Trajectories of alcohol consumption during life and the risk of developing breast cancer.

BACKGROUND: Whether there are lifetime points of greater sensitivity to the deleterious effects of alcohol intake on the breasts remains inconclusive. OBJECTIVE: To compare the influence of distinctive trajectories of alcohol consumption throughout a woman's life on development of breast cancer (BC). METHODS: 1278 confirmed invasive BC cases and matched (by age and residence) controls from the Epi-GEICAM study (Spain) were used. The novel group-based trajectory modelling was used to identify different alcohol consumption trajectories throughout women's lifetime. RESULTS: Four alcohol trajectories were identified. The first comprised women (45%) with low alcohol consumption (<5 g/day) throughout their life. The second included those (33%) who gradually moved from a low alcohol consumption in adolescence to a moderate in adulthood (5 to <15 g/day), never having a high consumption; and oppositely, women in the third trajectory (16%) moved from moderate consumption in adolescence, to a lower consumption in adulthood. Women in the fourth (6%) moved from a moderate alcohol consumption in adolescence to the highest consumption in adulthood (≥15 g/day), never having a low alcohol consumption. Comparing with the first trajectory, the fourth doubled BC risk (OR 2.19; 95% CI 1.27, 3.77), followed by the third (OR 1.44; 0.96, 2.16) and ultimately by the second trajectory (OR 1.17; 0.86, 1.58). The magnitude of BC risk was greater in postmenopausal women, especially in those with underweight or normal weight. When alcohol consumption was independently examined at each life stage, ≥15 g/day of alcohol consumption in adolescence was strongly associated with BC risk followed by consumption in adulthood. CONCLUSIONS: The greater the alcohol consumption accumulated throughout life, the greater the risk of BC, especially in postmenopausal women. Alcohol consumption during adolescence may particularly influence BC risk.

Physical activity and breast cancer risk by pathological subtype.

OBJECTIVE: To examine the influence of physical activity on breast cancer risk and evaluate whether adherence to international recommendations is associated with a decreased risk. METHODS: This is a multicenter matched case-control study where 698 pairs completed a physical activity questionnaire. Recreational physical activity during the last year was quantified in metabolic equivalent hours per week (MET-h/week) and categorized in activities of moderate (3.0-5.9 MET) and vigorous (>6 MET) intensity. The adherence to World Cancer Research Fund and the American Institute for Cancer Research recommendation was also assessed. The association with breast cancer risk, overall and by pathologic subtype, was evaluated using conditional and multinomial logistic regression models. RESULTS: Mean MET-h/week was 16.6 among cases and 20.4 among controls. Premenopausal breast cancer risk decreased by 5% (P=0.007) for every 6 MET-h/week increase in energy expenditure. By contrast, postmenopausal women needed to do more intense exercise to observe benefits. The protection was more pronounced for nulliparous women, as well as for hormone receptor positive and HER2+ tumors. Physically inactive women displayed a 71% increased risk when compared with those who met the international recommendation (P=0.001). Finally, women who were inactive during the previous year, regardless of the overall physical activity reported in previous periods, showed an increased risk when compared to always active women. CONCLUSIONS: Women who report adherence to international physical activity recommendations entail a significant decrease in risk for all pathologic breast cancer subtypes. This is of particular interest in Spain, where a significant increase in overweight and obesity in recent decades is observed.

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non-Small Cell Lung Carcinoma: the ROSING Study.

INTRODUCTION: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. METHODS: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). RESULTS: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). CONCLUSIONS: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm.

[Evolution of angiogenesis following anthracycline-based neoadjuvant chemotherapy in breast cancer]. / Efecto de la quimioterapia neoadyuvante con antraciclinas en la angiogenia del cáncer de mama.

BACKGROUND AND OBJECTIVE: The impact of chemotherapy on the extent of breast cancer angiogenesis is unknown. The aim of this study was to investigate the effect of primary chemotherapy on tumor microvessel density and vascular endothelial growth factor (VEGF), and correlate this changes with tumor response, post-chemotherapy changes and other biological variables. PATIENTS AND METHOD: In 41 consecutive patients with breast cancer stages II and III, treated with anthracycline-based neoadjuvant chemotherapy, immunohistochemical analysis of microvessel density and VEGF were performed before and after the administration of neoadjuvant chemotherapy. RESULTS: Microvessel density was the same in post-chemotherapy that in pre-chemotherapy samples (p = 0.29). There were no changes in the expression of VEGF (p = 0.23). The expression of VEGF and microvessel density did not show any relationship with the response in the pre-chemotherapy analysis (p = 0.60 and p = 0.30 respectively), nor in the post-chemotherapy analysis (p = 0.50 and p = 0.65 respectively). Changes post-chemotherapy were not associated with VEGF expression (p = 0.53 in the pre-chemotherapy samples and p = 0.43 in the post-chemotherapy samples) nor microvessel density (p = 0.72 in the pre-chemotherapy samples and p = 0.65 in the post-chemotherapy samples). CONCLUSIONS: Anthracycline-based neoadjuvant chemotherapy does not cause a reduction of the density of microvessel nor of the expression of VEGF in breast cancer.

