An analysis of screen-detected invasive cancers by grade in the English breast cancer screening programme: are we failing to detect sufficient small grade 3 cancers?

OBJECTIVE: Randomised controlled trials have shown a reduction in breast cancer mortality from mammography screening and it is the detection of high-grade invasive cancers that is responsible for much of this effect. We determined the detection rates of invasive cancers by grade, size and type of screen and estimated relative sensitivities with emphasis on grade 3 detection. METHODS: This observational study analysed data from over 11 million screening episodes (67,681 invasive cancers) from the English NHS breast screening programme over seven screening years 2009/2010 to 2015/2016 for women aged 45-70. RESULTS: At prevalent (first) screens (which are unaffected by screening interval), the detection rate of small (< 15 mm) invasive cancers was 0.95 per 1000 for grade 1, but for grade 3 only 0.30 per 1000. The ratio of small (< 15 mm) to large (≥ 15 mm) cancers was 1.8:1 for grade 1 but reversed to 0.5:1 for grade 3. We estimated that the relative sensitivity for grade 3 invasive cancers was 52% of that for grade 1 and the relative sensitivity for small (< 15 mm) grade 3 only 26% of that for small (< 15 mm) grade 1 invasive cancers. CONCLUSIONS: Sensitivity for small grade 3 invasive cancers is poor compared with that for grade 1 and 2 invasive cancers and larger grade 3 malignancies. This observation is likely a limitation of the current technology related to the absence of identifiable mammographic features for small high-grade cancers. Future work should focus on technologies and strategies to improve detection of these clinically most significant cancers. KEY POINTS: • The detection of small high-grade invasive cancers is vital to reduce breast cancer mortality. • We estimate the sensitivity for small grade 3 invasive cancers may be only 26% of that of small grade 1 invasive cancers. This is likely to be associated with the non-specific mammographic features for these cancers. • New technologies and appropriate strategies using current technology are required to maximise the detection of small grade 3 invasive cancers.

Correction to: An analysis of 11.3 million screening tests examining the association between recall and cancer detection rates in the English NHS breast cancer screening programme.

The original version of this article, published on 04 February 2019, unfortunately contained a mistake.

An analysis of 11.3 million screening tests examining the association between recall and cancer detection rates in the English NHS breast cancer screening programme.

OBJECTIVE: To develop methods to model the relationship between cancer detection and recall rates to inform professional standards. METHODS: Annual screening programme information for each of the 80 English NHSBSP units (totalling 11.3 million screening tests) for the seven screening years from 1 April 2009 to 31 March 2016 and some Dutch screening programme information were used to produce linear and non-linear models. The non-linear models estimated the modelled maximum values (MMV) for cancers detected at different grades and estimated how rapidly the MMV was reached (the modelled 'slope' (MS)). Main outcomes include the detection rate for combined invasive/micro-invasive and high-grade DCIS (IHG) detection rate and the low/intermediate grade DCIS (LIG) detection rate. RESULTS: At prevalent screens for IHG cancers, 99% of the MMV was reached at a recall rate of 7.0%. The LIG detection rate had no discernible plateau, increasing linearly at a rate of 0.12 per 1000 for every 1% increase in recall rate. At incident screens, 99% of the MMV for IHG cancer detection was 4.0%. LIG DCIS increased linearly at a rate of 0.18 per 1000 per 1% increase in recall rate. CONCLUSIONS: Our models demonstrate the diminishing returns associated with increasing recall rates. The screening programme in England could use the models to set recall rate ranges, and other countries could explore similar methodology. KEY POINTS: • Question: How can we determine optimum recall rates in breast cancer screening? • Findings: In this large observational study, we show that increases in recall rates above defined levels are almost exclusively associated with false positive recalls and a very small increase in low/intermediate grade DCIS. • Meaning: High recall rates are not associated with increases in detection of life-threatening cancers. The models developed in this paper can be used to help set recall rate ranges that maximise benefit and minimise harm.

Image processing can cause some malignant soft-tissue lesions to be missed in digital mammography images.

