UK National Health Service Breast Research Articles

Deep Learning for Breast Cancer Risk Prediction: Application to a Large Representative UK Screening Cohort.

Purpose To develop an artificial intelligence (AI) deep learning tool capable of predicting future breast cancer risk from a current negative screening mammographic examination and to evaluate the model on data from the UK National Health Service Breast Screening Program. Materials and Methods The OPTIMAM Mammography Imaging Database contains screening data, including mammograms and information on interval cancers, for more than 300 000 female patients who attended screening at three different sites in the United Kingdom from 2012 onward. Cancer-free screening examinations from women aged 50-70 years were performed and classified as risk-positive or risk-negative based on the occurrence of cancer within 3 years of the original examination. Examinations with confirmed cancer and images containing implants were excluded. From the resulting 5264 risk-positive and 191 488 risk-negative examinations, training (n = 89 285), validation (n = 2106), and test (n = 39 351) datasets were produced for model development and evaluation. The AI model was trained to predict future cancer occurrence based on screening mammograms and patient age. Performance was evaluated on the test dataset using the area under the receiver operating characteristic curve (AUC) and compared across subpopulations to assess potential biases. Interpretability of the model was explored, including with saliency maps. Results On the hold-out test set, the AI model achieved an overall AUC of 0.70 (95% CI: 0.69, 0.72). There was no evidence of a difference in performance across the three sites, between patient ethnicities, or across age groups. Visualization of saliency maps and sample images provided insights into the mammographic features associated with AI-predicted cancer risk. Conclusion The developed AI tool showed good performance on a multisite, United Kingdom-specific dataset. Keywords: Deep Learning, Artificial Intelligence, Breast Cancer, Screening, Risk Prediction Supplemental material is available for this article. ©RSNA, 2024.

Cohort profile of the Sloane Project: methodology for a prospective UK cohort study of >15 000 women with screen-detected non-invasive breast neoplasia

PurposeThe introduction of breast screening in the UK led to an increase in the detection of non-invasive breast neoplasia, predominantly ductal carcinoma in situ (DCIS), a non-obligatory precursor of invasive...

Performance of Radiologists and Radiographers in Double Reading Mammograms: The UK National Health Service Breast Screening Program.

Background Double reading can be used in screening mammography, but it is labor intensive. There is limited evidence on whether trained radiographers (ie, technologists) may be used to provide double reading. Purpose To compare the performance of radiologists and radiographers double reading screening mammograms, considering reader experience level. Materials and Methods In this retrospective study, performance and experience data were obtained for radiologists and radiographer readers of all screening mammograms in England from April 2015 to March 2016. Cancer detection rate (CDR), recall rate (RR), and positive predictive value (PPV) of recall based on biopsy-proven findings were calculated for first readers. Performance metrics were analyzed according to reader professional group and years of reading experience using the analysis of variance test. P values less than .05 were considered to indicate statistically significant difference. Results During the study period, 401 readers (224 radiologists and 177 radiographers) double read 1 404 395 screening digital mammograms. There was no difference in CDR between radiologist and radiographer readers (mean, 7.84 vs 7.53 per 1000 examinations, respectively; P = .08) and no difference for readers with more than 10 years of experience compared with 5 years or fewer years of experience, regardless of professional group (mean, 7.75 vs 7.71 per 1000 examinations respectively, P = .87). No difference in the mean RR was observed between radiologists and radiographer readers (5.0% vs 5.2%, respectively, P = .63). A lower RR was seen for readers with more than 10 years of experience compared with 5 years or fewer, regardless of professional group (mean, 4.8% vs 5.8%, respectively; P = .001). No variation in PPV was observed between them (P = .42), with PPV values of 17.1% for radiologists versus 16.1% for radiographers. A higher PPV was seen for readers with more than 10 years of experience compared with 5 years or less, regardless of professional group (mean, 17.5% and 14.9%, respectively; P = .02). Conclusion No difference in performance was observed between radiographers and radiologists reading screening mammograms in a program that used double reading. Published under a CC BY 4.0 license Online supplemental material is available for this article. See also the editorial by Hooley and Durand in this issue.

Diagnostic concordance of phyllodes tumour of the breast.

