Epirubicin and docetaxel with or without capecitabine as neoadjuvant treatment for early breast cancer: final results of a randomized phase III study (ABCSG-24)

BackgroundThis randomized phase III trial compared pathologic complete response (pCR) rates of early breast cancer (EBC) following neoadjuvant epirubicin–docetaxel (ED) ± capecitabine (C), and evaluated the addition of trastuzumab in HER2-positive tumors.Patients and methodsPatients with invasive breast cancer (except T4d) were randomly assigned to receive six 3-weekly cycles of ED (both 75 mg/m²) ± C (1000 mg/m², twice daily, days 1–14). Patients with HER2-positive disease were further randomized to receive trastuzumab (8 mg/kg, then 6 mg/kg every 3 weeks) or not. Primary end point: pCR rate at the time of surgery.ResultsFive hundred thirty-six patients were randomized to ED (n = 266) or EDC (n = 270); 93 patients were further randomized to trastuzumab (n = 44) or not (n = 49). pCR rate was significantly increased with EDC (23.0% versus 15.4% ED, P = 0.027), and nonsignificantly further increased with trastuzumab (38.6% EDC versus 26.5% ED, P = 0.212). Rates of axillary node involvement at surgery and breast conservation were improved with EDC versus ED, but not significantly; the addition of trastuzumab had no further impact. Hormone receptor status, tumor size, grade, and C (all P ≤ 0.035) were independent prognostic factors for pCR. Trastuzumab added to ED ± C significantly increased the number of serious adverse events (35 versus 18; P = 0.020), mainly due to infusion-related reactions.ConclusionThese findings show that the integration of C into a neoadjuvant taxane-/anthracycline-based regimen is a feasible, safe, and effective treatment option, with incorporation of trastuzumab in HER2-positive disease.Clinical trial numberNCT00309556, www.clinicaltrials.gov.     

Prospective cost-effectiveness analysis of genomic profiling in breast cancer

BackgroundThe cost-effectiveness of the 70-gene signature (70-GS) (MammaPrint®) has earlier been estimated using retrospective validation data. Based on the prospective 5-year survival data of the microarRAy-prognoSTics-in-breast-cancER (RASTER) study, the aim here was to evaluate the cost-effectiveness reflecting the actual use in clinical practice, including reality-based compliance rates.MethodsCosts and outcomes (quality-adjusted-life-years (QALYs)) were calculated in node-negative (N?) patients included in the RASTER study (n = 427). Sensitivity and specificity of the 70-gene and Adjuvant! Online (AO) were based on 5-year distant-disease-free survival (DDFS). Subgroup analyses were performed for two groups for whom benefit of the 70-gene had earlier been reported: (1) ductal, oestrogen receptor-positive (ER+), tumour diameter 10–30 mm, grade II, age 40–70; (2) ductal, oestrogen receptor-positive, tumour diameter 5–30 mm, grade II/III and age 40–70.ResultsBased on 5-year survival data, the cost-effectiveness of the 70-gene signature versus AO was prospectively confirmed. The total health care costs per patient were €26,786 for the 70-gene and €29,187 for AO. The quality adjusted life years yielded 12.49 and 11.88, respectively. The subgroups retrieved slightly higher life gains and higher costs, but all resulted finally in a favourable position for the 70-gene signature.ConclusionsThe use of the 70-gene signature, as judged appropriate by doctors and patients and supported by a low risk 70-gene signature as an oncological safe choice, was also found to be cost-effective.     

A possible significant role of zinc and GPR39 zinc sensing receptor in Alzheimer disease and epilepsy

Zinc the essential trace element, plays a significant role in the brain development and in the proper brain functions at every stage of life. Misbalance of zinc (Zn²⁺) ions in the central nervous system is involved in the pathogenesis of numerous neurodegenerative disorders such as Alzheimer's disease, Depression, and Epilepsy. In brain, Zn²⁺ has been identified as a ligand, capable of activating and inhibiting the receptors including the NMDA-type glutamate receptors (NMDARs), GABA_A receptors, nicotinic acetylcholine receptors (nAChRs), glycine receptors (glyR) and serotonin receptors (5-HT3). Recently GPR39 has been identified as a zinc-specific receptor, widely expressed in brain tissues including the frontal cortex, amygdala, and hippocampus. GPR39, when binding with Zn²⁺ has shown promising therapeutic potentials. This review presents current knowledge regarding the role of GPR39 zinc sensing receptor in brain, with a focus on Alzheimer’s disease and Epilepsy. Although the results are encouraging, further research is needed to clarify zinc and GPR39 role in the treatment of Alzheimer's disease and Epilepsy.     

