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1.
Introduction: Collaborative interactions between several diverse biological processes govern the onset and progression of breast cancer. These processes include alterations in cellular metabolism, anti-tumor immune responses, DNA damage repair, proliferation, anti-apoptotic signals, autophagy, epithelial-mesenchymal transition, components of the non-coding genome or onco-mIRs, cancer stem cells and cellular invasiveness. The last two decades have revealed that each of these processes are also directly regulated by a component of the cell cycle apparatus, cyclin D1.

Area covered: The current review is provided to update recent developments in the clinical application of cyclin/CDK inhibitors to breast cancer with a focus on the anti-tumor immune response.

Expert opinion: The cyclin D1 gene encodes the regulatory subunit of a proline-directed serine-threonine kinase that phosphorylates several substrates. CDKs possess phosphorylation site selectivity, with the phosphate-acceptor residue preceding a proline. Several important proteins are substrates including all three retinoblastoma proteins, NRF1, GCN5, and FOXM1. Over 280 cyclin D3/CDK6 substrates have b\een identified. Given the diversity of substrates for cyclin/CDKs, and the altered thresholds for substrate phosphorylation that occurs during the cell cycle, it is exciting that small molecular inhibitors targeting cyclin D/CDK activity have encouraging results in specific tumors.  相似文献   

2.
《The ocular surface》2020,18(1):108-113
PurposeAromatase inhibitors (AIs) limit the synthesis of oestrogen in peripheral tissues thus lowering levels of oestrogen. The primary aim was to evaluate whether women treated with AIs have altered dry eye symptoms and signs. A sub-aim was to investigate whether symptoms of dry eye in postmenopausal women were associated with symptoms of non-eye pain, ocular pain and self-rated pain perception.MethodsThis cross-sectional, observational, single visit study recruited 56 postmenopausal women (mean age 64.1 + 7.9 years) and 52 undergoing AI treatment (mean age 66.6 + 9.0). Ocular symptoms (OSDI, MGD14) and pain questionnaires (PSQ, OPAS) were administered and signs of dry eye and meibomian gland dysfunction were evaluated.ResultsAlmost half of each group reported dry eye symptoms, defined as OSDI>12 (48% control, 46% AI). The PSQ score was significantly higher in the AI group (p = 0.04). Neither frequency or severity of dry eye (or MGD) symptoms scores were significantly different between groups. In the AI group, meibomian gland expressibility score was worse (p = 0.003); there were no differences in any other signs. Higher OSDI scores were associated with higher OPAS eye-pain scores (r = 0.49, p < 0.001), but not OPAS non-eye pain (r = 0.09, p = 0.35). Pain perception (PSQ) showed a moderate positive association with OPAS eye-pain (r = 0.30, p = 0.003).ConclusionsIn this study elevated ocular symptoms were observed in both the AI treated and the untreated groups, with no difference between the groups. Women undergoing AI treatment for early stage breast cancer had worse meibum expressibility score and increased pain perception compared to an untreated group of women.  相似文献   
3.
In this review we summarize the impact of the various modalities of breast cancer therapy coupled with intrinsic patient factors on incidence of subsequent treatment-induced myelodysplasia and acute myelogenous leukemia (t-MDS/AML). It is clear that risk is increased for patients treated with radiation and chemotherapy at younger ages. Radiation is associated with modest risk, whereas chemotherapy, particularly the combination of an alkylating agent and an anthracycline, carries higher risk and radiation and chemotherapy combined increase the risk markedly. Recently, treatment with granulocyte colony-stimulating factor (G-CSF), but not pegylated G-CSF, has been identified as a factor associated with increased t-MDS/AML risk. Two newly identified associations may link homologous DNA repair gene deficiency and poly (ADP-ribose) polymerase inhibitor treatment to increased t-MDS/AML risk. When predisposing factors, such as young age, are combined with an increasing number of potentially leukemogenic treatments that may not confer large risk singly, the risk of t-MDS/AML appears to increase. Patient and treatment factors combine to form a biological cascade that can trigger a myelodysplastic event. Patients with breast cancer are often exposed to many of these risk factors in the course of their treatment, and triple-negative patients, who are often younger and/or BRCA positive, are often exposed to all of them. It is important going forward to identify effective therapies without these adverse associated effects and choose existing therapies that minimize the risk of t-MDS/AML without sacrificing therapeutic gain.

Implications for Practice

Breast cancer is far more curable than in the past but requires multimodality treatment. Great care must be taken to use the least leukemogenic treatment programs that do not sacrifice efficacy. Elimination of radiation and anthracycline/alkylating agent regimens will be helpful where possible, particularly in younger patients and possibly those with homologous repair deficiency (HRD). Use of colony-stimulating factors should be limited to those who truly require them for safe chemotherapy administration. Further study of a possible leukemogenic association with HRD and the various forms of colony-stimulating factors is badly needed.
  相似文献   
4.
目的 解析真实世界中乳腺恶性肿瘤患者的人群特征、诊断特征、中西医用药特征,为乳腺癌的临床防治提供参考。方法 采集2002年2月至2015年5月全国60家三级甲等医 院信息系统(Hospital Information System,HIS)中,出院诊断为“乳腺癌”的患者用药信息,采用SAS9.3统计软件,对人口学信息、诊断信息、医嘱用药信息等进行描述性分析。结果 39798例乳腺癌患者,平均年龄(50.93者,平均年龄)岁;多以门诊入院,入院病情以“一般”为主;合并疾病主要为高血压,骨肿瘤,联用西药以抑制肿瘤细胞增殖、治疗并发症、缓解放化疗不良反应为主;中医辨证以痰瘀互结证,气阴两虚证,肝气淤滞证,脾气亏虚证型最为常见,临床清热解毒剂、益气扶正剂,活血化瘀剂应用较多。结论 乳腺癌中西医结合治疗,联用药物广泛,临床治疗基本符合临床指南。  相似文献   
5.
Introduction: Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30–100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride has been successfully evaluated.

Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.

Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available.  相似文献   

6.

Purpose

The purpose of this study was to evaluate trends in demographics and outcomes of pediatric breast cancer in a United States population-based cohort.

Methods

The Surveillance, Epidemiology, and End Results (SEER) database was utilized to identify all pediatric patients with malignant breast tumors between 1973 and 2014. Analysis was performed using Stata Statistical Software version 13.1. Associations between categorical variables were made using X2 test. Log-rank test was used for univariate survival analysis. Kaplan–Meier analysis investigated five-year survival rates across several variables. Adjusted analysis was performed using a Cox Proportional-Hazards regression.

Results

134 patients with breast malignancies were identified. Carcinoma was the most prevalent histology (48.5%), followed by fibroepithelial tumors (FETs) (35.1%), and sarcoma (14.2%). FETs were twice as common in black compared to nonblack patients (56.3% vs. 29.0%, p?<?0.01). Analyzing histology by stage revealed that 100% of FETs were early stage disease (p?<?0.0001). 46.7% of the tumors tested were ER/PR negative, more than twice as many compared to the published adult estimate of 20.0%. Unadjusted survival analysis revealed worse survival for patients with adenocarcinoma/sarcomas, advanced stage, and high grade disease, without a survival difference between races.

Conclusion

Breast cancer remains a rare malignancy among pediatric patients. Although black patients were found to have more noncarcinomatous tumors with less advanced disease, this did not confer a survival advantage.

Type of study

Retrospective cohort study.

Level of evidence

Level III.  相似文献   
7.

Background

Controversy continues as to whether single-incision laparoscopic cholecystectomy, with the somewhat larger incision at the umbilicus, may lead to a worse postoperative quality of life and more pain compared with the more classic 4-port laparoscopic cholecystectomy. The aim of this study was to compare single-incision and 4-port laparoscopic cholecystectomy from the perspective of quality of life.

Methods

This study was a multicenter, parallel-group, open-label, randomized clinical trial. A total of 120 patients who were scheduled to undergo elective cholecystectomy were randomly assigned 1:1 into the single-incision laparoscopic cholecystectomy or the 4-port laparoscopic cholecystectomy group and then assessed continuously for 2 weeks during the postoperative period. The primary outcome was quality of life, defined as the time to resume normal daily activities. Postoperative pain was also assessed. To explore the heterogeneity of treatment effects, we assessed the interactions of sex, age, and working status on recovery time.

Results

A total of 58 patients in the single-incision group and 53 in the 4-port group (n?=?111, 47 male, mean age 57 years) were analyzed. The mean time to resume daily activities was 10.2 days and 8.8 days, respectively, for single-incision and 4-port laparoscopic cholecystectomy (95% confidence interval –0.4 to 3.2, P?=?.12). Similarly, the time to relief from postoperative pain did not differ significantly between the groups. Statistically insignificant but qualitative interactions were noted; in the subgroups of women, full-time workers, and patients younger than 60 years, recovery tended to be slower after single-incision laparoscopic cholecystectomy.

Conclusion

Postoperative quality of life did not differ substantially between single-incision laparoscopic cholecystectomy and 4-port laparoscopic cholecystectomy. Patients younger than 60 years, women, and full-time workers tended to have a somewhat slower recovery after single-incision laparoscopic cholecystectomy.  相似文献   
8.
弹性绷带在乳腺癌术后应用的效果观察   总被引:1,自引:0,他引:1  
目的 观察弹性绷带在乳腺癌术后应用效果。方法  4 8例乳腺癌根治术后应用弹性绷带包扎为实验组 ,4 5例用普通宽绷带包扎为对照组。然后 ,对两组患者术后并发症进行观察。结果 实验组患者的并发症明显低于对照组 ,两组比较有显著性差异 ,P <0 .0 5。结论 应用弹性绷带包扎 ,能明显减少并发症的发生 ,促进切口愈合 ,使患者术后术侧上肢功能锻炼可以提早进行。  相似文献   
9.
分子靶向药物bevacizumab是针对血管内皮生长因子(VEGF)的重组人源化单克隆抗体,在多种恶性肿瘤的治疗中显示了临床效果。现就bevacizumab的作用机制及其在乳腺癌治疗中的临床研究进展作一综述。  相似文献   
10.
采用免疫组织化学S-P法检测52例手术切除乳腺癌组织c-erbB-2蛋白和HSV-1、HSV-2表达情况。结果发现癌组织中c-erbB-2阳性34例(65.4%);HSV-1阳性38例(73.1%);HSV-2阳性15例(28.8%)。癌旁组织32例,阳性分别为3例(9.4%);12例(37.5%);2例(6.3%)。乳腺癌中c-erbB-2阳性率明显高于癌旁组织。乳腺癌及癌旁的HSV-1阳性率明  相似文献   
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