Phyllodes tumours (PT) are rare and distinct breast tumours, which span a morphological continuum. Classification into benign, borderline and malignant categories reflects their biology and clinical behaviour and is essential to guide management. This study aims to assess the diagnostic agreement of PT using the UK National Health Service Breast Screening Programme (NHSBSP) breast pathology external quality assurance (EQA) scheme data. Twenty-six PTs were identified in the EQA scheme, which were diagnosed by an average of 607 participants/circulation. Data on diagnostic categories were collected and representative slides were reviewed. The level of concordance between reporting pathologists was assessed. There were 14 benign, six borderline and six malignant PT. The overall rate of diagnosis agreement was 86% when analysed as benign lesions, borderline PT and malignant lesions, which decreased to 79% when diagnosed as PT (irrespective of grade) and to 63% when the diagnosis was further refined to PT categories (benign, borderline and malignant PTs). The highest agreement rate was observed in malignant PT (86%) and the lowest in borderline PT (42%). Malignant heterologous elements, stromal overgrowth and leaf-like architecture are features associated with higher concordance rates. Lower-priority features were stromal expansion, clefting and multinodularity. The concordance of PT diagnosis, as an entity, is high, but its classification into benign, borderline and malignant has variable agreement levels, with borderline tumours having the lowest concordance rate. More research to refine the diagnostic criteria for categorisation of PT is warranted to improve concordance between pathologists.

Abstract P4-06-05: Heterogeneity of DCIS does not appear to be a biomarker for development of subsequent invasive cancer

Abstract Genomic instability is a key feature of carcinogenesis, giving rise to tumour promoting aberrations. The inherent unpredictability of these processes leads to a high degree of intratumour heterogeneity, previously shown to be advantageous for cancer progression in a series of cancer types. We sought to explore the role of genomic instability and intratumour heterogeneity in the progression of ductal carcinoma in situ (DCIS) to invasive disease, in a cohort of 49 women with pure DCIS that developed subsequent ipsilateral invasive disease and 90 women with pure DCIS with no evidence of recurrence with a median follow up of 5.4 years. All samples were identified from within the Sloane project, a prospective national cohort study of DCIS within the UK National Health Service Breast Screening Programme. DNA extracted from bulk tissue samples was processed on the HumanCytoSNP array, and allele-specific copy number aberration (CNA) data was obtained from ASCAT. We measured genomic instability using Scores Of Chromosomal Instability Scarring (SCINS), as well as by calculating the Shannon diversity index for the different copy number states occurring in the tumour genome. We also attempted to deconvolute the clonal structure of the tumours by applying the Shannon diversity index on the raw copy number estimates provided by ASCAT. Non-integer copy number states were interpreted as indicative of the presence of subclonal CNAs. As a positive control, we compared ER+ and ER- DCIS in a larger cohort of 173 DCIS samples (129 ER+ and 44 ER-), using the same methods. We expect ER- tumours to be more genomically unstable, and consequentially more clonally diverse. Measured using SCINS, both copy-neutral loss of heterozygosity (≥ 4 Mbp) and allelic-imbalanced CNAs (≥ 8 Mbp) were shown to be higher in ER- tumours (Fisher’s exact test, p = 0.014 and p = 0.034, respectively). Overall genomic instability was also shown to be higher in ER- tumours using the Shannon diversity index (Fisher’s exact test, p = 0.0085). Our attempt at clonal structure deconvolution also indicates increased heterogeneity in ER- tumours (Fisher’s exact test, p = 0.027). However, no significant difference was identified in the genomic instability or heterogeneity of DCIS that developed subsequent invasive disease compared to that of indolent DCIS, using any of the aforementioned measures. We were therefore unable to identify evidence of a direct link between DCIS heterogeneity and progression to invasive cancer. Our methods did, however, demonstrate that DCIS in general is highly genomically diverse, with ER- tumours exhibiting increased diversity compared to ER+ ones. We aim to validate these findings using spatial sampling data from our cohort, as well as integrating mutation data to allow the use of established clonal heterogeneity deconvolution pipelines. Citation Format: Anargyros Megalios, Vandna Shah, Rana Shami, Salpie Nowinski, Jelmar Quist, Mathini Sridharan, Carolina Salinas de Souza, Karen Clements, Anita Grigoriadis, Sarah Pinder, Alastair Thompson, Elinor Sawyer. Heterogeneity of DCIS does not appear to be a biomarker for development of subsequent invasive cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-06-05.

