Factors Influencing Time From Diagnosis to Treatment of Breast Cancer and the Impact of Longer Waiting Time on Survival in Kathmandu Valley, Nepal: A Population-Based Study.

PURPOSE: Longer time between breast cancer (BC) diagnosis and treatment initiation is associated with poorer survival, and this may be a factor behind disparities in global survival rates. We assessed time to BC treatment in the Kathmandu Valley, Nepal, including factors associated with longer waiting times and their impact on survival. METHODS: We conducted a retrospective population-based study of BC cases recorded in the Kathmandu Valley Population-Based Cancer Registry between 2018 and 2019. Fieldwork survey through telephone was undertaken to collect additional sociodemographic and clinical information. Logistic regression was performed to identify factors associated with longer time to treatment, and Kaplan-Meier and Cox proportional hazard regression was used to examine survival time and evaluate the association between longer time to treatment and survival. RESULTS: Among the 385 patients with BC, one third waited >4 weeks from diagnosis to initial treatment. Lower education was associated with longer time to treatment (adjusted odds ratio, 1.63 [95% CI, 1.03 to 2.60]). The overall 3-year survival rate was 88.6% and survival was not associated with time to treatment (P = .50). However, advanced stage at diagnosis was associated with poorer survival (adjusted hazard ratio, 4.09 [95% CI, 1.27 to 13.23]). There was some indication that longer time to treatment was associated with poorer survival for advanced-stage patients, but data quality limited that analysis. CONCLUSION: In the Kathmandu Valley, Nepal, women with a lower education tend to wait longer from BC diagnosis to treatment. Patients with advanced-stage BC had poorer survival, and longer waiting time may be associated with poorer survival for women diagnosed with advanced-stage disease.

Contrast-enhanced mammography for surveillance in women with a personal history of breast cancer.

PURPOSE: Women with a personal history of breast cancer have an increased risk of subsequent breast malignancy and may benefit from more sensitive surveillance than conventional mammography (MG). We previously reported outcomes for first surveillance episode using contrast-enhanced mammography (CEM), demonstrating higher sensitivity and comparable specificity to MG. We now report CEM performance for subsequent surveillance. METHODS: A retrospective study of 1,190 women in an Australian hospital setting undergoing annual surveillance following initial surveillance CEM between June 2016 and December 2022. Outcome measures were recall rate, cancer detection rate, contribution of contrast to recalls, false positive rate, interval cancer rate and characteristics of surveillance detected and interval cancers. RESULTS: 2,592 incident surveillance episodes were analysed, of which 93% involved contrast-based imaging. Of 116 (4.5%) recall episodes, 40/116 (34%) recalls were malignant (27 invasive; 13 ductal carcinoma in situ), totalling 15.4 cancers per 1000 surveillance episodes. 55/116 (47%) recalls were contrast-directed including 17/40 (43%) true positive recalls. Tumour features were similar for contrast-directed recalls and other diagnoses. 8/9 (89%) of contrast-directed invasive recalls were Grade 2-3, and 5/9 (56%) were triple negative breast cancers. There were two symptomatic interval cancers (0.8 per 1000 surveillance episodes, program sensitivity 96%). CONCLUSION: Routine use of CEM in surveillance of women with PHBC led to an increase in the detection of clinically significant malignant lesions, with a low interval cancer rate compared to previous published series. Compared to mammographic surveillance, contrast-enhanced mammography increases the sensitivity of surveillance programs for women with PHBC.

Contrast-Enhanced Mammography in Local Staging of Screen-Detected Breast Cancer.

