Fatal and non-fatal breast cancers in women targeted by BreastScreen Norway: a cohort study.

BACKGROUND: Many breast cancer survivors experience anxiety related to dying from their disease even if it is detected at an early stage. We aimed to increase knowledge about fatal and non-fatal breast cancer by describing how histopathological tumour profiles and detection modes were associated with 10-year breast cancer-specific survival. METHODS: This cohort study included data from women targeted by BreastScreen Norway (aged 50-69) and diagnosed with invasive breast cancer during 1996-2011. Breast cancer was classified as fatal if causing death within 10 years after diagnosis and non-fatal otherwise. We described histopathologic characteristics of fatal and non-fatal cancers, stratified by mode of detection. Recursive partitioning identified subgroups with differing survival profiles. RESULTS: In total, 6.3% of 9954 screen-detected cancers (SDC) were fatal, as were 17.4% of 3205 interval cancers (IC) and 20.9% of 3237 cancers detected outside BreastScreen Norway. Four to five subgroups with differing survival profiles were identified within each detection mode. Women with lymph node-negative SDC or Grade 1-2, node-negative IC without distant metastases had the highest 10-year survival (95-96%). CONCLUSIONS: Two subgroups representing 53% of the cohort had excellent (95-96%) 10-year breast cancer-specific survival. Most women with SDC had excellent survival, as did nearly 40% of women diagnosed with IC.

Cumulative risk of a false-positive screening result: A retrospective cohort study using empirical data from 10 biennial screening rounds in BreastScreen Norway.

BACKGROUND: False-positive screening results are an inevitable and commonly recognized disadvantage of mammographic screening. This study estimated the cumulative probability of experiencing a first false-positive screening result in women attending 10 biennial screening rounds in BreastScreen Norway, which targets women aged 50 to 69 years. METHODS: This retrospective cohort study analyzed screening outcomes from 421,545 women who underwent 1,894,523 screening examinations during 1995-2019. Empirical data were used to calculate the cumulative risk of experiencing a first false-positive screening result and a first false-positive screening result that involved an invasive procedure over 10 screening rounds. Logistic regression was used to evaluate the effect of adjusting for irregular attendance, age at screening, and number of screens attended. RESULTS: The cumulative risk of experiencing a first false-positive screening result was 18.04% (95% confidence interval [CI], 18.00%-18.07%). It was 5.01% (95% CI, 5.01%-5.02%) for experiencing a false-positive screening result that involved an invasive procedure. Adjusting for irregular attendance or age at screening did not appreciably affect these estimates. After adjustments for the number of screens attended, the cumulative risk of a first false-positive screening result was 18.28% (95% CI, 18.24%-18.32%), and the risk of a false-positive screening result including an invasive procedure was 5.11% (95% CI, 5.11%-5.22%). This suggested that there was minimal bias from dependent censoring. CONCLUSIONS: Nearly 1 in 5 women will experience a false-positive screening result if they attend 10 biennial screening rounds in BreastScreen Norway. One in 20 will experience a false-positive screening result with an invasive procedure. LAY SUMMARY: A false-positive screening result occurs when a woman attending mammographic screening is called back for further assessment because of suspicious findings, but the assessment does not detect breast cancer. Further assessment includes additional imaging. Usually, it involves ultrasound, and sometimes, it involves a biopsy. This study has evaluated the chance of experiencing a false-positive screening result among women attending 10 screening examinations over 20 years in BreastScreen Norway. Nearly 1 in 5 women will experience a false-positive screening result over 10 screening rounds. One in 20 women will experience a false-positive screening result involving a biopsy.

Survival among women diagnosed with screen-detected or interval breast cancer classified as true, minimal signs, or missed through an informed radiological review.