Breast cancer risk status influences uptake, retention and efficacy of a weight loss programme amongst breast cancer screening attendees: two randomised controlled feasibility trials

BackgroundExcess body weight and sub-optimal lifestyle are modifiable causes of breast cancer and other diseases. There is little evidence that behaviour change is possible within screening programmes and whether this is influenced by prior knowledge of disease risk. We determined whether breast cancer risk influences uptake, retention and efficacy of a weight control programme in the UK National Health Service Breast Screening Programme, and whether additional cardiovascular disease and type 2 diabetes risk information improves uptake and retention further.MethodOverweight/obese women in the UK National Health Service Breast Screening Programme identified at high, moderately increased, average and low-risk of breast cancer were randomised to receive individualised breast cancer risk information (breast cancer prevention programme), or individualised breast cancer, cardiovascular disease (QRISK2) and type 2 diabetes (QDiabetes, HbA1c) information (multiple disease prevention programme). Personalised breast cancer risk feedback was given before randomisation in Study-1, and after randomisation in Study-2.ResultsRecruitment was 9% (126/1356) in Study-1 and 7% (52/738) in Study-2. With respect to breast cancer risk, odds ratio of uptake for high/moderately increased vs low risk women was 1.99 (95% CI 1.24–3.17, P = 0.004) in Study-1 and 3.58 (95% CI 1.59–8.07, P = 0.002) in Study-2. Odds ratio of retention for high/moderately increased -risk vs. low risk women was 2.98 (95% CI 1.05–8.47, P = 0.041) in Study-1 and 3.88 (95% CI 1.07–14.04, P = 0.039) in Study-2. Weight loss of ≥5% at 12 months was achieved by 63% high/moderate vs. 43% low-risk women in Study-1 (P = 0.083) and 39% vs. 8% in Study-2 (P = 0.008). Uptake, retention and weight loss were equivalent in both the breast cancer prevention programme and the multiple disease prevention programme in both studies.ConclusionsWomen who are informed that they are at increased breast cancer risk were significantly more likely to join and remain in the programmes and consequently lose more weight across both studies. High risk women are more likely engage in a lifetyle prevention programme and also have the greatest potential benefit fom risk reduction strategies.Trial registrationISRCTN91372184 Registered 28 September 2014.

Improving Workflow Efficiency for Mammography Using Machine Learning

ObjectiveThe aim of this study was to determine whether machine learning could reduce the number of mammograms the radiologist must read by using a machine-learning classifier to correctly identify normal mammograms and to select the uncertain and abnormal examinations for radiological interpretation. MethodsMammograms in a research data set from over 7,000 women who were recalled for assessment at six UK National Health Service Breast Screening Program centers were used. A convolutional neural network in conjunction with multitask learning was used to extract imaging features from mammograms that mimic the radiological assessment provided by a radiologist, the patient’s nonimaging features, and pathology outcomes. A deep neural network was then used to concatenate and fuse multiple mammogram views to predict both a diagnosis and a recommendation of whether or not additional radiological assessment was needed. ResultsTen-fold cross-validation was used on 2,000 randomly selected patients from the data set; the remainder of the data set was used for convolutional neural network training. While maintaining an acceptable negative predictive value of 0.99, the proposed model was able to identify 34% (95% confidence interval, 25%-43%) and 91% (95% confidence interval: 88%-94%) of the negative mammograms for test sets with a cancer prevalence of 15% and 1%, respectively. ConclusionMachine learning was leveraged to successfully reduce the number of normal mammograms that radiologists need to read without degrading diagnostic accuracy.

Higher risk breast screening: cancer detection rates, recall rates, and attendance rates in Northern Ireland

To evaluate the outcomes of higher risk screening in Northern Ireland (NI) and compare with the UK National Health Service Breast Screening Programme (NHSBSP). Higher risk breast screening commenced in NI in April 2013. Data on the programme were audited retrospectively through the Higher Risk screening centre. As there are no national standards for attendance rates and cancer detection rates, screening data and standards from the NHSBSP were used as a baseline for comparison. Attendance rates for the higher risk screening population have increased each of the last 3 years up to 77.7%. Recall rates have improved year on year from initial 14.2%-8.6%. Cancer detection rates have varied each year with a range from 21.5 per 1,000 women screened to 30.9 per 1,000 women screened. The Higher Risk Breast Screening Programme in NI represents a success story in risk stratified screening. Performance outcomes are excellent. The data outcomes may be used to inform standards of acceptable practice in the wider NHSBSP.

