Frequency and characteristics of errors by artificial intelligence (AI) in reading screening mammography: a systematic review.

PURPOSE: Artificial intelligence (AI) for reading breast screening mammograms could potentially replace (some) human-reading and improve screening effectiveness. This systematic review aims to identify and quantify the types of AI errors to better understand the consequences of implementing this technology. METHODS: Electronic databases were searched for external validation studies of the accuracy of AI algorithms in real-world screening mammograms. Descriptive synthesis was performed on error types and frequency. False negative proportions (FNP) and false positive proportions (FPP) were pooled within AI positivity thresholds using random-effects meta-analysis. RESULTS: Seven retrospective studies (447,676 examinations; published 2019-2022) met inclusion criteria. Five studies reported AI error as false negatives or false positives. Pooled FPP decreased incrementally with increasing positivity threshold (71.83% [95% CI 69.67, 73.90] at Transpara 3 to 10.77% [95% CI 8.34, 13.79] at Transpara 9). Pooled FNP increased incrementally from 0.02% [95% CI 0.01, 0.03] (Transpara 3) to 0.12% [95% CI 0.06, 0.26] (Transpara 9), consistent with a trade-off with FPP. Heterogeneity within thresholds reflected algorithm version and completeness of the reference standard. Other forms of AI error were reported rarely (location error and technical error in one study each). CONCLUSION: AI errors are largely interpreted in the framework of test accuracy. FP and FN errors show expected variability not only by positivity threshold, but also by algorithm version and study quality. Reporting of other forms of AI errors is sparse, despite their potential implications for adoption of the technology. Considering broader types of AI error would add nuance to reporting that can inform inferences about AI's utility.

Differential detection by breast density for digital breast tomosynthesis versus digital mammography population screening: a systematic review and meta-analysis.

BACKGROUND: We examined whether digital breast tomosynthesis (DBT) detects differentially in high- or low-density screens. METHODS: We searched six databases (2009-2020) for studies comparing DBT and digital mammography (DM), and reporting cancer detection rate (CDR) and/or recall rate by breast density. Meta-analysis was performed to pool incremental CDR and recall rate for DBT (versus DM) for high- and low-density (dichotomised based on BI-RADS) and within-study differences in incremental estimates between high- and low-density. Screening settings (European/US) were compared. RESULTS: Pooled within-study difference in incremental CDR for high- versus low-density was 1.0/1000 screens (95% CI: 0.3, 1.6; p = 0.003). Estimates were not significantly different in US (0.6/1000; 95% CI: 0.0, 1.3; p = 0.05) and European (1.9/1000; 95% CI: 0.3, 3.5; p = 0.02) settings (p for subgroup difference = 0.15). For incremental recall rate, within-study differences between density subgroups differed by setting (p < 0.001). Pooled incremental recall was less in high- versus low-density screens (-0.9%; 95% CI: -1.4%, -0.4%; p < 0.001) in US screening, and greater (0.8%; 95% CI: 0.3%, 1.3%; p = 0.001) in European screening. CONCLUSIONS: DBT has differential incremental cancer detection and recall by breast density. Although incremental CDR is greater in high-density, a substantial proportion of additional cancers is likely to be detected in low-density screens. Our findings may assist screening programmes considering DBT for density-tailored screening.

The Association of Surgical Margins and Local Recurrence in Women with Ductal Carcinoma In Situ Treated with Breast-Conserving Therapy: A Meta-Analysis.

PURPOSE: There is no consensus on adequate negative margins in breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). We systematically reviewed the evidence on margins in BCS for DCIS. METHODS: A study-level meta-analysis of local recurrence (LR), microscopic margin status and threshold distance for negative margins. LR proportion was modeled using random-effects logistic meta-regression (frequentist) and network meta-analysis (Bayesian) that allows for multiple margin distances per study, adjusting for follow-up time. RESULTS: Based on 20 studies (LR: 865 of 7883), odds of LR were associated with margin status [logistic: odds ratio (OR) 0.53 for negative vs. positive/close (p < 0.001); network: OR 0.45 for negative vs. positive]. In logistic meta-regression, relative to >0 or 1 mm, ORs for 2 mm (0.51), 3 or 5 mm (0.42) and 10 mm (0.60) showed comparable significant reductions in the odds of LR. In the network analysis, ORs relative to positive margins for 2 (0.32), 3 (0.30) and 10 mm (0.32) showed similar reductions in the odds of LR that were greater than for >0 or 1 mm (0.45). There was weak evidence of lower odds at 2 mm compared with >0 or 1 mm [relative OR (ROR) 0.72, 95 % credible interval (CrI) 0.47-1.08], and no evidence of a difference between 2 and 10 mm (ROR 0.99, 95 % CrI 0.61-1.64). Adjustment for covariates, and analyses based only on studies using whole-breast radiotherapy, did not change the findings. CONCLUSION: Negative margins in BCS for DCIS reduce the odds of LR; however, minimum margin distances above 2 mm are not significantly associated with further reduced odds of LR in women receiving radiation.

Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery with Whole-Breast Irradiation in Ductal Carcinoma In Situ.

PURPOSE: Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation. METHODS: A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7,883 patients and other published literature as the evidence base for consensus. RESULTS: Negative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS. A 2-mm margin minimizes the risk of IBTR compared with smaller negative margins. More widely clear margins do not significantly decrease IBTR compared with 2-mm margins. Negative margins narrower than 2 mm alone are not an indication for mastectomy, and factors known to affect rates of IBTR should be considered in determining the need for re-excision. CONCLUSION: Use of a 2-mm margin as the standard for an adequate margin in DCIS treated with whole-breast irradiation is associated with lower rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins narrower than 2 mm.

The association of surgical margins and local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy: a meta-analysis.

PURPOSE: There is no consensus on what constitutes adequate negative margins in breast-conserving therapy (BCT). We systematically review the evidence on surgical margins in BCT for invasive breast cancer to support the development of clinical guidelines. METHODS: Study-level meta-analysis of studies reporting local recurrence (LR) data relative to final microscopic margin status and the threshold distance for negative margins. LR proportion was modeled using random-effects logistic meta-regression. RESULTS: Based on 33 studies (LR in 1,506 of 28,162), the odds of LR were associated with margin status [model 1: odds ratio (OR) 1.96 for positive/close vs negative; model 2: OR 1.74 for close vs. negative, 2.44 for positive vs. negative; (P < 0.001 both models)] but not with margin distance [model 1: >0 mm vs. 1 mm (referent) vs. 2 mm vs. 5 mm (P = 0.12); and model 2: 1 mm (referent) vs. 2 mm vs. 5 mm (P = 0.90)], adjusting for study median follow-up time. There was little to no statistical evidence that the odds of LR decreased as the distance for declaring negative margins increased, adjusting for follow-up time [model 1: 1 mm (OR 1.0, referent), 2 mm (OR 0.95), 5 mm (OR 0.65), P = 0.21 for trend; and model 2: 1 mm (OR 1.0, referent), 2 mm (OR 0.91), 5 mm (OR 0.77), P = 0.58 for trend]. Adjustment for covariates, such as use of endocrine therapy or median-year of recruitment, did not change the findings. CONCLUSIONS: Meta-analysis confirms that negative margins reduce the odds of LR; however, increasing the distance for defining negative margins is not significantly associated with reduced odds of LR, allowing for follow-up time. Adoption of wider relative to narrower margin widths to declare negative margins is unlikely to have a substantial additional benefit for long-term local control in BCT.

Factors associated with private or public breast cancer screening attendance in Queensland, Australia: A retrospective cross-sectional study.

This study aimed to estimate participation in private breast screening in Queensland, Australia, where public-funded screening is implemented, and to identify factors associated with the screening setting, using an online survey (999 female respondents aged 40-74). Screening-specific and socio-demographic factors were collected. Multivariable logistic regression was used to identify factors associated with screening setting (public vs private) and screening recency (<2 vs ≥2 years). Participation estimates were 53.2% (95% confidence interval, CI: 50.0%-56.3%) and 10.9% (9.0%-13.0%) for national screening program and private screening, respectively. In the screening setting model, participation in private screening was significantly associated with longer time since last screening (>4 versus <2 years, odds ratio (OR) = 7.3, 95%CI: 4.1-12.9, p < 0.001), having symptoms (OR = 9.5, 5.8-15.5, p < 0.001), younger age (40-49 versus 50-74 years, OR = 1.8, 1.1-3.0, p = 0.018) and having children <18 years in household (OR = 2.4, 1.5-3.9, p < 0.001). In the screening recency model, only screening setting was statistically significant and private screening was associated with screening recency ≥2 years (OR = 4.0, 2.8-5.7, p < 0.001). Around one in nine women screen outside of the BreastScreen Queensland program. Clinical and socio-demographic factors associated with participation in private screening were identified, providing knowledge relevant to the program's endeavours to improve screening participation.

