Publications by authors named "Nehmat Houssami"

206 Publications

The impact of mandatory mammographic breast density notification on supplemental screening practice in the United States: a systematic review.

Breast Cancer Res Treat 2021 Mar 28. Epub 2021 Mar 28.

Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.

Purpose: Dense breast tissue is an independent risk factor for breast cancer and lowers the sensitivity of screening mammography. Supplemental screening with ultrasound or MRI improves breast cancer detection rate but has potential harms. Breast density notification (BDN) legislation has been introduced in the United States (US) and its impact on supplemental screening practice is unclear. This study systematically reviewed current evidence to explore the impact of BDN on supplemental screening practice in the US.

Methods: Medline, PubMed, Embase, Cochrane and the Cinhal Library databases were searched (2009-August 2020). Studies were assessed for eligibility, data were extracted and summarised, and study quality was evaluated.

Results: Evidence from the included studies (n = 14) predominantly showed that BDN legislation increased the overall utilisation of supplemental screening by 0.5-143%. This effect was amplified if the notification included a follow-up telephone call informing women about additional screening benefits, and if the state's law mandated insurance cover for supplemental screening. Likelihood of supplemental screening was also influenced by history of breast biopsy and family history of breast cancer, race, age, socioeconomic status, density category, and physician's specialty and region. Some studies reported increases in biopsy rate (up to 4%) and cancer detection rate (up to 11%) after implementation of BDN legislation.

Conclusion: BDN leads to increased use of supplemental screening. This has implications for women and the health system. These findings can help inform current and future screening programs, where breast density notification is currently implemented or being considered.
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http://dx.doi.org/10.1007/s10549-021-06203-wDOI Listing
March 2021

Meta-analysis of prospective studies evaluating breast cancer detection and interval cancer rates for digital breast tomosynthesis versus mammography population screening.

Eur J Cancer 2021 Mar 8;148:14-23. Epub 2021 Mar 8.

Section of Breast Screening, Cancer Registry of Norway, Oslo, Norway.

Introduction: Breast cancer (BC) screening using digital breast tomosynthesis (DBT) has been shown to increase cancer detection compared with mammography; however, it is unknown whether DBT impacts interval cancer rate (ICR).

Methods: We systematically identified prospective DBT studies reporting data on screen-detected and interval BCs to perform a study-level meta-analysis of the comparative effect of DBT on ICR in population screening. Meta-analysis of cancer detection rate (CDR), ICR, and the differences between DBT and mammography in CDR and ICR pooled estimates, included random-effects. Sensitivity analysis examined whether study methods (imaging used, comparison group design, interval BC ascertainment) affected pooled estimates.

Results: Five eligible prospective (non-randomised) studies of DBT population screening reported on 129,969 DBT-screened participants and 227,882 mammography-only screens, including follow-up publications reporting interval BC data. Pooled CDR was 9.03/1000 (95% confidence interval [CI] 8.53-9.56) for DBT, and 5.95/1000 (95% CI 5.65-6.28) for mammography: the pooled difference in CDR was 3.15/1000 (95% CI 2.53-3.77), and was evident for the detection of invasive and in-situ malignancy. Pooled ICR was 1.56/1000 DBT screens (95% CI 1.22-2.00), and 1.75/1000 mammography screens (95% CI 1.46-2.11): the estimated pooled difference in ICR was -0.15/1000 (95% CI -0.59 to 0.29) and was not substantially altered in several sensitivity analyses.

Conclusions: Meta-analysis shows consistent evidence that DBT significantly increased CDR compared with mammography screening; however, there was little difference between DBT and mammography in pooled ICR. This could suggest, but does not demonstrate, some over-detection. Meta-analysis using individual participant data, randomised trials and comparative studies quantifying cumulative detection and ICR over repeat DBT screen-rounds would provide valuable evidence to inform screening programs.
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http://dx.doi.org/10.1016/j.ejca.2021.01.035DOI Listing
March 2021

Breast Density Notification: A Systematic Review of the Impact on Primary Care Practitioners.

J Womens Health (Larchmt) 2021 Mar 3. Epub 2021 Mar 3.

Wiser Healthcare, Faculty of Medicine and Health, Sydney School of Public Health, The University of Sydney, Sydney, Australia.

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' (PCPs) knowledge, attitudes, and practice implications. 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. 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' 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. This review highlights important gaps in PCPs' 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.
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http://dx.doi.org/10.1089/jwh.2020.8898DOI Listing
March 2021

Impact of the age expansion of breast screening on screening uptake and screening outcomes among older women in BreastScreen western.

Breast 2021 Apr 11;56:96-102. Epub 2021 Feb 11.

Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.

Objectives: To assess the impact of age expansion of screening (EOS) of the target age group from 50 to 69 to 50-74 in Australia, which began mid-2013, by examining screening uptake and outcomes of older women, and by identifying factors associated with continuing screening after reaching the age of 75 years.

Methods: Retrospective study using data from women aged 65+ who attended BreastScreen Western Australia between 2010 and 2017 for free mammograms. Screening uptake and screening outcomes were calculated for the periods before (2010-2012) and after (2015-2017) the age EOS to women aged 70-74. Logistic regression was used to identify variables associated with continuing screening after reaching age 75 years, while controlling for possible confounding variables.

Results: Age EOS increased screening uptake amongst women aged 70-74 b y 36% and amongst women ≥75 years by 3% while screening uptake in women aged 65-69 decreased by 3%. Rate of invasive screened-detected cancers significantly decreased among women aged 70-74 from 11.4/1000 screens before to 8.1/1000 screens after age EOS. Likelihood of continuing screening into age ≥75 years was higher in women who had a personal history or a family history of breast cancer, or used hormone replacement therapy within six months of screening. Women who were born outside Australia were less likely to continue screening after reaching age 75 years.

Conclusions: Our study found that age EOS to women aged 70-74 was effective in increasing screening uptake in this age-group but was accompanied by a moderate increase in screening uptake amongst women ≥75 years via self-referral for whom potential benefit of screening may be limited.
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http://dx.doi.org/10.1016/j.breast.2021.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933533PMC
April 2021

The Impact of Breast Density Information or Notification on Women's Cognitive, Psychological, and Behavioral Outcomes: A Systematic Review.

