Aspirin Treatment Effect and Association with PIK3CA Mutation in Breast Cancer: A Biomarker Analysis

BackgroundStudies suggest regular aspirin use decreases breast cancer (BRCA) risk, with high doses exerting an “anti-cancer” effect. Despite reports suggesting aspirin’s protective role in BRCA, no findings on aspirin dose association(s) with treatment outcomes have been reported, nor have any molecular subtype associations by which aspirin influences outcomes been elucidated. To interrogate aspirin’s effect and determine which populations may benefit from its use, we retrospectively explored data from 1227 patients with BRCA. In this population, 32 used high-dose aspirin (325 mg), 121 used low-dose aspirin (81 mg), and 1074 used no aspirin before and/or after diagnosis.Patients and MethodsSeveral association tests were performed to examine the correlations of clinical variables and PIK3CA mutations from 45 patients with BRCA who used 81 mg of aspirin daily. Kaplan-Meyer survival curves and the log-rank test were utilized to compare survival outcome differences for aspirin dose, usage history, and PIK3CA mutation status. Cox proportional hazards models were used to compute the multivariate hazard ratio (HR) for death.ResultsPatients who regularly used high-dose aspirin (325 mg) had better survival outcomes than those who used low-dose aspirin (81 mg) (HR, 0.094; 95% confidence interval [CI], 0.014-0.62; P = .014). Patients who used aspirin post-diagnosis only achieved significant benefits in overall survival (HR, 0.082; 95% CI, 0.023-0.3; P = 1.39E-04). Also, a subgroup of patients in the low-dose, long-term aspirin group with a PIK3CA mutation showed a small beneficial effect (HR, 0.37; 95% CI, 0.04-3.25; P = .37).ConclusionHigh-dose aspirin after diagnosis may confer BRCA treatment benefits. Future studies should assess the comprehensive mechanism of aspirin for the PIK3CA mutant subgroup in a large study.     

Radiotherapeutic Management of Osseous Metastases: A Survey of Current Patterns of Care

Purpose: Radiotherapy plays a major role in the management of painful osseous metastases. This survey was conducted to study the current approaches to this clinical problem in the radiotherapy community.Methods and Materials: A questionnaire was sent to 2500 members of the American Society for Therapeutic Radiology and Oncology. It consisted of 30 multiple-choice questions regarding four hypothetical clinical scenarios likely to be encountered in daily practice. Questions related to the technique of choice [local field (LF) vs. hemibody radiotherapy (HBI)], the use of systemic radionuclides (SR), fractionation schemes, dose, the integration of modalities, and the follow-up of these patients. The analysis is based on 817 (33%) responses received regarding 3268 cases.Results: Local field is the most common form of therapy. Overall, LF was used, alone or in combination with other forms of therapy, in 54% and 74% of patients, respectively. LF was used more frequently in patients with breast cancer than in patients with prostate cancer (79% vs. 45%; p = 0.0001). Long fractionation schemes were used by 90% of physicians in 96% of cases. Short fractionation schemes were used by 7% of physicians in 4% of cases. This tendency was more pronounced in private practice than in the university or government/multidisciplinary settings (p = 0.008) and in physicians starting their practice before 1982 (p = 0.05). The most common schedule was 30 Gy in 10 fractions, used by 77% of physicians in 64% of cases. HBI was used, alone or in combination with other forms of therapy, in 1% and 2% of patients, respectively. It was used more frequently in patients with prostate cancer than in patients with breast cancer (1.2% vs. 0.1%, respectively; p < 0.0001). SR were used alone or in combination with local-field irradiation in 21% and 40% of cases, respectively. SR were used more frequently in patients with prostate cancer than in those with breast cancer (28% vs. 0.2%, respectively; p < 0.00001). The most common radionuclide in use is Sr-89 (99%) at a dose of 4 mCi (73%) or 10.8 mCi (26%).Conclusions: Although LF remains the mainstay of therapy, our results demonstrate the emergence of a new pattern of practice: LF to the painful site in combination with SR for clinically occult metastases. Despite an ongoing academic debate regarding fractionation schemes, the vast majority of American practitioners advocate long schedules.     

