Overdiagnosis due to screening mammography for women aged 40 years and over

This is a protocol for a Cochrane Review. The objective was to assess the effect of screening mammography for breast cancer on overdiagnosis in women aged 40 years and older at average risk of breast cancer

Adherence to prescribing restrictions for HER2-positive metastatic breast cancer in Australia: A national population-based observational study (2001-2016)

Background: Targeted cancer therapy is often complex, involving multiple agents and chemotherapeutic partners. In Australia, prescribing restrictions are put in place to reflect existing evidence of cost-effectiveness of these medicines. As therapeutic options continue to expand, these restrictions may not be perceived to align with best practice and it is not known if their use in the real-world clinic adheres to these restrictions. We examined the treatment of women receiving trastuzumab for HER2-positive metastatic breast cancer (HER2+MBC) to determine the extent to which treatment adhered to national prescribing restrictions. Patients and methods: Our population-based, retrospective cohort study used dispensing records for every Australian woman initiating publicly-subsidised trastuzumab for HER2+MBC between 2001±2013, followed through 2016. We used group-based trajectory models (GBTMs) to cluster patients, first on their patterns of trastuzumab exposure, and then on their patterns of lapatinib and chemotherapy exposure. We described the characteristics of patients within each cluster, and examined their treatments and combinations of treatments to determine restriction adherence. Results: Of 5,052 patients initiating trastuzumab, 1,795 (36%) received at least one non-adherent HER2-targeted treatment. The most common non-adherent treatments were trastuzumab combinations involving vinorelbine (24% of non-adherent treatments); capecitabine (24%); and anthracyclines (10%). Non-adherent lapatinib use was observed in 4% of patients. GBTM identified three trastuzumab exposure clusters, each containing three further subclusters. The largest proportions of non-adherent treatments were in sub-clusters with longer trastuzumab exposure and more non-taxane chemotherapy. Patients in these sub-clusters were younger than those in sub-clusters with less non-adherent treatment. Conclusions: Our study highlights that, even during the relatively simpler treatment era of our study period, a substantial amount of treatment did not adhere to prescribing restrictions. As more trials are conducted exploring pertuzumab and T-DM1 in combination with different chemotherapies and other HER2-targeted therapies, the regulation and funding of HER2-targeted treatment will become more challenging

Use and outcomes of targeted therapies in early and metastatic HER2-positive breast cancer in Australia: Protocol detailing observations in a whole of population cohort

Background: The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has changed dramatically with the introduction and widespread use of HER2-targeted therapies. However, there is relatively limited real-world information on patterns of use, effectiveness and safety in whole of population cohorts. The research programme detailed in this protocol will generate evidence on the prescribing patterns, safety monitoring and outcomes of patients with BC treated with HER2- targeted therapies in Australia. Methods/design: Our ongoing research programme will involve a series of retrospective cohort studies that include every patient accessing Commonwealth-funded HER2-targeted therapies for the treatment of early BC and advanced BC in Australia. At the time of writing, our cohorts consist of 11 406 patients with early BC and 5631 with advanced BC who accessed trastuzumab and lapatinib between 2001 and 2014. Pertuzumab and trastuzumab emtansine were publicly funded for metastatic BC in 2015, and future data updates will include patients accessing these medicines. We will use dispensing claims for cancer and other medicines, medical service claims and demographics data for each patient accessing HER2- targeted therapies to undertake this research. Ethics and dissemination: Ethics approval has been granted by the Population Health Service Research Ethics Committee and data access approval has been granted by the Australian Department of Human Services (DHS) External Review Evaluation Committee. Our findings will be reported in peer-reviewed publications, conference presentations and policy forums. By providing detailed information on the use and outcomes associated with HER2-targeted therapies in a national cohort treated in routine clinical care, our research programme will better inform clinicians and patients about the real-world use of these treatments and will assist third-party payers to better understand the use and economic costs of these treatments

Should tomosynthesis replace mammography for breast cancer screening?

Editorial - no abstract availabl

Accuracy and Outcomes of Screening Mammography in Women With a Personal History of Early-Stage Breast Cancer

Women with a personal history of breast cancer (PHBC) are at risk of developing another breast cancer and are recommended for screening mammography. Few high-quality data exist on screening performance in PHBC women

Radiological clinical trials: Proposal of a problem-finding questionnaire to improve study success

open5AIM To develop a survey to help define the main problems in radiological clinical trials. METHODS Since 2006, we have managed seven different radio-logical clinical trials recruiting patients in academic and non-academic centres. We developed a preliminary questionnaire using a four-round Delphi approach to identify problems occurring in radiological clinical trials run at our centre. We investigated the recruitment experience, involvement of all multi-disciplinary team members and main obstacles to completing the projects. A final round of Delphi processes elucidated solutions to the identified problems.openValdora, Francesca; Bignotti, Bianca; Calabrese, Massimo; Houssami, Nehmat; Tagliafico, AlbertoValdora, Francesca; Bignotti, Bianca; Calabrese, Massimo; Houssami, Nehmat; Tagliafico, Albert

