Diabetes and incidence of breast cancer and its molecular subtypes: A systematic review and meta-analysis.

Diabetes mellitus (DM) has been proposed to be positively associated with breast cancer (BCa) risk due to shared risk factors, metabolic dysfunction, and the use of antidiabetic medications. We conducted a systematic review and meta-analysis to evaluate the association between DM and BCa risk. We searched PubMed, Embase, and Web of Science for cohort and case-control studies assessing the association between DM and BCa published before 10 December 2021. Two reviewers independently screened the studies for inclusion, abstracted article data, and rated study quality. Random effects models were used to estimate summary risk ratios (RRs) and 95% confidence intervals (CIs). From 8396 articles identified in the initial search, 70 independent studies were included in the meta-analysis. DM was associated with an overall increased risk of BCa (RR = 1.20, 95% CI: 1.11-1.29). The 24 case-control studies demonstrated a stronger association (RR = 1.26, 95% CI: 1.13-1.40) than the 46 cohort studies (RR = 1.15, 95% CI: 1.05-1.27). Studies reporting risk by menopausal status found that postmenopausal women had an elevated risk of developing BCa (RR = 1.12, 95% CI: 1.07-1.17). No association between DM and BCa risk was observed among premenopausal women (RR = 0.95, 95% CI: 0.85-1.05). In addition, DM was associated with significantly increased risks of oestrogen receptor (ER)+ (RR = 1.09, 95% CI: 1.00-1.20), ER- (RR = 1.16, 95% CI: 1.04-1.30), and triple negative BCa (RR = 1.41, 95% CI: 1.01-1.96). The association estimate for human epidermal growth factor 2-positive BCa was also positive (RR = 1.21, 95% CI: 0.52-2.82), but the CI was wide and crossed the null. Our meta-analysis confirms a modest positive association between DM and BCa risk. In addition, our results suggest that the association between DM and BCa may be modified by menopausal status, and that DM may be differentially associated with BCa subtypes defined by receptor status. Additional studies are warranted to investigate the mechanisms underlying these associations and any influence of DM on BCa receptor expression.

The Impact of Neoadjuvant Chemotherapy on Patients With T1N0M0 Triple-Negative and HER-2 Positive Breast Cancer: A Retrospective Analysis Based on the SEER Database.

BACKGROUND: The utilization of neoadjuvant chemotherapy (NAC) originated in the treatment of locally advanced breast cancer (BC). Our study is designed to elucidate the effects of NAC on patients with T1N0M0 triple-negative and HER-2 positive BC. METHODS: This study involved the selection of 10,614 patients diagnosed with T1N0M0 triple-negative and HER-2 positive breast cancer (BC) from the surveillance, epidemiology, and end results (SEER) database. To ascertain the impact of neoadjuvant chemotherapy (NAC) on T1a, T1b, and T1c N0M0 BC, we conducted multivariate Cox regression analyses. Similarly, we performed multivariate Cox regression analyses to compare the effects of neoadjuvant chemotherapy against adjuvant chemotherapy on T1N0M0 BC. The Kaplan-Meier method was employed to delineate survival curves for different molecular subtypes and clinical stages. RESULTS: The data results from the SEER database reveal a significant enhancement of overall survival (OS) in T1c BC patients as a result of NAC. For T1b BC patients, NAC does not present any significant effect. Contrarily, NAC seems to adversely impact the OS of T1a triple-negative BC patients. However, the prognosis comparison between neoadjuvant and adjuvant chemotherapy for T1N0M0 breast cancer did not show any significant difference, with the exception of T1a triple-negative BC. CONCLUSIONS: Patients with T1cN0M0 triple-negative and HER-2 positive BC may derive OS benefits from NAC. Additionally, NAC could be detrimental to T1a triple-negative BC.

Prognostic Impact of HER2-Low and HER2-Zero in Resectable Breast Cancer with Different Hormone Receptor Status: A Landmark Analysis of Real-World Data from the National Cancer Center of China.

BACKGROUND: The prognostic impact of HER2-low on overall survival (OS) and disease-free survival (DFS) in patients with resectable breast cancer (BC) remains controversial, partly resulting from the hormone receptor (HR) status. OBJECTIVE: To investigate the prognostic impact of HER2-low in different HR subgroups. PATIENTS AND METHODS: We retrospectively retrieved medical records of treatment-naive primary HER2-low and HER2-zero BC patients who were diagnosed with invasive ductal carcinoma and underwent surgery in the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2009 to September 2017 (n = 7371). We compared the clinicopathologic features and performed Cox regression and landmark survival analyses to explore the prognostic impact of HER2-low on survival outcomes during distinct post-surgery intervals-36 months, 60 months, and 120 months. RESULTS: HER2-low BC, compared to HER2-zero BC, exhibited less aggressive clinicopathologic features, such as smaller invasion size, lower grade, increased nerve invasion, higher HR positivity, and a higher proportion of low-Ki67 cases. In the HR-positive subgroup, HER2-low demonstrated improved OS (p = 0.046) and DFS (p = 0.026) within 60 months. Conversely, HER2-low displayed worse DFS (p = 0.046) in the HR-negative subgroup after 36 months from surgery. The findings remained robust in uni- and multi-variable Cox models. CONCLUSIONS: HER2-low BCs manifested less aggressive clinicopathologic features than the HER2-zero cases. The prognostic impact of HER2-low in resectable BCs exhibits variability contingent upon the patients' HR status.

