Construction of a prognostic 6-gene signature for breast cancer based on multi-omics and single-cell data.

Background: Breast cancer (BC) is one of the females' most common malignant tumors there are large individual differences in its prognosis. We intended to uncover novel useful genetic biomarkers and a risk signature for BC to aid determining clinical strategies. Methods: A combined significance (p combined) was calculated for each gene by Fisher's method based on the RNA-seq, CNV, and DNA methylation data from TCGA-BRCA. Genes with a p combined< 0.01 were subjected to univariate cox and Lasso regression, whereby an RS signature was established. The predicted performance of the RS signature would be assessed in GSE7390 and GSE20685, and emphatically analyzed in triple-negative breast cancer (TNBC) patients, while the expression of immune checkpoints and drug sensitivity were also examined. GSE176078, a single-cell dataset, was used to validate the differences in cellular composition in tumors between TNBC patients with different RS. Results: The RS signature consisted of C15orf52, C1orf228, CEL, FUZ, PAK6, and SIRPG showed good performance. It could distinguish the prognosis of patients well, even stratified by disease stages or subtypes and also showed a stronger predictive ability than traditional clinical indicators. The down-regulated expressions of many immune checkpoints, while the decreased sensitivity of many antitumor drugs was observed in TNBC patients with higher RS. The overall cells and lymphocytes composition differed between patients with different RS, which could facilitate a more personalized treatment. Conclusion: The six genes RS signature established based on multi-omics data exhibited well performance in predicting the prognosis of BC patients, regardless of disease stages or subtypes. Contributing to a more personalized treatment, our signature might benefit the outcome of BC patients.

Clinicopathological characteristics of HER2-low breast cancer: a retrospective study.

Human Epidermal Growth Factor Receptor-2 (HER2)-negative breast cancers (BCs) contain HER2-low and HER2-zero ones. HER2-low breast cancer has been receiving wide-spread concerns as the marvelous effect of novel anti-HER2 antibody-drug conjugates, however, the characteristic remains unknown. Our aim was to explore the differences of clinicopathological indicators and survival outcomes between HER2-low and HER2-0 breast cancers. We retrospectively analyzed 501 invasive breast cancer patients with complete data on HER2 status from 2017 to 2021 in our single center, of whom 415 HER2 negative patients were included for subsequent analysis. Each cohort was further divided into hormone receptor (HR) positive and HR negative subgroup. Clinicopathological factors and survival outcomes were collected and compared between HER2-low BCs and HER2-0 BCs. HER2-low BCs was obviously higher in HR positive BCs, with 277 (90.5%) HER2-low HR positive patients, 29 (9.5%) HER2-low HR negative patients, 68 (62.4%) HER2-0 HR positive patients and 41 (37.6%) HER2-0 HR negative patients (P < 0.001). Significant differences between HER2-low BCs and Her2-0 BCs were observed in lymph node ratio (LNR) (mean rank, 215 vs. 188 P = 0.014), estrogen receptor (ER)expression (90.5% vs. 62.4% P < 0.001), progesterone receptor (PR) expression (84.3% vs. 56.9% P < 0.001), Ki-67 expression (46.4% vs. 61.5% P < 0.001), androgen receptor (AR) expression (68% vs. 50.5% P < 0.001), adjuvant chemotherapy (69% vs. 79.8% P = 0.03). HER2-low BCs had lower histological grade than HER2-0 BCs, with grade I-II (68.7% vs. 43.1%) and grade III (22.2% vs. 43.1%) P < 0.01. No statistical differences were detected between the two groups for DFS and DDFS. Our results demonstrated that HR and AR status was closely related to HER2-low breast cancers. Further exploration about survival prognosis of HER2-low breast cancer is badly needed.

Oncological safety of reconstruction with autologous fat grafting in breast cancer patients: a systematic review and meta-analysis.