Impact of computerised chemotherapy prescriptions on the prevention of medication errors.

OBJECTIVES: The authors sought to evaluate the impact of computerised chemotherapy prescription on the reduction of medication errors. The purpose of this study was to assess the incidence of errors present in electronic versus manual prescription. MATERIAL AND METHODS: The data gathered from computerised chemotherapy prescription sheets were submitted to a prospective analysis as cases of the intervention groups. The control group was comprised of the handwritten chemotherapy prescription sheets. Chemotherapy prescriptions for consecutive oncology patients were analysed by 2 independent examiners, who investigated errors of omission, commission, interpretation of dates, abbreviations and illegible handwriting. The proportion of treatment prescriptions containing one or more errors and the median of errors were calculated in order in both groups. RESULTS: At least one error was detected in 100% of the manual prescriptions and in 13% of computerised prescriptions (p < 0.001). The median of errors per computerised prescription was 0 (range: 0- 1), whereas in manual prescriptions the median was 5 (range: 1-12) (p < 0.001). Errors of omission were predominant in manual prescriptions. Errors of commission were limited to 1 case of unjustified cytostatic agent infra-dosage in a computerised prescription. This error was present in 3 cases in handwritten prescriptions and, in addition, 1 case of premedication drug substitution was detected. Errors of interpretation of the date, use of abbreviations and illegible handwriting were frequent among manual prescriptions and were absent from computerised prescriptions. CONCLUSIONS: Electronic chemotherapy prescription is a powerful tool. In this study it has been shown to decrease chemotherapy-related medication errors and ensure that safe chemotherapy practices were followed.

Evaluating the Applicability of Data-Driven Dietary Patterns to Independent Samples with a Focus on Measurement Tools for Pattern Similarity.

BACKGROUND: Diet is a key modifiable risk for many chronic diseases, but it remains unclear whether dietary patterns from one study sample are generalizable to other independent populations. OBJECTIVE: The primary objective of this study was to assess whether data-driven dietary patterns from one study sample are applicable to other populations. The secondary objective was to assess the validity of two criteria of pattern similarity. METHODS: Six dietary patterns-Western (n=3), Mediterranean, Prudent, and Healthy- from three published studies on breast cancer were reconstructed in a case-control study of 973 breast cancer patients and 973 controls. Three more internal patterns (Western, Prudent, and Mediterranean) were derived from this case-control study's own data. STATISTICAL ANALYSIS: Applicability was assessed by comparing the six reconstructed patterns with the three internal dietary patterns, using the congruence coefficient (CC) between pattern loadings. In cases where any pair met either of two commonly used criteria for declaring patterns similar (CC ≥0.85 or a statistically significant [P<0.05] Pearson correlation), then the true similarity of those two dietary patterns was double-checked by comparing their associations to risk for breast cancer, to assess whether those two criteria of similarity are actually reliable. RESULTS: Five of the six reconstructed dietary patterns showed high congruence (CC >0.9) to their corresponding dietary pattern derived from the case-control study's data. Similar associations with risk for breast cancer were found in all pairs of dietary patterns that had high CC but not in all pairs of dietary patterns with statistically significant correlations. CONCLUSIONS: Similar dietary patterns can be found in independent samples. The P value of a correlation coefficient is less reliable than the CC as a criterion for declaring two dietary patterns similar. This study shows that diet scores based on a particular study are generalizable to other populations.

Use of health-care services during chemotherapy for breast cancer.

AIM OF THE STUDY: The authors analyse the effect of chemotherapy on the use of additional health-care resources and report the clinical and demographic factors associated with such use. PATIENTS AND METHODS: In women with breast cancer, eligible to receive first-line (neo)-adjuvant or palliative chemotherapy, consultations with health-care practitioners (general practitioners [GPs] and specialists) and admissions to emergency department and to hospital were prospectively recorded. Differences were studied according to these clinical and demographic variables: age, tumour stage, performance status, weight, height, body mass index, surgery type, chemotherapy type, number of courses, comorbidity, marital status, educational level, social status and occupational status. RESULTS: Among 268 patients, 124 (42.2%) required one or more non-protocol health-care encounters. 180 visits were generated (GP 23.3%, specialist 35.5%, emergency department admission 21.1%, hospital admission 8.3%, others 3.3% and more than one resource 8.3%). Of total consultations 150 (83.3%) were chemotherapy-related. The number of visits was higher in the first courses. Fever and infection were the most frequent reasons for consultation in all resources. The dependent variable: 'need for non-protocol health-care encounter in any course' was statistically associated with age (p=0.002) and marital status (p=0.021); no association was found with other variables. In multivariate analysis, age (p=0.001) and marital status (p=0.009) remained statistically significant. Younger and married patients consumed less extra health resources. CONCLUDING STATEMENT: Many patients receiving chemotherapy consume health-care resources in addition to their routine visits, usually treatment-related. Patients consult less in the later courses. Older and unmarried women in particular need extra care during chemotherapy.