J Natl Cancer Inst 2021 Feb 5. Epub 2021 Feb 5.

Wiser Healthcare, Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, NSW, Australia.

Background: Breast density (BD) is an independent risk factor for breast cancer and reduces the sensitivity of mammography. This systematic review aims to synthesize evidence from existing studies to understand the impact of BD information and/or notification on women's cognitive, psychological and behavioral outcomes.

Methods: Studies were identified via relevant database searches up to March 2020. Two authors evaluated the eligibility of studies with verification from the study team, extracted and crosschecked data, and assessed the risk of bias.

Results: Of the 1134 titles identified, 29 studies were included. Twenty-three studies were quantitative, including only 1 randomised controlled trial of women receiving BD information, and 6 were qualitative. Twenty-seven studies were conducted in the United States, with 19 conducted post-BD legislation. The overall results in terms of BD awareness, knowledge, attitudes, perceptions and intentions were heterogeneous across included studies, with the strongest consistency demonstrated regarding the importance of communication with and involvement of healthcare professionals. Together the studies did however highlight that there is still limited awareness of BD in the community, especially in more socio-economic disadvantaged communities, and limited knowledge about what BD means and the implications for women. Importantly, BD information in the context of overall breast cancer risk has not yet been studied.

Conclusions: There are important gaps in the understanding of the impact of BD information or notification on women and how best to communicate BD information to women. More high-quality evidence to inform both current and future practice related to BD is still needed.
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http://dx.doi.org/10.1093/jnci/djab016DOI Listing
February 2021

Mammographic sensitivity as a function of tumor size: A novel estimation based on population-based screening data.

Breast 2021 Feb 9;55:69-74. Epub 2020 Dec 9.

University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands. Electronic address:

Background: Instead of a single value for mammographic sensitivity, a sensitivity function based on tumor size more realistically reflects mammography's detection capability. Because previous models may have overestimated size-specific sensitivity, we aimed to provide a novel approach to improve sensitivity estimation as a function of tumor size.

Methods: Using aggregated data on interval and screen-detected cancers, observed tumor sizes were back-calculated to the time of screening using an exponential tumor growth model and a follow-up time of 4 years. From the observed number of detected cancers and an estimation of the number of false-negative cancers, a model for the sensitivity as a function of tumor size was determined. A univariate sensitivity analysis was conducted by varying follow-up time and tumor volume doubling time (TVDT). A systematic review was conducted for external validation of the sensitivity model.

Results: Aggregated data of 22,915 screen-detected and 10,670 interval breast cancers from the Dutch screening program were used. The model showed that sensitivity increased from 0 to 85% for tumor sizes from 2 to 20 mm. When TVDT was set at the upper and lower limits of the confidence interval, sensitivity for a 20-mm tumor was 74% and 93%, respectively. The estimated sensitivity gave comparable estimates to those from two of three studies identified by our systematic review.

Conclusion: Derived from aggregated breast screening outcomes data, our model's estimation of sensitivity as a function of tumor size may provide a better representation of data observed in screening programs than other models.
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http://dx.doi.org/10.1016/j.breast.2020.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753195PMC
February 2021

Artificial intelligence (AI) in breast cancer care - Leveraging multidisciplinary skills to improve care.

Breast 2021 Apr 9;56:110-113. Epub 2020 Dec 9.

Sorbonne Université, Université Sorbonne Paris Nord, INSERM, LIMICS UMR_S 1142, F-75006, Paris, France; Assistance Publique - Hôpitaux de Paris, Département de Santé Publique, F-75020, Paris, France.

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http://dx.doi.org/10.1016/j.breast.2020.11.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982546PMC
April 2021

Views of healthcare professionals about the role of active monitoring in the management of ductal carcinoma in situ (DCIS): Qualitative interview study.

Breast 2020 Dec 15;54:99-105. Epub 2020 Sep 15.

Wiser Healthcare, Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, NSW, Australia; Sydney Health Literacy Lab, Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, NSW, Australia. Electronic address:

Background: Ductal carcinoma in situ (DCIS) is an in-situ (pre-cancerous) breast malignancy whereby malignant cells are contained within the basement membrane of the breast ducts. Increasing awareness that some low-risk forms of DCIS might remain indolent for many years has led to concern about overtreatment, with at least 3 clinical trials underway internationally assessing the safety of active monitoring for low-risk DCIS. This study aimed to understand healthcare professionals' (HCPs) views on the management options for patients with DCIS.

Methods: Qualitative study using semi-structured interviews with HCPs involved in the diagnosis and management of DCIS in Australia and New Zealand. Interviews were audio-recorded, transcribed and analysed thematically using Framework Analysis method.

Results: Twenty-six HCPs including 10 breast surgeons, 3 breast physicians, 6 radiation oncologists, and 7 breast care nurses participated. There was a strong overall consensus that DCIS requires active treatment. HCPs generally felt uncomfortable recommending active monitoring as a management option for low-risk DCIS as they viewed this as outside current standard care. Overall, HCPs felt that active monitoring was an unproven strategy in need of an evidence base; however, many acknowledged that active monitoring for low-risk DCIS could be appropriate for patients with significant co-morbidities or limited life expectancy. They believed that most patients would opt for surgery wherever possible.

Conclusions: This study highlights the important need for robust randomised controlled trial data about active monitoring for women with low-risk DCIS, to provide HCPs with confidence in their management recommendations and decision-making.
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http://dx.doi.org/10.1016/j.breast.2020.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509786PMC
December 2020

Changes in Reoperation After Publication of Consensus Guidelines on Margins for Breast-Conserving Surgery: A Systematic Review and Meta-analysis.

JAMA Surg 2020 Aug 26:e203025. Epub 2020 Aug 26.

Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.

Importance: The 2014 publication of the Society of Surgical Oncology-American Society for Radiation Oncology (SSO-ASTRO) Consensus Guideline on Margins for Breast-Conserving Surgery recommended a negative margin definition of no ink on tumor. Adoption of this guideline would represent a major change in surgical practice that could lower the rates of reoperation.