AIM: To investigate the effect of image processing on cancer detection in mammography. METHODS AND MATERIALS: An observer study was performed using 349 digital mammography images of women with normal breasts, calcification clusters, or soft-tissue lesions including 191 subtle cancers. Images underwent two types of processing: FlavourA (standard) and FlavourB (added enhancement). Six observers located features in the breast they suspected to be cancerous (4,188 observations). Data were analysed using jackknife alternative free-response receiver operating characteristic (JAFROC) analysis. Characteristics of the cancers detected with each image processing type were investigated. RESULTS: For calcifications, the JAFROC figure of merit (FOM) was equal to 0.86 for both types of image processing. For soft-tissue lesions, the JAFROC FOM were better for FlavourA (0.81) than FlavourB (0.78); this difference was significant (p=0.001). Using FlavourA a greater number of cancers of all grades and sizes were detected than with FlavourB. FlavourA improved soft-tissue lesion detection in denser breasts (p=0.04 when volumetric density was over 7.5%) CONCLUSIONS: The detection of malignant soft-tissue lesions (which were primarily invasive) was significantly better with FlavourA than FlavourB image processing. This is despite FlavourB having a higher contrast appearance often preferred by radiologists. It is important that clinical choice of image processing is based on objective measures.

Diagnostic quality of 50 and 100 µm computed radiography compared with screen-film mammography in operative breast specimens.

OBJECTIVE: To compare reader ratings of the clinical diagnostic quality of 50 and 100 µm computed radiography (CR) systems with screen-film mammography (SFM) in operative specimens. METHODS: Mammograms of 57 fresh operative breast specimens were analysed by 10 readers. Exposures were made with identical position and compression with three mammographic systems (Fuji 100CR, 50CR and SFM). Images were anonymised and readers blinded to the CR system used. A five-point comparative scoring system (-2 to +2) was used to assess seven quality criteria and overall diagnostic value. Statistical analysis was subsequently performed of reader ratings (n = 16,925). RESULTS: For most quality criteria, both CR systems were rated as equivalent to or better than SFM. The CR systems were significantly better at demonstrating skin edge and background tissue (p < 1 × 10(-5)). Microcalcification was best demonstrated on the CR50 system (p < 1 × 10(-5)). The overall diagnostic value of both CR systems was rated as being as good as or better than SFM (p < 1 × 10(-5)). CONCLUSION: In this clinical setting, the overall diagnostic performance of both CR systems was as good as or better than SFM, with the CR50 system performing better than the CR100.

Evaluation of computer-aided detection (CAD) devices.

We present a review of three major UK studies of computer-aided detection (CAD) for mammography. A short account of the motivation, methods and results is given for each of the three. A number of conclusions are drawn, particularly about the merits and difficulties of research in the field. The first two studies measured the impact of CAD on the sensitivity and specificity of film readers interpreting cases with known outcomes displayed on rollers with an artificially high frequency of cancers. In the first study 50 film readers each read 180 cases, including 60 cancers (40 screen-detected and 20 interval). In the second study 35 film readers viewed 120 cases including 44 cancers, of which 40 were selected to be difficult cases that CAD prompted correctly. The third study was carried out prospectively. 6111 films were independently double read by film readers who recorded a judgement before and after viewing CAD prompts. In addition to this, intraobserver measure of the impact of CAD, we compared the cancer detection rate in these cases with that in 1339 cases read over the same period without the benefit of CAD. None of the three studies showed a statistically significant effect attributable to CAD. There is evidence that a high proportion of missed cancers are prompted and that "emphasised" prompts, which have a greater positive predictive value, have a stronger impact on decision-making that other prompts.

The clinical importance of axillary lymphadenopathy detected on screening mammography: revisited.

AIM: The aim of this study was to re-evaluate our protocol for the management of isolated axillary lymphadenopathy (ALP) on mammographic screening. METHODS: In a retrospective review of 200,716 women screened at the South West London Breast Screening Service (SWLBSS) over 7 years, 72 women with ALP with an otherwise normal mammogram were identified. Thirteen patients were not recalled, nine of who had a known underlying diagnosis and the remainder had longstanding unchanged mammograms. Fifty-nine patients were recalled for further clinical assessment and investigations, including ultrasound, further mammographic views, fine-needle aspiration cytology (FNAC), blood tests and a chest radiograph. Those with a definite diagnosis were referred for appropriate management and those with benign reactive cytology on FNAC reviewed at 6 weeks with subsequent referral for excision of persisting abnormal nodes. RESULTS: The ultimate diagnosis was benign in 45 cases: 26 benign reactive changes, 11 arthritides, five with dermatological and viral conditions and three with tuberculosis. Malignancy was diagnosed in 13 cases: four with metastatic breast carcinoma and nine with lymphoma/leukaemia. The total number of newly diagnosed malignancies was 20% of women recalled. Another 5% of patients had active tuberculosis. Of the 22 patients with benign reactive cytology, one had significant pathology on excision biopsy: tuberculosis. Over 95% of the results from excision biopsy in these patients did not alter management. CONCLUSION: In the majority of patients, the FNAC results were representative of the final excision pathology. The present study suggests that excision biopsy could be omitted for those patients whose FNAC and culture are negative.