Hormone replacement therapy use dramatically increases breast oestrogen receptor expression in obese postmenopausal women

BACKGROUND: It is known that use of hormone replacement therapy (HRT) by postmenopausal women increases the risk of breast cancer. METHOD: In this study, oestrogen receptor (ER)-α expression is examined using standard immunoperoxidase technique. RESULTS: Normal breast samples of 11 Australian postmenopausal women have been included in the ER-α study; the result showed a strong correlation (r(2) = 0.80) between ER-α expression in normal breast epithelial cells and body mass index (BMI) in normal women who currently use HRT. CONCLUSION: This finding confirms that the possibility of increased risk of breast cancer associated with increased ER-α expression in normal breast epithelial cells, in turn associated with high BMI and the use of HRT

Development of a numerical and experimental framework to understand and predict the burning dynamics of porous fuel beds

Understanding the burning behaviour of litter fuels is essential before developing a complete understanding of wildfire spread. The challenge of predicting the fire behaviour of such fuels arises from their porous nature and from the strong coupling of the physico-chemical complexities of the fuel with the surrounding environment, which controls the burning dynamics. In this work, a method is presented to accurately understand the processes which control the burning behaviour of a wildland fuel layer using numerical simulations coupled with laboratory experiments. Simulations are undertaken with ForestFireFOAM, a modification of FireFOAM that uses a Large Eddy Simulation solver to represent porous fuel by implementing a multiphase formulation to conservation equations (mass, momentum, and energy). This approach allows the fire- induced behaviour of a porous, reactive and radiative medium to be simulated. Conservation equations are solved in an averaged control volume at a scale su cient to contain both coexisting gas and solid phases, considering strong coupling between the phases. Processes such as drying, pyrolysis, and char combustion are described through temperature-dependent interaction between the solid and gas phases. Di↵erent sub-models for heat transfer, pyrolysis, gas combustion, and smouldering have been implemented and tested to allow better representation of these combustion processes. Numerical simulations are compared with experiments undertaken in a controlled environment using the FM Global Fire Propagation Apparatus. Pine needle beds of varying densities and surface to volume ratios were subject to radiative heat fluxes and flows to interrogate the ignition and combustion behaviour. After including modified descriptions of the heat transfer, degradation, and combustion models, it is shown that key flammability parameters of mass loss rates, heat release rates, gas emissions and temperature fields agree well with experimental observations. Using this approach, we are able to provide the appropriate modifications to represent the burning behaviour of complex wildland fuels in a range of conditions representative of real fires. It is anticipated that this framework will support larger-scale model development and optimisation of fire simulations of wildland fuels

Perceptions and misperceptions of overdetection of breast cancer.

Editorial piece commenting on: Pappadis MR, Volk RJ, Krishnan S, et al. Perceptions of overdetection of breast cancer among women 70 years of age and older in the USA: a mixed-methods analysis. BMJ Open 2018;8:e022138

Breast density notification: A systematic review of the impact on primary care practitioners

Background: In the last decade, there has been an unprecedented amount of advocacy and attention surrounding the issue of breast density (BD) in relation to mammography screening. It is largely unknown what impact notifying women of their BD has had on clinical practice for PCPs. This systematic review aimed to synthesize evidence from existing studies to understand the impact of BD notification on primary care practitioners\u27 (PCPs) knowledge, attitudes, and practice implications. Methods: Empirical studies were identified through relevant database searches (database inception to May 2020). Two authors evaluated the eligibility of studies, extracted and crosschecked data, and assessed the risk of bias. Results were synthesized in a narrative form. Results: Six studies of the 232 titles identified and screened were included. All studies were undertaken in the United States, with five conducted postlegislation in their respective states, and one study conducted in states that were both prelegislation and postlegislation. Five studies were quantitative, including four cross-sectional surveys, and one study was qualitative. Findings consistently demonstrated PCPs\u27 overall lack of knowledge about BD, low level of comfort in discussing and managing patients in relation to dense breasts, and limited consensus on the most appropriate approach for managing women with dense breasts, particularly in relation to supplemental screening. Conclusions: This review highlights important gaps in PCPs\u27 understanding of BD and confidence in having discussions with women about the implications of dense breasts. It identifies the need for high-quality research and the development of evidence-based guidelines to better support PCPs