OBJECTIVES: "True" breast cancers, defined as not being visible on prior screening mammograms, are expected to be more aggressive than "missed" cancers, which are visible in retrospect. However, the evidence to support this hypothesis is limited. We compared the risk of death from any cause for women with true, minimal signs, and missed invasive screen-detected (SDC) and interval breast cancers (IC). METHODS: This nation-wide study included 1022 SDC and 788 IC diagnosed through BreastScreen Norway during 2005-2016. Cancers were classified as true, minimal signs, or missed by five breast radiologists in a consensus-based informed review of prior screening and diagnostic images. We used multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of death from any cause associated with true, minimal signs, and missed breast cancers, adjusting for age at diagnosis, histopathologic tumour diameter and grade, and subtype. Separate models were created for SDC and IC. RESULTS: Among SDC, 463 (44%) were classified as true and 242 (23%) as missed; among IC, 325 (39%) were classified as true and 235 (32%) missed. Missed SDC were associated with a similar risk of death as true SDC (HR = 1.20, 95% CI (0.49, 2.46)). Similar results were observed for missed versus true IC (HR = 1.31, 95% CI (0.77, 2.23)). CONCLUSIONS: We did not observe a statistical difference in the risk of death for women diagnosed with true or missed SDC or IC; however, the number of cases reviewed and follow-up time limited the precision of our estimates. KEY POINTS: • An informed radiological review classified screen-detected and interval cancers as true, minimal signs, or missed based on prior screening and diagnostic mammograms. • It has been hypothesised that true cancers, not visible on the prior screening examination, may be more aggressive than missed cancers. • We did not observe a statistical difference in the risk of death from any cause for women with missed versus true screen-detected or interval breast cancers.

Terminal digit preference: a source of measurement error in breast cancer diameter reporting.

Objectives: Women diagnosed with breast cancer are offered treatment and therapy based on tumor characteristics, including tumor diameter. There is scarce knowledge whether tumor diameter is accurately reported, or whether it is unconsciously rounded to the nearest half-centimeter (terminal digit preference). This study aimed to assess the precision (number of digits) of breast cancer tumor diameters and whether they are affected by terminal digit preference. Furthermore, we aimed to assess the agreement between mammographic and histopathologic tumor diameter measurements.Material and Methods: This national registry study included reported mammographic and registered histopathologic tumor diameter information from the Cancer Registry of Norway for invasive breast cancers diagnosed during 2012-2016. Terminal digit preference was assessed using histograms. Agreement between mammographic and histopathologic measurements was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman plots.Results: Mammographic, histopathologic, or both tumor measurements were available for 7792, 13,541 and 6865 cases, respectively. All mammographic and 97.2% of histopathologic tumor diameters were recorded using whole mm. Terminal digits of zero or five were observed among 38.7% and 34.8% of mammographic and histopathologic measurements, respectively. There was moderate agreement between the two measurement methods (ICC = 0.52, 95% CI: 0.50-0.53). On average, mammographic measurements were 1.26 mm larger (95% limits of agreement: -22.29-24.73) than histopathologic measurements. This difference increased with increasing tumor size.Conclusion: Terminal digit preference was evident among breast cancer tumor diameters in this nationwide study. Further studies are needed to investigate the potential extent of under-staging and under-treatment resulting from this measurement error.

Pathway times in the mammography programme before and after introduction of the breast cancer care pathway. / Forløpstider i Mammografi-programmet før og etter innføring av pakkeforløp for brystkreft.