An evaluation of the impact of computer-based prompts on screen readers' interpretation of mammograms.

The NHS Breast Screening Programme is changing working practices in response to increased workload and manpower shortages. Radiographers are being trained as film readers. Computer aids are being considered. We have evaluated the impact of prompts placed by the R2 ImageChecker 1000 on the sensitivity and specificity of film readers, including non-radiologist film readers. 30 radiologists, 5 breast clinicians and 15 radiographers each read 180 films, including 60 cancers (20 false negative interval cases and 40 screen detected cancers). Each reader read each case twice, once with and once without computer prompts. The order in which the reading sessions were carried out was randomized separately for each reader. 36 out of 40 screen-detected cases were prompted by the ImageChecker, a sensitivity of 90%. Eight out of 20 interval cases were prompted, a sensitivity of 40%. No significant difference was found for readers' sensitivity or specificity between the prompted and unprompted conditions. No significant difference was found between the sensitivity and specificity of the different groups of film reader. No difference in impact of prompts was found for well or poorly performing film readers. The result suggests that this version of the ImageChecker would not have a significant impact on the UK screening programme.

Mammographic casting-type calcification associated with small screen-detected invasive breast cancers: is this a reliable prognostic indicator?

AIM: The aim of the present study was to establish whether mammographic casting-type calcification associated with small screen-detected invasive breast cancers is a reliable prognostic indicator. METHODS AND MATERIALS: We retrospectively identified 50 consecutive women diagnosed with an invasive cancer less than 15 mm who showed associated casting calcification on their screening mammograms. Controls were identified that showed no microcalcification and were matched for tumour size, histological type and lymph node status. A minimum of 5 years follow-up was obtained, noting recurrence and outcome. Conditional and unconditional logistic regression, depending on the outcome variable, were used to analyse the data, taking the matched design into account in both cases. Where small numbers prohibited the use of logistic regression, Fisher's exact test was used. RESULTS: Five deaths from breast cancer occurred out of the 50 cases, of which three were lymph node positive, two were lymph node negative and none were grade 3. None of the 78 control cases died from breast cancer. The difference in breast cancer death rates was significant by Fisher's exact test (p=0.02). Risk of recurrence was also significantly increased in the casting cases (OR=3.55, 95% CI 1.02-12.33, p=0.046). CONCLUSION: Although the overall outcome for small screen-detected breast cancers is good, our study suggests that casting calcification is a poorer prognostic factor. The advantage of a mammographic feature as an independent prognostic indicator lies in early identification of high-risk patients, allowing optimization of management.

Incident screening cancers detected with a second mammographic view: pathological and radiological features.

Previous studies and epidemiological data from the UK National Health Service Breast Screening Programme (NHSBSP) have indicated significantly increased sensitivity for cancer detection with two-view rather than one-view mammographic screening. The radiological and pathological features of these extra cancers have not been previously reported in detail. We have studied all screen-detected cancers found as incident cases in the South West London Breast Screening Service between 1994-1997 on the second round of screening. To assess the effect of two-view versus one-view mammography on cancer detection, these cases were mixed with controls in a 1:2 ratio in nine test sets and each set read independently by three film readers. They initially read the oblique view, then the craniocaudal views, and recorded abnormalities on the films and likelihood of recall. Radiological and histological data were recorded for each case. Using two views, 8.9% (P < 0.05) more invasive cancers were detected. The sensitivity increase was highest for invasive cancers less than 10 mm (11%) and cancers of low grade (11.9%). These sensitivity increases may underestimate the increase in 'real life' because of over-recalling of normal mammograms, particularly with one view, under study conditions. The most significant radiological feature of invasive cancers was an irregular mass, which, seen on one view had a positive predictive value of 82.2% and 89.9% with two views. The craniocaudal view was helpful, firstly, because some cancers were not visible on the oblique view only. Secondly, benign appearing round masses and asymmetric densities seen with the oblique view only were resolved as more suspicious irregular masses with both views, leading to recall. In conclusion, there are cancers that cannot be adequately visualized on the oblique view alone. These are most commonly the small invasive cancers, which are of the greatest prognostic significance in breast cancer screening.

