Breast Cancer : Targets and Therapy最新文献

Purpose: Clinical outcomes have improved for women with early stage, HER2-positive breast cancer following the FDA approval of adjuvant trastuzumab use in 2006. However, only limited information exists on such patients' outcomes in real-world settings outside of clinical trials. We examined the risk of subsequent breast cancer in women with HER-2 positive disease, and the impact of trastuzumab use, in a large California community-based health plan.

Patients and methods: A cohort of 3550 women with HER2-positive breast cancer (stages I-III) from 2009-2017 were followed through December 2018. We calculated subsequent breast cancer (SBC) rates overall and by trastuzumab use. Multivariable Cox proportional hazards modeling was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for SBC by trastuzumab use.

Results: Within the cohort diagnosed with HER2-positive disease, 81% received adjuvant trastuzumab. After 4.1 mean years follow-up (maximum 10 years), the risk of SBC was 22% lower with adjuvant trastuzumab use (hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.66-0.92) compared with non-use. The cumulative incidence of SBC precipitously rose two years after diagnosis and by the 10th year, the cumulative incidence was 31% among those who had trastuzumab therapy versus 34% without this therapy.

Conclusion: In community practice settings, the cumulative incidence of SBC in patients with early stage HER2-positive BC was 31% at 10 years in a cohort treated with adjuvant trastuzumab. Trastuzumab use was associated with a 22% reduced risk of developing SBC. This residual disease burden suggests breast cancer outcomes may be improved with further treatment given the advent of next-generation HER2-targeted therapies.

Background: The rate of unfavorable outcomes, such as recurrence and death, in women with invasive breast cancer varies widely across countries and populations. Identifying those with high-risk profiles is critical so that early detection, prediction, and intervention can be made to improve their survival rate. Therefore, our study evaluated the rate of unfavorable outcomes and its association with clinicopathological characteristics in Vietnamese women with primary invasive breast cancer.

Methods: A retrospective open cohort study was conducted on Vietnamese women with invasive breast cancer who underwent a mastectomy and were regularly followed up by the hospitals. Kaplan-Meier method was used to estimate the rate of unfavorable outcomes to take into account the follow-up time of each patient. Univariate and multiple Cox regression analyses were conducted to examine the associations between unfavorable outcomes and clinicopathological characteristics.

Results: Among 204 women included in the data analysis, the mean age was 54.4 ± 10.9 years. The majority of patients were diagnosed with early-stage (76.5%) or locally advanced (22.5%) breast cancer. The 5-year rate of unfavorable outcomes was 12.8%, and the 8-year rate was 31.7%. Patients with advanced stages had a higher risk of unfavorable outcomes compared to those with early stages (IA, IIA, T2N1). Patients with lymph node metastases and those with triple-negative molecular classification had significantly higher rates of unfavorable outcomes.

Conclusion: Although Vietnamese women with breast cancer have a relatively low rate of unfavorable outcomes compared to other countries, findings from this study emphasize the importance of early detection and underscore the need for targeted interventions for patients with advanced stages, lymph node metastases, and triple-negative breast cancer to optimize their treatment, outcomes, and overall prognosis.

Introduction: Globally, breast cancer affects 2.5 million people annually. Younger women with advanced-stage cancers had a lower survival rate, but early detection enhanced survival chances by 27 to 47%. Breast self-examination (BSE) has led to early detection and higher rates of benign biopsies. Studies evaluating the psychosocial impact of BSE are few in India which has been attempted in the present study.

Methods: The community-based descriptive cross-sectional study was conducted among rural women aged 30 years and above, who have done BSE at least once without present or prior breast abnormalities in the field practice area of Model Rural Health Research Unit, Tirunelveli. The research questionnaire was developed based on the findings of focus group discussion (FGD) on the same objective in the study area.

Results: Among 379 participants, 146 (38.5%) felt confident in their BSE knowledge, 28.2% (n=107) and 5.5% (n=21) of the respondents experienced anxiety and depression while practising BSE, respectively. There is a significant difference between the mean anxiety levels (p-value=0.002) and depression (p-value=0.013) of individuals who have detected anomalies during BSE and those who have not.

Conclusion: Regular counselling has to improve knowledge about BSE, like the timing and method of examination, and decreases the anxiety and depression level.