Effectiveness of hybrid digital breast tomosynthesis/digital mammography compared to digital mammography in women presenting for routine screening at Maroondah BreastScreen: Study protocol for a co-designed, non-randomised prospective trial.

BACKGROUND: Digital breast tomosynthesis (DBT) for breast cancer screening has been shown in international trials to increase cancer detection compared with mammography; however, results have varied across screening settings, and currently there is limited and conflicting evidence on interval cancer rates (a surrogate for screening effectiveness). Australian pilot data also indicated substantially longer screen-reading time for DBT posing a barrier for adoption. There is a critical need for evidence on DBT to inform its role in Australia, including evaluation of potentially more feasible models of implementation, and quantification of screening outcomes by breast density which has global relevance. METHODS: This study is a prospective trial embedded in population-based Australian screening services (Maroondah BreastScreen, Eastern Health, Victoria) comparing hybrid screening comprising DBT (mediolateral oblique view) and digital mammography (cranio-caudal view) with standard mammography screening in a concurrent group attending another screening site. All eligible women aged ≥40 years attending the Maroondah service for routine screening will be enrolled (unless they do not provide verbal consent and opt-out of hybrid screening; are unable to provide consent; or where a 'pushback' image on hybrid DBT cannot be obtained). Each arm will enrol 20,000 women. The primary outcomes are cancer detection rate (per 1000 screens) and recall rate (percentage). Secondary outcomes include 'opt-out' rate; cohort characteristics; cancer characteristics; assessment outcomes; screen-reading time; and interval cancer rate at 24-month follow-up. Automated volumetric breast density will be measured to allow stratification of outcomes by mammographic density. Stratification by age and screening round will also be undertaken. An interim analysis will be undertaken after the first 5000 screens in the intervention group. DISCUSSION: This is the first Australian prospective trial comparing hybrid DBT/mammography with standard mammography screening that is powered to show differences in cancer detection. Findings will inform future implementation of DBT in screening programs world-wide and provide evidence on whether DBT should be adopted in the broader BreastScreen program in Australia or in subgroups of screening participants. TRIAL REGISTRATION: The trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR, ACTRN12623001144606, https://www.anzctr.org.au/). Registration will be updated to reflect trial progress and protocol amendments.

Artificial Intelligence-Driven Mammography-Based Future Breast Cancer Risk Prediction: A Systematic Review.

PURPOSE: To summarize the literature regarding the performance of mammography-image based artificial intelligence (AI) algorithms, with and without additional clinical data, for future breast cancer risk prediction. MATERIALS AND METHODS: A systematic literature review was performed using six databases (medRixiv, bioRxiv, Embase, Engineer Village, IEEE Xplore, and PubMed) from 2012 through September 30, 2022. Studies were included if they used real-world screening mammography examinations to validate AI algorithms for future risk prediction based on images alone or in combination with clinical risk factors. The quality of studies was assessed, and predictive accuracy was recorded as the area under the receiver operating characteristic curve (AUC). RESULTS: Sixteen studies met inclusion and exclusion criteria, of which 14 studies provided AUC values. The median AUC performance of AI image-only models was 0.72 (range 0.62-0.90) compared with 0.61 for breast density or clinical risk factor-based tools (range 0.54-0.69). Of the seven studies that compared AI image-only performance directly to combined image + clinical risk factor performance, six demonstrated no significant improvement, and one study demonstrated increased improvement. CONCLUSIONS: Early efforts for predicting future breast cancer risk based on mammography images alone demonstrate comparable or better accuracy to traditional risk tools with little or no improvement when adding clinical risk factor data. Transitioning from clinical risk factor-based to AI image-based risk models may lead to more accurate, personalized risk-based screening approaches.

Rates of reoperation after breast conserving cancer surgery in Western Australia before and after publication of the SSO-ASTRO margins guideline.