BACKGROUND: BreastScreen Australia, the population mammographic screening program for breast cancer, uses two-view digital screening mammography ± ultrasound followed by percutaneous biopsy to detect breast cancer. Secondary breast imaging for further local staging, not performed at BreastScreen, may identify additional clinically significant breast lesions. Staging options include further mammography, bilateral ultrasound, and/or contrast-based imaging (CBI) [magnetic resonance imaging (MRI) or contrast-enhanced mammography (CEM)]. CBI for local staging of screen-detected cancer was introduced at an academic hospital breast service in Melbourne, VIC, Australia. We report findings for otherwise occult disease and resulting treatment changes. MATERIAL AND METHODS: Patients staged using CEM between November 2018 and April 2022 were identified from hospital records. Data were extracted from radiology, pathology, and breast unit databases. CEM-detected abnormalities were documented as true positive (TP) for invasive cancer or ductal carcinoma in situ (DCIS), or otherwise false positive (FP). The impact on surgical decisions was assessed. RESULTS: Of 202 patients aged 44-84 years, 60 (30%) had 74 additional findings [34 (46%) TP, 40 (54%) FP]. These were malignant in 29/202 (14%) patients (79% invasive cancers, 21% DCIS). CEM resulted in surgical changes in 43/202 (21%) patients: wider resection (24/43), conversion to mastectomy (6/43), contralateral breast surgery (6/43), additional ipsilateral excision (5/43), and bracketing (2/43). Additional findings were more common for patients with larger index lesions and for invasive cancer, but there was no significant variation by age, breast density, or index lesion grade. CONCLUSIONS: CEM for local staging of screen-detected breast cancers identified occult malignancy in 14% of patients. CEM improves local staging and may facilitate appropriate management of screen-detected breast cancers.

Factors influencing the time to diagnosis and treatment of breast cancer among women in low- and middle-income countries: A systematic review.

PURPOSE: Shorter time from symptoms recognition to diagnosis and timely treatment would be expected to improve the survival of patients with breast cancer (BC). This review identifies and summarizes evidence on time to diagnosis and treatment, and associated factors to inform an improved BC care pathways in Low- and Middle-Income Countries (LMICs). METHODS: A systematic search was conducted in electronic databases including Medline, Embase, PsycINFO and Global Health, covering publications between January 1, 2010, and November 6, 2023. Inclusion criteria encompassed studies published in English from LMICs that reported on time from symptoms recognition to diagnosis and/or from diagnosis to treatment, as well as factors influencing these timelines. Study quality was assessed independently by two reviewers using a standard checklist. Pre-contact, post-contact and treatment intervals and delays in these intervals are presented. Barriers and facilitators for shorter time to diagnosis and treatment found by individual studies after adjusting with covariates are summarized. RESULTS: The review identified 21 studies across 14 countries and found that BC cases took a longer time to diagnosis than to treatment. However, time to treatment also exceeded the World Health Organization (WHO) recommended period for optimal survival. There was inconsistency in terminology and benchmarks for defining delays in time intervals. Low socioeconomic status and place of residence emerged as frequent barriers, while initial contact with a private health facility or specialist was commonly reported as a facilitator for shorter time to diagnosis and treatment. CONCLUSIONS: Guidelines or consensus recommendations are essential for defining the optimal time intervals to BC diagnosis and treatment. Our review supported WHO's Global Breast Cancer Initiative recommendations. Increasing public awareness, strengthening of healthcare professional's capacities, partial decentralization of diagnostic services and implementation of effective referral mechanisms are recommended to achieve a shorter time to diagnosis and treatment of BC in LMICs.

Benefits and harms of breast cancer screening: Cohort study of breast cancer mortality and overdiagnosis.

BACKGROUND: Quantifying the benefits and harms of breast cancer screening accurately is important for planning and evaluating screening programs and for enabling women to make informed decisions about participation. However, few cohort studies have attempted to estimate benefit and harm simultaneously. AIMS: We aimed to quantify the impact of mammographic screening on breast cancer mortality and overdiagnosis using a cohort of women invited to attend Australia's national screening program, BreastScreen. METHODS: In a cohort of 41,330 women without prior breast cancer diagnosis, screening, or diagnostic procedures invited to attend BreastScreen Western Australia in 1994-1995, we estimated the cumulative risk of breast cancer mortality and breast cancer incidence (invasive and ductal carcinoma in situ) from age 50 to 85 years for attenders and non-attenders. Data were obtained by linking population-based state and national health registries. Breast cancer mortality risks were estimated from a survival analysis that accounted for competing risk of death from other causes. Breast cancer risk for unscreened women was estimated by survival analysis, while accounting for competing causes of death. For screened women, breast cancer risk was the sum of risk of being diagnosed at first screen, estimated using logistic regression, and risk of diagnosis following a negative first screen estimated from a survival analysis. RESULTS: For every 1,000 women 50 years old at first invitation to attend BreastScreen, there were 20 (95% CI 12-30) fewer breast cancer deaths and 25 (95% CI 15-35) more breast cancers diagnosed for women who attended than for non-attendees by age 85. Of the breast cancers diagnosed in screened women, 21% (95% CI 13%-27%) could be attributed to screening. DISCUSSION: The estimated ratio of benefit to harm was consistent with, but slightly less favourable to screening than most other estimates from cohort studies. CONCLUSION: Women who participate in organised screening for breast cancer in Australia have substantially lower breast cancer mortality, while some screen-detected cancers may be overdiagnosed.

