Growth Factor Receptor 2-positive Patients Research Articles

ASSOCIATION BETWEEN TWENTY SERUM MIRNAS AND CLINICOPATHOLOGICAL VARIABLES IN PATIENTS WITH BREAST CANCER

Determining that miRNAs play a role in breast cancer pathogenesis suggests that it may be useful in the diagnosis and treatment of breast cancer. In this study, 39 patients with invasive breast cancer were diagnosed with serum levels of 20 miRNAs(miR-105, miR-21, miR-141, miR-200a, miR-200b, miR-200c, miR-203, miR-210, miR-375, miR-34a, miR-133a, miR-155, miR-139-5p, miR-143, miR-145, miR-365, miR-299-5p, miR-411, miR-452, miR-17) were analyzed during diagnosis and after treatment. In the analysis results, it is detected that serum levels of miR-200c(p=0.030), miR-375(p=0.045), miR-34a(p=0.042) were significantly higher in the local advanced/metastatic group. Serum level of miR-141(p=0.062) was lower in patients with positive lymph node involvement, whereas miR-133a(p=0.037) levels were higher in the same patient group. MiR-105(p=0.015), miR-203(p=0.015), miR-375(p=0.033), miR-145(p=0.025) serum levels were significantly higher in the progesterone receptor negative group, likewise miR-105(p=0.053) levels were high in the estrogen receptor negative patient group. The high levels of miR-375 and miR-133a were noticeable in human epidermal growth factor receptor-2 positive patients(p=0.037 and p=0.014, respectively). MiR-143(p=0.009) and miR-145(p=0.017) levels were observed to be higher in the patient group with a ki-67 index>20%. It was found that 2 miRNAs(miR-133a(p=0.018) and miR-139-5p(p=0.004)) were significantly higher in patients in the luminal B group, which were separated by molecular subgroups. Nine of miRNAs that evaluated(miR-105(p=0.0001), miR-21(p=0.001), miR-141(p=0.041), miR-200a(p=0.003), miR-200b(p=0.0001), miR-200c(p=0.0001), miR-203(p=0.0001), miR-34a(p=0.0001), miR-452(p=0.018)) significantly increased after treatment and 5 of the miRNAs(miR-155(p=0.0001), miR-143(p=0.0001), miR-145(p=0.0001), miR-365(p=0.0001), miR-299-5p(p=0.0001)) were significantly reduced after treatment. We think that miRNAs may help in evaluating the follow-up and prognosis of invasive breast cancer.

Meme kanserinde strain elastografi ile histopatolojik parametreler arasındaki ilişki

Purpose: This study aimed to evaluate the relationship between strain elastography and immunohistochemical markers, the histologic grade, and molecular subtyping in invasive breast cancer.
 Materials and Methods: The relationships between the elastography index values and progesterone receptor, estrogen receptor, human epidermal growth factor receptor 2, Ki-67, the histologic grade, and molecular subtype in 171 patients who had not received neoadjuvant treatment and underwent breast-conserving surgery were evaluated. Strain elastosonography were used to evaluate elastography index. 
 Results: The mean patient age was 46.871 ± 11.949 years. There were 135, 129, and 90 estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor receptor 2-positive patients, respectively. Forty-seven patients had the worst histological grade. Based on molecular subtyping, human epidermal growth factor receptor 2-positive, luminal A, luminal B, and triple-negative classifications were made for 25 (14.5%), 29 (17.0%), 109 (63.7%), and 8 (4.7%) cases, respectively. There was no statistically significant correlation between the elastography index values and estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki-67, histologic grade, or molecular subtype among these breast resection cases.
 Conclusion: The elastography index value was insufficient to predict the specified histopathological parameters.