To evaluate the oncological safety of autologous fat grafting and its effect on disease-free survival and local recurrence in breast cancer patients with autologous fat grafting (AFG) reconstruction. A literature search was performed using the Pubmed, Medline, Web of Science, and Cochrane libraries from January 2011 to March 2020, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to identify all relevant studies involving the application of autologous fat grafting in breast cancer reconstruction procedures. The primary outcome of the meta-analysis was a difference in incidence rates of locoregional recurrence and disease-free survival (DFS) between patients who had autologous fat grafting and controls. A total of 11 studies were included. Eight studies reported local-regional recurrences (LRR) and five studies reported disease-free survival (DFS) in 5,886 patients. Our meta-analysis of all included studies about survival outcomes showed AFG was not associated with increased LRR and DFS. Pooled hazard ratios (HRs) (95% CIs) for LRR and DFS were 1.26 (0.90-1.76) and 1.27 (0.96-1.69), respectively. According to the published literature, autologous fat grafting did not result in an increased rate of LRR and DFS in patients with breast cancer. Autologous fat grafting can, therefore, be performed safely in breast reconstruction after breast cancer.

Evaluation of a beneficial effect of adjuvant chemotherapy in patients with stage I triple-negative breast cancer: a population-based study using the SEER 18 database.

PURPOSE: To evaluate the effect of adjuvant chemotherapy on improving the prognosis of patients with stage I triple-negative breast cancer (TNBC). METHODS: TNBC patients diagnosed in the SEER 18 database from 2010 to 2015 were included. Kaplan-Meier plots and log-rank tests were used to compare the differences in breast cancer-specific survival (BCSS) and overall survival (OS) between subgroups of variables. A Cox proportional hazard model was used to determine the prognostic factors affecting BCSS and OS. RESULTS: A total of 9256 patients were enrolled in this study. Among these patients, 380 died from breast cancer, and 703 died from all causes. Patients who received chemotherapy had significantly better BCSS and OS than those who did not receive chemotherapy for stage T1cN0M0 (BCSS, hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.51-0.90; OS, HR = 0.54, 95% CI 0.44-0.67) and stage IB (BCSS, HR = 0.39, 95% CI 0.16-0.95; OS, HR = 0.41, 95% CI 0.19-0.87) disease. Patients who received chemotherapy did not have significantly better BCSS or OS than those who did not receive chemotherapy for stage T1aN0M0 or T1bN0M0 disease. The patients who received chemotherapy in the poorly differentiated and undifferentiated groups had better BCSS (HR = 0.68, 95% CI 0.52-0.88) and OS (HR = 0.54, 95% CI 0.44-0.66) than the patients who did not receive chemotherapy. CONCLUSION: According to current clinical guidelines, patients with stage T1bN0M0 TNBC are probably overtreated. The prognosis of these patients with stage T1aN0M0 or T1bN0M0 disease is good enough that adjuvant chemotherapy cannot improve it further.

Personal factors influencing breast cancer patients' perception of breast conservation surgery in West China.

BACKGROUND: Breast cancer patients' understanding of therapies is a very important factor during their surgical treatment decision-making. To date, there has been no report in this area about Chinese patients. Aiming to evaluate the perception of breast conservation surgery (BCS) in Chinese breast cancer patients (CBCP) and explore influencing factors. METHODS: A self-structured questionnaire was distributed to 1,496 CBCPs, eliciting information on patients' age, religion, sexual history, occupation, education, whether they were pre- or postoperative, understanding of BCS and their means of gaining information. RESULTS: A total of 1,324 (88.5%) patients completed the questionnaire. Only 2.42% of patients had more understanding of BCS. Patients' perception about BCS was associated with their age, religion, occupation, education background and whether they were postoperative or not (P<0.01). Surgeon was the most commonly way being used to obtain information (68.9%); however, this was not significant in affecting patients' perception [odds ratios (OR) =1.034; 95% confidence intervals (CI): 0.762-1.402]. Patients using books and/or internet to obtain information on BCS had better understanding (OR =1.665; 95% CI: 1.249-2.193), but only 20.2% patients used this way to search for information. CONCLUSIONS: The study indicated that CBCP' perception of BCS was poor, they lacked access to information. Therefore, educating patients and making them master knowledge about BCS were a hard work in China.