BACKGROUND: The purpose of introducing the 'cancer patient pathway for breast cancer' was to ensure a coherent treatment pathway without unnecessary delays. Radiologists and pathologists who work with breast diagnostics are involved in both cancer patient pathways and BreastScreen Norway. The extent to which this policy may have affected waiting times has not been analysed previously. This study presents waiting times in BreastScreen Norway before and after introduction of cancer patient pathway. MATERIAL AND METHOD: We analysed waiting times associated with 1 485 240 screening examinations undertaken as part of BreastScreen Norway in the period 01.7.2011-30.6.2018, stratified by breast diagnostic centre. Waiting times were defined as the number of calendar days from the a) screening examination to the dispatch of the negative results letter (dispatch time), b) screening examination to the date on which the follow-up examination was performed (follow-up examination time) and c) follow-up examination to diagnosis (diagnosis time). Data were retrieved from the Cancer Registry of Norway's databases. Use of these is set out in the Cancer Registry Regulations. We calculated median waiting times in addition to 90th percentiles. RESULTS: The median dispatch time was 13 days before the cancer patient pathway was introduced, and 12 days after. The median follow-up examination time increased from 23 to 27 days, while the median diagnosis time was 3 days both before and after introduction of the cancer patient pathway. INTERPRETATION: Dispatch and diagnosis times were unchanged, or slightly changed after introduction of the cancer patient pathway, while follow-up examination time increased somewhat. Introduction of the cancer patient pathway may have led to differential adjustments in priorities, workflows and access to resources between the breast diagnostic centres.

Automated Volumetric Analysis of Mammographic Density in a Screening Setting: Worse Outcomes for Women with Dense Breasts.

Purpose To describe screening outcomes from BreastScreen Norway stratified by volumetric breast density (VBD). Materials and Methods This retrospective study included data from 107 949 women aged 50-69 years (mean age ± standard deviation, 58.7 years ± 5.6) who underwent 307 015 screening examinations from 2007 to 2015. Automated software classified mammographic density as nondense (VBD <7.5%) or dense (VBD ≥7.5%). Rates and distributions of screening outcomes (recall, biopsy, screen-detected and interval breast cancer, positive predictive values of recall and of needle biopsy, sensitivity, specificity, and histopathologic tumor characteristics) were analyzed and stratified by density. Tests of proportions, including propensity score and t tests, were used. Results In 28% (87 021 of 307 015) of the screening examinations, the breasts were classified as dense. Recall rates for women with nondense versus dense breasts were 2.7% (5882 of 219 994) and 3.6% (3101 of 87 021); biopsy rates were 1.1% (2359 of 219 994) and 1.4% (1209 of 87 021); rates of screen-detected cancer were 5.5 (1210 of 219 994) and 6.7 (581 of 87 021) per 1000 examinations; and rates of interval breast cancer were 1.2 (199 of 165 324) and 2.8 (185 of 66 674) per 1000 examinations, respectively (P < .001 for all). Sensitivity was 82% (884 of 1083) for nondense breasts and 71% (449 of 634) for dense breasts, whereas specificity was 98% (160 973 of 164 440) and 97% (64 250 of 66 225), respectively (P < .001 for both). For screen-detected cancers, mean tumor diameter was 15.1 mm and 16.6 mm (P = .01), and lymph node-positive disease was found in 18% (170 of 936) and 24% (98 of 417) (P = .02) of women with nondense and dense breasts, respectively. Conclusion Screening examinations of women with dense breasts classified by using automated software resulted in higher recall rate, lower sensitivity, larger tumor diameter, and more lymph node-positive disease compared with women with nondense breasts.

Validity and reliability of self-reported health indicators among women attending organized mammographic screening.

AIMS: Risk factors for breast cancer are often used for adjustment in epidemiological studies, including in the evaluation of early performance measures in mammographic screening. Information about risk factors among participants in the Norwegian Breast Cancer Screening Program has been collected since 2006. We aimed to examine the validity of self-reported history of breast cancer and mammographic screening, as well as the reliability of weight and height amongt women attending the program. METHODS: Information from a questionnaire handed in by participants in the program, 2006-2015, was linked to outcomes from the Cancer Registry of Norway. Sensitivity, specificity, and positive predictive values (PPV) were calculated for self-reported histories of breast cancer and screening. Results were stratified by five-year age groups and evaluated using the χ2 statistic. The reliability of self-reported weight and height were assessed using descriptive statistics, histograms, and mean differences. RESULTS: A total of 538,907 of 611,711 (88%) women attending the program during the study period returned at least one part of the questionnaire. The overall sensitivity, specificity, and PPV for breast cancer and mammography were 96.5%, 99.8%, and 81.3%; and 99.9%, 84.4%, and 97.6% respectively. The mean difference in self-reported weight was 0.35 kg and for height was -0.14 cm, over a period of up to 10 years. CONCLUSIONS: Norwegian women attending the screening program are reasonably accurate in self-reporting their breast cancer and mammography histories. On average, women consistently reported weight and height within one kg/cm.

