA metabolism-related gene expression patterns, two TNBC subtypes were identified with distinct prognoses and genomic alterations. Patients exhibiting an upregulated EAA metabolism phenotype were more prone to chemoresistance but also expressed higher levels of immune checkpoint genes and may be better candidates for immune checkpoint inhibitor therapy. Conclusion: Metabolic classification based upon EAA profiles offers a novel biological insight into previously established TNBC subtypes and advances current understanding of TNBC's metabolic heterogeneity.

Lay abstract Breast cancer is the most common malignancy in women. Triple-negative breast cancer (TNBC) is a highly malignant subtype of breast cancer, accounting for about 12­17% of total breast cancer cases. This subtype is prone to liver and bone metastases, has a high risk of recurrence and carries a poor prognosis. In this study the authors explored the essential amino acid metabolism characteristics of TNBC tumors. They found that TNBC tumors exhibiting high essential amino acid metabolism were more malignant, associated with a worse prognosis and less sensitive to chemotherapy, but were also associated with better patient responses to immunotherapy. These results offer new insights into the precision treatment of TNBC. The results of the study are promising but require additional investigation.

The effectiveness of axillary reverse mapping in preventing breast cancer-related lymphedema: a meta-analysis based on randomized controlled trials.

BACKGROUND: Here, we carried out an extensive meta-analysis to investigate the effectiveness of the use of axillary reverse mapping (ARM) during axillary lymph node dissection (ALND) in preventing breast cancer-related lymphedema (BCRL). METHODS: Database searches to identify relevant randomized controlled trials (RCTs) were performed of MEDLINE (PubMed), Web of Science, Embase, and the Cochrane Library. Eligible articles with a publication date from database establishment to December 2020 were retrieved by combining keywords including: "breast cancer", "breast carcinoma", "breast neoplasm", "axillary reverse mapping", "axillary lymph node dissection", "lymphatic arm drainage", and "lymphedema". Independent data extraction was conducted, and Review Manager (version 5.3) was used for statistical analyses. RESULTS: Five eligible RCTs were included in the meta-analysis. A total of 37 patients suffered arm lymphedema (37/786, 4.71%) in the experimental group (ARM during ALND), compared with 164 arm lymphedemas (164/873, 18.79%) in the control group (ALND alone). The results showed that ARM during ALND was superior to ALND alone in reducing the incidence of BCRL [OR =0.20, 95% confidence intervals (CI): 0.13-0.29, P<0.00001]; however, the 2 procedures did not differ significantly in terms of oncological safety or shoulder movement (OR =0.30, 95% CI: 0.03-2.96, P=0.30; OR =0.44, 95% CI: 0.14-1.40, P=0.17). CONCLUSIONS: ARM during ALND can prevent and reduce the occurrence of BCRL in patients with early-stage BC during long-term follow-up. Due to the limited number of RCTs available, more in-depth, high-quality RCTs are urgently needed to provide a reliable and convincing basis for the application of ARM during ALND.

Establishment and Verification of a Predictive Model for Node Pathological Complete Response After Neoadjuvant Chemotherapy for Initial Node Positive Early Breast Cancer.

OBJECTIVE: Axillary node status after neoadjuvant chemotherapy (NCT) in early breast cancer patients influences the axillary surgical staging procedure. This study was conducted for the identification of the likelihood of patients being node pathological complete response (pCR) post NCT. We aimed to recognize patients most likely to benefit from sentinel lymph node biopsy (SLNB) following NCT and to reduce the risk of missed detection of positive lymph nodes through the construction and validation of a clinical preoperative scoring prediction model. METHODS: The existing data (from March 2010 to December 2018) of the Chinese Society of Clinical Oncology Breast Cancer Database (CSCO-BC) was used to evaluate the independent related factors of node pCR after NCT by Binary Logistic Regression analysis. A predictive model was established according to the score of considerable factors to identify ypN0. Model performance was confirmed in a cohort of NCT patients treated between January 2019 and December 2019 in Henan Cancer Hospital, and model discrimination was evaluated via assessing the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: Multivariate regression analysis showed that the node stage before chemotherapy, the expression level of Ki-67, biologic subtype, and breast pCR were all independent related factors of ypN0 after chemotherapy. According to the transformation and summation of odds ratio (OR) values of each variable, the scoring system model was constructed with a total score of 1-5. The AUC for the ROC curves was 0.715 and 0.770 for the training and the validation set accordingly. CONCLUSIONS: A model was established and verified for predicting ypN0 after chemotherapy in newly diagnosed cN+ patients and the model had good accuracy and efficacy. The underlined effective model can suggest axillary surgical planning, and reduce the risk of missing positive lymph nodes by SLNB after NCT. It has great value for identifying initial cN+ patients who are more appropriate for SLNB post-chemotherapy.

