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(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.

ObjectiveThis 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.ResultsAmong 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 ConclusionsIn 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

BackgroundMitoxantrone 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).MethodsThe 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%.ResultsSLN 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.ConclusionsMHI is a lymphatic tracer with comparable efficacy to radionuclides and can be used alone or in combination with radioactive substances for SLNB.Clinical Trial Registrationhttp://www.chinadrugtrials.org.cn, CTR20192435.

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

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.

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 (β) 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.

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

Aim:Mitoxantrone is an antineoplastic antibiotic used in the treatment of acute leukemia, lymphoma, prostate and breast cancer. Mitoxantrone Hydrochloride Injection for tracing has a high degree of lymph node tropism by changing the dosage form, which penetrates into lymphatic capillaries through the interstitial space and enriches regional lymph nodes through the gland to stain the lymph nodes blue to achieve lymph node tracing effect. This study is aim to evaluate the efficacy and safety of Mitoxantrone Hydrochloride injection(MHI) for tracing sentinel lymph nodes in patients with early-stage breast cancer.Materials & methods: This study was a phase 3, multicenter, self-controlled, non-inferiority trial designed to assess the efficacy and safety of sentinel lymph node tracing with the investigational drug in patients with early-stage breast cancer. All subjects received MHI combined with Technetium-99m(99mTc-Sc), prior to SLNB. The sentinel node identification rate was compared between MHI and 99mTc-Sc to evaluate non-inferiority and concordance. Results: Data were collected from 381 patients in 6 centers all across China. The SLN detection rate was 96.9% (369/381) when using MHI and 97.4% (371/381) when using the standard technique(Table 1). There was no significant difference in the success rate of SLN detection between the two groups(P > 0.05). Since the lower limit of 95% confidence interval was greater than or equal to -5%, the success rate of SLN detection of MHI was non-inferior to that of 99mTc-Sc. In the combination group, 380 cases (99.5%) were successfully detected with SLN. 202 nodes (13.1%) were detected by the MHI but not by the 99mTc-Sc, and 222 nodes (14.4%) were detected by the 99mTc-Sc but not by the MHI(Table 2). All adverse events recovered within one month after intervention.Conclusion: This prospective, multicenter study has shown the Mitoxantrone Hydrochloride injection for tracing to be non-inferior to the standard technique (99mTc-Sc) for breast SLNB. The Mitoxantrone Hydrochloride injection for tracing can be used alone or combined with radioactive material.Key words:Mitoxantrone Hydrochloride injection(MHI), Tracing, Technetium-99m(99mTc-Sc), sentinel lymph node (SLN), Early-Stage Breast Cancer. Attachments: Table 1.SLN detection rate - comparing the Mitoxantrone Hydrochloride Injection and 99mTc-Sc for TracingSLN detection rates [n (%)]Mitoxantrone Hydrochloride Injection for TracingTotalAt least one node detectedNo nodes detected99mTc-ScPositive361 (94.8%)10 (2.6%)371 (97.4%)Negative8 (2.1%)2 (0.5%)10 (2.6%)Total369 (96.9%)12 (3.1%)381(100%) Table 2.Detected nodes-comparing the Mitoxantrone Hydrochloride Injection and 99mTc-Sc for TracingPer node detection rates [n (%)]Mitoxantrone Hydrochloride Injection for TracingTotalPositiveNegative99mTc-ScPositive869 (56.3%)222 (14.4%)1091 (70.7%)Negative202 (13.1%)251 (16.3%)453 (29.3%)Total1071 (69.4%)473 (30.6%)1544 (100%) Citation Format: Benlong Yang, Dechuang Jiao, Jiajian Chen, Chunjian Wang, Lidan Jin, Wenhe Zhao, Xueqiang Gao, Haibo Wang, Jun Li, Haidong Zhao, Di Wu, Zhiming Fan, Shujun Wang, Zhenzhen Liu, Yongsheng Wang, Jiong Wu. A phase 3, multicenter, self-controlled, non-inferiority trial comparing mitoxantrone hydrochloride injection for tracing versus technetium-99m in the detection of axillary sentinel nodes in patients with early-stage breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-01-10.