BACKGROUND: A 2014 SSO-ASTRO guideline on surgical margins aimed to reduce unnecessary reoperation after breast conserving surgery (BCS). We investigate whether publication of the guideline was associated with a reduction in reoperation in Western Australia (WA). METHODS: In this retrospective, population-based cohort study, cases of newly-diagnosed breast cancer were identified from the WA Cancer Registry. Linkage to the Hospital Morbidity Data Collection identified index BCS for invasive cancer between January 2009 and June 2018 (N = 8059) and reoperation within 90 days. Pre-guideline (2009-2013) and post-guideline (2014-2018) reoperation proportions were compared, and temporal trends were estimated with generalised linear regression. RESULTS: The pre-guideline reoperation proportion was 25.8% compared with 21.7% post-guideline (difference -4.0% [95% CI -5.9, -2.2, p < 0.001], odds ratio [OR] 0.80 [95% CI 0.72, 0.89, p < 0.001]). Absolute reductions were similar for repeat BCS (16.3% versus 14.6%; difference -1.8% [95% CI -3.4, -0.2, p = 0.03]) and conversion to mastectomy (9.4% versus 7.2%; difference -2.2% [95% CI -3.4, -1.0, p < 0.001]). Over the study period, there was an annual absolute change in reoperation of -0.8% (95% CI -1.2, -0.5, p < 0.001). Accounting for this linear trend, the difference in reoperation between time periods was -0.5% (95% CI -4.3, 3.3; p = 0.81), reflecting a non-significant reduction in conversion to mastectomy. CONCLUSIONS: Comparisons of pre- versus post-guideline time periods in WA showed reductions in reoperation that were similar to international estimates; however, an annual decline in reoperation predated the guideline. Analyses that do not account for temporal trends are likely to overestimate changes in reoperation associated with the guideline.

A systematic review of the impact of the COVID-19 pandemic on breast cancer screening and diagnosis.

BACKGROUND: Breast cancer care has been affected by the COVID-19 pandemic. This systematic review aims to describe the observed pandemic-related changes in clinical and health services outcomes for breast screening and diagnosis. METHODS: Seven databases (January 2020-March 2021) were searched to identify studies of breast cancer screening or diagnosis that reported observed outcomes before and related to the pandemic. Findings were presented using a descriptive and narrative approach. RESULTS: Seventy-four studies were included in this systematic review; all compared periods before and after (or fluctuations during) the pandemic. None were assessed as being at low risk of bias. A reduction in screening volumes during the pandemic was found with over half of studies reporting reductions of ≥49%. A majority (66%) of studies reported reductions of ≥25% in the number of breast cancer diagnoses, and there was a higher proportion of symptomatic than screen-detected cancers. The distribution of cancer stage at diagnosis during the pandemic showed lower proportions of early-stage (stage 0-1/I-II, or Tis and T1) and higher proportions of relatively more advanced cases than that in the pre-pandemic period, however population rates were generally not reported. CONCLUSIONS: Evidence of substantial reductions in screening volume and number of diagnosed breast cancers, and higher proportions of advanced stage cancer at diagnosis were found during the pandemic. However, these findings reflect short term outcomes, and higher-quality research examining the long-term impact of the pandemic is needed.

Two-year follow-up of participants in the BreastScreen Victoria pilot trial of tomosynthesis versus mammography: breast density-stratified screening outcomes.

OBJECTIVE: This follow-up study of BreastScreen Victoria's pilot trial of digital breast tomosynthesis aimed to report interval cancer rates, screening sensitivity, and density-stratified outcomes for tomosynthesis vs mammography screening. METHODS: Prospective pilot trial [ACTRN-12617000947303] in Maroondah BreastScreen recruited females ≥ 40 years presenting for screening (August 2017-November 2018) to DBT; concurrent screening participants who received mammography formed a comparison group. Follow-up of 24 months from screen date was used to ascertain interval cancers; automated breast density was measured. RESULTS: There were 48 screen-detected and 9 interval cancers amongst 4908 tomosynthesis screens, and 34 screen-detected and 16 interval cancers amongst 5153 mammography screens. Interval cancer rate was 1.8/1000 (95%CI 0.8-3.5) for tomosynthesis vs 3.1/1000 (95%CI 1.8-5.0) for mammography (p = 0.20). Sensitivity of tomosynthesis (86.0%; 95% CI 74.2-93.7) was significantly higher than mammography (68.0%; 95% CI 53.3-80.5), p = 0.03. Cancer detection rate (CDR) of 9.8/1000 (95%CI 7.2-12.9) for tomosynthesis was higher than that of 6.6/1000 (95%CI 4.6-9.2) for mammography (p = 0.08); density-stratified analyses showed CDR was significantly higher for tomosynthesis than mammography (10.6/1000 vs 3.5/1000, p = 0.03) in high-density screens. Recall rate for tomosynthesis was significantly higher than for mammography (4.2% vs 3.0%, p < 0.001), and this increase in recall for tomosynthesis was evident only in high-density screens (5.6% vs 2.9%, p < 0.001). CONCLUSION: Although interval cancer rates did not significantly differ between screened groups, sensitivity was significantly higher for tomosynthesis than mammography screening. ADVANCES IN KNOWLEDGE: In a program-embedded pilot trial, both increased cancer detection and recall rates from tomosynthesis were predominantly observed in high-density screens.