Comparison of survival in non-metastatic inflammatory and other T4 breast cancers: a SEER population-based analysis.

BACKGROUND: Previous studies have reported poor survival rates in inflammatory breast cancer (IBC) patients than non-inflammatory local advanced breast cancer (non-IBC) patients. However, until now, the survival rate of IBC and other T4 non-IBC (T4-non-IBC) patients remains unexplored. METHODS: Surveillance, Epidemiology, and End Results (SEER) database was searched to identify cases with confirmed non-metastatic IBC and T4-non-IBC who had received surgery, chemotherapy, and radiotherapy between 2010 and 2015. IBC was defined as per the American Joint Committee on Cancer (AJCC) 7th edition. Breast Cancer-Specific Survival (BCSS) was estimated by plotting the Kaplan-Meier curve and compared across groups by using the log-rank test. Cox model was constructed to determine the association between IBC and BCSS after adjusting for age, race, stage of disease, tumor grade and surgery type. RESULTS: Out of a total of 1986 patients, 37.1% had IBC and mean age was 56.6 ± 12.4. After a median follow-up time of 28 months, 3-year BCSS rate for IBC and T4-non-IBC patients was 81.4 and 81.9%, respectively (log-rank p = 0.398). The 3-year BCSS rate in HR-/HER2+ cohort was higher for IBC patients than T4-non-IBC patients (89.5% vs. 80.8%; log-rank p = 0.028), and in HR-/HER2- cohort it was significantly lower for IBC patients than T4-non-IBC patients (57.4% vs. 67.5%; log-rank p = 0.010). However, it was identical between IBC and T4-non-IBC patients in both HR+/HER2- (85.0% vs. 85.3%; log-rank p = 0.567) and HR+/HER2+ (93.6% vs. 91.0%, log-rank p = 0.510) cohorts. After adjusting for potential confounding variables, we observed that IBC is a significant independent predictor for survival of HR-/HER2+ cohort (hazards ratio [HR] = 0.442; 95% CI: 0.216-0.902; P = 0.025) and HR-/HER2- cohort (HR = 1.738; 95% CI: 1.192-2.534; P = 0.004). CONCLUSIONS: Patients with IBC and T4-non-IBC had a similar BCSS in the era of modern systemic treatment. In IBC patients, the HR-/HER2+ subtype is associated with a better outcome, and HR-/HER2- subtype is associated with poorer outcomes as compared to the T4-non-IBC patients.

Development of a predictive model utilizing the neutrophil to lymphocyte ratio to predict neoadjuvant chemotherapy efficacy in early breast cancer patients.

