Backgrounds: HER-2 positive breast cancer is a subtype of breast cancer with poor clinical outcome. The aim of this study was to identify differentially expressed genes (DEGs) for HER-2 positive breast cancer and elucidate the potential interactions among them. Material and methods: Three gene expression profiles (GSE29431, GSE45827, and GSE65194) were derived from the Gene Expression Omnibus (GEO) database. GEO2R tool was applied to obtain DEGs between HER-2 positive breast cancer and normal breast tissues. Gene ontology (GO) annotation analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis was performed by the Database for Annotation, Visualization and Integrated Discovery (David) online tool. Protein-protein interaction (PPI) network, hub gene identification and module analysis was conducted by Cytoscape software. Online Kaplan–Meier plotter survival analysis tool was also used to investigate the prognostic values of hub genes in HER-2 positive breast cancer patients. Results: A total of 54 upregulated DEGs and 269 downregulated DEGs were identified. Among them, 10 hub genes including CCNB1, RAC1, TOP2A, KIF20A, RRM2, ASPM, NUSAP1, BIRC5, BUB1B, and CEP55 demonstrated by connectivity degree in the PPI network were screened out. In Kaplan–Meier plotter survival analysis, the overexpression of RAC1 and RRM2 were shown to be associated with an unfavorable prognosis in HER-2 positive breast cancer patients. Conclusions: This present study identified a number of potential target genes and pathways which might impact the oncogenesis and progression of HER-2 positive breast cancer. These findings could provide new insights into the detection of novel diagnostic and therapeutic biomarkers for this disease.

Background Breast surgery for stage IV breast cancer remains controversial. The aim of this study was to investigate the impact of breast surgery on survival of stage IV breast cancer patients based on the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Methods In total, 13,034 patients were selected and divided into surgery and non-surgery groups. Univariate and multivariable analyses were conducted to determine factors related to survival. Propensity score matching method was utilized to achieve balanced covariates across different groups. One-to-one (1:1) PSM was conducted to construct a matched sample consisting of pairs of surgery and non-surgery subjects. Breast cancer-specific survival (BCSS) and overall survival (OS) of the two groups were assessed by Kaplan–Meier plots and Cox proportional hazard regression models. Stratified analysis according to different variables was also performed. Results Patients treated with breast surgery were more likely to be younger, smaller tumor size, more advanced nodal status, higher histology grade and higher proportion of bone-only metastasis. Those who received chemotherapy and radiotherapy also tended to be treated with surgery. After adjustment for potential confounders, breast surgery group exhibited a better survival both in BCSS (HR = 0.557, 95% CI [0.523–0.594], p < 0.001) and OS (HR = 0.571, 95% CI [0.537–0.607], p < 0.001). After propensity score matching, the surgery and non-surgery group consisted of 2,269 patients respectively. The median survival time was 43 months for the surgery group and 27 months for the non-surgery group. Kaplan–Meier curves indicated that breast surgery could clearly improve both the BCSS and OS for patients with stage IV breast cancer. On multivariate analysis, surgery group was associated with a better survival compared with the non-surgery group (BCSS: HR = 0.542, 95% CI [0.499–0.589], p < 0.001; OS: HR = 0.555, 95% CI [0.512–0.601], p < 0.001). Furthermore, this survival advantage persisted in all subgroups irrespective of age, race, tumor size, nodal status, histology grade, molecular subtype, chemotherapy status, radiotherapy status or status of distant metastasis. Conclusion Our study provided additional evidence that patients with stage IV breast cancer could benefit from breast surgery and it might play a more important role in multimodality therapy.

Background: Small tyrosine kinase inhibitors (TKIs) show activity against breast cancer brain metastases (BCBM) of the human epidermal growth factor receptor 2 (HER2)‐positive subtype. This meta‐analysis aimed to objectively explore the efficacy and safety of TKIs.Methods: Electronic databases were searched for relevant clinical trials. We conducted a pairwise meta‐analysis, pooled analysis, and estimated summary survival curves to compare survival outcomes following TKIs therapy for BCBM patients using Stata version 16.0 or R x64 4.0.5.Results: Thirteen clinical trials involving 987 HER2‐positive BCBM patients were analyzed. A trend of longer progression‐free survival (PFS) was observed in the TKI‐containing arm compared to the non‐TKI‐containing arm (hazard ratio = 0.64, 95% confidence interval [CI]: 0.35–1.15, p = 0.132), although the difference is not statistically significant. Summary survival curves reported the summary median PFS and overall survival were 7.9 months and 12.3 months. Subgroup analysis revealed that TKIs combined with capecitabine (TKI + Cap) regimens resulted in improved survival outcomes. Tucatinib may be more effective in BCBM patients. The main grade 3–5 adverse events (AEs) were diarrhea (22%, 95% CI: 14%–32%), neutropenia (11%, 95% CI: 5%–18%), hepatic toxicity (7%, 95% CI: 1%–16%), and sensory neuropathy (6%, 95% CI: 2%–12%).Conclusion: TKIs therapy improved the survival outcomes of HER2‐positive BCBM patients, especially when combined with capecitabine and tolerable AEs. We also identified the clinical value of tucatinib, which appears to be the most favorable TKI drug for BCBM patients.