Artificial intelligence (AI) for breast cancer screening: BreastScreen population-based cohort study of cancer detection.

BACKGROUND: Artificial intelligence (AI) has been proposed to reduce false-positive screens, increase cancer detection rates (CDRs), and address resourcing challenges faced by breast screening programs. We compared the accuracy of AI versus radiologists in real-world population breast cancer screening, and estimated potential impacts on CDR, recall and workload for simulated AI-radiologist reading. METHODS: External validation of a commercially-available AI algorithm in a retrospective cohort of 108,970 consecutive mammograms from a population-based screening program, with ascertained outcomes (including interval cancers by registry linkage). Area under the ROC curve (AUC), sensitivity and specificity for AI were compared with radiologists who interpreted the screens in practice. CDR and recall were estimated for simulated AI-radiologist reading (with arbitration) and compared with program metrics. FINDINGS: The AUC for AI was 0.83 compared with 0.93 for radiologists. At a prospective threshold, sensitivity for AI (0.67; 95% CI: 0.64-0.70) was comparable to radiologists (0.68; 95% CI: 0.66-0.71) with lower specificity (0.81 [95% CI: 0.81-0.81] versus 0.97 [95% CI: 0.97-0.97]). Recall rate for AI-radiologist reading (3.14%) was significantly lower than for the BSWA program (3.38%) (-0.25%; 95% CI: -0.31 to -0.18; P < 0.001). CDR was also lower (6.37 versus 6.97 per 1000) (-0.61; 95% CI: -0.77 to -0.44; P < 0.001); however, AI detected interval cancers that were not found by radiologists (0.72 per 1000; 95% CI: 0.57-0.90). AI-radiologist reading increased arbitration but decreased overall screen-reading volume by 41.4% (95% CI: 41.2-41.6). INTERPRETATION: Replacement of one radiologist by AI (with arbitration) resulted in lower recall and overall screen-reading volume. There was a small reduction in CDR for AI-radiologist reading. AI detected interval cases that were not identified by radiologists, suggesting potentially higher CDR if radiologists were unblinded to AI findings. These results indicate AI's potential role as a screen-reader of mammograms, but prospective trials are required to determine whether CDR could improve if AI detection was actioned in double-reading with arbitration. FUNDING: National Breast Cancer Foundation (NBCF), National Health and Medical Research Council (NHMRC).

Incidence of metastatic breast cancer in an Australian population-based cohort of women with non-metastatic breast cancer at diagnosis.

OBJECTIVES: To estimate the incidence of metastatic breast cancer (MBC) in Australian women with an initial diagnosis of non-metastatic breast cancer. DESIGN, SETTING AND PARTICIPANTS: A population-based cohort study of all women with non-metastatic breast cancer registered on the New South Wales Central Cancer Register (CCR) in 2001 and 2002 who received care in a NSW hospital. MAIN OUTCOME MEASURES: 5-year cumulative incidence of MBC; prognostic factors for MBC. RESULTS: MBC was recorded within 5 years in 218 of 4137 women with localised node-negative disease (5-year cumulative incidence, 5.3%; 95% CI, 4.6%-6.0%); and 455 of 2507 women with regional disease (5-year cumulative incidence, 18.1%; 95% CI, 16.7%-19.7%). The hazard rate for developing MBC was highest in the second year after the initial diagnosis of breast cancer. Determinants of increased risk of MBC were regional disease at diagnosis, age less than 50 years and living in an area of lower socio-economic status. CONCLUSIONS: Our Australian population-based estimates are valuable when communicating average MBC risks to patients and planning clinical services and trials. Women with node-negative disease have a low risk of developing MBC, consistent with outcomes of adjuvant clinical trials. Regional disease at diagnosis remains an important prognostic factor.

Independent External Validation of Artificial Intelligence Algorithms for Automated Interpretation of Screening Mammography: A Systematic Review.