A modelled evaluation of the impact of COVID-19 on breast, bowel, and cervical cancer screening programmes in Australia.

Australia introduced COVID-19 infection prevention and control measures in early 2020. To help prepare health services, the Australian Government Department of Health commissioned a modelled evaluation of the impact of disruptions to population breast, bowel, and cervical cancer screening programmes on cancer outcomes and cancer services. We used the Policy1 modelling platforms to predict outcomes for potential disruptions to cancer screening participation, covering periods of 3, 6, 9, and 12 mo. We estimated missed screens, clinical outcomes (cancer incidence, tumour staging), and various diagnostic service impacts. We found that a 12-mo screening disruption would reduce breast cancer diagnoses (9.3% population-level reduction over 2020-2021) and colorectal cancer (up to 12.1% reduction over 2020-21), and increase cervical cancer diagnoses (up to 3.6% over 2020-2022), with upstaging expected for these cancer types (2, 1.4, and 6.8% for breast, cervical, and colorectal cancers, respectively). Findings for 6-12-mo disruption scenarios illustrate that maintaining screening participation is critical to preventing an increase in the burden of cancer at a population level. We provide programme-specific insights into which outcomes are expected to change, when changes are likely to become apparent, and likely downstream impacts. This evaluation provided evidence to guide decision-making for screening programmes and emphasises the ongoing benefits of maintaining screening in the face of potential future disruptions.

Contrast enhanced mammography in breast cancer surveillance.

PURPOSE: Mammography (MG) is the standard imaging in surveillance of women with a personal history of breast cancer or DCIS (PHBC), supplemented with ultrasound. Contrast Enhanced Mammography (CEM) has higher sensitivity than MG and US. We report the performance of CEM compared with MG ± US. METHODS: A retrospective study of patients undergoing their first surveillance CEM in an Australian hospital setting between June 2006 and October 2020. Cases where a patient was recalled for assessment were identified, recording radiology, pathology and treatment details. Blinded re-reading of recalled cases was performed to determine the contribution of contrast. Use of surveillance US across the board was assessed for the period. RESULTS: 73/1191 (6.1%) patients were recalled. 35 (48%) were true positives (TP), with 26 invasive cancers and 9 cases of DCIS, while 38 (52%) were false positive (FP) with a positive predictive value (PPV) 47.9%. 32/73 were recalled due to MG findings, while 41/73 were only recalled due to Contrast. 14/73 had 'minimal signs' with a lesion identifiable on MG with knowledge of the contrast finding, while 27/73 were visible only with contrast. 41% (17/41) recalled due to contrast were TP. Contrast-only TPs were found with low and high mammographic density (MD). Screening breast US reduced by 55% in the year after CEM was implemented. CONCLUSION: Compared to MG, CEM as a single surveillance modality for those with PHBC has higher sensitivity and comparable specificity, identifying additional malignant lesions that are clinically significant. Investigation of interval cancer and subsequent round outcomes is warranted.

Breast Cancer Risk Assessment Tools for Stratifying Women into Risk Groups: A Systematic Review.

BACKGROUND: The benefits and harms of breast screening may be better balanced through a risk-stratified approach. We conducted a systematic review assessing the accuracy of questionnaire-based risk assessment tools for this purpose. METHODS: Population: asymptomatic women aged ≥40 years; Intervention: questionnaire-based risk assessment tool (incorporating breast density and polygenic risk where available); Comparison: different tool applied to the same population; Primary outcome: breast cancer incidence; Scope: external validation studies identified from databases including Medline and Embase (period 1 January 2008-20 July 2021). We assessed calibration (goodness-of-fit) between expected and observed cancers and compared observed cancer rates by risk group. Risk of bias was assessed with PROBAST. RESULTS: Of 5124 records, 13 were included examining 11 tools across 15 cohorts. The Gail tool was most represented (n = 11), followed by Tyrer-Cuzick (n = 5), BRCAPRO and iCARE-Lit (n = 3). No tool was consistently well-calibrated across multiple studies and breast density or polygenic risk scores did not improve calibration. Most tools identified a risk group with higher rates of observed cancers, but few tools identified lower-risk groups across different settings. All tools demonstrated a high risk of bias. CONCLUSION: Some risk tools can identify groups of women at higher or lower breast cancer risk, but this is highly dependent on the setting and population.