Management and 5-year outcomes in 9938 women with screen-detected ductal carcinoma in situ: the UK Sloane Project

BackgroundManagement of screen-detected ductal carcinoma in situ (DCIS) remains controversial. MethodsA prospective cohort of patients with DCIS diagnosed through the UK National Health Service Breast Screening Programme (1st April 2003 to 31st March 2012) was linked to national databases and case note review to analyse patterns of care, recurrence and mortality. ResultsScreen-detected DCIS in 9938 women, with mean age of 60 years (range 46–87), was treated by mastectomy (2931) or breast conserving surgery (BCS) (7007; 70%). At 64 months median follow-up, 697 (6.8%) had further DCIS or invasive breast cancer after BCS (7.8%) or mastectomy (4.5%) (p < 0.001). Breast radiotherapy (RT) after BCS (4363/7007; 62.3%) was associated with a 3.1% absolute reduction in ipsilateral recurrent DCIS or invasive breast cancer (no RT: 7.2% versus RT: 4.1% [p < 0.001]) and a 1.9% absolute reduction for ipsilateral invasive breast recurrence (no RT: 3.8% versus RT: 1.9% [p < 0.001]), independent of the excision margin width or size of DCIS. Women without RT after BCS had more ipsilateral breast recurrences (p < 0.001) when the radial excision margin was <2 mm. Adjuvant endocrine therapy (1208/9938; 12%) was associated with a reduction in any ipsilateral recurrence, whether RT was received (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.41–0.80) or not (HR 0.68; 95% CI 0.51–0.91) after BCS. Women who developed invasive breast recurrence had a worse survival than those with recurrent DCIS (p < 0.001). Among 321 (3.2%) who died, only 46 deaths were attributed to invasive breast cancer. ConclusionRecurrent DCIS or invasive cancer is uncommon after screen-detected DCIS. Both RT and endocrine therapy were associated with a reduction in further events but not with breast cancer mortality within 5 years of diagnosis. Further research to identify biomarkers of recurrence risk, particularly as invasive disease, is indicated.

Association between Screening Mammography Recall Rate and Interval Cancers in the UK Breast Cancer Service Screening Program: A Cohort Study.

Purpose To determine whether low levels of recall lead to increased interval cancers and the magnitude of this effect. Materials and Methods The authors retrospectively analyzed prospectively collected data from the UK National Health Service Breast Screening Programme during a 36-month period (April 1, 2005 to March 31, 2008), with 3-year follow-up in women aged 50-70 years. Data on recall, cancers detected at screening, and interval cancers were available for each of the 84 breast screening units and for each year (n = 252). The association between interval cancers and recalls was modeled by using Poisson regression on aggregated data and according to age (5-year intervals) and screening type (prevalent vs incident). Results The authors analyzed 5 126 689 screening episodes, demonstrating an average recall to assessment rate (RAR) of 4.56% (range, 1.64%-8.42%; standard deviation, 1.15%), cancer detection rate of 8.1 per 1000 women screened, and interval cancer rate (ICR) of 3.1 per 1000 women screened. Overall, a significant negative association was found between RAR and ICR (Poisson regression coefficient: -0.039 [95% confidence interval: -0.062, -0.017]; P = .001), with approximately one fewer interval cancer for every additional 80-84 recalls. Subgroup analysis revealed similar negative correlations in women aged 50-54 years (P = .002), 60-64 years (P = .01), and 65-69 years (P = .008) as well as in incident screens (P = .001) and prevalent screens (P = .04). No significant relationship was found in women aged 55-59 years (P = .46). Conclusion There was a statistically significant negative correlation between RAR and ICR, which suggests the merit of a minimum threshold for RAR. © RSNA, 2018 Online supplemental material is available for this article.

Diagnostic concordance of reporting lymphovascular invasion in breast cancer

AimsThis study aims to assess the diagnostic agreement of lymphovascular invasion (LVI) in invasive breast cancer (BC).MethodsData on LVI were collected from the UK National Health Service Breast Screening Programme...