Objective: To assess changes in reoperation rates after publication of the SSO-ASTRO guideline.

Data Sources: A systematic search of Embase, PREMEDLINE, Evidence-Based Medicine Reviews, Scopus, and Web of Science for biomedical literature published from January 2014 to July 2019 was performed. This search was supplemented by web searches and manual searching of conference abstracts.

Study Selection: Included studies compared the reoperation rates in preguideline vs postguideline cohorts (actual change), retrospectively applied the SSO-ASTRO guideline to a preguideline cohort (projected change), or described the economic outcomes of the guideline.

Data Extraction And Synthesis: Study characteristics and reoperation rates were extracted independently by 2 reviewers. Odds ratios (ORs) were pooled by random effects meta-analysis. Analyses were stratified by study setting (institutional or population) and preguideline accepted margins. The economic outcomes of the guideline were summarized narratively. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed.

Main Outcomes And Measures: Odds ratios for postguideline vs preguideline reoperation rates.

Results: From 1114 citations, 30 studies (with 599 016 participants) reported changes in reoperation rates. Studies included a median (range) of 487 (100-521 578) participants, and 20 studies were undertaken in the US, 6 in the UK, 3 in Canada, and 1 in Australia. Among 21 studies of actual changes, pooled ORs showed a statistically significant reduction in reoperation, with an OR lower in institution-based studies than in population-based studies (OR, 0.62 [95% CI, 0.52-0.74] vs 0.76 [95% CI, 0.72-0.80]; P = .04 for subgroup differences). Among 9 studies of projected changes, the pooled OR was lower for preguideline margin thresholds of 2 mm or more compared with 1 mm (OR, 0.47 [95% CI, 0.40-0.56] vs 0.85 [95% CI, 0.79-0.91; P < .001 for subgroup differences). Projected changes were likely to overestimate actual changes. Six studies that estimated the postguideline economic outcome found the guideline to be potentially cost saving, with a median (range) saving of US $3540 ($1800-$25 650) per woman avoiding reoperation.

Conclusions And Relevance: This study found a decrease in reoperation rates after the publication of the SSO-ASTRO guideline; this reduction was greater at an institutional level than a population level, the latter reflecting the differences in guideline adoption between centers. These early outcomes may be conservative estimates of longer-term implications.
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http://dx.doi.org/10.1001/jamasurg.2020.3025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450409PMC
August 2020

Lesions of uncertain malignant potential of the breast (B3) on vacuum-assisted biopsy for microcalcifications: Predictors of malignancy.

Eur J Radiol 2020 Sep 24;130:109194. Epub 2020 Jul 24.

Screening and Test Evaluation Program, School of Public Health, Sydney Medical School, University of Sydney, Sydney 2006, NSW, Australia. Electronic address:

Purpose: To investigate clinical, radiologic and pathologic features of B3 lesions diagnosed on VABB targeting microcalcifications, for identifying predictors of malignancy.

Method: This retrospective multi-centre study included consecutive VABBs performed over a 10-year period on suspicious microcalcifications not associated with other radiological signs diagnosed as B3 on histology from VABB, with outcomes ascertained by surgical excision. Clinical, demographic, radiological and histological (B3 subcategory) data were collected. For statistical analysis (univariate and binary logistic regression), the primary outcome variable was the upgrade rate to malignancy after surgery. Predictors of upgrade to malignancy were identified from clinical, demographic, radiological and pathological variables (including B3 subcategory).

Results: Amongst 447 VABBs, there were 57(12.7 %) upgrades to malignancy at surgical histology (36 DCIS and 21 invasive cancer). At univariate analysis, variables significantly associated with increased risk of upgrade to malignancy were age>55 years (p = 0.01), lesion size>10 mm (p < 0.0001), BI-RADS 4b-c and 5 (p = 0.0001), and fine pleomorphic morphology (p = 0.002) of microcalcifications. Binary logistic regression confirmed as significant independent risk factors age, lesion size and BI-RADS category (p = 0.02, 0.02 and 0.0006 respectively). Amongst subcategories of B3 lesions, lobular neoplasia was significantly(p = 0.04) associated with upgrade, confirmed as an independent risk factor [p = 0.03, OR = 2.3(1.1-4.7)]. Flat epithelial atypia was significantly(p = 0.004) associated with reduced odds of upgrade, but binary logistic regression showed only borderline association [p = 0.052, OR = 0.4(0.2-1.01)].

Conclusions: Across B3 lesions diagnosed on histology from VABB of suspicious microcalcifications, older age, size>10 mm, BI-RADS category≥ 4b on imaging, and lobular neoplasia were risk factors for upgrade to malignancy. This information can be used to discuss patients' tailored management options.
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http://dx.doi.org/10.1016/j.ejrad.2020.109194DOI Listing
September 2020

Breast density notification: evidence on whether benefit outweighs harm is required to inform future screening practice.

BMJ Evid Based Med 2020 Jul 14. Epub 2020 Jul 14.

Wiser Healthcare, Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.

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http://dx.doi.org/10.1136/bmjebm-2020-111364DOI Listing
July 2020

Impact of Full-Field Digital Mammography Versus Film-Screen Mammography in Population Screening: A Meta-Analysis.

J Natl Cancer Inst 2021 Jan;113(1):16-26

Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia.

Background: Breast screening programs replaced film mammography with digital mammography, and the effects of this practice shift in population screening on health outcomes can be measured through examination of cancer detection and interval cancer rates.

Methods: A systematic review and random effects meta-analysis were undertaken. Seven databases were searched for publications that compared film with digital mammography within the same population of asymptomatic women and reported cancer detection and/or interval cancer rates.

Results: The analysis included 24 studies with 16 583 743 screening examinations (10 968 843 film and 5 614 900 digital). The pooled difference in the cancer detection rate showed an increase of 0.51 per 1000 screens (95% confidence interval [CI] = 0.19 to 0.83), greater relative increase for ductal carcinoma in situ (25.2%, 95% CI = 17.4% to 33.5%) than invasive (4%, 95% CI = -3% to 13%), and a recall rate increase of 6.95 (95% CI = 3.47 to 10.42) per 1000 screens after the transition from film to digital mammography. Seven studies (80.8% of screens) reported interval cancers: the pooled difference showed no change in the interval cancer rate with -0.02 per 1000 screens (95% CI = -0.06 to 0.03). Restricting analysis to studies at low risk of bias resulted in findings consistent with the overall pooled results for all outcomes.

