Background & objectivesAn effective tool for forecasting the survival of BCLM is lacking. This study aims to construct nomograms to predict overall survival (OS) and breast cancer-specific survival (BCSS) in breast cancer patients with de novo lung metastasis, and to help clinicians develop appropriate treatment regimens for breast cancer lung metastasis (BCLM) individuals. MethodsWe gathered clinical data of 2,537 patients with BCLM between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Cox regression analysis was employed to identify independent prognostic parameters for BCLM, which were integrated to establish nomograms by R software. The discriminative ability and predictive accuracy of the nomograms were assessed using the concordance index (C-index), receiver operating characteristic (ROC) curves, and calibration plots. Kaplan-Meier analyses were applied to evaluate the clinical utility of the risk stratification system and investigate the survival benefit of primary site surgery, chemotherapy, and radiotherapy for BCLM patients. ResultsTwo nomograms shared common prognostic indicators including age, marital status, race, laterality, grade, AJCC T stage, subtype, bone metastasis, brain metastasis, liver metastasis, surgery, and chemotherapy. The results of the C-index, ROC curves, and calibration curves demonstrated that the nomograms exhibited an outstanding performance in predicting the prognosis of BCLM patients. Significant differences in the Kaplan-Meier curves of various risk groups corroborated the nomograms' excellent stratification. Primary site surgery and chemotherapy remarkably improved OS and BCSS of BCLM patients whether the patients were at low-risk or high-risk, but radiotherapy did not. ConclusionsWe successfully developed prognostic stratification nomograms to forecast prognosis in BCLM patients, which provide important information for indicating prognosis and facilitating individualized treatment regimens for BCLM patients.

BACKGROUND:Breast neuroendocrine carcinoma (NEC) is a rare malignancy with unclear treatment options and prognoses. This study aimed to construct a high-quality model to predict overall survival (OS) and breast cancer-specific survival (BCSS) and help clinicians choose appropriate breast NEC treatments.PATIENTS AND METHODS:A total of 378 patients with breast NEC and 349,736 patients with breast invasive ductal carcinoma (IDC) were enrolled in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018. Propensity score matching (PSM) was performed to balance the clinical baseline. Prognostic factors determined by multivariate Cox analysis were included in the nomogram. C-index and calibration curves were used to verify the performance of the nomogram.RESULTS:Nomograms were constructed for the breast NEC and breast IDC groups after PSM. The C-index of the nomograms ranged from 0.834 to 0.880 in the internal validation and 0.818-0.876 in the external validation, indicating that the nomogram had good discrimination. The risk stratification system showed that patients with breast NEC had worse prognoses than those with breast IDC in the low-risk and intermediate-risk groups but had a similar prognosis that those in the high-risk group. Moreover, patients with breast NEC may have a better prognosis when undergoing surgery plus chemotherapy than when undergoing surgery alone or chemotherapy alone.CONCLUSIONS:We established nomograms with a risk stratification system to predict OS and BCSS in patients with breast NEC. This model could help clinicians evaluate prognosis and provide individualized treatment recommendations for patients with breast NEC.

Purpose The aim of this study was to explore the role of galectin-3 in human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells and the potential mechanism. Methods Kaplan-Meier (KM)-plot and The Cancer Genome Atlas (TCGA) databases were used to study the role of galectin-3 in the prognosis of HER2-positive breast cancer. The effects of galectin-3 on cell proliferation, migration, invasion, and colony formation ability in HER2-positive breast cancer cells were examined. The relationship between galectin-3 and important components in the HER2 pathways, including HER2, epidermal growth factor receptor (EGFR), protein kinase B (AKT), and phosphatase and tensin homolog (PTEN), was further studied. Lentivirus and CRISPR/Cas9 were used to construct stable cell lines. Cell counting kit-8 (CCK-8) and apoptosis assays were used to study the relationship between galectin-3 and trastuzumab. The effect of galectin-3 on cell stemness was studied by mammosphere formation assay. The effects of galectin-3 on stemness biomarkers and the Notch1 pathway were examined. Tumorigenic models were used to evaluate the effects of galectin-3 on tumorigenesis and the therapeutic effect of trastuzumab in vivo. Results HER2-positive breast cancer patients with a high expression level of LGALS3 (the gene encoding galectin-3) messenger RNA (mRNA) showed a poor prognosis. Galectin-3 promoted cancer malignancy through phosphoinositide 3-kinase (PI3K)/AKT signaling pathway activation and upregulated stemness by activating the Notch1 signaling pathway in HER2-positive breast cancer cells. These two factors contributed to the enhancement of trastuzumab resistance in cells. Knockout of LGALS3 had a synergistic therapeutic effect with trastuzumab both in vitro and in vivo. Conclusions Galectin-3 may represent a prognostic predictor and therapeutic target for HER2-positive breast cancer.