Background: Lymph node micrometastasis is an important prognostic factor in breast cancer, but patients with different numbers of involved lymph nodes are all divided into the same N1mi stage without distinction. We designed this study to compare the prognosis and local treatment recommendations of N1mi breast cancer patients with different numbers of micrometastatic lymph nodes. Patients and methods: A total of 27,032 breast cancer patients with T1-2N1miM0 stage from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2019) who underwent breast surgery were included in this retrospective study. Patients were divided into three groups for prognosis comparison according to the number of micrometastatic lymph nodes: N1mi with 1 (Nmi = 1), 2 (Nmi = 2), or more (Nmi ≥ 3) involved lymph nodes. We explored the characteristics and survival outcomes of the population receiving different local treatments, including different axillary surgery types and whether receiving radiotherapy or not. Univariate and multivariate Cox proportional hazards regression analysis were used to compare the overall survival (OS) and breast cancer-specific survival (BCSS) in different groups. Stratified analyses and interaction analyses were also applied to explore the predictive significance of different involved lymph nodes numbers. Propensity score matching (PSM) method was utilized to balance the differences between groups. Results: Univariate and multivariate Cox regression analysis indicated that nodal status was an independent prognostic factor. After adjustment for other prognostic factors, there was a significant difference in prognosis between Nmi = 1 group and Nmi = 2 group [adjusted hazard ratio (HR) 1.145, 95% confidence interval (CI): 1.047–1.251, P = 0.003], and patients with Nmi ≥ 3 group had a significantly poorer prognosis (adjusted HR 1.679, 95% CI 1.589–2.407; P < 0.001). The proportion of N1mi patients only underwent sentinel lymph nodes biopsy (SLNB) gradually increased from 2010 (P_trend < 0.001). After adjusting for other factors, N1mi patients who underwent axillary lymph nodes dissection (ALND) was associated with significant survival benefit than SLNB (adjusted HR 0.932, 95%CI 0.874–0.994; P = 0.033), the same goes for receiving radiotherapy (adjusted HR 1.107, 95%CI 1.030–1.190; P = 0.006). Further stratified analysis showed that in the SLNB subgroup, radiotherapy was associated with a significant survival benefit (HR 1.695, 95%CI 1.534–1.874; P < 0.001), whereas in the ALND subgroup, there was no significant prognostic difference with or without radiotherapy (HR 1.029, 95%CI 0.933–1.136; P = 0.564). Conclusion: Our study indicates that the increasing number of lymph node micrometastases was associated a worse prognosis of N1mi breast cancer patients. In addition, ALND does provide a significant survival benefit for these patients, while the benefit from local radiotherapy may be of even greater importance.

Purpose: Breast cancer-related lymphedema (BCRL) is a common complication among breast cancer survivors. Most BCRL studies have focused on patients receiving adjuvant chemotherapy, with relatively little attention paid to BCRL in patients undergoing neoadjuvant chemotherapy (NAC). This study aimed to investigate the risk factors associated with BCRL in Chinese women undergoing NAC and axillary lymph node dissection (ALND).Methods: At our institution, this cohort study collected data from 336 women with breast cancer and documented axillary nodal metastasis at diagnosis, who received NAC and ALND surgery between 2015 and 2020. BCRL was assessed through both objective limb circumference measurements and subjective self-reported symptoms. Multivariate logistic regression was employed to identify risk factors for BCRL, considering clinical, demographic, and lifestyle-related characteristics.Results: The cumulative incidence of BCRL within 2.5 years was 43.75%. Factors independently associated with BCRL included radiotherapy (versus no radiotherapy; hazard ratio (HR) = 1.611; P = 0.020), NAC duration of 105 days or shorter (versus 105-143 days; HR = 0.471; P = 0.020), removal of more than 15 lymph nodes (versus 15 or fewer lymph nodes; HR = 1.593; P = 0.036), drainage duration of 20-29 days (versus 10-19 days; HR = 1.568; P = 0.028), and sleeping biased toward the affected arm (versus sleeping biased toward the healthy arm; HR = 2.033; P = 0.019).Conclusion: This study identified several risk factors for BCRL in breast cancer patients following NAC and ALND. Patients presenting with one or more of these factors should be monitored closely for early detection and intervention. Further research is warranted to explore the impact of drainage duration and sleep position on the development of BCRL.

Background: Currently, the value of oral selective estrogen receptor degraders (SERDs) for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (aBC) after progression on ≥ 1 line of endocrine therapy (ET) remains controversial. We conducted a meta-analysis to evaluate progression-free survival (PFS) and safety benefits in several clinical trials. Materials and methods: Cochrane Library, Embase, PubMed, and conference proceedings (SABCS, ASCO, ESMO, and ESMO Breast) were searched systematically and comprehensively. Random effects models or fixed effects models were used to assess pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for treatment with oral SERDs versus standard of care. Results: A total of four studies involving 1,290 patients were included in our analysis. The hazard ratio (HR) of PFS showed that the oral SERD regimen was better than standard of care in patients with HR+/HER2- aBC after progression on ≥ 1 line of ET (HR: 0.75, 95% CI: 0.62-0.91, p = 0.004). In patients with ESR1 mutations, the oral SERD regimen provided better PFS than standard of care (HR: 0.58, 95% CI: 0.47-0.71, p < 0.00001). Regarding patients with disease progression following previous use of CDK4/6 inhibitors, PFS benefit was observed in oral SERD-treatment arms compared to standard of care (HR: 0.75, 95% CI: 0.64-0.87, p = 0.0002). Conclusions: The oral SERD regimen provides a significant PFS benefit compared to standard-of-care ET in patients with HR+/HER2- aBC after progression on ≥ 1 line of ET. In particular, we recommend oral SERDs as a preferred choice for those patients with ESR1m, and it could be a potential replacement for fulvestrant. The oral SERD regimen is also beneficial after progression on CDK4/6 inhibitors combined with endocrine therapy.