Combined Hormonal Contraceptive Use and Risk of Breast Cancer in a Population of Women With a Family History

Background

We estimated the association between combined hormonal contraceptive (CHC) use and breast cancer (BC) incidence in a well-selected population of women at familial risk of BC at the Modena Family Cancer Clinic.

Complementary and alternative therapy use before and after breast cancer diagnosis: the Pathways Study

Many women use complementary and alternative medicine (CAM) to maintain or improve their health. We describe CAM use among the first 1,000 participants enrolled in the Pathways Study, an ongoing prospective cohort study of women diagnosed with breast cancer (BC). Participants, identified by rapid case ascertainment in Kaiser Permanente Northern California, are women ≥ 21 years diagnosed with first invasive BC. Comprehensive baseline data are collected on CAM use through in-person interviews. Study participants include 70.9% non-Hispanic whites, 10.2% Hispanics, 9.0% Asians, 6.5% African–Americans, and 3.4% others. Most women (82.2%) were diagnosed with AJCC stage I/II BC at average (±SD) age 59.5 (±12.0) years and reported prior use of at least one form of CAM (96.5% of participants). In the 5 years before diagnosis, CAM therapies used at least weekly by >20% of women included green tea, glucosamine, omega-3 fatty acids, prayer and religion. CAM use was high (86.1% of participants) in the period immediately following diagnosis; 47.5% used botanical supplements, 47.2% used other natural products, 28.8% used special diets, 64.2% used mind-body healing, and 26.5% used body/energy/other treatments. In multivariable analyses, frequent use of each CAM modality before and after diagnosis was associated with use of other CAM modalities and other health behaviors (i.e., high fruit/vegetable intake, lower BMI). CAM use before and after BC diagnosis is common in this diverse group of women. Our results emphasize the need for clinicians to discuss CAM use with all BC patients.     

Individual inflammatory marker abnormalities or inflammatory marker scores to identify primary care patients with unexpected weight loss for cancer investigation?

Background Combinations of inflammatory markers are used as prognostic scores in cancer patients with cachexia. We investigated whether they could also be used to prioritise patients attending primary care with unexpected weight loss for cancer investigation.Methods We used English primary care electronic health records data linked to cancer registry data from 12,024 patients with coded unexpected weight loss. For each individual inflammatory marker and score we estimated the sensitivity, specificity, likelihood ratios, positive predictive value (PPV) and the area under the curve along with 95% confidence intervals for a cancer diagnosis within six months.Results The risk of cancer associated with two abnormal inflammatory markers combined in a score was higher than the risk associated with individual inflammatory marker abnormalities. However, the risk of cancer in weight loss associated with individual abnormalities, notably a raised C-reactive protein, was sufficient to trigger further investigation for cancer under current NICE guidelines.Conclusions If scores including pairs of inflammatory marker abnormalities were to be used, in preference to individual abnormalities, fewer people would be investigated to diagnose one cancer with fewer false positives, but fewer people with cancer would be diagnosed overall.Subject terms: Cancer epidemiology, Digestive signs and symptoms, Diagnostic markers     

UPF1在肺腺癌中的表达及其临床意义的研究

  目的  探索上游移码突变体（up-frameshift mutant 1,UPF1）在肺腺癌（adenocarcinoma,ADC）中的表达及其与各临床病理指标的关系,探讨其在临床预后判断中的作用及意义。  方法  应用免疫组织化学方法测定2011年1月至2011年12月150例就诊于天津医科大学肿瘤医院ADC患者的UPF1表达情况。Kaplane-Meier分析UPF1的表达与无复发生存期（recurrence-free survival,RFS）以及总生存期（overall survival,OS）之间的关系。  结果  UPF1表达水平随ADC恶性程度的增大而降低（P < 0.01）,也与TNM分期（P=0.014）、是否有淋巴结转移（P=0.016）及远处转移（P=0.035）相关。UPF1的表达水平显著影响ADC的患者RFS和OS,UPF1表达低患者的RFS和OS较短（P < 0.05）。  结论  UPF1在ADC中可能起到抑瘤的作用,可以作为ADC治疗及预后评估的参考指标,并且UPF1有可能成为新的ADC药物治疗靶点。      