Purpose: The aim of this study was to establish individualized nomograms to predict survival outcomes in older female patients with stage IV breast cancer who did or did not undergo local surgery, and to determine which patients could benefit from surgery. Methods: A total of 3,129 female patients with stage IV breast cancer aged ≥70 years between 2010 and 2015 were included in the Surveillance, Epidemiology, and End Results program. Multivariate Cox regression analysis was used to identify risk factors for overall survival (OS) and breast cancer-specific survival (BCSS). Survival analysis was performed using the Kaplan–Meier plot and log-rank test. Nomograms and risk stratification models were constructed. Results: Patients who underwent surgery had better OS (HR = 0.751, 95% CI [0.668–0.843], P < 0.001) and BCSS (HR = 0.713, 95% CI [0.627–0.810], P < 0.001) than patients who did not undergo surgery. Patients with human epidermal growth factor receptor 2-positive, lung or liver metastases may not benefit from surgery. In the stratification model, low-risk patients benefited from surgery (OS, HR = 0.688, 95% CI [0.568–0.833], P < 0.001; BCSS, HR = 0.632, 95% CI [0.509–0.784], P < 0.001), while patients in the high-risk group had similar outcomes (OS, HR = 0.920, 95% CI [0.709–1.193], P = 0.509; BCSS, HR = 0.953, 95% CI [0.713–1.275], P = 0.737). Conclusion: Older female patients with stage IV breast cancer who underwent surgery had better OS and BCSS than those who did not in each specific subgroup. Patients in low- or intermediate-risk group benefit from surgery while those in the high-risk group do not.

Objective:To compare the survival and prognostic factors of intraoperative radiotherapy (IORT) and postoperative radiotherapy (PORT) in female patients, aged≥50 years, diagnosed with node-negative breast cancer (≤ 3 cm in size).Methods:Clinical data of eligible early breast cancer patients between 2010 and 2015 were obtained from the SEER database. Patients were divided into the IORT and PORT groups according to the radiotherapy record and propensity score matching (PSM) was subsequently conducted. Kaplan-Meier curve was used to evaluate the overall survival (OS) and breast cancer-specific survival (BCSS) between two groups and Cox proportional hazard regression analysis was used to explore the risk factors of clinical prognosis.Results:7 068 patients were included after PSM. The median follow-up time was 32.0 months. The 5-year OS rates in the IORT and PORT groups were 96.8% and 93.8%, respectively. Univariate Cox analysis showed that radiotherapy, age, histological grade, T stage, estrogen receptor (ER) status and progesterone receptor (PR) status were the independent risk factors for OS, and histological grade, T stage, ER status, PR status and chemotherapy were the independent risk factors for BCSS. Multivariate Cox regression analysis demonstrated that patients who received IORT had better OS than PORT counterparts ( P=0.020). Besides, patients aged≥60 years obtained worse OS than those aged<60 years ( P=0.003). Patients with T 2 stage or ER-negative tumors had worse OS than those with T 1 stage tumors ( P<0.001) or ER-positive tumors ( P=0.001). Patients with grade Ⅲ-Ⅳ tumors achieved worse BCSS ( P=0.004). Subgroup analysis showed that IORT yielded better OS for elderly patients (≥60 years), grade Ⅲ-Ⅳ tumors, infiltrating duct carcinoma, T 2 stage tumors, ER-positive tumors, PR-positive tumors and patients without chemotherapy. Conclusions:IORT may bring benefit for highly selected patients with low risk of recurrence, which is not inferior to PORT in terms of short-term survival. Prospective studies with longer follow-up time are needed to confirm the findings.