Monthly variation in mammographic screening attendance in Norway.

Breast Cancer Awareness Month (BCAM) increases screening attendance in the USA. However, this effect has not been investigated in Europe, where organized screening is widespread. We examined monthly attendance within the Norwegian Breast Cancer Screening Programme, 2005-15. Relative to October, the odds of attending screening in January, February, March, August, September or December were slightly decreased (ORadj 0.93-0.98, P ≤ 0.003 for all). BCAM may marginally increase attendance in October but seasonal factors such as weather may also explain this observed variation. Furthermore, it is possible that organized screening with predetermined appointments evens out the effect BCAM has on screening attendance.

ChatGPT performance on radiation technologist and therapist entry to practice exams.

BACKGROUND: The aim of this study was to describe the proficiency of ChatGPT (GPT-4) on certification style exams from the Canadian Association of Medical Radiation Technologists (CAMRT), and describe its performance across multiple exam attempts. METHODS: ChatGPT was prompted with questions from CAMRT practice exams in the disciplines of radiological technology, magnetic resonance (MRI), nuclear medicine and radiation therapy (87-98 questions each). ChatGPT attempted each exam five times. Exam performance was evaluated using descriptive statistics, stratified by discipline and question type (knowledge, application, critical thinking). Light's Kappa was used to assess agreement in answers across attempts. RESULTS: Using a passing grade of 65 %, ChatGPT passed the radiological technology exam only once (20 %), MRI all five times (100 %), nuclear medicine three times (60 %), and radiation therapy all five times (100 %). ChatGPT's performance was best on knowledge questions across all disciplines except radiation therapy. It performed worst on critical thinking questions. Agreement in ChatGPT's responses across attempts was substantial within the disciplines of radiological technology, MRI, and nuclear medicine, and almost perfect for radiation therapy. CONCLUSION: ChatGPT (GPT-4) was able to pass certification style exams for radiation technologists and therapists, but its performance varied between disciplines. The algorithm demonstrated substantial to almost perfect agreement in the responses it provided across multiple exam attempts. Future research evaluating ChatGPT's performance on standardized tests should consider using repeated measures.

Detection and significance of small and low proliferation breast cancer.

OBJECTIVES: To determine the frequency and discuss possible implications of early breast cancer with particularly good prognosis and defined by tumor diameter and cell proliferation. SETTING: Detection of small and slowly growing tumors presents a challenge in breast cancer management, due to the risk of over-treatment. Here, we attempted to define a group of such tumors by combining small diameter (≤10 mm, T1ab tumors) with low tumor cell proliferation (≤10% Ki67 expression rate). These tumors were termed small low proliferation cancers (SLPC). METHODS: Two population-based cohorts were studied: a small research series (n = 534), and a nation-wide registry-based series of prospectively collected routine data (n = 8433). In the latter, we stratified by detection mode; screen-detected, interval, and breast cancers detected outside of screening. Patients were treated according to national guidelines at time of their diagnosis. For both cohorts, we compared tumor histopathology and risk of breast cancer death using a log-rank test for cases with SLPC versus non-SLPC. RESULTS: In the research series (median follow-up 151 months), the frequency of SLPC was 10% (54/534), with one breast cancer death compared with 78 among the remaining 480 cases of non-SLPC (p = 0.008). In the registry series (median follow-up 42 months), the frequency of SLPC was 10% (854/8433), with five deaths compared to 187 among the remaining 7579 cases (p = 0.0004). CONCLUSIONS: SLPC was associated with very low risk of breast cancer death. Prospective randomized trials are needed to clarify whether less aggressive treatment could be a safe option for women with such early breast cancers.