Role of aggressive locoregional surgery in treatment strategies for ipsilateral supraclavicular lymph node metastasis of breast cancer: a real-world cohort study.

Background: Breast cancer patients with synchronous ipsilateral supraclavicular lymph node metastases (ISLNM) have unfavorable prognoses. The role of supraclavicular lymph node dissection (SLND) as a surgical intervention in the treatment of this condition remains controversial. In this study, we aimed to evaluate the prognostic factors associated with breast cancer with ISLNM and to assess the potential impact of aggressive locoregional surgical management on patient outcomes. Methods: We conducted a retrospective analysis of 250 breast cancer patients with ISLNM who were treated with curative intent at our institution between 2000 and 2020. The cohort was stratified into groups based on the extent of axillary surgery. The first group, comprising 185 patients, underwent level I/II axillary dissection. The second group, consisting of 65 patients, underwent aggressive locoregional surgery, including levels I/II/III (infraclavicular) dissection in 37 patients and levels I/II/III + SLND in 28 patients. Our study evaluated overall survival (OS) and disease-free survival (DFS) as primary endpoints, and locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) as secondary endpoints. Results: The median follow-up time among all patients was 5.92 years (1.05-15.36 years). The 5-year OS rate was 71.89%, while the DFS rate, LRRFS rate, and DMFS rates were 59.25%, 66.38%, and 64.98%, respectively. A significant difference in OS, DFS, LRRFS, and DMFS was observed between the second group and the first group (p < 0.01). No beneficial impact on recurrence, metastasis, or survival outcomes was observed in the levels I/II/III + SLND group compared to the levels I/II/III dissection group. Multivariate logistic regression analysis revealed that levels I/II/III ± SLND surgery and T stage were associated with OS (p = 0.006 and p = 0.026), while levels I/II/III ± SLND surgery, ER+/HER2-, and histologic grade were associated with DFS (p = 0.032, p = 0.001, p = 0.032). Conclusion: Breast cancer with ISLNM may be considered a locoregional disease, requiring a combination of systemic and local therapies. Aggressive locoregional surgery has been shown to positively impact recurrence, metastasis, and survival outcomes. This approach may provide improved management of the ISLNM for breast cancer patients.

Identifying clinicopathological risk factors for regional lymph node metastasis in Chinese patients with T1 breast cancer: a population-based study.

Objectives: To analyze clinicopathological risk factors and regular pattern of regional lymph node metastasis (LNM) in Chinese patients with T1 breast cancer and the effect on overall survival (OS) and disease-free survival (DFS). Materials and methods: Between 1999 and 2020, breast cancer patients meeting inclusion criteria of unilateral, no distant metastatic site, and T1 invasive ductal carcinoma were reviewed. Clinical pathology characteristics were retrieved from medical records. Survival analysis was performed using Kaplan-Meier methods and an adjusted Cox proportional hazards model. Results: We enrolled 11,407 eligible patients as a discovery cohort to explore risk factors for LNM and 3484 patients with stage T1N0 as a survival analysis cohort to identify the effect of those risk factors on OS and DFS. Compared with patients with N- status, patients with N+ status had a younger age, larger tumor size, higher Ki67 level, higher grade, higher HR+ and HER2+ percentages, and higher luminal B and HER2-positive subtype percentages. Logistic regression indicated that age was a protective factor and tumor size/higher grade/HR+ and HER2+ risk factors for LNM. Compared with limited LNM (N1) patients, extensive LNM (N2/3) patients had larger tumor sizes, higher Ki67 levels, higher grades, higher HR- and HER2+ percentages, and lower luminal A subtype percentages. Logistic regression indicated that HR+ was a protective factor and tumor size/higher grade/HER2+ risk factors for extensive LNM. Kaplan-Meier analysis indicated that grade was a predictor of both OS and DFS; HR was a predictor of OS but not DFS. Multivariate survival analysis using the Cox regression model demonstrated age and Ki67 level to be predictors of OS and grade and HER2 status of DFS in stage T1N0 patients. Conclusion: In T1 breast cancer patients, there were several differences between N- and N+ patients, limited LNM and extensive LNM patients. Besides, HR+ plays a dual role in regional LNM. In patients without LNM, age and Ki67 level are predictors of OS, and grade and HER2 are predictors of DFS.

