Dog Ownership During Pregnancy, Maternal Activity, and Obesity: A Cross-Sectional Study

The Avon Longitudinal Study of Parents and Children (ALSPAC) is an observational study of 14273 UK pregnant singleton mothers in 1990/1991. We examined outcomes of self report of strenuous activity (hours per week) at 18 and 32 weeks of gestation, hours spent in leisure-time physical activities and types, and pre-pregnancy body mass index (BMI); overweight status was defined as pre-pregnancy BMI$25 and obesity BMI$30. Pet ownership and activity data were reported for 11,466 mothers. Twenty-five percent of mothers owned at least one dog. There was a positive relationship between participation in activity at least once a week and dog ownership (at 18 weeks, Odds ratio 1.27, 95% confidence interval 1.11– 1.44, P,0.001). Dog owners were 50% more likely to achieve the recommended 3 hours activity per week, equivalent to 30 minutes per day, most days of the week (1.53, 1.35–1.72, P,0.001). Dog owners were also more likely to participate in brisk walking activity than those who did not have a dog (compared to no brisk walking 2–6 hrs per week 1.43, 1.23 to 1.67, P,0.001; 7+ hrs per week 1.80, 1.43 to 2.27, P,0.001). However, no association was found with any other types of activities and there was no association between dog ownership and weight status. During the time period studied, pregnant women who had dogs were more active, through walking, than those who did not own dogs. As walking is a low-risk exercise, participation of pregnant women in dog walking activities may be a useful context to investigate as part of a broader strategy to improve activity levels in pregnant women

Breast-cancer adjuvant therapy with zoledronic acid

Background: Data suggest that the adjuvant use of bisphosphonates reduces rates of recurrence and death in patients with early-stage breast cancer. We conducted a study to determine whether treatment with zoledronic acid, in addition to standard adjuvant therapy, would improve disease outcomes in such patients. Methods: In this open-label phase 3 study, we randomly assigned 3360 patients to receive standard adjuvant systemic therapy either with or without zoledronic acid. The zoledronic acid was administered every 3 to 4 weeks for 6 doses and then every 3 to 6 months to complete 5 years of treatment. The primary end point of the study was disease-free survival. A second interim analysis revealed that a prespecified boundary for lack of benefit had been crossed. Results: At a median follow-up of 59 months, there was no significant between-group difference in the primary end point, with a rate of disease-free survival of 77% in each group (adjusted hazard ratio in the zoledronic acid group, 0.98; 95% confidence interval [CI], 0.85 to 1.13; P=0.79). Disease recurrence or death occurred in 377 patients in the zoledronic acid group and 375 of those in the control group. The numbers of deaths — 243 in the zoledronic acid group and 276 in the control group — were also similar, resulting in rates of overall survival of 85.4% in the zoledronic acid group and 83.1% in the control group (adjusted hazard ratio, 0.85; 95% CI, 0.72 to 1.01; P=0.07). In the zoledronic acid group, there were 17 confirmed cases of osteonecrosis of the jaw (cumulative incidence, 1.1%; 95% CI, 0.6 to 1.7; P<0.001) and 9 suspected cases; there were no cases in the control group. Rates of other adverse effects were similar in the two study groups. Conclusions: These findings do not support the routine use of zoledronic acid in the adjuvant management of breast cancer. (Funded by Novartis Pharmaceuticals and the National Cancer Research Network; AZURE Current Controlled Trials number, ISRCTN79831382.

Phase II randomized preoperative window-of-opportunity study of the PI3K inhibitor pictilisib plus anastrozole compared with anastrozole alone in patients with estrogen receptor-positive breast cancer

Purpose: Preclinical data support a key role for the PI3K pathway in estrogen receptor-positive breast cancer and suggest that combining PI3K inhibitors with endocrine therapy may overcome resistance. This preoperative window study assessed whether adding the PI3K inhibitor pictilisib (GDC-0941) can increase the antitumor effects of anastrozole in primary breast cancer and aimed to identify the most appropriate patient population for combination therapy. Patients and Methods: In this randomized, open-label phase II trial, postmenopausal women with newly diagnosed operable estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers were recruited. Participants were randomly allocated (2:1, favoring the combination) to 2 weeks of preoperative treatment with anastrozole 1 mg once per day (n = 26) or the combination of anastrozole 1 mg with pictilisib 260 mg once per day (n = 49). The primary end point was inhibition of tumor cell proliferation as measured by change in Ki-67 protein expression between tumor samples taken before and at the end of treatment. Results: There was significantly greater geometric mean Ki-67 suppression of 83.8% (one-sided 95% CI, ≥ 79.0%) for the combination and 66.0% (95% CI, ≤ 75.4%) for anastrozole (geometric mean ratio [combination: anastrozole], 0.48; 95% CI, ≤ 0.72; P = .004). PIK3CA mutations were not predictive of response to pictilisib, but there was significant interaction between response to treatment and molecular subtype (P =.03);for patients with luminal B tumors, the combination:anastrozole geometric mean ratio of Ki-67 suppression was 0.37 (95% CI, ≤ 0.67; P = .008), whereas no significant Ki-67 response was observed for pictilisib in luminal A tumors (1.01; P = .98). Multivariable analysis confirmed Ki-67 response to the combination treatment of patients with luminal B tumors irrespective of progesterone receptor status or baseline Ki-67 expression. Conclusion: Adding pictilisib to anastrozole significantly increases suppression of tumor cell proliferation in luminal B primary breast cancer

Gender differences in the clinical management of patients with angina pectoris: a cross-sectional survey in primary care

Non peer reviewedPublisher PD

HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer

BACKGROUND: Oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. METHODS: All available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki672wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. FINDINGS: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki672wk (p<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. INTERPRETATION: Our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse

Prevalence of overweight and obese children between 1989 and 1998: population based series of cross sectional studies

OBJECTIVE: To determine trends in weight, height, and body mass index in children between 1989 and 1998. DESIGN: Retrospective series of cross sectional studies of routinely collected data. SETTING: Primary care in the Wirral Health Authority. PARTICIPANTS: 35 662 infants aged 1-3 months (representing 88% of live births) and 28 768 children aged 2.9-4.0 years. 21 582 infants and children (25.1%) were excluded because of missing or inaccurate data. MAIN OUTCOME MEASURES: Weight, height, sex, and age routinely recorded by health visitors. Height, weight, and body mass index standardised for age and sex. SD score >1.04 for body mass index (>85th centile) was defined as overweight and >1.64 (>95th centile) as obese. Body mass index was not calculated in infants as it is difficult to interpret. RESULTS: From 1989 to 1998 there was a highly significant increasing trend in the proportion of overweight children (14.7% to 23.6%; P<0.001) and obese children (5.4% to 9.2%; P<0.001). There was also a highly significant increasing trend in the mean SD score for weight (0.05 to 0.29; P<0.001) and body mass index (−0.15 to 0.31; P<0.001) but not height. Infants showed a small but significantly increasing trend in mean SD score for weight (−0.17 to −0.05; P=0.005). CONCLUSIONS: From 1989 to 1998 there was a highly significant increase in weight and body mass index in children under 4 years of age. Routinely collected data are valuable in identifying anthropometric trends in populations