Long-term follow-up results of intensity-modulated radiotherapy with helicoïdal tomotherapy for non-metastatic breast cancers: Single centre experience

PurposeIntensity-modulated radiotherapy with helical Tomotherapy is a novel radiation therapy technique, which may be beneficial in several features compared to traditional methods. Our aim was to evaluate the local control, overall survival, progression free survival and adverse events in breast cancer patients treated with this new technique. Material and methodsThis is retrospective analysis of patients irradiated with intensity-modulated radiotherapy with helical Tomotherapy. Overall survival and progression free survival curves were plotted with Kaplan-Meier method. We also analysed the overall survival and progression-free survival data by molecular subgroups. Long-term toxicity including skin, cardiac and pulmonary complications were also evaluated. Multivariant logistic regression analysis was performed to determine the predictors of the side effects. ResultsBetween 2009–2015, 179 consecutive patients with 194 treated breasts were irradiated with intensity-modulated radiotherapy with helical Tomotherapy. The median follow-up were 65 months. The overall survival rate was 89.2% (95% confidence interval [95CI]: 83.5–95.4%), while disease-free survival rate was 85.4% (95CI: 80.2–91%). The Human epidermal growth factor receptor 2-positive patients had the best 5-year overall survival data of 95% (95CI: 85.9–100%). Long-term skin toxicity was the most common, seen in a total of 20.7% of the patients. ConclusionIntensity-modulated radiotherapy with helical Tomotherapy could be safely used for adjuvant breast cancer irradiation in patients with complex anatomy and provides favourable long-term prognosis with acceptable late toxicity.

Impact of public health insurance coverage of novel anticancer medication on medical expenditure and patient affordability in a provincial medical centre of China: a propensity score-matching analysis with the quasi-experimental design

IntroductionLittle is known about the impact of the government’s efforts in having novel anticancer medicines covered by the public health insurance system in China. This study targeted the above policy...

Long-term heart-specific mortality among 347476 breast cancer patients treated with radiotherapy or chemotherapy: a registry-based cohort study.

Breast cancer survival has improved throughout the last decades, but treatment-induced cardiotoxicity remains a major concern. This study aimed to investigate competing causes of death and prognostic factors within a large cohort of breast cancer patients and to describe the heart-specific mortality in relation to the general population. In this registry-based cohort study, women diagnosed with breast cancer between 2000 and 2011, who were treated with radiotherapy or chemotherapy and followed until 2014, were identified from the Surveillance, Epidemiology, and End Results-18 (SEER-18) database. Cumulative mortality functions were computed. To investigate heart-specific mortality relative to the general population, long-term (≥10 years) standardized mortality ratios (SMRs) were calculated. Prognostic factors for heart-specific mortality were assessed by calculating cause-specific hazard ratios (HRcs) with corresponding 95% confidence intervals using the Cox proportional hazards regression. Subgroup analysis on intermediate-term mortality according to molecular subtypes, for which information was available since 2010, was performed. In total, 347476 breast cancer patients were eligible to be included in the study. Among all possible competing causes of death, breast cancer accounted for the highest cumulative mortality. Compared with the general population, heart-specific mortality of breast cancer patients treated with radiotherapy or chemotherapy was lower [SMRoverall 0.84 (0.79-0.90)]. In subgroup analysis, human epidermal growth factor receptor 2 (HER2)-positive subtype was not associated with increased heart-specific mortality relative to HER2-negative patients [HRcs 0.96 (0.70-1.32)]. Heart-specific mortality among breast cancer survivors is not increased compared with the general population. Human epidermal growth factor receptor 2-positive patients do not have increased heart-specific mortality compared to HER2-negative patients.

Multigene Signature Panels and Breast Cancer Therapy: Patterns of Use and Impact on Clinical Decision Making

A growing body of evidence supports the use of multigene signature panels (MSPs) in predicting recurrence risk in patients with invasive breast cancer. This study aimed to evaluate trends in MSP use over time and the effect of MSPs on administration of postoperative chemotherapy. The National Cancer Database was queried for all women with invasive breast cancer who underwent resection between 2011 and 2014 and had information about performance of an MSP, hormone receptor status, and receipt of chemotherapy. Multigene signature panel use over time was evaluated, and patterns of use of Oncotype DX (ODX) and MammaPrint (MP) were compared. In a total of 476,128 patients, an MSP was obtained in 153,782 (30.2%). Multigene signature panel use increased over time and was associated with a decreased rate of chemotherapy administration (24.6% MSP vs 37.2% no MSP; p < 0.001). Oncotype DX remained the most common MSP used throughout the study period. Oncotype DX was used more commonly in stage I disease than MP, and MP was used more commonly in stage II and III disease. MammaPrint was more commonly used in hormone receptor-negative patients, human epidermal growth factor receptor 2-positive patients, and patients with positive lymph nodes. Postoperative chemotherapy was administered to a higher proportion of patients assessed with MP than with ODX (41.3% vs 23.4%, respectively; p < 0.001). Use of MSPs among patients with breast cancer has increased over time and is associated with a decreased use of adjuvant chemotherapy. Oncotype DX continues to be the most widely used MSP, although MP use has increased over time. Future studies are warranted to determine the optimal use of these MSPs in risk assessment and postoperative decision making.

