BackgroundPatient-reported outcome validation needs to achieve validity and reliability standards. Among reliability analysis parameters, test-retest reliability is an important psychometric property. Retested patients must be in a clinically stable condition. This is particularly problematic in palliative care (PC) settings because advanced cancer patients are prone to a faster rate of clinical deterioration. The aim of this study was to evaluate the methods by which multi-symptom and health-related qualities of life (HRQoL) based on patient-reported outcomes (PROs) have been validated in oncological PC settings with regards to test-retest reliability.MethodsA systematic search of PubMed (1966 to June 2013), EMBASE (1980 to June 2013), PsychInfo (1806 to June 2013), CINAHL (1980 to June 2013), and SCIELO (1998 to June 2013), and specific PRO databases was performed. Studies were included if they described a set of validation studies. Studies were included if they described a set of validation studies for an instrument developed to measure multi-symptom or multidimensional HRQoL in advanced cancer patients under PC. The COSMIN checklist was used to rate the methodological quality of the study designs.ResultsWe identified 89 validation studies from 746 potentially relevant articles. From those 89 articles, 31 measured test-retest reliability and were included in this review. Upon critical analysis of the overall quality of the criteria used to determine the test-retest reliability, 6 (19.4%), 17 (54.8%), and 8 (25.8%) of these articles were rated as good, fair, or poor, respectively, and no article was classified as excellent. Multi-symptom instruments were retested over a shortened interval when compared to the HRQoL instruments (median values 24 hours and 168 hours, respectively; p = 0.001). Validation studies that included objective confirmation of clinical stability in their design yielded better results for the test-retest analysis with regard to both pain and global HRQoL scores (p < 0.05). The quality of the statistical analysis and its description were of great concern.ConclusionTest-retest reliability has been infrequently and poorly evaluated. The confirmation of clinical stability was an important factor in our analysis, and we suggest that special attention be focused on clinical stability when designing a PRO validation study that includes advanced cancer patients under PC.

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.

Background.Neratinib has efficacy in central nervous system (CNS) metastases from HER2-positive metastatic breast cancer (MBC). We report outcomes among patients with CNS metastases at baseline from the phase III NALA trial of neratinib plus capecitabine (N + C) versus lapatinib plus capecitabine (L + C). Materials and Methods. NALA was a randomized, activecontrolled trial in patients who received two or more previous HER2-directed regimens for HER2-positive MBC. Patients with asymptomatic/stable brain metastases (treated or untreated) were eligible. Patients were assigned to N + C (neratinib 240 mg per day, capecitabine 750 mg/m 2 twice daily) or L + C (lapatinib 1,250 mg per day, capecitabine 1,000 mg/m 2 twice daily) orally. Independently adjudicated progression-free survival (PFS), overall survival (OS), and CNS endpoints were considered. Results. Of 621 patients enrolled, 101 (16.3%) had known CNS metastases at baseline (N + C, n = 51; L + C, n = 50); 81 had received prior CNS-directed radiotherapy and/or surgery. In the CNS subgroup, mean PFS through 24 months was 7.8 months with N + C versus 5.5 months with L + C (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.41-1.05), and mean OS through 48 months was 16.4 versus 15.4 months (HR, 0.90; 95% CI, 0.59-1.38). At 12 months, cumulative incidence of interventions for CNS disease was 25.5% for N + C versus 36.0% for L + C, and cumulative incidence of progressive CNS disease was 26.2% versus 41.6%, respectively. In patients with target CNS lesions at baseline (n = 32), confirmed intracranial objective response rates were 26.3% and 15.4%, respectively. No new safety signals were observed. Conclusion. These analyses suggest improved PFS and CNS outcomes with N + C versus L + C in patients with CNS metastases from HER2-positive MBC. The Oncologist ;9999:• • Implications for Practice: In a subgroup of patients with central nervous system (CNS) metastases from HER2-positive breast cancer after two or more previous HER2-directed regimens, the combination of neratinib plus capecitabine was associated with improved progression-free survival and CNS outcomes compared with lapatinib plus capecitabine. These findings build on previous phase II and III studies describing efficacy of neratinib in the prevention and treatment of CNS metastases,

PurposeThis study identifies the personal and professional profiles of researchers with a greater potential to publish high-impact academic articles.MethodThe study involved conducting an international survey of journal authors using a web-based questionnaire. The survey examined personal characteristics, funding, and the perceived barriers of research quality, work-life balance, and satisfaction and motivation in relation to career. The processes of manuscript writing and journal publication were measured using an online questionnaire that was developed for this study. The responses were compared between the two groups of researchers using logistic regression models.ResultsA total of 269 questionnaires were analysed. The researchers shared some common perceptions; both groups reported that they were seeking recognition (or to be leaders in their areas) rather than financial remuneration. Furthermore, both groups identified time and funding constraints as the main obstacles to their scientific activities. The amount of time that was spent on research activities, having >5 graduate students under supervision, never using text editing services prior to the publication of articles, and living in a developed and English-speaking country were the independent variables that were associated with their article getting a greater chance of publishing in a high-impact journal. In contrast, using one’s own resources to perform studies decreased the chance of publishing in high-impact journals.ConclusionsThe researchers who publish in high-impact journals have distinct profiles compared with the researchers who publish in low-impact journals. English language abilities and the actual amount of time that is dedicated to research and scientific writing, as well as aspects that relate to the availability of financial resources are the factors that are associated with a successful researcher’s profile.

Breast cancer (BC) is a highly heterogeneous disease. The treatment of BC is complicated owing to intratumoral complexity. Tissue biopsy and immunohistochemistry are the current gold standard techniques to guide breast cancer therapy; however, these techniques do not assess tumoral molecular heterogeneity. Personalized medicine aims to overcome these biological and clinical complexities. Advances in techniques and computational analyses have enabled increasingly sensitive, specific, and accurate application of liquid biopsy. Such progress has ushered in a new era in precision medicine, where the objective is personalized treatment of breast cancer, early screening, accurate diagnosis and prognosis, relapse detection, longitudinal monitoring, and drug selection. Liquid biopsy can be defined as the sampling of components of tumor cells that are released from a tumor and/or metastatic deposits into the blood, urine, feces, saliva, and other biological substances. Such components include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or circulating tumor RNA (ctRNA), platelets, and exosomes. This review aims to highlight the role of liquid biopsy in breast cancer and precision medicine.