Conclusions: The increase in cancer detection following the practice shift to digital mammography did not translate into a reduction in the interval cancer rate. Recall rates were increased. These results suggest the transition from film to digital mammography did not result in health benefits for screened women. This analysis reinforces the need to carefully evaluate effects of future changes in technology, such as tomosynthesis, to ensure new technology leads to improved health outcomes and beyond technical gains.
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http://dx.doi.org/10.1093/jnci/djaa080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781455PMC
January 2021

The cost-effectiveness of digital breast tomosynthesis in a population breast cancer screening program.

Eur Radiol 2020 Oct 7;30(10):5437-5445. Epub 2020 May 7.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Objectives: To evaluate at which sensitivity digital breast tomosynthesis (DBT) would become cost-effective compared to digital mammography (DM) in a population breast cancer screening program, given a constant estimate of specificity.

Methods: In a microsimulation model, the cost-effectiveness of biennial screening for women aged 50-75 was simulated for three scenarios: DBT for women with dense breasts and DM for women with fatty breasts (scenario 1), DBT for the whole population (scenario 2) or maintaining DM screening (reference). For DM, sensitivity was varied depending on breast density from 65 to 87%, and for DBT from 65 to 100%. The specificity was set at 96.5% for both DM and DBT. Direct medical costs were considered, including screening, biopsy and treatment costs. Scenarios were considered to be cost-effective if the incremental cost-effectiveness ratio (ICER) was below €20,000 per life year gain (LYG).

Results: For both scenarios, the ICER was more favourable at increasing DBT sensitivity. Compared with DM screening, 0.8-10.2% more LYGs were found when DBT sensitivity was at least 75% for scenario 1, and 4.7-18.7% when DBT sensitivity was at least 80% for scenario 2. At €96 per DBT, scenario 1 was cost-effective at a DBT sensitivity of at least 90%, and at least 95% for scenario 2. At €80 per DBT, these values decreased to 80% and 90%, respectively.

Conclusion: DBT is more likely to be a cost-effective alternative to mammography in women with dense breasts. Whether DBT could be cost-effective in a general population highly depends on DBT costs.

Key Points: • DBT could be a cost-effective screening modality for women with dense breasts when its sensitivity is at least 90% at a maximum cost per screen of €96. • DBT has the potential to be cost-effective for screening all women when sensitivity is at least 90% at a maximum cost per screen of €80. • Whether DBT could be used as an alternative to mammography for screening all women is highly dependent on the cost of DBT per screen.
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http://dx.doi.org/10.1007/s00330-020-06812-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476964PMC
October 2020

Solving the preoperative breast MRI conundrum: design and protocol of the MIPA study.

Eur Radiol 2020 Oct 6;30(10):5427-5436. Epub 2020 May 6.

Unit of Radiology, IRCCS Policlinico San Donato, Via Morandi 30, 20097, San Donato Milanese, Italy.

Despite its high diagnostic performance, the use of breast MRI in the preoperative setting is controversial. It has the potential for personalized surgical management in breast cancer patients, but two of three randomized controlled trials did not show results in favor of its introduction for assessing the disease extent before surgery. Meta-analyses showed a higher mastectomy rate in women undergoing preoperative MRI compared to those who do not. Nevertheless, preoperative breast MRI is increasingly used and a survey from the American Society of Breast Surgeons showed that 41% of respondents ask for it in daily practice. In this context, a large-scale observational multicenter international prospective analysis (MIPA study) was proposed under the guidance of the European Network for the Assessment of Imaging in Medicine (EuroAIM). The aims were (1) to prospectively and systematically collect data on consecutive women with a newly diagnosed breast cancer, not candidates for neoadjuvant therapy, who are offered or not offered breast MRI before surgery according to local practice; (2) to compare these two groups in terms of surgical and clinical endpoints, adjusting for covariates. The underlying hypotheses are that MRI does not cause additional mastectomies compared to conventional imaging, while reducing the reoperation rate in all or in subgroups of patients. Ninety-six centers applied to a web-based call; 36 were initially selected based on volume and quality standards; 27 were active for enrollment. On November 2018, the target of 7000 enrolled patients was reached. The MIPA study is presently at the analytic phase. Key Points • Breast MRI has a high diagnostic performance but its utility in the preoperative setting is controversial. • A large-scale observational multicenter prospective study was launched to compare women receiving with those not receiving preoperative MRI. • Twenty-seven centers enrolled more than 7000 patients. The study is presently at the analytic phase.
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http://dx.doi.org/10.1007/s00330-020-06824-7DOI Listing
October 2020

Recommendations for triage, prioritization and treatment of breast cancer patients during the COVID-19 pandemic.

Breast 2020 Aug 16;52:8-16. Epub 2020 Apr 16.

Breast Unit, Champalimaud Clinical Centre/Champalimaud Foundation, Portugal.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) associated disease (COVID-19) outbreak seriously challenges globally all health care systems and professionals. Expert projections estimate that despite social distancing and lockdown being practiced, we have yet to feel the full impact of COVID-19. In this manuscript we provide guidance to prepare for the impact of COVID-19 pandemic on breast cancer patients and advise on how to triage, prioritize and organize diagnostic procedures, surgical, radiation and medical treatments.
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http://dx.doi.org/10.1016/j.breast.2020.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162626PMC
August 2020

Corrigendum to "Preoperative breast cancer staging with multi-modality imaging and surgical outcomes" [Eur. J. Radiol. 122 (2020) 108766].

Eur J Radiol 2020 May 26;126:108919. Epub 2020 Feb 26.

Screening and Test Evaluation Program, School of Public Health, Sydney Medical School, University of Sydney, Sydney, 2006, NSW, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.ejrad.2020.108919DOI Listing
May 2020

Intraoperative breast specimen assessment in breast conserving surgery: comparison between standard mammography imaging and a remote radiological system.