Benefits of antihypertensive medications for anthracycline- and trastuzumab-induced cardiotoxicity in patients with breast cancer: Insights from recent clinical trials

Advances in oncologic therapies have allowed many patients with breast cancer to achieve better outcomes and longer survival. However, this progress has been tempered by cardiotoxicity, associated with anticancer therapies, ranging from subclinical abnormalities to irreversible life-threatening complications, such as congestive heart failure or cardiomyopathy. In particular, exposure to chemotherapy (CHT), including anthracyclines and trastuzumab, can lead to cardiac dysfunction with short- or long-term consequences, among patients with breast cancer. The aim of this study is to highlight the potential role of commonly used cardiac medications in the prevention of anthracycline- and trastuzumab-mediated cardiotoxicity, in women with breast cancer, based on evidence from recent clinical trials. This overview is focused on the use of antihypertensive medications, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, outlining their cardioprotective effects in this patient population. In addition, the importance of biomarkers and modern imaging tests, as potential tools for detection and monitoring of cardiac dysfunction, induced by CHT, as well as some practical preventive and therapeutic strategies for cardio-oncology treatment teams, involved in the management of a growing number of women with breast cancer have been outlined. The content of this overview is based on a literature search of PubMed, within the last 5 years, mostly in relevance to the human epidermal growth factor receptor 2-positive patients with breast cancer, treated with anthracycline or trastuzumab therapy (in addition to surgery and/or radiation therapy [RT] regimen).

Serum HER2 levels and HER2 status in tumor cells in advanced gastric cancer patients.

Increased serum human epidermal growth factor receptor 2 levels have been found in metastatic breast cancer patients and are correlated with human epidermal growth factor receptor 2 overexpression in tumor cells. However, the prevalence of serum human epidermal growth factor receptor 2 in gastric cancer patients has not been elucidated. We retrospectively analyzed formalin-fixed paraffin-embedded tumor tissues and serum samples from 96 advanced gastric cancer patients. Human epidermal growth factor receptor 2 expression and gene amplification in tumor cells were determined by immunohistochemistry and fluorescence in situ hybridization. Serum human epidermal growth factor receptor 2 levels were measured using a chemiluminescent immunoassay. Human epidermal growth factor receptor 2 positivity in tumor cells was defined as immunohistochemistry 2+ with fluorescence in situ hybridization positive or immunohistochemistry 3+ with any fluorescence in situ hybridization results. All tissue samples and serum samples were successfully measured. Nineteen patients (20%) were human epidermal growth factor receptor 2-positive in tumor cells. The median serum human epidermal growth factor receptor 2 level was 9.3 ng/ml (range, 5.0-332.4 ng/ml), and serum human epidermal growth factor receptor 2 levels were significantly separated according to human epidermal growth factor receptor 2 status in tumor cells (P < 0.0001, Wilcoxon's rank sum test); median serum human epidermal growth factor receptor 2 levels in human epidermal growth factor receptor 2-negative patients and -positive patients were 8.9 (range, 5.0-20.5) and 24.0 (range, 9.7-332.4), respectively. There were 15 serum human epidermal growth factor receptor 2-positive patients (16%) using a cutoff value of 15 ng/ml. The sensitivity and the specificity of serum human epidermal growth factor receptor 2 with respect to human epidermal growth factor receptor 2 positivity in tumor cells were 53 and 94%, respectively. Serum human epidermal growth factor receptor 2 measurements cannot be substituted for tissue human epidermal growth factor receptor 2 diagnosis in advanced gastric cancer patients. However, serum human epidermal growth factor receptor 2 levels are associated with human epidermal growth factor receptor 2 overexpression in tumor cells. Further investigations of clinical significance of serum human epidermal growth factor receptor 2 as a predictive marker and a therapy-monitoring marker are warranted.

Targeting receptor tyrosine kinases in gastric cancer.