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

BACKGROUND: Breast cancer with ipsilateral supraclavicular lymph node metastasis is one of the indicators of poor prognosis. Patients who attain pathologic complete response in breast and axillary sites have improved survival and are highest in aggressive HR–HER2– and HER2-positive tumor subtypes. However, there is no study on the related factors and prognostic value of supraclavicular pathologic complete response in breast cancer after neoadjuvant chemotherapy. The aim of our work was to investigate the factors and prognostic significance of pathologic complete response of ipsilateral supraclavicular lymph node metastasis in breast cancer after neoadjuvant chemotherapy. METHODS: A total of 214 patients with breast cancer who had primary ISLN metastasis, receiving NAC and subsequent ISLN dissection, were retrospectively and consecutively reviewed. Univariate and multivariate analyses were performed using χ(2) test and the logistic regression model, and the prognosis was analyzed by Kaplan-Meier curve. RESULTS: All patients included were women who were 26–74 years old. The rate of supraclavicular pathologic complete response (pCR) was 53.7%. Multivariate analysis showed that the expression of Ki67, breast pCR, and axillary pCR were independent predictors of supraclavicular pCR (P

The purpose of the present study was to determine the tissue and plasma levels of microRNA (miR)-155 and miR-31 in 67 patients with invasive intraductal breast cancer and their correlation with the clinicopathological characteristics. Using a quantitative real-time-PCR (qRT-PCR) assay, it was demonstrated that the plasma levels of miR-155 and miR-31 in patients were 6- and 5-fold higher than those in healthy individuals, respectively (P0.05). The expression levels of miR-155, but not miR-31, were inversely correlated with estrogen receptor (ER) and progesterone receptor (PR) expression (ER, r=−0.353, P=0.003; PR, r=−0.357, P=0.003). The tissue and plasma levels of miR-155 and miR-31 were not correlated with epidermal growth factor receptor-2 (HER-2) expression levels. Furthermore, high levels of plasma miR-155 and miR-31 were identified in the tumors of TNM stage II, lymph node metastasis 0–3 and tumor sizes of 2–5 cm in patients who were aged over 52 years. miR-155 was mainly expressed in patients with a pathology score of 3 for ER or PR expression; miR-31 expression was higher in patients with a pathology score of 2. These results suggest that miR-155 and miR-31 are differentially expressed in breast cancer patients. Their correlation with the clinicopathological characteristics may aid the diagnosis and treatment of invasive intraductal breast cancer.

Background Restin belongs to MAGE superfamily and is known as MAGE H1. Restin was firstly cloned from HL-60 cells treated with all-trans retinoic acid (ATRA). Previous studies showed a pro-apoptotic role of Restin in several cell lines. However, little information is available on its expression patterns and functions in vivo. Our study was performed to detect if Restin plays a role in breast cancer cells in vitro and in vivo. Methods and results Real-time PCR and western blot were conducted to detect Restin expression in multiple breast cancer cell lines and Restin level was negatively related with cell motility. Restin overexpression and knockdown stable cell lines were established by transducing lentivirus into MCF-7 and MDA-MB-231 cells. Cell morphology, wound closure assay, transwell migration and invasion assays were performed to detect if Restin inhibited EMT. Our data showed that Restin overexpressed cells exhibited classical epithelial cell morphology, and Restin overexpression resulted in activation of epithelial markers and suppression of mesenchymal markers, and inhibition of cell migration and invasion. Tumor xenograft model was used to characterize the biological functions of Restin in vivo. We found that Restin overexpression led to reduced lung metastasis. Real-time PCR, western blot, luciferase assay and ChIP assay were performed to identify the potential targets of Restin and the underlying molecular mechanisms. Among several master regulators of EMT, only ZEB1/2 levels were dramatically inhibited by Restin. Unexpectedly, Restin indirectly regulated ZEB1/2 expression at post-transcriptional level. We further identified mir-200a/b, well-characterized mediators controlling ZEB1/2 expression, were transcriptionally activated by Restin and the regulation was dependent on the p53 binding site in mir-200b/a/429 promoter. Further mechanical studies demonstrated Restin interacted with p73, one of p53 family members, which contributed to Restin-mediated activation of mir-200a/b and suppression of ZEB1/2. Conclusions Taken together, our results suggest that Restin inhibits EMT and tumor metastasis by controlling the expression of the tumor metastasis suppressor mir-200a/b via association with p73. Our findings not only establish a mechanistic link between Restin, EMT and tumor metastasis, but also provide strong evidence supporting the notion that MAGE Group II proteins may exert a tumor suppressive effect in vivo. Electronic supplementary material The online version of this article (doi:10.1186/s12943-015-0370-9) contains supplementary material, which is available to authorized users.