Br J Radiol 2020 May 28;93(1109):20190785. Epub 2020 Feb 28.

Screening and Test Evaluation Program, School of Public Health, Sydney Medical School, University of Sydney, Sydney, 2006, NSW, Australia.

Objective: To compare standard specimen mammography (SSM) with remote intraoperative specimen mammography (ISM) assessment in breast conserving-surgery (BCS) based on operative times, intraoperative additional excision (IAE) and re-intervention rates.

Methods And Materials: We retrospectively compared 129 consecutive patients (136 lesions) who had BCS with SSM at our centre between 11/2011 and 02/2013 with 138 consecutive patients (144 lesions) who underwent BCS with ISM between 08/2014 and 02/2015.SSM or ISM were performed to confirm the target lesions within the excised specimen and margin adequacy. The utility of SMM and ISM was evaluated considering pathology as gold-standard, using χ or Fisher's exact tests for comparison of categorical variables, and non-parametric Mann-Whitney test for continuous variables.

Results: The two groups did not statistically differ for age ( = 0.20), lesion size ( = 0.29) and morphology ( = 0.82) or tumor histology type ( = 0.65). Intraoperative time was significantly longer ( < 0.00001) for SSM (132 ± 43 min) than for ISM (90 ± 42 min). The proportions requiring IAE did not significantly differ between SSM group (39/136 lesions (40%)) and ISM group (52/144 lesions (57%)) ( = 0.19), overall and in stratified analysis by mammographic features. Re-intervention rates were not statistically different between the two groups [SSM:19/136 (14%), ISM:13/144 (9%); = 0.27].

Conclusion: The introduction of ISM in BCS significantly reduced surgical time but did not change IAE and re-intervention rates, highlighting facilitated communication between surgeons and radiologists.

Advances In Knowledge: Compared to standard mammography imaging, the use of ISM significantly reduced surgical time.
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http://dx.doi.org/10.1259/bjr.20190785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217569PMC
May 2020

Preoperative breast cancer staging with multi-modality imaging and surgical outcomes.

Eur J Radiol 2020 Jan 22;122:108766. Epub 2019 Nov 22.

Screening and Test Evaluation Program, School of Public Health, Sydney Medical School, University of Sydney, Sydney, 2006, NSW, Australia. Electronic address:

Purpose: To compare the rates of mastectomy and re-operation after breast-conserving surgery (BCS) among patients who had different pre-operative multi-modality imaging, hence identifying significant predictors of mastectomy and re-operations within each group.

Method: Retrospective study of consecutive patients with primary breast cancer treated January 2010 - December 2016, divided in 3 groups, undergoing pre-operative local staging respectively with conventional imaging modalities only (2D mammography, ultrasound (US)), conventional imaging and tomosynthesis (DBT) and/or MRI. The primary outcome was identification of significant predictors of surgical outcomes, within each group. Study variables examined in univariate analysis were age, lesion dimension, breast density, multifocality, tumor size, histology, and if associated with outcomes they were included in binary logistic regression analysis.

Results: Amongst 1547 patients, patient and tumor characteristics differed across the three groups, as did mastectomy rates which were 18 % (102/562) for 2D + US, 36 % (154/428) for 2D + DBT + US, 45 % (250/557) for 2D+/-DBT + US + MRI(p < 0.001). Variables strongly associated with mastectomy were larger lesions and multifocality (as was multi-modality group). Re-operation rate showed an opposite trend: 12.2 % (56/459) for 2D + US, 8 % (22/272) for 2D + DBT + US, 6.5 % (20/306) for 2D+/-DBT + US + MRI. Re-operation rate for 2D+/-DBT + US + MRI was lower than for 2D + US (p = 0.01) but similar to 2D + DBT + US (p = 0.58). Patients who had 2D + US and re-operations had significantly larger lesions, more underestimation, higher proportion of invasive carcinoma with in-situ component than those who did not require re-operation.

Conclusions: Patients who had larger tumors and multifocal disease were more frequently staged by adding DBT and/or MRI to conventional imaging (mammography and US) which was associated with more extensive surgical treatment but lower reoperation rates.
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http://dx.doi.org/10.1016/j.ejrad.2019.108766DOI Listing
January 2020

Overview of radiomics in breast cancer diagnosis and prognostication.

Breast 2020 Feb 6;49:74-80. Epub 2019 Nov 6.

Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, NSW, Australia.

Diagnosis of early invasive breast cancer relies on radiology and clinical evaluation, supplemented by biopsy confirmation. At least three issues burden this approach: a) suboptimal sensitivity and suboptimal positive predictive power of radiology screening and diagnostic approaches, respectively; b) invasiveness of biopsy with discomfort for women undergoing diagnostic tests; c) long turnaround time for recall tests. In the screening setting, radiology sensitivity is suboptimal, and when a suspicious lesion is detected and a biopsy is recommended, the positive predictive value of radiology is modest. Recent technological advances in medical imaging, especially in the field of artificial intelligence applied to image analysis, hold promise in addressing clinical challenges in cancer detection, assessment of treatment response, and monitoring disease progression. Radiomics include feature extraction from clinical images; these features are related to tumor size, shape, intensity, and texture, collectively providing comprehensive tumor characterization, the so-called radiomics signature of the tumor. Radiomics is based on the hypothesis that extracted quantitative data derives from mechanisms occurring at genetic and molecular levels. In this article we focus on the role and potential of radiomics in breast cancer diagnosis and prognostication.
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http://dx.doi.org/10.1016/j.breast.2019.10.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375670PMC
February 2020

The ethical, legal and social implications of using artificial intelligence systems in breast cancer care.

Breast 2020 Feb 11;49:25-32. Epub 2019 Oct 11.