Present status of endoscopic mastectomy for breast cancer

Endoscopy is now being used for breast cancer surgery. Though it is used for mastectomy, lymph node dissection, and breast reconstruction, its prime use is for mastectomy. Because an incision can be placed inconspicuously in the axillary site, a relatively large incision can be created. A retractor with an endoscope, CO₂, and an abrasion device with the endoscope are used for operation space security. It is extremely rare that an endoscope is used for lymph node dissection. For breast reconstruction, it may be used for latissimus muscle flap making, but an endoscope is rarely used for other reconstructions. Endoscopic mastectomy is limited to certain institutions and practiced hands, and it has not been significantly developed in breast cancer surgery. On the other hand, endoscopic surgery may be used widely in breast reconstruction. With respect to the spread of robotic surgery, many factors remain uncertain.     

残胃贲门癌和食管癌的外科术式选择

目的 探讨残胃贲门癌和食管癌的外科术式选择及处理要点。方法 1991-2003年间18例残胃贲门癌和食管癌患者，其中食管中段癌3例，食管下段癌2例，贲门癌13例。行残胃代食管2例，结肠代食管3例，空肠代食管胃13例。结果 全部治疗病例中术后吻合口瘘1例，17天死亡，上切缘阳性1例。1年生存率72.2%(14/18)。3年生存率50%（9/18）。结论 结肠代食管是颈部吻合较理想的选择。胸腔内吻合可视具体情况选择残胃、空肠代部分食管及胃。     

Einsatz eines MR-kompatiblen Organperfusionssystems für physiologische Ex-vivo-Experimente im MRT – Erste Erfahrungen mit einem Tierversuchsersatzsystem

PurposeTo represent a MRI-compatible perfusion-system for extracorporeal perfusion of vital organs which permits the realisation of realistic experiments in a MR scanner.Material and methodsWe performed MR examinations of explanted porcine livers and MR-guided interventions in porcine livers. Explanted organs were hemo-perfused under physiological conditions during the experiments. MR-sequences for diagnostic and interventional examinations were used.ResultsThe evaluated system was MRI-compatible. The achieved image quality of the used sequences showed excellent anatomical resolution. Planned experiments can be carried out with relatively low expenditure. Diagnostic as well as interventional investigations can be carried out. The used organs showed a stable function within physiological parameters up to 4 hours.ConclusionIt is possible to perform ex vivo experiments under in vivo conditions with this system. With the used MR-compatible system MR-guided experimental interventions and thermal ablations can be carried out in explanted organs under in vivo conditions.     

A prospective survey of radiotherapy practice 2001 in Sweden

A prospective survey of radiotherapy practice in Sweden was conducted during 12 weeks in the autumn of 2001. All hospitals that provided radiotherapy participated, and all patients who started radiotherapy during the study period were included. The final patient sample comprised 5,105 treatments given to 4,171 patients. The results were compared with those of a similar survey conducted in 1992, and the following conclusions were drawn: A substantial increase in the use of radiotherapy was noted; The estimated proportion of cancer cases receiving radiotherapy (compared to the incident number of cases) had increased from 32% in 1992 to 47%; The proportion of cancer patients receiving radiotherapy was estimated at between 37 and 46%; 54% of treatments were given with curative intent, a small increase since 1992; The difference between regional and county departments for proportion of treatments with curative intent had diminished; Treatments with curative intent used a higher proportion of resources measured in terms of fractions; The proportion of palliative treatment was slightly lower than in 1992, but the absolute number of treatments had increased by more than 20%; No improvement in participation in clinical trials was noted; Treatments given with curative intent were more complex with more fields; Hyperfractionation was used, mainly in treatments of cancers of the head and neck, lung, and bladder; The use of brachytherapy for non-gynaecological malignancies had increased dramatically; Treatment of bone metastases with a single or few fractions was used much more frequently; Dose planning and patient set-up showed a high standard but quality control of dosimetry of given treatment did not fully comply with Swedish and European recommendations; The treatment devices seem to be used more efficiently.     