Molecularly targeted therapeutic agents are constantly being developed and have been shown to be effective in various clinical trials. One group of representative targeted oncogenic kinases, the receptor tyrosine kinases (RTKs), has been associated with gastric cancer development. Trastuzumab, an inhibitor of ERBB2, has been approved for the treatment of gastric cancer, although other receptor tyrosine kinases, such as epidermal growth factor receptor, vascular endothelial growth factor, platelet-derived growth factor receptor, c-Met, IGF-1R and fibroblast growth factor receptor 2, are also activated in gastric cancer. The promising results of the trastuzumab clinical trial for gastric cancer resulted in the approval of trastuzumab-based therapy as a first-line treatment for human epidermal growth factor receptor 2-positive patients. On the other hand, the trial examining bevacizumab in combination with conventional chemotherapy did not meet its primary goal of increasing the overall survival time of gastric cancer patients; however, a significantly higher response rate and a longer progression-free survival were observed in the bevacizumab arm of the trial. Other clinical trials, especially phase III trials that have tested drugs targeting RTKs, such as cetuximab, panitumumab, gefitinib, erlotinib, figitumumab, sorafenib, sunitinib and lapatinib, have shown that these drugs have modest effects against gastric cancer. This review summarizes the recent results from the clinical trials of molecularly targeted drugs and suggests that further improvements in the treatment of advanced gastric cancer can be achieved through the combination of conventional drugs with the new molecularly targeted therapies.

Clinical Features and Survival Analysis of T1mic, a, bN0M0 Breast Cancer

To analyze the clinicopathological features and prognosis of T1mic, a, bN0M0 breast cancer. The clinical data and survival status of 4487 cases of operable breast cancer treated in our hospital from 2002 to 2005 were collected, including 372 cases with T1mic, a, bN0M0 breast cancers. These patients were divided into four subtypes: Luminal A, Luminal B, triple-negative and human epidermal growth factor receptor 2-positive. Disease-free survival and risk factors for recurrence were identified. We identified 372 eligible patients. The median follow-up was 78 months (range: 5-106 months). Univariate analysis showed age, adjuvant endocrine therapy, hormonal receptor and human epidermal growth factor receptor 2 were prognostic factors. Multivariate analysis showed that hormonal receptor and human epidermal growth factor receptor 2 were prognostic factors. In the hormonal receptor-positive group, human epidermal growth factor receptor 2-positive patients (Luminal B) had a four times higher recurrence risk than human epidermal growth factor receptor 2 negative (Luminal A) patients. However, there was no statistically significant difference between hormonal receptor-negative groups (triple-negative and human epidermal growth factor receptor 2-positive). Hormonal receptor and human epidermal growth factor receptor 2 were independent factors of 5-year disease-free survival for patients with T1mic, a, bN0M0 breast cancer. The Luminal B group had a worse prognosis than the Luminal A group, but there was no statistically significant difference between triple-negative and human epidermal growth factor receptor 2-positive groups.

Human epidermal growth factor receptor 2 testing in breast cancer

Testing for human epidermal growth factor receptor-2 in breast cancer at the time of primary diagnosis is now the standard of care. Positivity for epidermal growth factor receptor-2 in breast cancer is a prognostic factor regarding tumor aggressiveness and a predictive factor for response to Herceptin. Accurate assessment is essential to ensure that all patients who may benefit from Herceptin are correctly identified. The principal testing methods used for determination of epidermal growth factor receptor-2 status are immunohistochemistry for protein overexpression and in situ hybridization using either fluorescence or a chromogen. Immunohistochemical testing method allows identification of epidermal growth factor receptor-2 positive patients (3+) who may benefit from Herceptin therapy, whereas negative patients (0/1+) can be excluded. A proportion of specimens defined as equivocal by immunohistochemistry (2+) must be retested by in situ hybridization to determine their status. Chromogen in situ hybridization is a method for determination of gene amplification using a peroxidase-based chromogenic reaction, which can be viewed using a conventional bright field microscope and it determines the actual degree of gene amplification. Various factors can affect the results achieved with these assays, including the assay antibody/probe, the methodology and the experience of personnel. Many countries implemented national testing guidelines in an attempt to standardize testing procedures and make results more accurate. The key point underlined by this review is that whatever method is used to test HER2 status, the technology must be validated first, and there must be regular internal and external quality assurance procedures.