PURPOSE: The aim of this study was to describe the current state of science regarding independent external validation of artificial intelligence (AI) technologies for screening mammography. METHODS: A systematic review was performed across five databases (Embase, PubMed, IEEE Explore, Engineer Village, and arXiv) through December 10, 2020. Studies that used screening examinations from real-world settings to externally validate AI algorithms for mammographic cancer detection were included. The main outcome was diagnostic accuracy, defined by area under the receiver operating characteristic curve (AUC). Performance was also compared between radiologists and either stand-alone AI or combined radiologist and AI interpretation. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: After data extraction, 13 studies met the inclusion criteria (148,361 total patients). Most studies (77% [n = 10]) evaluated commercially available AI algorithms. Studies included retrospective reader studies (46% [n = 6]), retrospective simulation studies (38% [n = 5]), or both (15% [n = 2]). Across 5 studies comparing stand-alone AI with radiologists, 60% (n = 3) demonstrated improved accuracy with AI (AUC improvement range, 0.02-0.13). All 5 studies comparing combined radiologist and AI interpretation with radiologists alone demonstrated improved accuracy with AI (AUC improvement range, 0.028-0.115). Most studies had risk for bias or applicability concerns for patient selection (69% [n = 9]) and the reference standard (69% [n = 9]). Only two studies obtained ground-truth cancer outcomes through regional cancer registry linkage. CONCLUSIONS: To date, external validation efforts for AI screening mammographic technologies suggest small potential diagnostic accuracy improvements but have been retrospective in nature and suffer from risk for bias and applicability concerns.

Artificial intelligence (AI) to enhance breast cancer screening: protocol for population-based cohort study of cancer detection.

INTRODUCTION: Artificial intelligence (AI) algorithms for interpreting mammograms have the potential to improve the effectiveness of population breast cancer screening programmes if they can detect cancers, including interval cancers, without contributing substantially to overdiagnosis. Studies suggesting that AI has comparable or greater accuracy than radiologists commonly employ 'enriched' datasets in which cancer prevalence is higher than in population screening. Routine screening outcome metrics (cancer detection and recall rates) cannot be estimated from these datasets, and accuracy estimates may be subject to spectrum bias which limits generalisabilty to real-world screening. We aim to address these limitations by comparing the accuracy of AI and radiologists in a cohort of consecutive of women attending a real-world population breast cancer screening programme. METHODS AND ANALYSIS: A retrospective, consecutive cohort of digital mammography screens from 109 000 distinct women was assembled from BreastScreen WA (BSWA), Western Australia's biennial population screening programme, from November 2016 to December 2017. The cohort includes 761 screen-detected and 235 interval cancers. Descriptive characteristics and results of radiologist double-reading will be extracted from BSWA outcomes data collection. Mammograms will be reinterpreted by a commercial AI algorithm (DeepHealth). AI accuracy will be compared with that of radiologist single-reading based on the difference in the area under the receiver operating characteristic curve. Cancer detection and recall rates for combined AI-radiologist reading will be estimated by pairing the first radiologist read per screen with the AI algorithm, and compared with estimates for radiologist double-reading. ETHICS AND DISSEMINATION: This study has ethical approval from the Women and Newborn Health Service Ethics Committee (EC00350) and the Curtin University Human Research Ethics Committee (HRE2020-0316). Findings will be published in peer-reviewed journals and presented at national and international conferences. Results will also be disseminated to stakeholders in Australian breast cancer screening programmes and policy makers in population screening.

Ductal carcinoma in situ at core-needle biopsy: meta-analysis of underestimation and predictors of invasive breast cancer.