Women's conceptual knowledge about breast cancer screening and overdiagnosis in Norway: a cross-sectional study.

OBJECTIVE: To investigate conceptual knowledge about mammographic screening among Norwegian women. DESIGN: We administered a cross-sectional, web-based survey. We used multiple-choice questions and a grading rubric published by a research group from Australia. SETTING: Our Norwegian-language survey was open from April to June 2020 and targeted women aged 45-74 years. PARTICIPANTS: 2033 women completed our questionnaire. We excluded 13 women outside the target age range and 128 women with incomplete data. Responses from 1892 women were included in the final study sample. PRIMARY AND SECONDARY OUTCOME MEASURES: The questionnaire focused on women's knowledge about the breast cancer mortality reduction, false positive results and overdiagnosis associated with mammographic screening. The primary outcome was the mean number of marks assigned in each of the three themes and overall. There were three potential marks for questions about breast cancer mortality, one for false positives and six for overdiagnosis. RESULTS: Most women (91.7%) correctly reported that screened women are less likely to die of breast cancer than non-screened women. 39.7% of women reported having heard of a 'false positive screening result' and 86.2% identified the term's definition; 51.3% of women had heard of 'overdiagnosis' and 14.8% identified the term's definition. The mean score was 2.59 of 3 for questions about breast cancer mortality benefit and 0.93 of 1 for the question about false positive screening results. It was 2.23 of 6 for questions about overdiagnosis. CONCLUSIONS: Most participants correctly answered questions about the breast cancer mortality benefit and false positive results associated with screening. The proportion of correct responses to questions about overdiagnosis was modest, indicating that conceptual knowledge about overdiagnosis was lower. Qualitative studies that can obtain in-depth information about women's understanding of overdiagnosis may help improve Norwegian-language information about this challenging topic.

Screening at stationary versus mobile units in BreastScreen Norway.

Objective: To compare breast characteristics, compression parameters, and early performance measures (rates of recall, screen-detected and interval breast cancer, and histopathologic tumour characteristics) for mammographic screening at a stationary versus mobile screening unit. Methods: Results from 92,408 mammographic screening examinations performed as part of BreastScreen Norway during 2008­2017 at either a stationary (n = 52,620) or mobile (n = 39,788) unit in Hordaland county were compared using descriptive statistics and generalized estimating equations. A generalized estimating equation for a binary outcome was used to estimate crude and adjusted odds ratios with 95% confidence intervals for the outcomes of interest. Adjusted generalized estimating equation models included age, breast volume, and density grade as covariates. Results: Screening at the stationary unit was performed on smaller breasts with higher mammographic density, using lower compression force but higher pressure than at the mobile unit. Using the stationary screening unit as reference, for women screened at the mobile unit, the adjusted odds ratio was: for recall 0.94 (95% CI: 0.87--1.01), screen-detected breast cancer 0.92 (95% CI: 0.78--1.10), and interval breast cancer 1.17 (95% CI: 0.83­1.64). Conclusions: The quality of care did not differ for women screened at the stationary versus the mobile unit, but there were differences between the women who attended the two units. Sociodemographic factors should be included in future analyses to fully understand the risk of breast cancer among women residing in urban versus rural areas.

Impact of Detection Method and Age on Survival Outcomes in Triple-Negative Breast Cancer: A Population-Based Cohort Analysis.