Observer variability in cancer detection during routine repeat (incident) mammographic screening in a study of two versus one view mammography.

OBJECTIVE: To examine the reasons for observer variability of cancer detection using one and two view mammography at incident (subsequent) screening and determine whether false negative results (non-recall of a cancer) are due to failure to detect the associated features(s) of the cancer on the mammogram, or misinterpretation of the observed feature(s) as not indicative of malignancy. SETTING: A random selection of cancers (invasive and in situ) seen as incident cases during the second screening round (January 1994-January 1997) in the South West London Breast Screening Service were used. This service uses two view mammography and double reading with arbitration by a third or further readers for all screens. METHODS: Mammograms of cases were mixed with those of controls in a 1:2 ratio in two test sets. Eleven experienced film readers, each reading both test sets, took part in the study. Initially the oblique view only was read, then, additionally, the craniocaudal view. Previous films were available to the readers. Data on abnormalities noted on the films and probability of recall were recorded and analysed. RESULTS: 387 valid readings of 36 cancers (30 invasive and six ductal carcinoma in situ) were made by 11 readers. The overall sensitivity increased from 79% with one view to 85% with two views. For invasive cancers < 10 mm the sensitivity was 71% with one view, but increased to 85% with two views. Recall of individual cancers by the readers varied substantially. With one view 15 (50%) of the 30 invasive cancers were recalled by all 11 readers, increasing to 18 (60%) with two views. Of the invasive cancers not recalled by all 11 readers, there was considerable disagreement, particularly for the smaller cancers. With one view 69% of invasive cancers < 10 mm were correctly marked on the proforma compared with 87% with two views. Invasive cancers > 10 mm were almost all marked on the proforma with one or two views. For invasive cancers, the misinterpreted feature that did not lead to recall was most commonly an asymmetry (42%), whereas for in situ cancers it was calcifications (67%). The finding of an irregular mass was the least misinterpreted feature. CONCLUSION: The study showed that of those invasive cancers detected at routine repeat screening by a programme using two view mammography and double reading with arbitration, at least 50% could be described as "difficult" (for example, "minimal" signs) to recall using the single reading of one view, even under "favourable" study conditions with two normal subjects per case. The finding that at least 87% of invasive cancers < 10 mm are detected (marked on the proforma) with two views, but only 69% with the one view, suggests that for single reading of mammograms with one view the detection of small invasive cancers is a major problem. This problem is helped by the second view. For invasive cancers > or = 10 mm, interpretation (benign or malignant) rather than detection (under these study conditions) was the major cause of recall failure. The most common signs to be misinterpreted were calcifications and asymmetries; once visualised an irregular mass was least likely to be misinterpreted. This study provides evidence that detection and interpretation of most invasive cancers is improved by increasing the number of views, and by increasing the number of readers.

The significance of spontaneous resolution of breast calcification.

Spontaneously resolving breast microcalcification is a rarely reported occurrence. A retrospective review was carried out on 33 cases of resolving benign and indeterminate microcalcification identified from 108,000 screening mammograms from the South West London Breast Screening Service. Four further cases are reported from The Jarvis Breast Screening Centre. No interval cancers were identified in women with microcalcification which initially showed benign appearances. However, 36.4% of the group with resolving indeterminate microcalcification subsequently developed cancers. It is recommended that this change should prompt full investigation and close follow-up or excision. While the majority of spontaneously resolving microcalcification is associated with benign processes, it is concluded that a significant proportion of disappearing indeterminate microcalcification is associated with malignancy.

Efficiency of cancer detection during routine repeat (incident) mammographic screening: two versus one view mammography.