Neutrophils and lymphocytes are key regulators of breast cancer (BC) development and progression. Neutrophil to lymphocyte ratio (NLR) values have been found to offer clear prognostic utility when evaluating BC patients. In this study, we sought to determine whether BC patient baseline NLR values are correlated with pathological complete response (pCR) following neoadjuvant chemotherapy (NCT) treatment. In total, 346 BC patients underwent NCT at our hospital from January 1, 2014 to October 31, 2019, and data pertaining to these patients were retrospectively analyzed. Correlations between clinicopathological characteristics and pCR rates were assessed via multivariate logistic regression analyses. A predictive scoring model was used to gauge the likelihood of pCR based upon regression coefficient (ß) values for each significant variable identified through these analyses. NLR cut-off values suitable for identifying patients likely to achieve pCR following NCT treatment were calculated using receiver operating characteristic (ROC) curves. All patients in the present study were females with a median age of 48 years old (range 22-77). An optimal NLR cut-off value of 1.695 was identified and was associated with respective sensitivity and specificity values of 63.6% and 45.5%. We found that higher NLR values were significantly associated with younger age, premenopausal status, and non-pCR status. Logistic regression analyses indicated that NLR, tumor size, hormone receptor (HR) status, and Ki-67 expression were all independent predictors of pCR. The area under the curve (AUC) for the resultant predictive scoring model was 0.705, and this model was assessed via K-fold cross-validation (k = 10) and bootstrapping validation, yielding respective AUC values of 0.68 and 0.694. Moreover, the incorporation of NLR into this predictive model incrementally improved its overall prognostic value relative to that of a model not incorporating NLR (AUC = 0.674). BC patients with a lower baseline NLR are more likely to exhibit pCR following NCT treatment, indicating that NLR may be a valuable biomarker for BC patient prognostic evaluation and treatment planning. Overall, our results demonstrate that this NLR-based predictive model can efficiently predict NCT efficacy in early BC patients with a high degree of accuracy.

HN1L promotes migration and invasion of breast cancer by up-regulating the expression of HMGB1.

Recent reports showed that haematological and neurological expressed 1-like (HN1L) gene participated in tumorigenesis and tumour invasion. However, the expression and role of HN1L in breast cancer remain to be investigated. Here, bioinformatics, western blot and immunohistochemistry were used to detect the expression of HN1L in breast cancer. Wound healing, transwell assay, immunofluorescence assay and mass spectrum were used to explore the role and mechanism of HN1L on the migration and invasion of breast cancer, which was confirmed in vivo using a nude mice model. Results showed that HN1L was significantly over-expressed in breast cancer tissues, which was positively correlated with M metastasis of breast cancer patients. Silencing HN1L significantly inhibited the invasion and metastasis of breast cancer cells in vitro and lung metastasis in nude mice metastasis model of breast cancer. Mechanistically, HN1L interacted with HSPA9 and affected the expression of HMGB1, playing a key role in promoting the invasion and metastasis of breast cancer cell. These results suggested that HN1L was an appealing drug target for breast cancer.

The predictive value of inflammatory markers for pathological response of ipsilateral supraclavicular lymph nodes and for prognosis in breast cancer after neoadjuvant chemotherapy.

BACKGROUND: Inflammatory tumor microenvironment is closely related to cancer. In this study, we mainly explore the predictive value of inflammatory markers for pathological response of ipsilateral supraclavicular lymph nodes (ISLN) and for prognosis in breast cancer with ISLN metastasis after neoadjuvant chemotherapy (NAC). METHODS: In this study, 117 breast cancer patients with ISLN metastasis were collected from the Affiliated Hospital of Zhengzhou University. The best cut-off value was determined by using the receiver operating characteristics (ROC) curve. Chi-square test and binary Logistic regression were used to analyze the correlation between clinical pathological data and pathological response of ISLN and to determine independent predictors. Correlation analysis between inflammatory markers and prognosis used time-dependent COX regression. RESULTS: The pathological complete response (pCR) rate of ISLN after NAC was 64.4%. Multivariate analysis showed that breast pCR (OR 9.67, 95% CI: 2.64-35.31, P<0.01) was an independent predictor of ISLN pathological response after NAC. After a median follow-up of 25 months, multivariate time-dependent COX results showed that higher platelet levels were correlated with poor disease-free survival (DFS) (HR 1.008, 95% CI: 1.001-1.015, P=0.028). Meanwhile, menopausal status (HR 0.35, 95% CI: 0.15-0.79, P=0.01) and supraclavicular pCR (HR 0.33, 95% CI: 0.15-0.77, P=0.01) were also independent predictors of DFS. CONCLUSIONS: Peripheral blood inflammatory markers have limited predictive value for pathological response of ISLN after NAC for breast cancer. High platelet count is associated with poor prognosis of breast cancer patients with ISLN metastasis.