Background: Mammogram screening (MS) is the gold-standard method for early detection of breast cancer (BC), and its use has been proven to minimize BC-related deaths and reduce treatment costs. However, recent epidemiological surveys have reported that rates of mammogram uptake by the Saudi female population are low. Here, we assessed the knowledge of BC and perceived barriers to MS uptake among pre-eligible northern Saudi women.

Participants and methods: We administered a standard and validated Arabic questionnaire to 400 women aged 40-69 years. SPSS version 21.0 (IBM Corporation, Armonk, NY, USA) was used for data analysis. We applied logistic regression analysis to find the factors associated with participants' knowledge of BC and MS. Spearman correlation test was applied to find the correlation between knowledge and barrier scores.

Results: The study participants reported that smoking habits (61.3%) and unhealthy food habits (57.8%) were the most common risk factors for BC. Of the studied participants, 56.3% had low or medium degrees of knowledge about BC risk factors and MS. The degree of knowledge was significantly associated with education level (adjusted odds ratio [aOR], 2.35; 95% confidence interval [CI]. = 1.61-3.13; P = 0.008) and a family history of BC (aOR, 3.66; 95% CI, 1.94-5.49; P < 0.001). Fear of a BC diagnosis (50.8%) and concerns regarding test procedures were the most common barriers to MS uptake. We also found a negative correlation between participants' knowledge and perceived barriers to MS (rho = -0.389, P < 0.001).

Conclusion: We recommend that concerned authorities offer women multiple health education sessions covering BC risk factors and the necessity for pre-eligible women to undergo MS spaced at regular intervals at different facilities. Furthermore, a multicentric mixed-methods survey is warranted to find the qualitative aspects of barriers to MS.

Purpose: Granzyme A (GZMA) is a potential prognostic target for various cancer types. However, its therapeutic significance in breast cancer with immune infiltration remains controversial. We analyzed GZMA expression and its prognostic value in breast cancer with immune cell infiltration.

Patients and methods: Data was obtained from patients with breast cancer registered at The Cancer Genome Atlas. A correlation was performed between GZMA expression and patient's clinicopathological features such as age, pathologic stage, metastasis stage, overall survival (OS), disease-specific survival (DSS), and progress free interval (PFI). Kaplan-Meier analyses and Cox proportional hazard regression model were used to examine the predictive significance of GZMA expression for breast cancer. The co-expression pattern of GZMA was assessed by the LinkedOmics web portal. The relationship between GZMA expression and immune cells was analyzed using the TIMER database. The correlation between GZMA and lymphocytes and immunomodulators was established with the TISIDB database.

Results: There was a lower GZMA expression in breast cancer tissue than in normal tissue. Interestingly, GZMA expression was associated with age, pathologic stage, and the Tumour, Node, and Metastasis stage. Overexpression of GZMA was also associated with better OS, DSS, and PFI. Based on the Cox regression analysis, GZMA was identified as an independent favorable prognostic factor for breast cancer. Our findings demonstrated a strong association between GZMA and T-cell checkpoints (PD-1, PD-L1, and cytotoxic T lymphocyte-associated antigen (CTLA-4)) in breast cancer. Moreover, we evaluated the interactions between GZMA expression and markers of dendritic and CD8+ T cells using quantitative immunofluorescence. We discovered that increased infiltration of dendritic and CD8+ T cells was associated with GZMA expression in breast cancer.

Conclusion: GZMA expression is associated with a favorable prognosis in breast cancer and is significantly correlated with immune cell infiltration. GZMA may be considered a promising therapeutic target for patients with breast cancer.

Objective: To explore the validation of a disease-free survival (DFS) model for predicting disease progression based on the combination of ubiquitin-conjugating enzyme E2 C (UBE2C) levels and clinical indicators in breast cancer patients.

Methods: We enrolled 121 patients with breast cancer, collected their baseline characteristics and follow-up data, and analyzed the UBE2C levels in tumor tissues. We studied the relationship between UBE2C expression in tumor tissues and disease progression events of patients. We used the Kaplan-Meier method for identifying the disease-free survival rate of patients, and the multivariate Cox regression analysis to study the risk factors affecting the prognosis of patients. We sought to develop and validate a model for predicting disease progression.