Lipid-rich Carcinoma of the Breast: a Case Report

Lipid-rich carcinoma is a rare variant and accounts for < 2% of all breast cancer diagnoses. We report a case occurring in a 53-year-old female. The patient presented with a painless, right breast mass. Clinical examination and mammography suggested malignancy. Subsequent modified radical mastectomy revealed the diagnosis of lipid-rich carcinoma. The morphological features, differential diagnosis and treatment along with a brief review of the literature are discussed in this article.

Lipid-rich carcinoma (L-RC) is a very rare variant of breast carcinomas with an aggressive clinical course and poor prognosis. It presents only 1% to 2% of all breast cases (1,2). It is classified as a specific variety of mammary carcinoma because the tumour cells possess abundant vacuolated cytoplasm which is strongly positive when stained for neutral fat. Aboumrad (2) first described it in 1963 as lipid-secreting carcinoma. However, Ramos and Taylor (1) renamed it as lipid-rich breast carcinoma. In China, the first case was reported in 1984 (3). Herein, we report a case of lipid-rich carcinoma occurring in a 53-year-old female patient, and the literature is reviewed.     

Pathological Controversies in Breast Cancer: Classification of Ductal Carcinoma In Situ,Sentinel Lymph Nodes and Low Volume Metastatic Disease and Reporting of Neoadjuvant Chemotherapy Specimens

The pathological classification of breast cancer is constantly being updated to reflect the advances in our clinical and biological understanding of the disease. This overview examines new insights into the classification and molecular biology of ductal carcinoma in situ, the pathological handling of sentinel lymph node biopsies and the identification of low volume disease (micrometastases and isolated tumour cells) and the handling and reporting of specimens after neoadjuvant therapy. The molecular subtypes of invasive breast cancer are also represented in ductal carcinoma in situ. It is hoped that alongside traditional histological features, such as cytological grade and the presence of necrosis, this will lead to better classification systems with improved prediction of clinical behaviour, in particular the risk of progression to invasive cancer, and enable more targeted management. Sentinel lymph node biopsy is now the standard of care for early stage breast cancer in clinically node-negative patients. However, the handling and reporting of these specimens remains controversial, largely related to the uncertainties regarding the clinical significance of micrometastases and isolated tumour cells. The increasing use of neoadjuvant therapies has introduced challenges for the pathologist in the handling and interpretation of these specimens. Grading the tumour response, particularly the identification of a complete pathological response, is prognostically important. However, there is still marked variability in reporting these specimens in routine practice, and consensus guidelines for the histopathology reporting of breast cancers after neoadjuvant chemotherapy based on robust, validated evidence are presently lacking.     

综合干预联合认知行为疗法对甲状腺癌患者术后治疗期间依从性的影响

目的 手术是治疗甲状腺癌的主要方法之一,能有效改善预后,但是也会给患者带来极大的负面影响,为此需要加强术后治疗与护理;认知行为疗法是符合现代理念的护理方法,可以通过改变患者的理念与行为而达到促进健康的目的。本研究探讨综合干预联合认知行为疗法对甲状腺癌患者术后治疗期间依从性的影响。 方法 选择2011年2月—2015年2月在哈尔滨医科大学附属第一医院诊治的甲状腺癌患者130例,根据随机数字表法分为治疗组与对照组各65例,所有患者都给予放射性核素131I口服治疗,对照组在治疗期间给予常规综合干预护理,在此基础上治疗组加用积极的认知行为疗法干预,护理观察周期为3个月。 结果 2组护理后的血清总三碘甲腺原氨酸(TT3)与总甲状腺素(TT4)值明显高于护理前(P<0.05),同时护理后治疗组的血清TT3与TT4值明显高于对照组(P<0.05)。治疗组护理期间的喉返神经损伤、低钙血症、甲状旁腺功能低下、切口感染等并发症发生情况明显少于对照组(P<0.05)。护理期间治疗组的依从性明显好于对照组(P<0.05)。护理后治疗组的躯体功能、生理职能、社会功能、情感职能、精神健康、躯体疼痛、总体健康、活力等评分明显高于对照组(P<0.05)。 结论 综合干预联合认知行为疗法在甲状腺癌患者术后的应用能有效提高依从性,促进机体甲状腺激素分泌的平衡,减少并发症的发生,从而提高患者的生活质量。