Prognostic values of EDNRB in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) has a high degree of malignancy. The endothelin B receptor (EDNRB) serves an important role in the occurrence and development of cancer. The present study aimed to investigate the prognostic value of EDNRB in TNBC. A total of 99 cases of TNBC were collected from the Henan Cancer Hospital database and 159 cases of TNBC were collected from The Cancer Genome Atlas database. A χ2 test was used to analyze the association between EDNRB and clinicopathological data. Kaplan-Meier analysis and multivariate Cox regression analysis were used to analyze the association between EDNRB and prognosis, and to establish two models. The discrimination degree of the models was evaluated using time-dependent receiver operating characteristic curves and concordance index (C-index), whereas the accuracy and net benefit of the models were evaluated using integrated discriminant improvement (IDI) and decision curves. EDNRB expression was low in TNBC samples (P<0.01). Age (P=0.01), tumor size (P=0.04) and N stage (P=0.01) were associated with EDNRB expression. EDNRB expression was positively associated with stromal score (P<0.01), but not immune score. High expression levels of EDNRB indicated favorable disease-free survival time (hazard ratio, 0.38; 95% CI, 0.15-0.98; P=0.04). The integrated area under the curve and C-index of the new model were increased compared with the old model following the addition of EDNRB expression as a parameter. The IDI values for prediction of the 3- and 5-year survival rates were 0.04 (P=0.02) and 0.05 (P=0.01), respectively. The results of decision curve analysis showed that the new model had higher clinical net benefit than the old model in the range of 3-year survival rate <0.52. In conclusion, EDNRB was associated with a favorable prognosis in patients with TNBC, and may be used as a novel prognostic biomarker.

Elevated Platelet Count Predicts Poor Prognosis in Breast Cancer Patients with Supraclavicular Lymph Node Metastasis.

BACKGROUND: More and more studies show that platelets are closely related to the occurrence and development of tumors. This study aims to explore the predictive value of peripheral blood platelet count on the prognosis of breast cancer patients with ipsilateral supraclavicular lymph node (ISLN) metastasis. METHODS: Eighty-five breast cancer patients with ISLN metastasis in the Affiliated Cancer Hospital of Zhengzhou University were collected retrospectively in this study. Chi-square test was used to analyze the correlation between clinical pathological data and platelet count. DFS rate was estimated by K-M curve and Log Rank test was performed. Univariate and multivariate Cox regression were used to determine the prognostic value of platelets. Time-dependent Cox regression was used to further analyze the correlation between peripheral blood platelets and prognosis to determine the stability of the results. RESULTS: The pathological complete response rate of ISLN after neoadjuvant chemotherapy (NAC) was 51.8%. Platelet count was correlated with PR status of breast cancer at first visit (P=0.01). After a median follow-up of 30 months, multivariate Cox analysis showed that high platelet count (HR=3.18, 95% CI=1.13-8.93, P=0.028), premenopausal status (HR=0.40, 95% CI=0.17-0.97, P=0.043), and ISLN pathological failure (HR=0.25 95%, CI=0.10-0.62, P<0.01) were associated with poor prognosis. K-M curve analysis showed that the prognosis of patients with a high platelet count was worse than that of patients with low platelet count (HR=5.32, 95% CI=2.41-11.75, P<0.01). To further verify the stability of this result, multivariate time-dependent Cox model also suggested that higher platelet level was related to poor prognosis (HR=1.009, 95% CI=1.003-1.016, P<0.01). Meanwhile, menopausal status (HR=0.32, 95% CI=0.14-0.76, P=0.01) and sPCR (HR=0.29, 95% CI=0.12-0.70, P=0.01) were also independent predictors of DFS. CONCLUSION: Platelets have important predictive value for the prognosis of breast cancer patients with ISLN metastasis, which indicates that platelet count can be used to distinguish high-risk patients so as to obtain clinical benefits.