BreastScreen Australia national data by factors of interest for risk-based screening: routinely reported data and opportunities for enhancement.

OBJECTIVE: There is growing interest in more risk-based approaches to breast cancer screening in Australia. This would require more detailed reporting of BreastScreen data for factors of interest in the assessment and monitoring of risk-based screening. This review assesses the current and potential availability and reporting of BreastScreen data for this purpose. METHODS: We systematically searched governmental BreastScreen reports and peer-reviewed literature to assess current and potential availability of outcomes for predetermined factors including breast cancer risk factors and factors important for implementing, monitoring or evaluating risk-based screening. Outcomes evaluated were BreastScreen Performance Indicators routinely included in BreastScreen Australia monitoring reports, and key tumour characteristics. RESULTS: All outcomes were reported annually by age group, except for tumour hormone receptor status, nodal involvement and grade. Screening participation was reported nationally for many factors important for risk-based screening; other reporting was ad hoc or unavailable. CONCLUSIONS: There is potential to build on BreastScreen's existing high-quality national data collection and reporting systems to inform and support risk-based breast screening. IMPLICATIONS FOR PUBLIC HEALTH: Enhanced BreastScreen data collection and reporting would improve the evidence base and support evaluation of risk-based screening and improve the detail available for benchmarking any future changes to the program.

The impact of the Covid-19 pandemic on breast cancer early detection and screening.

The COVID-19 pandemic affects mortality and morbidity, with disruptions expected to continue for some time, with access to timely cancer-related services a concern. For breast cancer, early detection and treatment is key to improved survival and longer-term quality of life. Health services generally have been strained and in many settings with population breast mammography screening, efforts to diagnose and treat breast cancers earlier have been paused or have had reduced capacity. The resulting delays to diagnosis and treatment may lead to more intensive treatment requirements and, potentially, increased mortality. Modelled evaluations can support responses to the pandemic by estimating short- and long-term outcomes for various scenarios. Multiple calibrated and validated models exist for breast cancer screening, and some have been applied in 2020 to estimate the impact of breast screening disruptions and compare options for recovery, in a range of international settings. On behalf of the Covid and Cancer Modelling Consortium (CCGMC) Working Group 2 (Breast Cancer), we summarize and provide examples of such in a range of settings internationally, and propose priorities for future modelling exercises. International expert collaborations from the CCGMC Working Group 2 (Breast Cancer) will conduct analyses and modelling studies needed to inform key stakeholders recovery efforts in order to mitigate the impact of the pandemic on early diagnosis and treatment of breast cancer.

Breast cancer screening and overdiagnosis.

Overdiagnosis is a harmful consequence of screening which is particularly challenging to estimate. An unbiased setting to measure overdiagnosis in breast cancer screening requires comparative data from a screened and an unscreened cohort for at least 30 years. Such randomised data will not become available, leaving us with observational data over shorter time periods and outcomes of modelling. This collaborative effort of the International Cancer Screening Network quantified the variation in estimated breast cancer overdiagnosis in organised programmes with evaluation of both observed and simulated data, and presented examples of how modelling can provide additional insights. Reliable observational data, analysed with study design accounting for methodological pitfalls, and modelling studies with different approaches, indicate that overdiagnosis accounts for less than 10% of invasive breast cancer cases in a screening target population of women aged 50 to 69. Estimates above this level are likely to derive from inaccuracies in study design. The widely discrepant estimates of overdiagnosis reported from observational data could substantially be reduced by use of a cohort study design with at least 10 years of follow-up after screening stops. In contexts where concomitant opportunistic screening or gradual implementation of screening occurs, and data on valid comparison groups are not readily available, modelling of screening intervention becomes an advantageous option to obtain reliable estimates of breast cancer overdiagnosis.

Moving beyond the stage: how characteristics at diagnosis dictate treatment and treatment-related quality of life year losses for women with early stage invasive breast cancer.

