Inflammation and Performance Status: The Cornerstones of Prognosis in Advanced Cancer.

CONTEXT: In advanced cancer, although performance status (PS), systemic inflammatory response and nutritional status are known to have prognostic value, geographical variations and sociodemographic indexes may also impact survival. OBJECTIVES: This study compares validated prognostic factors in two international cohorts and establishes a prognostic framework for treatment. METHODS: Two international biobanks of patients (n=1.518) with advanced cancer were analyzed. Prognostic factors (Eastern Cooperative Oncology Group Performance Status [ECOG-PS], body mass index [BMI] and modified Glasgow Prognostic Score [mGPS]) were assessed. The relationship between these and survival was examined using Kaplan-Meier and Cox regression methods. RESULTS: According to multivariate analysis, in the European cohort the most highly predictive factors were BMI <20 kg/m2 (hazard ratio [HR] 1.644), BMI 20-21.9 kg/m2 (HR 1.347), ECOG-PS (HR 1.597-11.992) and mGPS (HR 1.843-2.365). In the Brazilian cohort, the most highly predictive factors were ECOG-PS (HR 1.678-8.938) and mGPS (HR 2.103-2.837). Considering gastrointestinal cancers in particular (n=551), the survival rate at 3 months in both cohorts together ranged from 93% (mGPS 0, PS 0-1) to 0% (mGPS 2, PS 4), and from 81% (mGPS 0, BMI >28 kg/m2) to 44% (mGPS 2, BMI <20 kg/m2). CONCLUSION: The established prognostic factors that were compared had similar prognostic capacity in both cohorts. A high ECOG-PS and a high mGPS as outlined in the ECOG-PS/mGPS framework were consistently associated with poorer survival of patients with advanced cancer in the prospective European and Brazilian cohorts.

A Novel Detection Method of Breast Cancer through a Simple Panel of Biomarkers.

Circulating tumor cells (CTCs) have been identified as responsible for the spread of tumors to other organs of the body. In this sense, the development of sensitive and specific assays for their detection is important to reduce the number of deaths due to metastases. Here, we assessed whether the detection of CTCs in peripheral blood can serve in the construction of a panel of diagnosis and monitoring treatments of breast cancer (BC), focusing on the expression of markers of epithelial-mesenchymal transition. Through analyzing the blood from women without breast alterations (control), women with benign alterations, women with breast cancer without chemotherapy, and women with breast cancer with chemotherapy, we identified the best markers by transcriptional levels and determined three profiles of CTCs (mesenchymal, intermediate, and epithelial) by flow cytometry which, combined, can be used for diagnosis and therapy monitoring with sensitivity and specificity between 80% and 100%. Therefore, we have developed a method for detecting breast cancer based on the analysis of CTC profiles by epithelial-mesenchymal transition markers which, combined, can be used for the diagnosis and monitoring of therapy.

Eating Earlier and More Frequently Is Associated With Better Diet Quality in Female Brazilian Breast Cancer Survivors Using Tamoxifen.

BACKGROUND: Emerging literature demonstrates that eating time and frequency are associated with quality and quantity of food consumption and anthropometric measurements. Considering that unhealthy dietary choices and obesity are important modifiable risk factors for breast cancer incidence and recurrence, this subject is relevant and has not been studied sufficiently in breast cancer survivors. OBJECTIVE: This study's aim was to examine the association of eating time and frequency with diet quality, quantity of food consumption, anthropometric measurements, and body composition parameters in female breast cancer survivors using tamoxifen. DESIGN: This was a cross-sectional study. PARTICIPANTS/SETTING: This study was conducted from March 2015 to March 2016 at a Brazilian university hospital (Clinic's Hospital, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil) and included an assessment of 84 female breast cancer survivors using tamoxifen (mean [SD] age was 53.1 [8.7] years). MAIN OUTCOME MEASURES: Quantitative dietary assessment consisted of three 24-hour dietary recalls. The Brazilian Healthy Eating Index Revised was used for the qualitative diet analysis. Participants were classified by median eating time (early or late eaters of breakfast, lunch, and dinner), as well as by considering the middle time point between the first and last meal of the day (early or late midpoint eaters). Participants were also classified by median eating frequency (<5 or ≥5 eating episodes per day). Anthropometric measurements and body fat percentage by bioelectrical impedance were obtained. STATISTICAL ANALYSIS: Generalized linear models and generalized mixed models were used to assess the associations between variables. RESULTS: Early breakfast and dinner eating and early midpoint eating were associated with better scores for specific Brazilian Healthy Eating Index Revised components (P < .05). Early breakfast and dinner eating were also associated with better scores for the total index (P = .035 and P = .017, respectively). Early dinner eaters and early midpoint eaters had significantly lower daily energy consumption (P = .007 and P = .002, respectively). Eating ≥5 episodes per day was also associated with better scores of specific Brazilian Healthy Eating Index Revised components and the total index (P < .05). No significant associations between eating time and frequency with anthropometric measurements and body composition parameters were found (P > .05). However, women in the healthy body mass index category vs women in the overweight/obesity category had higher energy consumption at breakfast (P = .046). CONCLUSIONS: Earlier food intake time was associated with better diet quality and lower daily energy consumption. Higher frequency of eating was also associated with better diet quality. Future studies, such as randomized controlled trials, are needed to evaluate interventions addressing the timing and frequency of meals and their effect on diet quality and quantity in breast cancer survivors.

A protective effect of morning radiotherapy on acute skin toxicity in patients with breast cancer: A prospective cohort study.