Successful Repatriation of Breast Cancer Surveillance for High-Risk Women to the UK National Health Service Breast Screening Programme

BackgroundSince April 2013, the UK’s National Health Service Breast Screening Programme (NHSBSP) centers have been obliged to provide services for women at the highest risk of breast cancer, including those carrying highly penetrant single gene mutations (BRCA1, BRCA2, TP53). Since then, such individuals previously undergoing surveillance in the Royal Marsden Hospital were referred to their local NHSBSP centers. We aimed to assess patient experience of surveillance provided by local NHSBSP services at 1 and 3 years after repatriation. Patients and MethodsHigh-risk gene mutation carriers referred to the NHSBSP for breast cancer surveillance were identified from a departmental database in the Cancer Genetics Unit and invited to complete questionnaires about their experience of surveillance under this new pathway, first in 2014 and again in 2016. ResultsThree hundred forty-six individuals were invited to participate in 2014, of whom 182 responded (53%). A total of 464 patients were invited in 2016, of whom 246 (53%) completed the second questionnaire. Ninety-four percent of patients with residual breast tissue received some screening at the first (n = 161) and second (n = 185) time points. Ninety-one percent of patients (n = 146) received at least recommended surveillance in the year preceding the initial survey, a proportion decreasing slightly by the second time point (n = 164, 87%). Seventeen percent of individuals required additional diagnostic investigations, with cancers detected in 2%. These proportions remained stable between surveys. ConclusionRepatriation of high-risk individuals from Royal Marsden Hospital to NHSBSP centers has been successfully accomplished. Most individuals received appropriate recommended annual surveillance. Further improvements are required to ensure equal and timely provision of recommended surveillance.

Abstract OT1-03-01: The UK LORIS trial: Randomizing patients with low or low intermediate grade ductal carcinoma in situ (DCIS) to surgery or active monitoring

Abstract Background: The independent review of the UK National Health Service Breast Screening Programme reported (The Lancet, Volume 380, Issue 9855, Page 1778, 17 Nov 2012) on the benefits and harms of breast screening. It concluded that breast screening saves lives and acknowledged the existence of overtreatment. It encouraged randomized trials to elucidate the appropriate treatment of screen-detected DCIS to gain a better understanding of its natural history. The LORIS trial addresses the possible overtreatment of low and low/intermediate grade screen-detected (low risk) DCIS by randomizing patients to standard surgical treatment or active monitoring, each with long term follow up. Trial Design: LORIS is a phase III, multicentre, 2 arm study, with a built in 2 year Feasibility Phase, in patients confirmed to have low risk DCIS defined by strict criteria and determined by central pathology review. Patients will be randomized between standard surgery and active monitoring with annual mammography. Patients will be followed up for a minimum of 10 years. Eligibility Criteria: 1) Female, age ≥ 46 years 2) Screen-detected or incidental microcalcification (with no mass lesion clinically or on imaging) 3) Low risk DCIS on large volume vacuum-assisted biopsy, confirmed by central pathology review 4) Patient fit to undergo surgery 5) No previous breast cancer or ipsilateral DCIS diagnosis 6) Written informed consent Specific Aims: The LORIS Trial aims to establish whether patients with newly diagnosed low risk DCIS can safely avoid surgery without detriment to their wellbeing (psychological and physical) and whether those patients that do require surgery can be identified by pathological and radiological means. Primary endpoint: Ipsilateral invasive breast cancer free survival time Secondary endpoints: Overall survival; mastectomy rate; time to mastectomy; time to surgery; patient reported outcomes; health resource utilisation and assessment of predictive biomarkers. A digital image data repository and tissue bank will provide a prospective resource for both translational and imaging studies. Statistical Methods: A total of 932 patients will be randomized to a non-inferiority design to test the null hypothesis that active monitoring of women diagnosed with low risk DCIS is not non-inferior in terms of ipsilateral invasive breast cancer free survival (iiBCFS) time compared to treatment with surgery. The iiBCFS time will be compared across the two arms on a per protocol and intent-to-treat basis, using a 1-sided (α=0.05) log-rank test for non-inferiority. The iiBCFS rate is assumed to be 97.5% in the surgery arm at 5 years, utilizing 80% power to exclude a difference of more than 2.5% in the active monitoring arm. Present Accrual and Target Accrual: 32 UK centres are open for the Feasibility Phase of the trial which is nearing completion. The web-based central pathology review process is functioning efficiently, with a one week maximum turn around. Registrations and sites randomizing patients are on or above target. Randomizations are currently approximately 70% of target. A total of 60 centres will open in the main trial. Contact Information: For further information, please email the LORIS Trial Office LORIS@trials.bham.ac.uk. Citation Format: Francis A, Bartlett J, Billingham L, Bowden S, Brookes C, Dodwell D, Evans A, Fairbrother P, Fallowfield L, Gaunt C, Hanby A, Jenkins V, Matthews L, Pinder S, Pirrie S, Rea D, Reed M, Roberts T, Thomas J, Wallis M, Wilcox M, Young J. The UK LORIS trial: Randomizing patients with low or low intermediate grade ductal carcinoma in situ (DCIS) to surgery or active monitoring [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-03-01.