OBJECTIVE: To examine the influence of one view versus two view mammography on cancer detection and recall for further investigation of women attending incident (subsequent) screening. SETTING: All cancers (invasive and in situ) detected as incident cases during the second screening round (January 1994 to January 1997) at the South West London Breast Screening Service were used. This service uses two view mammography and double reading, with arbitration by a third or further readers for all screens. METHODS: Mammograms of cases were mixed with those of controls in a 1:2 ratio in nine test sets; each set was read independently by three film readers. Fourteen readers, each reading from one to four test sets, took part in the study. Initially, the oblique view only was read, then the craniocaudal view was read in addition. Previous films were available to the readers. Data on abnormalities noted on the films and probability of recall were recorded and analysed. RESULTS: 10 of the 14 readers obtained increased sensitivity using two views (p = 0.04), for two readers there was no difference, and for two readers sensitivity decreased. The mean sensitivity increase was 6.1% (p = 0.01). The overall increase in sensitivity from all readings of invasive cancers was 8.9%, with no increase seen for in situ cancers. 11 of the 14 readers obtained an increase in specificity (p = 0.006), two readers showed no increase, and the specificity for one reader was decreased. The mean increase in specificity using two views was 5.7% (p = 0.006). CONCLUSION: This study showed an increase of 8.9% in sensitivity for the detection of invasive cancers when two views are used at incident screening, with a ratio of two control mammograms for every case. This is equivalent to a sample from population screening with a cancer detection rate of 333 per 1000. Such a study is considered to be likely to underestimate the benefit of two views in screening under non-test conditions where the cancer detection rate is of the order of five per 1000. The use of two view mammography for the detection of in situ cancers showed no increased benefit. A randomised controlled trial is needed to obtain a reliable estimate of the increase in cancer detection rate for incident screening in normal populations.

Assessment of a scoring system for breast imaging.

BACKGROUND: Triple assessment is the standard method of assessing symptomatic breast lumps. There is an accepted format for reporting cytology but not for the reporting of mammograms or breast ultrasonographic images. This study describes a scoring system for reporting breast imaging methods. METHODS: Patients with symptomatic breast lumps seen during 1 year were included. All patients underwent triple assessment. Imaging studies were reported using a grading system from 1 to 5. The results of triple assessment were compared with the final histology. RESULTS: Some 127 women had both mammography and ultrasonographic imaging; the final grade was identical in 60 per cent. The positive predictive value of imaging reported as grade 5 or 4 combined with cytology of C5 or C4 was 100 per cent. All lesions with C3 cytology and benign imaging were benign on histological examination whereas if a C3 grade was combined with imaging grade 5 or 4, all the lesions were malignant. CONCLUSION: Combining the imaging grade with the results of aspiration cytology and clinical examination often predicts the final histology in patients with breast disease.

The clinical importance of axillary lymphadenopathy detected on screening mammography.

The aim of this study was to determine the incidence and cause of axillary lymphadenopathy detected by screening mammography and to devise a management protocol for this pathology. In a retrospective study of 95,806 consecutive screening mammograms, 37 cases of 'pathological' axillary nodes were identified using two or more of the following criteria: size > 2 cm, replacement of fatty hilum, rounded shape and generalized increased density. In 16 cases with an additional mammographic abnormality, 12 had a mass (10 malignant and two benign) and four had suspicious calcification (all malignant). In 12 of these cases, the lymph nodes showed malignancy (75%). In 21 patients with lymphadenopathy alone on screening, six patients had a known underlying diagnosis and were not recalled from screening. The remaining 15 patients were recalled for further assessment including fine needle aspiration cytology (FNAC). The ultimate diagnosis was benign in 10 cases (48%)--six reactive changes, one healed granulomatous disease, one rheumatoid arthritis, one amyloid and one acute infection--and malignant in 11 cases (52%)--six non-Hodgkin's lymphoma, four metastatic carcinoma and one leukaemia. In conclusion, there is a high incidence of malignant nodal involvement in cases of screen detected lymphadenopathy (62% of cases in our series). We would advise that patients with lymphadenopathy as the sole finding on screening mammography and in whom there is no known underlying cause should undergo FNAC followed by excision biopsy. Fifty per cent of such patients in this study had underlying malignancy.

Bilateral communicating bronchopulmonary foregut malformations in an infant with multiple congenital anomalies.

Communicating bronchopulmonary foregut malformations (BPFMs) are uncommon congenital lesions which usually present in infancy with respiratory distress, which is exacerbated during feeding. We present an unusual case of bilateral oesophageal BPFM in an infant with multiple congenital anomalies.