Results: We found that the level of expression of UBE2C could effectively distinguish the prognosis of patients. In the Receiver Operating Characteristic (ROC) curve analysis, the Area under the ROC Curve (AUC) = 0.826 (0.714-0.938) indicating that high levels of UBE2C was a high-risk factor for poor prognosis. After evaluating different models using the ROC curve, Concordance index (C-index), calibration curve, Net Reclassification Index (NRI), Integrated Discrimination Improvement Index (IDI), and other methods, we finally developed a model for the expression of Tumor-Node (TN) staging using Ki-67 and UBE2C, which had an AUC=0.870, 95% CI of 0.786-0.953. The traditional TN model had an AUC=0.717, and 95% CI of 0.581-0.853. Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) analysis indicated that the model had good clinical benefits and it was relatively simple to use.

Conclusion: We found that high levels of UBE2C was a high-risk factor for poor prognosis. The use of UBE2C in addition to other breast cancer-related indicators effectively predicted the possible disease progression, thus providing a reliable basis for clinical decision-making.

Purpose: This study aimed to compare the clinical behavior, clinicopathological and sociodemographic characteristics of patients with early-stage triple-negative breast cancer (TNBC) who belong to the HER2-low and HER2-zero subgroups.

Patients and methods: This study involved a thorough search in the internal database of a single Brazilian institution to identify women with TNBC who underwent neoadjuvant chemotherapy (NACT) followed by curative surgery within the period from January 2010 to December 2014. HER2 analysis through immunohistochemistry (IHC) and, if required, amplification by in situ hybridization, was conducted using core biopsy samples. The study assesses outcomes of residual cancer burden (RCB), event-free survival (EFS), and overall survival (OS).

Results: A total of 170 cases were analyzed, with a mean age of 51.4 years (standard deviation, SD 11.2). The HER2 status was categorized as IHC 0, 1+, or 2+ in 80 (47.1%), 73 (42.9%), and 17 (10%) patients, respectively. No significant differences were observed in the prevalence of clinical pathological characteristics among the subgroups. The absence of significant results for clinicopathological and demographic features hindered the multivariate analysis of HER2 subgroups. Similarly, no significant differences were found in the RCB, EFS, and OS outcomes between HER2 subgroups.

Conclusion: The findings of this study suggest that, in early-stage TNBC, the clinical behavior and survival outcomes of the HER2-low subgroup may not differ significantly from those of the HER2-zero subgroup.

Breast cancer has become the most common malignant tumor worldwide. Triple-negative breast cancer (TNBC) is a type of breast cancer that is negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Compared with other molecular subtypes of breast cancer, TNBC is the most aggressive and highly heterogeneous. TNBC is insensitive to endocrine and anti-HER2 therapy, and chemotherapy is currently the main systemic treatment. With the continuous development of detection techniques and deepening research on TNBC molecular subtypes, drugs targeting immune checkpoints and different targets have emerged, such as atezolizumab, pembrolizumab, poly (ADP-ribose) polymerase (PARP) inhibitors, trophoblast cell-surface antigen 2 (TROP-2), and antibody-drug conjugates. These therapies provide new hope for TNBC treatment. Based on the analysis and classification of TNBC, this article summarizes the immunotherapy, targeted therapy, and new treatment combinations, providing references for the precise treatment of TNBC in the future.

Background: We have reported that serum progranulin (PGRN) levels are clinically significant in predicting recurrence in patients with HR-positive breast cancer. The aim of the present study was to examine whether PGRN levels might be associated with breast cancer mortality.

Methods: This was a cohort study of 695 newly diagnosed breast cancer patients who underwent curative surgery between 2001 and 2004. The relationship between breast cancer mortality and pre-operative serum PGRN levels in these patients with a median follow-up of 12.7 years was evaluated until May 2020.

Results: A total of 118 (17%) deaths were identified in the cohort. According to the HR status, (10, 15, and 20)-year overall survival (OS) rates were (91.4, 81.1, and 75.9) % for HR-positive patients, and (76.5, 74.2, and 69.8) % for HR-negative patients, respectively (p = 0.003). Higher levels of PGRN were significantly associated with poor OS in the HR-positive group (p for trend = 0.001). In particular, hazard ratios for PGRN quartiles suggested a dose-response relationship, with the highest quartile having the worst OS in the HR-positive group (highest vs lowest: 15-year OS, (68.3 vs 90.0) %; 20-year OS, (62.3 vs 84.8) %, even after adjusting for age, tumor stage, and metabolic confounders.

Conclusion: Pre-operative serum PGRN levels had clinical significance for predicting cancer mortality in breast cancer patients independent of tumor stage and metabolic parameters, especially in HR-positive tumors.