Background:Although evaluations of breast cancer screening programs frequently estimate quality-adjusted life-year (QALY) losses by stage, other breast cancer characteristics influence treatment and vary by mode of detection - i.e. whether the cancer is detected through screening (screen-detected), between screening rounds (interval-detected) or outside screening (community-detected). Here, we estimate the association between early-stage invasive breast cancer (ESIBC) characteristics and treatment-related QALY losses.Methods:Using clinicopathological and treatment information from 675 women managed for ESIBC, we estimated the average five-year treatment-related QALY loss by detection group. We then used regression analysis to estimate the extent to which known cancer characteristics and the detection mode, are associated with treatment and treatment-related QALY losses.Results:Community-detected cancers had the largest QALY loss (0.76 QALYs [95% CI 0.73;0.80]), followed by interval-detected cancers (0.75 QALYs [95% CI 0.68;0.82]) and screen-detected cancers (0.69 QALYs [95%CI 0.67;0.71]). Adverse prognostic factors more common in community-detected and interval-detected breast cancers (large tumours, lymph node involvement, high grade) were largely associated with QALY losses from mastectomies and chemotherapy. Receptor-positive subtypes, more common in screen-detected cancers, were associated with QALY losses related to endocrine therapy.Conclusions:The associations between ESIBC characteristics and treatment-related QALY losses should be considered when evaluating breast cancer screening and treatment strategies.

How has COVID-19 impacted cancer screening? Adaptation of services and the future outlook in Australia.

The coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions to many aspects of life in Australia and globally. This includes actual and potential future impacts on Australia's three national screening programs for breast, bowel and cervical cancer. These programs aim to improve cancer outcomes through an organised approach to the early detection of cancer and precancer in asymptomatic populations. The design of each program varies according to biological differences in the three cancers, the available screening technology, the target population, and variations in their administration of Australia's federal, state and territory jurisdictions. The observed and potential impacts of COVID-19 on these programs, and on related activities such as the current national enquiry into lung cancer screening feasibility, therefore vary significantly. This article focuses on observed short-term impacts, adaptations and the longer-term outlook for cancer screening in relation to COVID-19. It summarises potential responses to minimise the harms of disruptions caused by COVID-19, and highlights research and policy opportunities in the pandemic response and recovery which could inform and accelerate optimisation of cancer screening in the long term.

The TP53 mutation rate differs in breast cancers that arise in women with high or low mammographic density.

Mammographic density (MD) influences breast cancer risk, but how this is mediated is unknown. Molecular differences between breast cancers arising in the context of the lowest and highest quintiles of mammographic density may identify the mechanism through which MD drives breast cancer development. Women diagnosed with invasive or in situ breast cancer where MD measurement was also available (n = 842) were identified from the Lifepool cohort of >54,000 women participating in population-based mammographic screening. This group included 142 carcinomas in the lowest quintile of MD and 119 carcinomas in the highest quintile. Clinico-pathological and family history information were recorded. Tumor DNA was collected where available (n = 56) and sequenced for breast cancer predisposition and driver gene mutations, including copy number alterations. Compared to carcinomas from low-MD breasts, those from high-MD breasts were significantly associated with a younger age at diagnosis and features associated with poor prognosis. Low- and high-MD carcinomas matched for grade, histological subtype, and hormone receptor status were compared for somatic genetic features. Low-MD carcinomas had a significantly increased frequency of TP53 mutations, higher homologous recombination deficiency, higher fraction of the genome altered, and more copy number gains on chromosome 1q and losses on 17p. While high-MD carcinomas showed enrichment of tumor-infiltrating lymphocytes in the stroma. The data demonstrate that when tumors were matched for confounding clinico-pathological features, a proportion in the lowest quintile of MD appear biologically distinct, reflective of microenvironment differences between the lowest and highest quintiles of MD.

The financial impact of a breast cancer detected within and outside of screening: lessons from the Australian Lifepool cohort.