Intraglandular flap technique for tumors located in the upper outer quadrant of the breast

BackgroundThe intraglandular flap is a volume replacement technique in which glandular tissue is used to close the tissue defect. We applied the intraglandular flap technique with racquet incision for tumors located in the upper outer quadrant of medium to small size breasts of 47 patients. In this report, we present our preliminary results of this technique.Patients and MethodsThe intraglandular flap technique using a racquet incision was used on 47 consecutive breast cancer patients with T1 and T2 tumors, and analyzed prospectively.ResultsThe median age of the patients was 46.5 (range, 24-63 years). The mean tumor size was 2.53 ± 0.8 cm. The volume of the resected specimen was 185 ± 29 cm³. The mean length of incision was 9.68 ± 1.8 cm. The mean distance from the tumor to the nearest surgical margin was 1.65 ± 0.4 cm. Fat necrosis was evident in 8 patients (17%) and hematoma in 2 patients (4.2%). The other complications like seroma, glandular, and flap necrosis were not observed.DiscussionIntraglandular flap technique with racquet incision used for tumors located in the upper outer quadrant of patients with medium and small breasts is an easy and safe technique with respect to cosmetic results, surgical margins and complications. The learning period of this technique is quite short. When used in patients with dense breasts the incidence of fat necrosis was found to be low.     

Effects of using systematic assessment instruments on patient and nurse satisfaction with nursing care

To determine the effects of using systematic assessment instruments on patient and nurse satisfaction with the nursing process, a single-group, pre- and postintervention quasi-experimental design was used in a three-phase study. In the pre- and postintervention control phases, nurses used a routine clinical assessment instrument to implement the nursing process; in the intervention phase they used the Derdiarian Behavioral System Model (DBSM) self-report and the DBSM-O (observational) instruments. The Comprehensiveness of Nursing Assessment and the System of Practice instruments were used to evaluate the comprehensiveness and quality of care respectively; the Patient-Satisfaction and Nurse-Satisfaction instruments were used to evaluate patient and nurse satisfaction with care. The findings showed that the increase in patient and nurse satisfaction was statistically significant when the DBSM and DBSM-O instruments were used.     

Coping strategies used by children hospitalized with cancer: an exploratory study

Objectives: The treatment of cancer is a stressful and threatening experience, particularly for children. Knowing how children cope with cancer is a crucial step toward designing appropriate psychological interventions that help them ease the burden of cancer treatment. The purpose of this study was to examine the coping strategies used by Chinese children hospitalized with cancer, an area of research that is under‐represented in the existing literature. Methods: Hong Kong Chinese children (9–16‐year olds) admitted for cancer treatment to the pediatric oncology units of two different regional acute public hospitals were invited to participate. A short one‐to‐one structured interview was conducted with each participant. Content analysis was conducted to analyze the interview data. Results: A convenience sample of 88 children was recruited and participated in the interviews during an 8‐month period. The coping strategies used by Chinese children hospitalized with cancer did not differ according to gender and diagnosis, but only according to age, with younger children using less problem‐focused and more emotion‐focused coping strategies than older children. The overall results indicated that 30% of these Chinese patients used problem‐focused coping strategies, while 70% used emotion‐focused coping. Conclusions: Findings from this study indicated that children use different coping strategies at different developmental stages. The study also revealed that Chinese children used more emotion‐focused than problem‐focused coping strategies than their Western counterparts. The information derived from this study will help health‐care professionals design and shape appropriate psychological interventions that can help reduce the burden of cancer treatment. Copyright © 2010 John Wiley & Sons, Ltd.     