Sydney School of Public Health, Faculty of Medicine and Health, Fisher Road, The University of Sydney, New South Wales, 2006, Australia. Electronic address:

Breast cancer care is a leading area for development of artificial intelligence (AI), with applications including screening and diagnosis, risk calculation, prognostication and clinical decision-support, management planning, and precision medicine. We review the ethical, legal and social implications of these developments. We consider the values encoded in algorithms, the need to evaluate outcomes, and issues of bias and transferability, data ownership, confidentiality and consent, and legal, moral and professional responsibility. We consider potential effects for patients, including on trust in healthcare, and provide some social science explanations for the apparent rush to implement AI solutions. We conclude by anticipating future directions for AI in breast cancer care. Stakeholders in healthcare AI should acknowledge that their enterprise is an ethical, legal and social challenge, not just a technical challenge. Taking these challenges seriously will require broad engagement, imposition of conditions on implementation, and pre-emptive systems of oversight to ensure that development does not run ahead of evaluation and deliberation. Once artificial intelligence becomes institutionalised, it may be difficult to reverse: a proactive role for government, regulators and professional groups will help ensure introduction in robust research contexts, and the development of a sound evidence base regarding real-world effectiveness. Detailed public discussion is required to consider what kind of AI is acceptable rather than simply accepting what is offered, thus optimising outcomes for health systems, professionals, society and those receiving care.
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http://dx.doi.org/10.1016/j.breast.2019.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375671PMC
February 2020

Effect of implementing digital breast tomosynthesis (DBT) instead of mammography on population screening outcomes including interval cancer rates: Results of the Trento DBT pilot evaluation.

Breast 2020 Apr 30;50:135-140. Epub 2019 Sep 30.

Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, NSW, Australia. Electronic address:

Background/aim: The Trento screening program transitioned to digital breast tomosynthesis (DBT) screening based on evidence that DBT improves breast cancer (BC) detection compared to mammography; an evaluation of the transition to DBT is reported in this pilot study.

Methods: Prospective implementation of DBT screening included women aged ≥50 years who attended the Trento program for biennial screening. DBT screening included DBT acquisitions with synthesized 2D-images. A historical cohort of women who attended the program (January 2013-October 2014) and received digital mammography (DM) provided a comparison group. Independent double-reading (with a third arbitrating read for discordance) was used for DBT and DM screening. Screening outcomes included cancer detection rate (CDR/1000 screens), percentage of screens recalled to assessment (recall%), interval cancer rate (ICR/1000 screens) at 2-year follow-up, and screening sensitivity. Rate ratios (RR) and 95% confidence interval (95%CI) examined outcomes for DBT versus DM screening.

Results: From women aged 50-69 years who accepted an invitation to screening (October 2014-October 2016) 46,343 comprised the DBT-screened group: amongst these 402 BCs (includes 50 ductal carcinoma in-situ (DCIS)) were detected (CDR 8.67/1000), whereas 205 BCs (includes 33 DCIS) were detected amongst 37,436 DM screens (CDR 5.48/1000) [RR for CDR:1.58 (1.34-1.87)]. Recall% was lower for DBT (2.55%) than DM (3.21%) [RR:0.79 (0.73-0.86)]. Compared to DM, DBT screening increased CDR for stage I-II BC, for all tumour size and grade categories, and for node-negative BC, but did not increase CDR for DCIS. Estimated ICR for DBT was 1.1/1000 whereas ICR for DM was 1.36/1000 [RR:0.81 (0.55-1.19)]. Screening sensitivity was 88.74% for DBT versus 80.08% for DM [RR:1.11 (0.94-1.31)].

Conclusion: DBT significantly improved early-detection measures but did not significantly reduce ICR (relative to DM screening), suggesting that it could add benefit as well as adding over-detection in population BC screening.
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http://dx.doi.org/10.1016/j.breast.2019.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375541PMC
April 2020

Breast cancer.

Nat Rev Dis Primers 2019 09 23;5(1):66. Epub 2019 Sep 23.

Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal.

Breast cancer is the most frequent malignancy in women worldwide and is curable in ~70-80% of patients with early-stage, non-metastatic disease. Advanced breast cancer with distant organ metastases is considered incurable with currently available therapies. On the molecular level, breast cancer is a heterogeneous disease; molecular features include activation of human epidermal growth factor receptor 2 (HER2, encoded by ERBB2), activation of hormone receptors (oestrogen receptor and progesterone receptor) and/or BRCA mutations. Treatment strategies differ according to molecular subtype. Management of breast cancer is multidisciplinary; it includes locoregional (surgery and radiation therapy) and systemic therapy approaches. Systemic therapies include endocrine therapy for hormone receptor-positive disease, chemotherapy, anti-HER2 therapy for HER2-positive disease, bone stabilizing agents, poly(ADP-ribose) polymerase inhibitors for BRCA mutation carriers and, quite recently, immunotherapy. Future therapeutic concepts in breast cancer aim at individualization of therapy as well as at treatment de-escalation and escalation based on tumour biology and early therapy response. Next to further treatment innovations, equal worldwide access to therapeutic advances remains the global challenge in breast cancer care for the future.
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http://dx.doi.org/10.1038/s41572-019-0111-2DOI Listing
September 2019

Pathways to breast cancer screening artificial intelligence algorithm validation.

Breast 2020 Aug 9;52:146-149. Epub 2019 Sep 9.

Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.

As more artificial intelligence (AI)-enhanced mammography screening tools enter the clinical market, greater focus will be placed on external validation in diverse patient populations. In this viewpoint, we outline lessons learned from prior efforts in this field, the need to validate algorithms on newer screening technologies and diverse patient populations, and conclude by discussing the need for a framework for continuous monitoring and recalibration of these AI tools. Sufficient validation and continuous monitoring of emerging AI tools for breast cancer screening will require greater stakeholder engagement and the creation of shared policies and guidelines.
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http://dx.doi.org/10.1016/j.breast.2019.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061055PMC
August 2020

Pilot trial of digital breast tomosynthesis (3D mammography) for population-based screening in BreastScreen Victoria.

Med J Aust 2019 10 26;211(8):357-362. Epub 2019 Aug 26.

Sydney School of Public Health, University of Sydney, Sydney, NSW.

Objectives: To estimate detection measures for tomosynthesis and standard mammography; to assess the feasibility of using tomosynthesis in population-based screening for breast cancer.

Design, Setting: Prospective pilot trial comparing tomosynthesis (with synthesised 2D images) and standard mammography screening of women attending Maroondah BreastScreen, a BreastScreen Victoria service in the eastern suburbs of Melbourne.

