Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer

The AZURE trial is an ongoing phase III, academic, multi-centre, randomised trial designed to evaluate the role of zoledronic acid (ZOL) in the adjuvant therapy of women with stage II/III breast cancer. Here, we report the safety and tolerability profile of ZOL in this setting. Eligible patients received (neo)adjuvant chemotherapy and/or endocrine therapy and were randomised to receive neither additional treatment nor intravenous ZOL 4 mg. ZOL was administered after each chemotherapy cycle to exploit potential sequence-dependent synergy. ZOL was continued for 60 months post-randomisation (six doses in the first 6 months, eight doses in the following 24 months and five doses in the final 30 months). Serious (SAE) and non-serious adverse event (AE) data generated during the first 36 months on study were analysed for the safety population. 3,360 patients were recruited to the AZURE trial. The safety population comprised 3,340 patients (ZOL 1,665; control 1,675). The addition of ZOL to standard treatment did not significantly impact on chemotherapy delivery. SAE were similar in both treatment arms. No significant safety differences were seen apart from the occurrence of osteonecrosis of the jaw (ONJ) in the ZOL group (11 confirmed cases; 0.7%; 95% confidence interval 0.3–1.1%). ZOL in the adjuvant setting is well tolerated, and can be safely administered in addition to adjuvant therapy including chemotherapy. The adverse events were consistent with the known safety profile of ZOL, with a low incidence of ONJ

The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour response: exploratory evidence for direct anti-tumour activity in breast cancer

Background: Pre-clinical studies have demonstrated synergistic anti-tumour effects of chemotherapy (CT) and zoledronic acid (ZOL). Within the AZURE trial, designed to determine whether the addition of ZOL to neoadjuvant therapy improves disease outcomes, a subgroup received neoadjuvant CT. We report a retrospective evaluation comparing pathological response in the primary tumour between treatment groups. Methods: In total, 205 patients received neoadjuvant CT±ZOL (CT+ZOL, n=102; CT, n=103). The primary end point was pathologically assessed residual invasive tumour size (RITS) at surgery. Secondary end points were pathological complete response (pCR) rate and axillary nodal involvement. Following review of surgical pathology reports (n=195), outcome differences between groups were assessed adjusting for potential response modifiers. Results: Baseline characteristics and CT treatments were similar. In multivariate analysis, allowing for biological and clinical factors known to influence tumour response, the adjusted mean RITS in CT and CT+ZOL groups were 27.4 and 15.5 mm, respectively, giving a difference in means of 12 mm (95% confidence interval: 3.5–20.4 mm; P=0.006). The pCR rate was 6.9% in the CT group and 11.7% in the CT+ZOL group (P=0.146). There was no difference in axillary nodal involvement (P=0.6315). Conclusion: These data suggest a possible direct anti-tumour effect of ZOL in combination with CT, warranting formal evaluation in prospective studies

Post-operative exercises after breast cancer surgery: results of a RCT evaluating standard care versus standard care plus additional yoga exercise

Introduction: There is a lack of standardisation in the guidelines for post-operative exercises following breast cancer surgery. Adherence to exercise programmes is low, and complementary therapies such as yoga often appeal to patients and may encourage practise. A step-by-step guide to yoga DVD was evaluated in addition to the standard care exercises (SC) compared to SC alone. Methods: Women with early-stage breast cancer were randomised to SC plus or minus a yoga DVD for 10-weeks. Patient-reported outcomes were collected at baseline, 10 weeks and 6 months. The primary study-endpoint was the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Treatment-Breast; a recognised quality of life (QoL) tool with an arm morbidity subscale (FACT-B+4). Results: 92/103 (89%) women were randomised to the study. The SC group reported practising post-operative exercises more often than the yoga DVD group. There was a 69% improvement from baseline in FACT-B+4 TOI, which included an arm subscale, at 10 weeks and 6 months in the SC group. This was 62% and 81% respectively for the yoga DVD group. Numbness in the affected arm was greater in the SC group (OR= 2.5, 95% CI: 1.1, 5.6) and in patients receiving chemotherapy (OR=2.17, 95% CI: 1, 4.6). Despite no group differences, 74% of women would definitely recommend following the yoga DVD after surgery. Conclusions: Practising post-operative exercises does improve arm and shoulder morbidity following breast cancer surgery. The addition of a self-practise general yoga programme was well received and appeared to improve QoL at 6 months

The curious under‐representation of women impact case leaders: Can we disengender inequality regimes?

Universities are increasingly expected to demonstrate the wider societal impacts of academic research. Yet women management scholars were disproportionately under‐represented in leading impact cases in the UK's REF (Research Excellence Framework) 2014. An analysis of 395 REF impact cases for business and management studies with an identifiable lead author revealed that only 25 per cent were led by women, of which 54 per cent were sole authored. Based on 12 in‐depth interviews with women impact case writers, we use Acker's inequality regimes framework to understand invisible and socially constructed gendering of the UK's policy that is designed to evaluate research impact. In a knowledge‐intensive workplace dominated by men, the shape and degree of gendered bases of inequality, systemic practices, processes and controls result in sub‐optimal talent management and gendered knowledge. We call for university leaders to be proactive in addressing barriers that fail to support or recognize women's leadership of research impact

A user-centred approach to developing bWell, a mobile app for arm and shoulder exercises after breast cancer treatment

Purpose: The study aim was to develop a mobile application (app) supported by user preferences to optimise self-management of arm and shoulder exercises for upper-limb dysfunction (ULD) after breast cancer treatment. Methods: Focus groups with breast cancer patients were held to identify user needs and requirements. Behaviour change techniques were explored by researchers and discussed during the focus groups. Concepts for content were identified by thematic analysis. A rapid review was conducted to inform the exercise programme. Preliminary testing was carried out to obtain user feedback from breast cancer patients who used the app for 8 weeks post-surgery. Results: Breast cancer patients’ experiences with ULD and exercise advice and routines varied widely. They identified and prioritised several app features: tailored information, video demonstrations of the exercises, push notifications, and tracking and progress features. An evidence-based programme was developed with a physiotherapist with progressive exercises for passive and active mobilisation, stretching and strengthening. The exercise demonstration videos were filmed with a breast cancer patient. Early user testing demonstrated ease of use, and clear and motivating app content. Conclusions: bWell, a novel app for arm and shoulder exercises was developed by breast cancer patients, health care professionals and academics. Further research is warranted to confirm its clinical effectiveness. Implications for Cancer Survivors: Mobile health has great potential to provide patients with information specific to their needs. bWell is a promising way to support breast cancer patients with exercise routines after treatment and may improve future self-management of clinical care

Genders at Work: Gender as a Geography of Power in the Academy

This chapter discusses contemporary research investigating how gender operates as a geography of power in the contemporary academy, particularly in relation to notions of ‘career’. Massey’s understanding of space as ‘a simultaneity of stories-so-far and places as collections of those stories’ (2005, p.11) shapes the research questions and a methodology of ‘spatial storytelling’ which foregrounds relationships between space and power in considering lived experiences of work and career. The chapter presents a selection of participants’ ‘stories-so-far’ which illustrate the complexity and dimensionality of lived, gendered experiences in the workplace and provide a basis for reflection on the opportunities these afford to resist sexism in the academy