Predictors of local recurrence after conservative surgery and whole-breast irradiation

Purpose To identify independent factors associated with increased risk of local recurrence (LR) in patients with breast cancer treated with conservative surgery and radiotherapy with or without systemic therapy.Methods and materials Between January 1997 and December 2001, 969 women were treated at the Radiation Oncology Department in Chieti. We retrospectively analyzed 802 of them who were treated with conservative surgery and whole breast irradiation with or without systemic therapy. Tangential fields delivering 50 Gy to the whole breast were used and a boost was added for a total dose of 60 Gy. χ²-test or Fisher’s exact test were used to identify independent significant factors that are predictive for LR. Kaplan–Meier method was used to calculate the 8-year rates of recurrence according to age, histologic findings, tumor size, number of positive nodes, margin status, receptor status and systemic therapy use: log-rank test was used to compare these curves. Cox proportional hazard model was used to obtain hazard ratios and 95% CI of LR for each covariate.Results Median follow-up time was 63.1 months. LR occurred in 33 (4.1%) of 802 patients. Percentage of LR was greater in <50 year-olds compared with 50–64 year-olds and ≥65 year-olds (9.8% versus 4.1 and 2.0%, respectively). LR was 18.8% in women with a tumor size >3 cm versus 3.5, 4.0, 5.5% in women with a tumor size of 0.1–1, 1.1–2, 2.1–3 cm, respectively. The 8-year LR rate calculated with Kaplan–Meier method was 6.54±1.51. Multivariate Cox regression analysis showed that independent significant factors that are predictive for LR were: age <50, tumor size >3 cm, positive margin or unknown status, and hormonal therapy alone versus chemotherapy or combined therapy.Conclusions Age and tumor size were the most important and statistically significant factors that correlated independently with higher rates of LR. Women <50 years old and with a tumor size >3 cm had a higher risk of LR. Also margin status and systemic therapy could influence LR risk.     

rs4779584 C/T、rs4444235 T/C单核苷酸多态性与江苏泰州地区结直肠癌的发病风险研究

目的 了解单核苷酸多态性（SNP）与泰州地区人群中结直肠癌发病的关系。方法 收集泰州人民医院的76例结肠癌、84例直肠癌患者外周血样本作为疾病组,另选170例健康体检正常人群外周血样本作为对照组,选取与结直肠癌高度相关的SNP位点（rs4779584和rs4444235）进行检测,分析不同基因型和等位基因分布情况及其与结直肠癌总体和不同部位的患病风险。结果 两组rs4779584 C/T和rs4444235 T/C基因型分布均符合Hardy-Weinberg平衡。疾病组rs4779584 C/T和rs4444235 T/C的基因型和等位基因分布与对照组相比,差异均有统计学意义（P<0.05）。rs4779584 C/T中,以CC基因型为参照,CT和TT基因型与结直肠癌的患病风险无关联;以CC+CT基因型为参照,TT基因型的结直肠癌患病风险升高,以C等位基因为参照,T等位基因的结直肠癌患病风险升高,差异均有统计学意义（P<0.05）。rs4444235 T/C中,以TT、TT+TC基因型为参照,CC基因型的结直肠癌患病风险均升高;以T等位基因为参照,C等位基因的结直肠癌的患病风险升高,差异均有统计学意义（P<0.05）。结论 在江苏泰州地区人群中,rs4779584和rs4444235 位点SNP与结直肠肿瘤发病风险高度相关。     

In- Vitro Activity of Commonly Used Antifungal Agents in the Presence of Rifampin,Polymyxin B and Norfloxacin against Candida albicans

Abstract

This study assessed the in-vitro antifungal activity against Candida albicans of amphotericin B, ketocona-zole and miconazole, each in the presence of rifampin, polymyxin B and norfloxacin. Evaluation of drug interactions was estimated by the checkerboard pattern broth dilution method and by time-kill studies. Rifampin reduced the activity of the three antifungal agents used, with the reduction being more pronounced with amphotericin B. Synergy was observed when polymyxin B was combined with any of the antifungal agents used. The addition of norfloxacin resulted in minimal, if any, change in the activity.     

Pharmacokinetics of cyclophosphamide enantiomers in patients with breast cancer

Purpose  

Adjuvant chemotherapy with cyclophosphamide (CYC) is used for the treatment of breast cancer. CYC is used as a racemic mixture, although preclinical data have demonstrated differences in the efficacy and toxicity of its enantiomers, with (S)-(−)-CYC exhibiting a higher therapeutic index. The present study investigated the enantioselectivity and influence of CYP2B6, CYP2C9, CYP2C19, and CYP3A on the kinetic disposition of CYC in patients with breast cancer.