Diagnostic concordance of breast pathologists: lessons from the National Health Service Breast Screening Programme Pathology External Quality Assurance Scheme.

Previous concordance studies examining accuracy of breast diagnosis by pathologists, typically targeting difficult, histologically challenging breast lesions using artificial and restrictive environments, have reported aberrantly high levels of diagnostic discordance. The results of these studies may be misinterpreted by non-pathologists and raise concerns relating to routine practice. This study aims to assess the diagnostic agreement among UK breast pathologists. Two hundred and forty consecutive breast lesions, submitted by participants from their routine practice, included in the UK National Health Service Breast Screening Programme (NHSBSP) breast pathology EQA scheme during the last 10 years were reviewed. An average of approximately 600 participants viewed each case. Data on diagnostic categories (benign, atypical, in-situ malignant and invasive malignant) were collected. In this study, benign and atypical diagnoses were grouped together. The overall diagnostic agreement level was in the almost perfect range. Thirty-five cases (14.6%) showed diagnostic concordance of ≤95%. Reasons for discordance included one or more of: (1) scheme methodology limitations such as: (i) miscoding of certain lesions (e.g. phyllodes tumours and lobular neoplasia) (n = 7) and (ii) variable representation of the index lesion on glass slides (n = 18); and (2) diagnostically challenging cases that may be interpreted more easily using immunohistochemistry (n = 28). These latter included benign and malignant papillary lesions (n = 12), complex sclerosing lesions (n = 7), intraductal epithelial proliferative lesions (n = 6) and an unusual special tumour type (n = 1). Further review identified pathologists' misinterpretation in 13 cases (5.4%), with an average discordance rate of only 4.2%. The performance of breast pathologists is high. Exclusion of the effect of the scheme methodology limitations highlights further the high performance rate and identifies true diagnostically challenging entities. These difficult cases may benefit from additional diagnostic work-up and second opinions.

Papillary carcinoma of the breast: diagnostic agreement and management implications

Papillary carcinoma (PC), which is a rare type of breast cancer, comprises a heterogeneous group of tumours. The diagnostic categorization of PC as in-situ and invasive disease remains a matter of debate with respect to interpretation of its overlapping histological features, and with respect to the uncertainty in clinical behaviour that this dilemma raises. The aim of this study was to assess the diagnostic agreement regarding PC among reporting breast pathologists. Six cases of PC included in the UK National Health Service Breast Screening Programme breast pathology interpretive external quality assurance scheme in the last 10 years were reviewed. In this scheme, one representative haematoxylin and eosin-stained slide from each case is circulated to an average of 600 participants. Data on diagnostic categories were collected and slides were reviewed according to the World Health Organization (WHO) diagnostic criteria. The number of final diagnoses of malignancy (in situ or invasive) was highest for invasive PC (99% of the participants diagnosed it as malignant), followed by solid PC (94% and 95%, respectively), encapsulated PC (92% and 92%, respectively), and papillary ductal carcinoma in situ (DCIS) (88%). Most cases of papillary DCIS were correctly classified as in-situ disease (77%), but 28% of the participants classified invasive PC cases as in-situ disease. Of the participants, 24% reported encapsulated PC as invasive disease. Of the two solid PC cases, one showed some features consistent with the WHO description of invasive solid PC, whereas the other showed features of classic (non-invasive) solid PC. Both cases were reported as invasive by 75% and 77% of participants, respectively. Breast specialists more frequently classified PC as an in-situ carcinoma than did non-specialist participants, and the difference was significant (P = 0.013). Recognition of PC as a malignant entity (in situ or invasive) is high, but concordance of its classification into in-situ and invasive disease is low. Histological features that can define invasion in PC should be better defined. These rare lesions require additional diagnostic work-up, and difficult cases should trigger consensus opinion or expert referral.