Clinical Features and Prognoses of Patients With Breast Cancer Who Underwent Surgery.

Importance: Breast cancer (BC) remains a pervasive malignant neoplasm worldwide, with increasing incidence. However, there are a scarcity of studies examining the clinical characteristics and prognosis of Chinese patients with BC who have undergone surgery. Objective: To evaluate overall survival (OS) and disease-free survival (DFS) in patients with surgically treated BC in China, focusing on histopathology and surgical approach. Design, Setting, and Participants: This cohort study included a retrospective review of the medical records of patients with unilateral BC who underwent surgery between January 2009 and September 2017, with a median follow-up time of 7.69 years. Clinical features were extracted from these records, and survival analysis was performed. Data analysis was conducted in March 2023. Main Outcomes and Measures: Patients' OS and DFS. Results: The study included 14 782 patients (14 724 [99.6%] female patients; mean [SD] age, 51.6 [10.9] years). Invasive ductal carcinoma (IDC) was the most prevalent type, observed in 12 671 patients (85.6%). Stages 0, I, II, III, and IV accounted for 6.4% (919 patients), 32.0% (4579 patients), 40.5% (5791 patients), 20.2% (2896 patients), and 0.9% (126 patients) of cases, respectively. Hormone receptor (HR) positivity was observed in 10 241 patients (75.1%), and 3665 (29.1%) tested positive for ERBB2 (formerly HER2/neu). The HR-negative-ERBB2-negative, HR-negative-ERBB2-positive, HR-positive-ERBB2-negative, and HR-positive-ERBB2-positive subtypes constituted 13.3% (1666 patients), 12.7% (1595 patients), 57.8% (7251 patients), and 16.2% (2034 patients) of cases, respectively. Breast-conserving surgery (BCS) was performed in 2884 patients (19.5%). The 5-year and 10-year OS rates were 92.9% (13 689 of 14 732) and 87.4% (3287 of 3760), while the 5-year and 10-year DFS rates were 89.0% (12 916 of 14 512) and 82.9% (3078 of 3713), respectively. Multivariate analysis found that for patients with IDC, age, BCS, invasive tumor size, tumor grade, lymphovascular invasion (LVI), the number of lymph node metastases (LNMs), distant metastasis, Ki67, and HR status were associated with OS, whereas invasive tumor size, tumor grade, LVI, the number of LNMs, HR status, and ERBB2 status were associated with DFS. After propensity score matching, BCS was equivalent to mastectomy with respect to survival in patients with IDC. Conclusions and Relevance: This cohort study of patients with BC who underwent surgery in China provides valuable insights into the histopathological characteristics and survival outcomes of this population. The diverse histopathological features emphasize the necessity for customized treatment strategies. The relatively low BCS rate in the study population suggests the need for heightened awareness and adoption of this approach, considering its potential advantages for survival.

A signature for pan-cancer prognosis based on neutrophil extracellular traps.

BACKGROUND: Neutrophil extracellular traps (NETs) were originally thought to be formed by neutrophils to trap invading microorganisms as a defense mechanism. Increasing studies have shown that NETs play a pivotal role in tumor progression and diffusion. In this case, transcriptome analysis provides an opportunity to unearth the association between NETs and clinical outcomes of patients with pan-cancer. METHODS: The transcriptome sequencing data of The Cancer Genome Atlas pan-cancer primary focus was obtained from UCSC Xena, and a 19-gene NETs score was then constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model based on the expression levels of 69 NETs initial biomarkers we collected from multistudies. In addition, multiple datasets covering multiple cancer types from other databases were collected and used to validate the signature. Gene ontology enrichment analyses were used to annotate the functions of NETs-related pathways. Immunohistochemistry (IHC) was implemented to evaluate the role of NETs-related genes in clinical patients across types of tumors, including lung adenocarcinoma (n=58), colorectal carcinoma (n=93), kidney renal clear cell carcinoma (n=90), and triple-negative breast cancer (n=80). RESULTS: The NETs score was calculated based on 19-NETs related genes according to the LASSO Cox model. The NETs score was considered a hazardous factor in most cancer types, with a higher score indicating a more adverse outcome. In addition, we found that NETs were significantly correlated to various malignant biological processes, such as the epithelial to mesenchymal transition (R=0.7444, p<0.0001), angiogenesis (R=0.5369, p<0.0001), and tumor cell proliferation (R=0.3835, p<0.0001). Furthermore, in IHC cohorts of a variety of tumors, myeloperoxidase, a gene involved in the model and a classical delegate of NETs formation, was associated with poor clinical outcomes. CONCLUSIONS: Collectively, these constitutive and complementary biomarkers represented the ability of NETs formation to predict the development of patients' progression. Integrative transcriptome analyses plus clinical sample validation may facilitate the biomarker discovery and clinical transformation.