ABSTRACT: The focus of this prospective cohort study was to evaluate the risk factors of severe acute skin toxicity (grade ≥2) in 100 patients with breast cancer (BC) during radiotherapy (RT).The patients were evaluated weekly during RT and 3 months after treatment. The endpoint included the occurrence of skin toxicity grade ≥2, according to Radiation Therapy Oncology Group (RTOG). Survival analysis was conducted by univariate and multivariate Cox regression analysis.In the multivariate analysis, RT in the afternoon (0-3 pm) (hazard ratios [HR] = 1.566, P = .042) was significantly associated with the early occurrence of skin toxicity, indicating a potential effect of chronotherapy related to this adverse event. In the univariate and multivariate analysis, skin phototype moderate brown (HR = 1.586, P = .042; HR = 1.706, P = .022, respectively) and dark brown or black (HR = 4.517, P < .001; HR = 5.336, P < 0.001, respectively) was significantly associated with the skin toxicity. Tangential field separation >21 cm (HR = 2.550, P = .009, HR = 2.923, P = .003), in women that were submitted to conservative surgery indicates indirectly that large breast size was also significantly associated with skin toxicity.Women with large breasts and dark brown or black skin should be followed more carefully during RT, which should be undergone in the morning, especially when submitted to conventional RT techniques, common in developing countries.

Breast Cancer Survivors Undergoing Endocrine Therapy Have a Worrying Risk Factor Profile for Cardiovascular Diseases.

The increased risk for cardiovascular diseases (CVDs) in breast cancer survivors has been widely discussed in the literature and occurs due to the cardiotoxicity of antineoplastic treatments, and also to the common risk factors between these diseases. Thus, the objective of our study was to evaluate, prospectively, the number of risk factors (NRF) for CVDs in women during endocrine therapy, and to associate the NRF with C reactive protein (CRP) and phase angle (PhA). The following risk factors for CVD were evaluated at three times: anthracycline chemotherapy, radiotherapy, comorbidities, inadequate diet, overweight, abdominal adiposity, alcoholism, smoking, physical inactivity and altered lipid profile. There was inadequacy in the most components of the Brazilian Healthy Eating Index-Revised and inadequate consumption of various types of fats and fibers. Most women in this study presented excessive abdominal fat and overweight, but these parameters have not changed over time (p < 0.005). Moreover, a high frequency of systemic arterial hypertension and physical inactivity was observed. The average NRF for CVDs was above ten, at the three evaluation times. Women with higher NRF had higher levels of CRP (p = 0.003), a predictor of cardiovascular risk, however, there was no significance with PhA (p = 0.256). Thus, intervention is needed to improve lifestyle.

Effects of Type 2 Diabetes Mellitus in Patients on Treatment With Glibenclamide and Metformin on Carvedilol Enantiomers Metabolism.

Carvedilol is available in clinical practice as a racemate in which (S)-(-)-carvedilol is a ß- and α1 -adrenergic antagonist and (R)-(+)-carvedilol is only an α1 -adrenergic antagonist. Carvedilol is mainly metabolized by glucuronidation, by CYP2D6 to hydroxyphenylcarvedilol (OHC), and by CYP2C9 to O-desmethylcarvedilol (DMC). This study evaluated the pharmacokinetics of carvedilol enantiomers and their metabolites OHC and DMC in healthy volunteers (n = 13) and in type 2 diabetes mellitus patients with good glycemic control (n = 13). The healthy subjects were enrolled to receive either a 25-mg oral single dose of carvedilol alone (no DDI) or carvedilol simultaneously with 5 mg glibenclamide and 500 mg metformin (DDI), whereas type 2 diabetes mellitus patients who were on long-term treatment with glibenclamide (5 mg/8 h) and metformin (500 mg/8 h) were enrolled to receive only a single oral dose of 25 mg carvedilol. The plasma concentrations of the (R)-(+)-carvedilol, (R)-(+)-DMC, and (R)-(+)-OHC were higher than those of (S)-(-)-carvedilol, (S)-(-)-DMC, and (S)-(-)-OHC in all investigated groups. The pharmacokinetics of the carvedilol enantiomers did not differ between the groups. However, the AUC values of the DMC enantiomers were lower in the type 2 diabetes mellitus patients than in the healthy volunteers (DDI and no DDI) [(R)-(+), 6.9, 10.4, 11.9 ng·h/mL; and (S)-(-), 2.4, 4.3, 4.0 ng·h/mL, respectively]. In contrast, the AUC values of the OHC enantiomers were higher in the type 2 diabetes mellitus patients [(R)-(+), 13.9, 6.6, 4.9 ng·h/mL; and (S)-(-), 7.2, 1.5, 1.5 ng·h/mL], which explains the fact that the carvedilol pharmacokinetics was unchanged.

A novel highly reactive Fab antibody for breast cancer tissue diagnostics and staging also discriminates a subset of good prognostic triple-negative breast cancers.

The discovery of novel markers for breast cancer (BC) has been recently relied on antibody combinatorial libraries and selection through phage display. We constructed a recombinant Fab library, and after selections against BC tissues, the FabC4 clone was thoroughly investigated by immunohistochemistry in 232 patients with long-term follow-up. The FabC4 ligand was determined by mass spectrometry. The FabC4 expression was associated with younger age, lack of progesterone receptor, higher histological grades and non-luminal subtypes, and it also identified a subset of good prognostic triple-negative BCs, possibly targeting a conformational epitope of Cytokeratin-10 (CK10). This new CK10-epitope specific antibody may open new possibilities in diagnostic and therapeutic strategies.