OBJECTIVE: To determine the government and out-of-pocket community costs (out-of-hospital medical services and prescription medicines) associated with screen-detected and community-detected cancers (i.e. cancers detected outside of Australia's organised screening program [BreastScreen]). METHODS: We analyse administrative data on government-subsidised medical services and prescription medicines for 568 Victorian women diagnosed with breast cancer or ductal carcinoma in situ (DCIS). Using multivariable regression analysis, we estimate the government and out-of-pocket community costs incurred in the three years after diagnosis for screen-detected cancers and community-detected cancers. Additionally, we estimate the government costs associated with diagnosis within and outside of BreastScreen. RESULTS: Average government costs for breast cancer diagnosis were similar within and outside of BreastScreen [$808 (lower limit 676; upper limit 940) vs $837 (95%CI 671; 1,003) respectively]; however, women with community-detected cancers incurred an additional $254 (95%CI 175; 332) out-of-pocket. Controlling for differences in known cancer characteristics, compared to screen-detected cancers, community-detected breast cancers were associated with an additional $2,622 (95%CI 644; 4,776) in government expenditure in the three years following diagnosis. Adverse cancer characteristics that were more prevalent in community-detected cancers (high grade, lymph node involvement, HER2 positive receptor status) were associated with increased government and out-of-pocket costs. CONCLUSIONS: Community-detected breast cancers were associated with increased government and out-of-pocket costs. Implications for public health: These costs should be considered when evaluating current and alternative breast cancer screening strategies.

Valuing preferences for treating screen detected ductal carcinoma in situ.

BACKGROUND: Mammographic screening reduces breast cancer mortality but may lead to the overdiagnosis and overtreatment of low-risk breast cancers. Conservative management may reduce the potential harm of overtreatment, yet little is known about the impact upon quality of life. OBJECTIVES: To quantify women's preferences for managing low-risk screen detected ductal carcinoma in situ (DCIS), including the acceptability of active monitoring as an alternative treatment. METHODS: Utilities (cardinal measures of quality of life) were elicited from 172 women using visual analogue scales (VASs), standard gambles, and the Euro-Qol-5D-5L questionnaire for seven health states describing treatments for low-risk DCIS. Sociodemographics and breast cancer history were examined as predictors of utility. RESULTS: Both patients and non-patients valued active monitoring more favourably on average than conventional treatment. Utilities were lowest for DCIS treated with mastectomy (VAS: 0.454) or breast conserving surgery (BCS) with adjuvant radiotherapy (VAS: 0.575). The utility of active monitoring was comparable to BCS alone but was rated more favourably as progression risk was reduced from 40% to 10%. Disutility for active monitoring was likely driven by anxiety around progression, whereas conventional management impacted other dimensions of quality of life. The heterogeneity between individual preferences could not be explained by sociodemographic variables, suggesting that the factors influencing women's preferences are complex. CONCLUSIONS: Active monitoring of low-risk DCIS is likely to be an acceptable alternative for reducing the impact of overdiagnosis and overtreatment in terms of quality of life. Further research is required to determine subgroups more likely to opt for conservative management.

Improving breast cancer screening in Australia: a public health perspective.

There are currently no single disruptors to breast cancer screening akin to the impact of human papillomavirus testing and vaccination on cervical cancer screening. However, there is a groundswell of interest to review the BreastScreen Australia program to consider more risk-based screening protocols and to establish whether to routinely inform women about their breast density. We propose a framework for a considered, evidence-based review. Population-level effectiveness of breast cancer screening is ultimately measured through its impact on breast cancer mortality, and this has been realised in Australia. Effectiveness can also be measured through treatment intensity, estimated overdiagnosis, false-positive screens and health economics measures. Key levers to improve such population-level outcomes include screening participation, screening test sensitivity and specificity, risk assessment and screening protocols. We propose that the review of the program should fall under an evidence-based, consensus-guided framework comprising four complementary elements: improved evidence on current program performance for population risk subgroups; regularly updated evidence on key levers for change; clinical trials and population simulation modelling working in tandem; and consensus-based decision making about the degree of improvement required to justify change. Informing women about their breast density is feasible and would be valued by some BreastScreen clients to help understand the accuracy of their screening test. However, without agreed protocols for screening women with dense breasts, increases in supplemental screening as observed in other settings would, in Australia, shift screening costs to clients and Medicare. This would reduce equity of access to population screening, and maintaining BreastScreen's usual standard of monitoring and quality management (such as screen-detected and interval cancer diagnoses, and imaging and biopsy rates) would require data linkage between BreastScreen and other services. The proposed framework assesses screening effectiveness in the era of personalised medicine, allows review of multiple factors that may together warrant change, and gives full, evidence-based consideration of the benefits, harms and costs of various approaches to breast cancer screening. To be effective, the framework requires a coordinated approach to generating the evidence required for policy makers, with time to prepare appropriate health services.