Abstract OT2-02-04: The LORIS trial: A multicentre, randomised phase III trial of standard surgery versus active monitoring in women with newly diagnosed low risk ductal carcinoma in situ

Abstract Background: The independent review of the UK National Health Service Breast Screening Programme reported (The Lancet, Volume 380, Issue 9855, Pages 1778 - 1786, 17 November 2012) on the benefits &amp; harms of breast screening. It concluded that breast screening saves lives &amp; acknowledged overtreatment. It encouraged randomized trials to elucidate the appropriate treatment of screen-detected ductal carcinoma in situ (DCIS) to gain a better understanding of its natural history. The LORIS trial addresses overtreatment of low &amp; low/Intermediate grade screen detected (low risk) DCIS by randomizing patients to standard surgical treatment or active monitoring. Trial Design: LORIS is a phase III, multicentre, 2 arm study, with a 2 year feasibility phase, in patients confirmed to have low risk DCIS by central pathology review. Patients are randomised to standard surgery or active monitoring with annual mammography. Patients will be followed up for a minimum of 10 years. Key Eligibility Criteria: 1) Female 46 years or over. 2) Screen-detected or incidental microcalcification (with no mass lesion clinically or on imaging) 3) Low risk DCIS on large volume vacuum-assisted biopsy, confirmed by central pathology review 4) Patient fit to undergo surgery Specific Aims: The LORIS Trial aims to establish whether patients with newly diagnosed low risk DCIS can safely avoid surgery without detriment to their wellbeing (psychological and physical) &amp; whether those patients that do require surgery can be identified by pathological and radiological means. Primary endpoint: Ipsilateral invasive breast cancer free survival rate at 5 years Secondary endpoints: Overall survival; mastectomy rate; time to mastectomy; time to surgery; patient reported outcomes &amp; health resource utilisation. A digital image data repository and tissue bank provide a prospective resource for both translational &amp; imaging studies. Statistical Methods: A total of 932 patients will be randomized to a non-inferiority design to test the null hypothesis that active monitoring of women diagnosed with low risk DCIS is not non-inferior in terms of 5 year ipsilateral invasive breast cancer free survival (iiBCFS) rate compared to treatment with surgery. The iiBCFS rate will be compared across the two arms on a per protocol and intent-to-treat basis, using a 1-sided (α=0.05) log-rank test for non-inferiority. The iiBCFS rate is assumed to be 97.5% in the surgery arm giving 80% power to exclude a difference of more than 2.5% in the active monitoring arm at 5 years. Present Accrual and Target Accrual: 21 UK centres are open &amp; the feasibility phase of the trial is recruiting to target. The web based central pathology review process is functioning well with a one week maximum turn around. A further 40 centres will be opened on completion of the feasibility phase. Contact: LORIS@trials.bham.ac.uk This project was funded by the National Institute for Health Research [Health Technology Assessment Programme] (project number 11/36/16) Department of Health Disclaimer: The views &amp; opinions expressed therein are those of the authors &amp; do not necessarily reflect those of the Health Technology Assessment Programme, NIHR, NHS or the Department of Health. Citation Format: Francis A, Fallowfield L, Bartlett J, Thomas J, Wallis M, Hanby A, Pinder S, Evans A, Billingham L, Brookes C, Dodwell D, Fairbrother P, Gaunt C, Jenkins V, Matthews L, Pirrie S, Reed M, Roberts T, Wilcox M, Young J, Rea D. The LORIS trial: A multicentre, randomised phase III trial of standard surgery versus active monitoring in women with newly diagnosed low risk ductal carcinoma in situ. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT2-02-04.

Digital breast tomosynthesis at screening assessment: are two views always necessary?

The current recommendation from the UK National Health Service Breast Screening Programme is that digital breast tomosynthesis (DBT) can be used for further assessment of possible screen-detected soft-tissue abnormalities in place of spot compression views and when used should be performed in two projections. The aim of the study was to assess whether two-view DBT is necessary if the abnormality is seen only in one view on initial full-field digital mammography (FFDM). 617 cases with possible masses, distortions and asymmetrical densities visualized only in one view on screening FFDM were included. All of these females underwent two-view DBT, clinical examination and ultrasound. The FFDM and DBT findings on each view were compared and correlated with the histological diagnosis. 586 of 617 cases had normal or benign findings on further assessment, and no additional information was obtained on the other DBT view. There were 31 confirmed cancers. In 26 cases (84%), the cancer was seen on the corresponding DBT view. No cancer was seen on the other DBT view alone. Five cancers (16%) were not seen on either view on DBT owing to technical reasons. No cancers would have been missed if only the corresponding DBT view was performed. Two-view DBT may not be necessary when used for further assessment of possible screen-detected soft-tissue abnormalities. Larger studies should be undertaken to investigate this further. One-view DBT may be adequate in assessing soft-tissue abnormalities seen only on one FFDM view.