Participants: Women at least 40 years of age who presented for routine breast screening between 18 August 2017 and 8 November 2018.

Main Outcome Measures: Cancer detection rate (CDR); proportion of screens that led to recall for further assessment.

Results: 5018 tomosynthesis and 5166 standard mammography screens were undertaken in 10 146 women; 508 women (5.0% of screens) opted not to undergo tomosynthesis screening. With tomosynthesis, 49 cancers (40 invasive, 9 in situ) were detected (CDR, 9.8 [95% CI, 7.2-13] per 1000 screens); with standard mammography, 34 cancers (30 invasive, 4 in situ) were detected (CDR, 6.6 [95% CI, 4.6-9.2] per 1000 screens). The estimated difference in CDR was 3.2 more detections (95% CI, -0.32 to 6.8) per 1000 screens with tomosynthesis; the difference was greater for repeat screens and for women aged 60 years or more. The recall rate was greater for tomosynthesis (4.2%; 95% CI, 3.6-4.8%) than standard mammography (3.0%; 95% CI, 2.6-3.5%; estimated difference, 1.2%; 95% CI, 0.46-1.9%). The median screen reading time for tomosynthesis was 67 seconds (interquartile range [IQR] 46-105 seconds); for standard mammography, 16 seconds (IQR, 10-29 seconds).

Conclusions: Breast cancer detection, recall for assessment, and screen reading time were each higher for tomosynthesis than for standard mammography. Our preliminary findings could form the basis of a large scale comparative evaluation of tomosynthesis and standard mammography for breast screening in Australia.

Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12617000947303.
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http://dx.doi.org/10.5694/mja2.50320DOI Listing
October 2019

Breast cancer Ki-67 expression prediction by digital breast tomosynthesis radiomics features.

Eur Radiol Exp 2019 08 14;3(1):36. Epub 2019 Aug 14.

Sydney School of Public Health, Sydney Medical School, University of Sydney, Sydney, Australia.

Background: To investigate whether quantitative radiomic features extracted from digital breast tomosynthesis (DBT) are associated with Ki-67 expression of breast cancer.

Materials And Methods: This is a prospective ethically approved study of 70 women diagnosed with invasive breast cancer in 2018, including 40 low Ki-67 expression (Ki-67 proliferation index <14%) cases and 30 high Ki-67 expression (Ki-67 proliferation index ≥ 14%) cases. A set of 106 quantitative radiomic features, including morphological, grey/scale statistics, and texture features, were extracted from DBT images. After applying least absolute shrinkage and selection operator (LASSO) method to select the most predictive features set for the classifiers, low versus high Ki-67 expression was evaluated by the area under the curve (AUC) at receiver operating characteristic analysis. Correlation coefficient was calculated for the most significant features.

Results: A combination of five features yielded AUC of up to 0.698. The five most predictive features (sphericity, autocorrelation, interquartile range, robust mean absolute deviation, and short-run high grey-level emphasis) showed a statistical significance (p ≤ 0.001) in the classification. Thirty-four features were significantly (p ≤ 0.001) correlated with Ki-67, and five of these had a correlation coefficient of > 0.5.

Conclusion: The present study showed that quantitative radiomic imaging features of breast tumour extracted from DBT images are associated with breast cancer Ki-67 expression. Larger studies are needed in order to further evaluate these findings.
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http://dx.doi.org/10.1186/s41747-019-0117-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694353PMC
August 2019

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

Public Health Res Pract 2019 Jul 31;29(2). Epub 2019 Jul 31.

Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, NSW, Australia.

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.
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http://dx.doi.org/10.17061/phrp2921911DOI Listing
July 2019

Two-view digital breast tomosynthesis versus digital mammography in a population-based breast cancer screening programme (To-Be): a randomised, controlled trial.

Lancet Oncol 2019 06 8;20(6):795-805. Epub 2019 May 8.

Department of Pathology, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Haukeland University Hospital, Bergen, Norway; Deparment of Clinical Medicine, University of Bergen, Bergen, Norway.

Background: Digital breast tomosynthesis is an advancement of mammography, and has the potential to overcome limitations of standard digital mammography. This study aimed to compare first-generation digital breast tomo-synthesis including two-dimensional (2D) synthetic mammograms versus digital mammography in a population-based screening programme.

Methods: BreastScreen Norway offers all women aged 50-69 years two-view (craniocaudal and mediolateral oblique) mammographic screening every 2 years and does independent double reading with consensus. We asked all 32 976 women who attended the programme in Bergen in 2016-17, to participate in this randomised, controlled trial with a parallel group design. A study-specific software was developed to allocate women to either digital breast tomosynthesis or digital mammography using a 1:1 simple randomisation method based on participants' unique national identity numbers. The interviewing radiographer did the randomisation by entering the number into the software. Randomisation was done after consent and was therefore concealed from both the women and the radiographer at the time of consent; the algorithm was not disclosed to radiographers during the recruitment period. All data needed for analyses were complete 12 months after the recruitment period ended. The primary outcome measure was screen-detected breast cancer, stratified by screening technique (ie, digital breast tomosynthesis and digital mammography). A log-binomial regression model was used to estimate the efficacy of digital breast tomosynthesis versus digital mammography, defined as the crude risk ratios (RRs) with 95% CIs for screen-detected breast cancer for women screened during the recruitment period. A per-protocol approach was used in the analyses. This trial is registered at ClinicalTrials.gov, number NCT02835625, and is closed to accrual.

Findings: Between, Jan 14, 2016, and Dec 31, 2017, 44 266 women were invited to the screening programme in Bergen, and 32 976 (74·5%) attended. After excluding women with breast implants and women who did not consent to participate, 29 453 (89·3%) were eligible for electronic randomisation. 14 734 women were allocated to digital breast tomosynthesis and 14 719 to digital mammography. After randomisation, women with a previous breast cancer were excluded (digital breast tomosynthesis group n=314, digital mammography group n=316), women with metastases from melanoma (digital breast tomosynthesis group n=1), and women who informed the radiographer about breast symptoms after providing consent (digital breast tomosynthesis group n=39, digital mammography group n=34). After exclusions, information from 28 749 women were included in the analyses (digital breast tomosynthesis group n=14 380, digital mammography group n=14 369). The proportion of screen-detected breast cancer among the screened women did not differ between the two groups (95 [0·66%, 0·53-0·79] of 14 380 vs 87 [0·61%, 0·48-0·73] of 14 369; RR 1·09, 95% CI 0·82-1·46; p=0·56).

