IntroductionImmunohistochemistry of primary breast cancer is routinely used to guide changes in therapy at the time of relapse. Retrospective reviews suggest that the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor type 2 (HER2) receptor may differ between the primary and loco-regional recurrence or distant metastases. The Breast Recurrence In Tissues Study (BRITS) was a large, multicentre, prospective study to examine changes in ER, PR and HER2.MethodsMatched primary and recurrent breast cancer tissue samples were prospectively collected from 205 women attending 20 institutions. Central laboratory immunohistochemical analysis of core biopsies and tissue microarrays of ER and PR using the Allred and Quickscore methods and HER2 (confirmed by fluorescence in situ hybridisation (FISH) for HER2 2+) were performed.ResultsFrom 205 consenting women, 18 (8.8%) did not have recurrent disease on biopsy, 35 were ineligible, 13 had insufficient paired tissue and 2 were excluded for safety reasons. Paired samples from 137 women, mean age 62.6 years (range 27-87 years), 83/137 (60.6%) postmenopausal with a median 92.2 months (range 5-327 months) from primary to recurrence and 88 (64.2%) as locoregional recurrence were successfully analysed. A switch in receptor status, in either direction, by Allred score, was identified for ER in 14 patients (10.2%; P = 0.983 Wilcoxon sign rank test), PR in 34 (24.8%; P = 0.003 Wilcoxon sign rank test) and HER2 in 4 (2.9%; P = 0.074 Wilcoxon sign rank test). There was no difference between locoregional or distant recurrence in the proportion who switched. The switch in receptor status led to a change in the subsequent treatment plan for 24 patients (17.5%).ConclusionsThis prospective study confirms retrospective evidence that the management of relapsed breast cancer should include confirmatory tissue sampling and identify switches of ER, PR or HER2 which change therapeutic management for one in six patients.

3D cell tumour models are generated mainly in non-scalable culture systems, using bioactive scaffolds. Many of these models fail to reflect the complex tumour microenvironment and do not allow long-term monitoring of tumour progression. To overcome these limitations, we have combined alginate microencapsulation with agitation-based culture systems, to recapitulate and monitor key aspects of the tumour microenvironment and disease progression. Aggregates of MCF-7 breast cancer cells were microencapsulated in alginate, either alone or in combination with human fibroblasts, then cultured for 15 days. In co-cultures, the fibroblasts arranged themselves around the tumour aggregates creating distinct epithelial and stromal compartments. The presence of fibroblasts resulted in secretion of pro-inflammatory cytokines and deposition of collagen in the stromal compartment. Tumour cells established cell-cell contacts and polarised around small lumina in the interior of the aggregates. Over the culture period, there was a reduction in oestrogen receptor and membranous E-cadherin alongside loss of cell polarity, increased collective cell migration and enhanced angiogenic potential in co-cultures. These phenotypic alterations, typical of advanced stages of cancer, were not observed in the mono-cultures of MCF-7 cells. The proposed model system constitutes a new tool to study tumour-stroma crosstalk, disease progression and drug resistance mechanisms.

Purpose: This phase II randomized trial evaluated the efficacy and tolerability of anastrozole combined with gefitinib or anastrozole with placebo in women with hormone receptor-positive metastatic breast cancer (MBC).Experimental Design: Postmenopausal women with hormone receptor-positive measurable or evaluable MBC who had not received prior endocrine therapy for this disease stage or who developed metastatic disease during/after adjuvant tamoxifen were eligible. The primary response variable was progression-free survival (PFS) and secondary response variables included clinical benefit rate, objective response rate, overall survival, safety and tolerability, and pharmacokinetics. Tumor biomarker evaluation was an exploratory objective.Results: Forty-three patients were randomized to anastrozole plus gefitinib and 50 patients were randomized to anastrozole plus placebo of a planned total of 174 patients (enrollment was prematurely discontinued due to slow recruitment). PFS for patients receiving the combination of anastrozole and gefitinib was longer than for patients receiving anastrozole plus placebo [hazard ratio (gefitinib/placebo), 0.55; 95% confidence interval, 0.32-0.94; median PFS, 14.7 versus 8.4 months]. The clinical benefit rate was 49% versus 34%, and the objective response rate was 2% versus 12% with anastrozole plus gefitinib and anastrozole plus placebo, respectively. No evidence of interaction between baseline biomarker levels and relative treatment effect was found. No unexpected adverse events were observed.Conclusion: This small randomized study showed that anastrozole in combination with gefitinib is associated with a marked advantage in PFS compared with anastrozole plus placebo, and that the combination was tolerated in postmenopausal women with hormone receptor-positive MBC. Further investigation of epidermal growth factor receptor inhibition in combination with endocrine therapy may be warranted.

Mobile health (mHealth) technologies are increasingly used across health programming including intimate partner violence (IPV) prevention to optimize screening, educational outreach, and linkages to care via telehealth. We systematically evaluated current web-based and mHealth interventions, which include web- or mobile-based delivery methods for primary, secondary, and tertiary IPV victimization prevention. We searched MEDLINE/PubMed, Embase, CINAHL, PsycINFO, Open Grey, and Google Scholar for empirical studies published 1998–2019. Studies were included if they considered empirical data, participants in adult romantic relationships, IPV as a primary or secondary outcome, and an mHealth component. The Mixed Methods Appraisal Tool was used to record critical ratings of quality among studies selected for inclusion. We assessed variation in targeted populations, types of IPV addressed, and mHealth approaches used. Of 133 studies identified for full-text review, 31 were included. Computer-based screening with or without integrated education was the most common mHealth approach ( n = 8, 26%), followed by safety decision aids ( n = 7, 23%). Feasibility and acceptability were found to be generally high where assessed (23% of studies, n = 7). There was limited evidence around whether mHealth interventions better addressed population needs compared to conventional interventions. mHealth tools for IPV prevention are especially acceptable in health-care settings, on mobile phone platforms, or when connecting victims to health care. Despite enthusiasm in pilot projects, evidence for efficacy compared to conventional IPV prevention approaches is limited. A major strength of mHealth IPV prevention programming is the ability to tailor interventions to individual victim needs without extensive human resource expenditure by providers.