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.

Brain metastasis in de novo breast cancer: An updated population-level study from SEER database.

PURPOSE: Although there are current studies on breast cancer brain metastasis, population-level analysis is still lacking. As treatment for metastatic breast cancer has improved, an updated population-level analysis is necessary. Our aim was to use the SEER database to characterize the incidence and survival of patients with brain metastases at the initial diagnosis of breast cancer. PATIENTS AND METHODS: Patients with breast cancer from 2010 to 2018 were identified using the SEER database. The stratified incidence and median survival of patients with BM at diagnosis were described. Multivariate logistic and Cox regression were performed to determine the covariates associated with brain metastasis and survival outcomes, respectively. Multiple comparisons based on Cox proportional hazards model were performed for the analysis of interactive effects on overall survival. RESULTS: A total of 2,248 patients with brain metastases at the initial diagnosis of breast cancer were identified, accounting for 0.40% of all patients with breast cancer, and 7.26% of patients with metastatic disease. Incidence proportions were highest, and survival outcomes were worst among patients with hormone receptor (HR)-negative human epidermal growth factor receptor 2 (HER2)-positive and triple-negative subtypes. For patients with brain metastases, the prognostic differences among different molecular subtypes have been gradually narrowing, and the survival benefits from various treatment methods have been all increased over time. CONCLUSION: Our study provides an updated population-level estimate of the incidence and survival for patients with brain metastases at the diagnosis of breast cancer, thus may help early identification, prognostic stratification and treatment planning for such patients.

Survival Benefit of Surgical Treatment Added Into Systemic Treatment for Isolated Breast Cancer Liver Metastases: A Systematic Review and Meta-Analysis.

Background: Compared with systemic treatment alone, whether surgical treatment combined with systemic treatment can improve survival outcomes of patients with isolated breast cancer liver metastases (BCLM) is still controversial. This meta-analysis was designed to evaluate the efficacy of surgical treatment for patients with isolated BCLM. Methods: A systematic search of PubMed, Embase, and Cochrane Library up to May 13, 2021 was conducted for relevant studies. The primary outcome was overall survival. The meta-analysis was performed using R software. The quality of the pooled study was assessed using the Newcastle-Ottawa scale. The publication bias was evaluated by funnel plots and Begg's and Egger's tests. Fixed- and random-effects models were applied according to heterogeneity. Results: 9 retrospective studies involving 13 cohorts (7 unmatched cohorts and 6 matched cohorts) were included in this study. The surgical cohorts had better overall survival than the systemic cohorts in the pooled analysis of all the included studies, in the subgroup analysis of liver resection, and in the subset of the matched cohorts. Conclusions: Compared with systemic treatment alone, surgical treatment combined with systemic treatment was proven to be associated with superior survival outcomes, which should be considered in selected patients with isolated BCLM.

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.