Interpretation: This study indicated that digital breast tomosynthesis including synthetic 2D mammograms was not significantly different from standard digital mammography as a screening tool for the detection of breast cancer in a population-based screening programme. Economic analyses and follow-up studies on interval and consecutive round screen-detected breast cancers are needed to better understand the effect of digital breast tomosynthesis in population-based breast cancer screening.

Funding: Cancer Registry of Norway, Department of Radiology at Haukeland University Hospital, University of Oslo, and Research Council of Norway.
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http://dx.doi.org/10.1016/S1470-2045(19)30161-5DOI Listing
June 2019

Artificial Intelligence (AI) for the early detection of breast cancer: a scoping review to assess AI's potential in breast screening practice.

Expert Rev Med Devices 2019 05 3;16(5):351-362. Epub 2019 May 3.

b Department of Radiology , University of Washington School of Medicine , Seattle , WA , USA.

Introduction: Various factors are driving interest in the application of artificial intelligence (AI) for breast cancer (BC) detection, but it is unclear whether the evidence warrants large-scale use in population-based screening.

Areas Covered: We performed a scoping review, a structured evidence synthesis describing a broad research field, to summarize knowledge on AI evaluated for BC detection and to assess AI's readiness for adoption in BC screening. Studies were predominantly small retrospective studies based on highly selected image datasets that contained a high proportion of cancers (median BC proportion in datasets 26.5%), and used heterogeneous techniques to develop AI models; the range of estimated AUC (area under ROC curve) for AI models was 69.2-97.8% (median AUC 88.2%). We identified various methodologic limitations including use of non-representative imaging data for model training, limited validation in external datasets, potential bias in training data, and few comparative data for AI versus radiologists' interpretation of mammography screening.

Expert Opinion: Although contemporary AI models have reported generally good accuracy for BC detection, methodological concerns, and evidence gaps exist that limit translation into clinical BC screening settings. These should be addressed in parallel to advancing AI techniques to render AI transferable to large-scale population-based screening.
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http://dx.doi.org/10.1080/17434440.2019.1610387DOI Listing
May 2019

Should women with a BRCA1/2 mutation aged 60 and older be offered intensified breast cancer screening? - A cost-effectiveness analysis.

Breast 2019 Jun 12;45:82-88. Epub 2019 Mar 12.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Objectives: This study aimed to investigate the cost-effectiveness of intensified breast cancer (BC) screening for women with a BRCA1/2 mutation aged 60-74. Simulated strategies were: (0) annual mammography as reference, (1) alternating annual mammography and MRI for women with dense breasts only; (2) addition of annual MRI for women with dense breasts only; (3) addition of annual MRI for all women.

Materials And Methods: A validated micro-simulation model of invasive BC was updated and validated for interval BC rates and tumor size distribution. Incremental cost-effectiveness ratios (ICER) of all three intensified strategies were compared to the next best strategy and stratified for BRCA1 and BRCA2. Discount rates for costs and life years gained (LYG) were 1.5% and 4% for the Dutch situation; 3% and 3% for international comparison. A threshold of €20,000 per LYG was applied.

Results: All intensified strategies showed more detected BCs and LYG, reduced BC deaths, and increased false positives. The Dutch discounted ICER of intensified strategy 1 compared to annual mammography was €38,000 per LYG in BRCA1 mutation carriers and €18,000 per LYG in BRCA2 mutation carriers. Further intensified strategies showed an ICER above the threshold when compared to this strategy. With international discount rate, the ICERs of all intensified strategies were above the threshold.

Conclusion: Of the three alternative strategies, only alternating annual MRI and mammography for BRCA2 mutation carriers and dense breasts aged 60-75 is cost-effective compared to annual mammography. For BRCA1 mutation carriers, none of the alternative strategies is cost-effective compared to the next best strategy.
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http://dx.doi.org/10.1016/j.breast.2019.03.004DOI Listing
June 2019

Metastatic breast cancer incidence, site and survival in Australia, 2001-2016: a population-based health record linkage study protocol.

BMJ Open 2019 02 1;9(2):e026414. Epub 2019 Feb 1.

Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.

Introduction: Advances in systemic therapy for early and metastatic breast cancer (BC) over the last two decades have improved patients' survival, but their impact on metastatic disease outcomes at a population level is not well described. The aim of this study is to investigate changes in the incidence, site and survival of metastatic disease for women with a first diagnosis of BC in 2001-2002 vs 2006-2007.

Methods And Analysis: Population-based retrospective cohort study of women with first primary invasive BC registered in the New South Wales (NSW) Cancer Registry in 2001-2002 and 2006-2007. We will use linked records from NSW hospitals, dispensed medicines, outpatient services and death registrations to determine: women's demographic and tumour characteristics; treatments received; time to first distant metastasis; site of first metastasis and survival. We will use the Kaplan-Meier method to estimate cumulative incidence of distant metastasis, distant recurrence-free interval and postmetastasis survival by extent of disease at initial diagnosis, site of metastasis and treatment-defined tumour receptor type (hormone receptor-positive, human epidermal growth factor receptor-2-positive, triple negative). We will use Cox proportional hazards regression to estimate the relative effects of prognostic factors, and we will compare systemic therapy patterns by area-of-residence and area-level socioeconomic status to examine equity of access to healthcare.

Ethics And Dissemination: Research ethics committee approval was granted by the Australian Institute of Health and Welfare (#EO2017/2/255), NSW Population and Health Services (#HREC/17/CIPHS/19) and University of Notre Dame Australia (#0 17 144S). We will disseminate research findings to oncology, BC consumer and epidemiology audiences through national and international conference presentations, lay summaries to BC consumer groups and publications in international peer-reviewed oncology and cancer epidemiology journals.
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http://dx.doi.org/10.1136/bmjopen-2018-026414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367965PMC
February 2019