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Background
While human epidermal growth factor receptor 2 (HER2) overexpression is an adverse breast cancer prognostic factor, it is unclear whether there are differences in outcomes between types of local treatment in this population. This retrospective study examined locoregional recurrence and survival in women with node-negative, HER2+ breast cancer treated with breast-conserving therapy (BCT) versus mastectomy.Methods
Subjects were 748 patients with pT1–2, N0, M0 HER2+ breast cancer, treated with BCT (n = 422) or mastectomy (n = 326). Trastuzumab was used in 54 % of subjects. The 5-year Kaplan–Meier locoregional recurrence free survival (LRRFS), breast cancer specific survival (BCSS), and overall survival (OS) were compared between cohorts treated with BCT versus mastectomy. Subgroup analyses of LRR and survival were performed separately among patients treated with BCT or mastectomy to examine the effect of trastuzumab on outcomes in each group.Results
Median follow-up was 4.4 years. Patients treated with mastectomy had higher proportions of grade 3 histology (69 vs 60 %, p = 0.004) and lower rates of hormone therapy (51 vs 64 %, p < 0.001) and trastuzumab therapy (50 vs 57 %, p = 0.04). The 5-year outcomes in women treated with BCT compared with mastectomy were: LRRFS 98.0 versus 98.3 % (p = 0.88), BCSS 97.2 versus 96.1 % (p = 0.70), and OS 95.5 versus 93.4 % (p = 0.19). Trastuzumab was associated with similar LRRFS and improved OS in both local treatment groups.Conclusions
BCT is safe in the population of women with pT1–2, N0, HER2+ breast cancer, providing high rates of locoregional control and survival equivalent to mastectomy. Trastuzumab was associated with improved survival in both groups. 相似文献Purpose
To investigate whether delivery of a histone deacetylase inhibitor, vorinostat (VOR), by using solid lipid nanoparticles (SLNs) enhanced its bioavailability and effects on multidrug-resistant cancer cells.Methods
VOR-loaded SLNs (VOR-SLNs) were prepared by hot homogenization using an emulsification-sonication technique, and the formulation parameters were optimized. The cytotoxicity of the optimized formulation was evaluated in cancer cell lines (MCF-7, A549, and MDA-MB-231), and pharmacokinetic parameters were examined following oral and intravenous (IV) administration to rats.Results
VOR-SLNs were spherical, with a narrowly distributed average size of ~100 nm, and were physically stable for 3 months. Drug release showed a typical bi-phasic pattern in vitro, and was independent of pH. VOR-SLNs were more cytotoxic than the free drug in both sensitive (MCF-7 and A549) and resistant (MDA-MB-231) cancer cells. Importantly, SLN formulations showed prominent cytotoxicity in MDA-MB-231 cells at low doses, suggesting an ability to effectively counter the P-glycoprotein-related drug efflux pumps. Pharmacokinetic studies clearly demonstrated that VOR-SLNs markedly improved VOR plasma circulation time and decreased its elimination rate constant. The areas under the VOR concentration-time curve produced by oral and IV administration of VOR-SLNs were significantly greater than those produced by free drug administration. These in vivo results clearly highlighted the remarkable potential of SLNs to augment the bioavailability of VOR.Conclusions
VOR-SLNs successfully enhanced the oral bioavailability, circulation half-life, and chemotherapeutic potential of VOR. 相似文献Prenatal diagnosis of congenital heart disease (CHD) is continuously evolving with each passing decade. Early efforts in fetal cardiology focused on identifying CHD in mid-gestation and understanding of fetal circulation in pathologic conditions. Improving prenatal detection rates for CHD remains an ongoing challenge and increasingly the field of fetal cardiology is moving to not only diagnosing CHD prenatally but also assessing the impact of prenatal diagnosis of CHD outcomes. Future directions include earlier diagnosis of fetal CHD, improved diagnostic rates, widespread sonographer education, and a better understanding of antenatal factors that impact outcomes. Our goal in this review is to describe the past, present, and future of prenatal diagnosis of CHD.
Recent findingsThere has been a steady improvement in the prenatal diagnosis rate for CHD; however, there remains a significant variation between countries and within the USA. Prenatal diagnosis of CHD allows for counseling and delivery planning in those fetuses with critical CHD, thereby providing parents with resources and important tools while dealing with a challenging situation of carrying a child with heart disease and helping them with important decisions for their family and their future. There are several specific conditions which continue to pose a challenge from a diagnostic standpoint as they may appear mild at the time of initial diagnosis and may be missed but progress through the pregnancy and lead to significant CHD in the neonatal period.
SummaryIn summary, continued efforts aimed at collaborative research and education are needed in order to be able to improve CHD detection rates. We need to cautiously assess lesions that appear minor in mid-gestation but have the potential to progress in late gestation. Earlier detection of CHD by means of a transvaginal or a first-trimester fetal echocardiogram may further help families with delivery planning and decision-making.
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