BACKGROUND: Most investigations have compared triple-negative breast cancer (TNBC) to non-TNBC to elucidate clinical or epidemiologic differences between subtypes. We examined a contemporary cohort of patients with primary TNBC by detection and age at diagnosis within a population-based breast screening program to examine survival outcomes. PATIENTS AND METHODS: All women with a diagnosis of primary TNBC between January 1, 2005, and December 31, 2012, in Nova Scotia, Canada, were included. Clinicopathologic and detection variables were abstracted from the Nova Scotia Breast Screening Program. Patient charts were abstracted for adjuvant therapies and survival outcomes, supplemented by provincial vital statistical data. RESULTS: A total of 412 patients comprised the study population, with almost half aged over 60 years (46.3%) and 30.2% having screen-detected disease. There were no significant differences in prognostic variables between age groups. Younger patients were more likely to receive adjuvant chemotherapy (96.3% ≤ 49 years vs. 31.2% ≥ 70 years), but there were no differences in disease-free or breast cancer-specific survival between the age groups. For those with disease recurrence, median time to recurrence and death was shorter for younger patients (17 vs. 26 months, 16 vs. 33 months respectively; age 40-49 vs. 70+). Those with screen-detected disease had better disease-free, breast cancer-specific, and overall survival outcomes. CONCLUSION: Detection method may play a role in TNBC survival outcomes, thus supporting novel screening strategies for TNBC. Shorter time to survival events in the younger patient groups suggests that TNBC is a clinically heterogeneous disease despite similarities in prognostic factors across age.

Breast density scales: the metric matters.

OBJECTIVE: Measures of percent mammographic density (PMD) are often categorized using various density scales. The purpose of this study was to examine information loss associated with the use of categorical density scales. METHODS: Baseline PMD was assessed at 1% precision for 2,374 females. The data were used to create 21-category, 4-category and 2-category density scales. R-squared and root mean square error were used to evaluate the effect of categorizing PMD. The area under the receiver operator characteristic curves were compared between cancer risk models employing solely categorical PMD scales and solely baseline PMD for a subset of females (424 cases, 848 controls). RESULTS: R-squared value decreased from 1.00 (1% PMD) to 0.56 (2-category scale), while root mean square error increased from 0.00 (1% PMD) to 10.83 (2-category scale). The area under the receiver operator characteristic curve decreased from 0.64 for a cancer risk model using 1% PMD to 0.58 for a risk model using a 21-category density scale (p < 0.0001), 0.55 for a 4-category Breast Imaging, Reporting and Data System-like scale (p < 0.0001) and 0.50 for a 2-category Breast Imaging, Reporting and Data System-like scale (high vs low) (p < 0.0001). CONCLUSION: Categorizing PMD measures into categorical density scales leads to a significant loss of information. Indeed, a simple high versus low split of PMD using a 50% cut point yields a cancer risk model with no discriminatory power. Advances in knowledge: Use of categorical mammographic density scales rather than continuous percent mammographic density measures leads to significant loss of information. Breast cancer risk models using categorical mammographic density scales perform more poorly than models using continuous PMD measures.

Utility of relative and absolute measures of mammographic density vs clinical risk factors in evaluating breast cancer risk at time of screening mammography.

OBJECTIVE: Various clinical risk factors, including high breast density, have been shown to be associated with breast cancer. The utility of using relative and absolute area-based breast density-related measures was evaluated as an alternative to clinical risk factors in cancer risk assessment at the time of screening mammography. METHODS: Contralateral mediolateral oblique digital mammography images from 392 females with unilateral breast cancer and 817 age-matched controls were analysed. Information on clinical risk factors was obtained from the provincial breast-imaging information system. Breast density-related measures were assessed using a fully automated breast density measurement software. Multivariable logistic regression was conducted, and area under the receiver-operating characteristic (AUROC) curve was used to evaluate the performance of three cancer risk models: the first using only clinical risk factors, the second using only density-related measures and the third using both clinical risk factors and density-related measures. RESULTS: The risk factor-based model generated an AUROC of 0.535, while the model including only breast density-related measures generated a significantly higher AUROC of 0.622 (p < 0.001). The third combined model generated an AUROC of 0.632 and performed significantly better than the risk factor model (p < 0.001) but not the density-related measures model (p = 0.097). CONCLUSION: Density-related measures from screening mammograms at the time of screen may be superior predictors of cancer compared with clinical risk factors. ADVANCES IN KNOWLEDGE: Breast cancer risk models based on density-related measures alone can outperform risk models based on clinical factors. Such models may support the development of personalized breast-screening protocols.