随着检测手段的更新,越来越多乳腺癌在早期就被发现及治疗,大多数女性患者的预后都很好,常规的乳腺癌保留乳房改良根治术加全乳放疗的模式已经无法满足女性对于生活质量及美观性的追求.乳腺癌术中放疗是指在手术过程中直接针对瘤床的单次大剂量照射,具有治疗周期短、经济花费少、安全美观的优势.对于经严格挑选的低危患者,术中放疗是传统放疗的安全的替代方式.文章将通过对乳腺癌术中放疗的简介、优势及局限性、循证医学证据、补救措施及前景等方面进行综述.

In recent years, several approaches have been applied to modify metal-organic frameworks (MOFs) owing to their excellent structural tunability such as higher extraction efficiency than that of primitive crystals. Herein, Zr-based MOFs (UiO-66-NH2) with a suitable size modulated by acetic acid were successfully synthesized for effective DNA extraction. The bonding conformations and adsorption mechanism indicated a high affinity between UiO-66-NH2 and the DNA molecules. Furthermore, Fe3O4 nanoparticles were immobilized on the UiO-66-NH2 surface to allow MOFs with magnetism. The magnetic zirconium-organic framework (MZMOF) retained the intact structure of MOFs and simplified subsequent extraction operations. In the DNA recovery investigation, MZMOF showed high recovery efficiency for both short-stranded DNA (90.4%) and pseudovirus DNA (95.1%). In addition, it showed superior DNA extraction efficiency from plasma (57.6%) and swab preservation solution (86.5%). The prepared MZMOF was employed for highly specific extraction of viral DNA and cfDNA from samples. To further simplify the extraction process, MZMOF was applied to immiscible phase filtration assisted by a surface tension (IFAST) chip for facilitating rapid DNA extraction with sensitive point-of-care testing. The developed MZMOF-based extraction method has significant potential for increasing the demand for rapid and efficient nucleic acid extraction.

Background Neuroendocrine carcinoma (NEC) of the breast is a very rare malignant tumor whose clinic pathological features and prognosis are not well defined. The aim of this study was to compare the clinic pathological features and clinical outcome between breast neuroendocrine carcinoma and breast invasive ductal carcinoma (IDC) and to know the independent prognostic risk factors of NEC. Method Patients with breast NEC and breast IDC were identified through the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Then we compared the clinic pathological features and outcome between the two cohorts. Propensity score matching (PSM) was performed to balance the effects of baseline clinic pathological differences. Potential prognostic factors of breast NEC were identified by the univariate and multivariate Cox analysis. Results In total, we identified 208 patients with breast NEC and 275,878 cases with breast IDC.Compared with IDC, NEC was significantly correlated with higher stage, larger tumor size, more distant transfers and no population of HER2 enriched subtype. There were significant differences on the choice of treatment therapy between NEC and IDC (p=0.000). More patients chose not to undergo surgery (35.1% vs. 9.0%), and fewer patients chose breast conserving surgery than IDC patients (32.2% vs. 51.1%). Compared with IDC patients, NEC patients were more likely to choose chemotherapy (p=0.039) and more conservative in radiotherapy (p=0.000). The 66-month overall survival (OS) rate in NEC and IDC was 44.5% and 80.2% before PSM and was 49.8% and 71.4% after PSM, respectively. The 66-month breast cancer specific survival (BCSS) rate in NEC and IDC was 56.3% and 88.8% before PSM and was 54.1% and 80.5% after PSM, respectively. Finally, we identified independent prognostic factors, age, stage, pathological type, distant metastasis, chemotherapy, and molecular typing. Conclusions Breast NEC has distinct clinic pathological features and a significantly worse clinical outcome than common IDC.

半乳糖凝集素3(Gal-3)是糖粘合蛋白家族的一员,在多种肿瘤的发生、进展、侵袭和转移中起重要作用.Gal-3的过表达增强了肿瘤细胞的活性、侵袭性,并且抑制细胞的凋亡,促进血管生成并诱导肿瘤免疫逃逸.文章主要就乳腺癌诊断、预后、治疗、转移等方面对Gal-3与乳腺癌相关性进行综述.