PURPOSE: To perform a meta-analysis to report pooled estimates for underestimation of invasive breast cancer (where core-needle biopsy [CNB] shows ductal carcinoma in situ [DCIS] and excision histologic examination shows invasive breast cancer) and to identify preoperative variables that predict invasive breast cancer. MATERIALS AND METHODS: Studies were identified by searching MEDLINE and were included if they provided data on DCIS underestimates (overall and according to preoperative variables). Study-specific and pooled percentages for DCIS underestimates were calculated. By using meta-regression (random effects logistic modeling) the association between each study-level preoperative variable and understaged invasive breast cancer was investigated. RESULTS: Fifty-two studies that included 7350 cases of DCIS with findings at excision histologic examination as the reference standard met the eligibility criteria and were included. There were 1736 underestimates (invasive breast cancer at excision); the random-effects pooled estimate was 25.9% (95% confidence interval: 22.5%, 29.5%). Preoperative variables that showed significant univariate association with higher underestimation included the use of a 14-gauge automated device (vs 11-gauge vacuum-assisted biopsy, P = .006), high-grade lesion at CNB (vs non-high grade lesion, P < .001), lesion size larger than 20 mm at imaging (vs lesions ≤ 20 mm, P < .001), Breast Imaging Reporting and Data System (BI-RADS) score of 4 or 5 (vs BI-RADS score of 3, P for trend = .005), mammographic mass (vs calcification only, P < .001), and palpability (P < .001). CONCLUSION: About one in four DCIS diagnoses at CNB represent understaged invasive breast cancer. Preoperative variables significantly associated with understaging include biopsy device and guidance method, size, grade, mammographic features, and palpability.

Accuracy of a preoperative model for predicting invasive breast cancer in women with ductal carcinoma-in-situ on vacuum-assisted core needle biopsy.

BACKGROUND: Core needle biopsy (CNB) diagnoses of ductal carcinoma-in-situ (DCIS) may represent understaged invasive breast cancer (IBC). We aimed to develop a model that helps identify preoperatively women with IBC after a CNB diagnosis of DCIS. METHODS: Retrospective study of all women with DCIS on vacuum-assisted CNB of microcalcifications (1999-2008), with prospective classification of imaging variables independently by two radiologists. Variables included lesion size and level of suspicion on imaging, morphology and distribution of microcalcifications, DCIS nuclear grade on CNB, number of cores, and age. Multivariate logistic regression models of the probability of IBC were developed; the accuracy of these models was examined for each radiologist. RESULTS: Excision histology showed IBC in 77 (17.4%) of 442 subjects with DCIS on CNB. Lesion size on imaging yielded the best model fit and highest accuracy, and had the highest agreement between radiologists. Addition of grade to a model which included size improved model fit (P < 0.0001). However, model fit and accuracy were not improved by inclusion of any other variables. A model based on size and grade had similar areas under the receiver operating characteristic curve (accuracy of 74%) for each radiologist. Modeled sensitivity, specificity, and predictive values for different combinations of size and grade thresholds are reported. If the imaging lesion is >50 mm and the CNB grade is high, the model's positive predictive value is ≥50%. CONCLUSIONS: A model based on imaging size of microcalcifications and CNB nuclear grade can identify women at high risk of having IBC with moderate accuracy and may be used to guide informed preoperative discussion in women with newly diagnosed DCIS on CNB.

Interpregnancy intervals and adverse birth outcomes in high-income countries: An international cohort study.

BACKGROUND: Most evidence for interpregnancy interval (IPI) and adverse birth outcomes come from studies that are prone to incomplete control for confounders that vary between women. Comparing pregnancies to the same women can address this issue. METHODS: We conducted an international longitudinal cohort study of 5,521,211 births to 3,849,193 women from Australia (1980-2016), Finland (1987-2017), Norway (1980-2016) and the United States (California) (1991-2012). IPI was calculated based on the time difference between two dates-the date of birth of the first pregnancy and the date of conception of the next (index) pregnancy. We estimated associations between IPI and preterm birth (PTB), spontaneous PTB, and small-for-gestational age births (SGA) using logistic regression (between-women analyses). We also used conditional logistic regression comparing IPIs and birth outcomes in the same women (within-women analyses). Random effects meta-analysis was used to calculate pooled adjusted odds ratios (aOR). RESULTS: Compared to an IPI of 18-23 months, there was insufficient evidence for an association between IPI <6 months and overall PTB (aOR 1.08, 95% CI 0.99-1.18) and SGA (aOR 0.99, 95% CI 0.81-1.19), but increased odds of spontaneous PTB (aOR 1.38, 95% CI 1.21-1.57) in the within-women analysis. We observed elevated odds of all birth outcomes associated with IPI ≥60 months. In comparison, between-women analyses showed elevated odds of adverse birth outcomes for <12 month and >24 month IPIs. CONCLUSIONS: We found consistently elevated odds of adverse birth outcomes following long IPIs. IPI shorter than 6 months were associated with elevated risk of spontaneous PTB, but there was insufficient evidence for increased risk of other adverse birth outcomes. Current recommendations of waiting at least 24 months to conceive after a previous pregnancy, may be unnecessarily long in high-income countries.