Search

Background: The PHERGain study (NCT03161353) is assessing early metabolic responses to neoadjuvant treatment with trastuzumab-pertuzumab and chemotherapy de-escalation using a [18Fluorine]fluorodeoxyglucose-positron emission tomography ([18F]FDG-PET) and a pathological complete response-adapted strategy in HER2-positive (HER2+) early breast cancer (EBC). Herein, we present RESPONSE, a PHERGain substudy, where clinicopathological and molecular predictors of [18F]FDG-PET disease detection were evaluated. Methods: A total of 500 patients with HER2 + EBC screened in the PHERGain trial with a tumor size > 1.5 cm by magnetic resonance imaging (MRI) were included in the RESPONSE substudy. PET[−] criteria entailed the absence of ≥ 1 breast lesion with maximum standardized uptake value (SUVmax) ≥ 1.5 × SUVmean liver + 2 standard deviation. Among 75 PET[−] patients screened, 21 with SUVmax levels < 2.5 were randomly selected and matched with 21 PET[+] patients with SUVmax levels ≥ 2.5 based on patient characteristics associated with [18F]FDG-PET status. The association between baseline SUVmax and [18F]FDG-PET status ([−] or [+]) with clinicopathological characteristics was assessed. In addition, evaluation of stromal tumor-infiltrating lymphocytes (sTILs) and gene expression analysis using PAM50 and Vantage 3D™ Cancer Metabolism Panel were specifically compared in a matched cohort of excluded and enrolled patients based on the [18F]FDG-PET eligibility criteria. Results: Median SUVmax at baseline was 7.2 (range, 1–39.3). Among all analyzed patients, a higher SUVmax was associated with a higher tumor stage, larger tumor size, lymph node involvement, hormone receptor-negative status, higher HER2 protein expression, increased Ki67 proliferation index, and higher histological grade (p < 0.05). [18F]FDG-PET [−] criteria patients had smaller tumor size (p = 0.014) along with the absence of lymph node involvement and lower histological grade than [18F]FDG-PET [+] patients (p < 0.01). Although no difference in the levels of sTILs was found among 42 matched [18F]FDG-PET [−]/[+] criteria patients (p = 0.73), [18F]FDG-PET [−] criteria patients showed a decreased risk of recurrence (ROR) and a lower proportion of PAM50 HER2-enriched subtype than [18F]FDG-PET[+] patients (p < 0.05). Differences in the expression of genes involved in cancer metabolism were observed between [18F]FDG-PET [−] and [18F]FDG-PET[+] criteria patients. Conclusions: These results highlight the clinical, biological, and metabolic heterogeneity of HER2+ breast cancer, which may facilitate the selection of HER2+ EBC patients likely to benefit from [18F]FDG-PET imaging as a tool to guide therapy. Trial registration: Clinicaltrials.gov; NCT03161353; registration date: May 15, 2017. [ABSTRACT FROM AUTHOR]

Adolescence represents a fundamental stage for interactions between excessive food intake and drug consumption. The association between obesity and drug use is unclear, but inhibitory control has been proposed as a common mechanism. The current study aimed to examine differences in inhibitory control measures in adolescents with overweight and/or substance use. Eighty-five adolescents 15–16 years of age were grouped according to a factorial design as cannabis users (n = 44) versus abstainers (n = 41), and alcohol users (n = 50) versus abstainers (n = 35). Participants were also classified depending on their BMI range as normal weight (n = 47) or overweight (n = 38). To measure inhibitory control, participants completed a Go-Nogo task while their brain activity was registered through electroencephalography, recording the event-related potentials during the task. No behavioral differences were found, but overweight teens exhibited lower P3 amplitudes (for both Go and Nogo conditions) compared with normal-BMI teens, indicating general difficulties in recruiting cognitive resources. Also, alcohol users showed higher Nogo-P3 amplitudes compared with alcohol abstainers, suggesting increased need of inhibitory control effort to achieve a good behavioral performance. Results indicate distinct altered inhibitory control functions in overweight adolescents and alcohol users. These findings suggest that different specific mechanisms of modulation of inhibitory control brain processes are involved in excessive food versus drug consumption, against the notion of food-drug competition. Understanding of associations between excessive food intake and substance use in adolescence will require identification of both common and specific risk factors. [ABSTRACT FROM AUTHOR]

Variations in parenting across large populations have rarely been described. It also remains unclear which specific domains of parenting are important for which specific offspring developmental outcomes. This study describes different domains of early parenting behaviours and their genetic heritability, then determines the extent to which specific domains of parenting are associated with later offspring outcomes. Parenting behaviours (birth to 3 years) were extracted from self-reported questionnaires administered to 12,358 mothers from the UK-based birth cohort study, the Avon Longitudinal Study of Parents and Children and modelled as a latent factor using Confirmatory Factor Analysis. Genetic heritability and correlations between parenting factors were estimated using genome-wide complex trait analysis. Three parenting factors were derived: parental enjoyment, conflictual relationships and stimulation; all showed low genetic heritability. There was no evidence of association between parental enjoyment and offspring behavioural disorders and depressed mood. Stimulation was associated with better English grades (standardised β = 0.195, p < 0.001) and enjoyment was negatively associated with English grades (β = − 0.244, p = < 0.001). Conflictual relationships were associated with higher risk of offspring behavioural disorders (β = 0.228, p = 0.010) and depressed mood (β = 0.077, p = 0.005). Higher enjoyment reduced the association between conflict and behavioural problems (interaction term β = 0.113, p < 0.001). We found evidence for predictive specificity of early parenting domains for offspring outcomes in adolescence. Early stimulation, unlike enjoyment, promoted later educational achievement. Conflictual relationships were associated with greater risk of behavioural problems, buffered by increased enjoyment. These findings hold implications for parenting interventions, guiding their focus according to the specificity of parenting domains and their long-term outcomes in children. [ABSTRACT FROM AUTHOR]