8LBA Assessing individual breast cancer risk within the UK National Health Service Breast Screening Programme: First prospective results from PROCAS

8LBA Assessing individual breast cancer risk within the UK National Health Service Breast Screening Programme: First prospective results from PROCAS

Abstract OT2-3-01: The LORIS trial: A multicentre, randomized phase III trial of standard surgery versus active monitoring in women with newly diagnosed low risk ductal carcinoma in situ

Abstract Background: The independent review of the UK National Health Service Breast Screening Programme reported recently on the benefits and harms of breast screening (The Lancet, Volume 380, Issue 9855, Pages 1778 - 1786, 17 November 2012). This concluded that breast screening saves lives but acknowledged the existence of overtreatment. Consequently, randomized trials were recommended to elucidate the appropriate treatment of screen-detected ductal carcinoma in situ (DCIS) and to gain a better understanding of its natural history. The LORIS trial will address these issues in low and low/intermediate grade screen detected (low risk) DCIS. Trial Design: LORIS is a phase III, multicentre, 2 arm study, with a built in 2 year feasibility phase, in women confirmed by central pathology review to have low risk DCIS. Comprehensive site training will be complimented by a patient friendly DVD designed to ensure consistent and appropriate use of terminology. Patients will be randomised between standard surgery and active monitoring with annual mammography. Follow-up will be for a minimum of 10 years. Eligibility Criteria: 1) Female, age ≥ 46 years 2) Screen-detected or incidental microcalcification (with no mass lesion clinically or on imaging) 3) Low risk DCIS on large volume vacuum-assisted biopsy, confirmed by central pathology review 4) Patient fit to undergo surgery 5) No previous breast cancer or DCIS diagnosis 6) Written informed consent Specific Aims: The LORIS Trial aims to establish whether patients with newly diagnosed low risk DCIS can safely avoid surgery without detriment to their wellbeing (psychological and physical) and whether those patients who do require surgery can be identified by pathological and radiological means. Primary endpoint: Ipsilateral invasive breast cancer free survival rate at 5 years Secondary endpoints: Overall survival; mastectomy rate; time to mastectomy; time to surgery; patient reported outcomes; health resource utilisation and assessment of predictive biomarkers. A digital image data repository and tissue bank will provide a prospective resource for both translational and imaging studies. Statistical Methods: A total of 932 patients will be randomized to a non-inferiority design to test the null hypothesis that active monitoring of women diagnosed with low risk DCIS is not non-inferior in terms of 5 year ipsilateral invasive breast cancer free survival (iiBCFS) rate compared to treatment with surgery. The iiBCFS rate will be compared across the two arms on a per protocol and intent-to-treat basis, using a 1-sided (α = 0.05) log-rank test for non-inferiority. The iiBCFS rate is assumed to be 97.5% in the surgery arm giving 80% power to exclude a difference of more than 2.5% in the active monitoring arm at 5 years. Present Accrual and Target Accrual: 20 UK sites have been identified to contribute to the feasibility phase of the trial. Enrolment of the first patient is expected in late 2013/early 2014. A further 40 sites will be recruited upon successful completion of the feasibility phase. For further information, please contact the LORIS Trial Office LORIS@trials.bham.ac.uk. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT2-3-01.

The effect of false positive breast screening examinations on subsequent attendance: retrospective cohort study

To investigate the effect of false positive breast screening examination results on subsequent attendance in the UK National Health Service Breast Screening Programme. 253,017 previously screened women who were invited for rescreening were studied. Attendance rates of women who had received a normal result at the last (index) screen were compared with those of women who had received a false positive result. The effects of age, type of index screening examination (prevalent or incident) and tissue sampling at assessment were investigated. Women who had a false positive prevalent index screening examination were significantly more likely to reattend than those who had a normal prevalent index screening examination (87.7% vs. 86.0%). There was no significant difference in reattendance rates between women who had a false positive incident index screening examination and those with a normal incident index screening examination. However, women who underwent needle sampling or open biopsy following false positive incident index screening examinations were 12% and 60% less likely to reattend, respectively, than women whose index screening examinations were normal (p < 0.001), although there was variation between centres. Increasing age significantly reduced the likelihood of reattendance. The overall reattendance of women who had been screened only once was six percentage points lower than that of women who had been screened more than once. The findings suggest that most women who undergo the breast screening assessment process retain confidence in breast screening. Needle sampling and open biopsy should be used judiciously in the assessment of screen-detected abnormalities in view of the reduced reattendance that results from their use after incident screening examinations.