Optimum screening mammography reading volumes: evidence from the NHS Breast Screening Programme.

OBJECTIVES: Minimum caseload standards for professionals examining breast screening mammograms vary from 480 (US) to 5000 (Europe). We measured the relationship between the number of women's mammograms examined per year and reader performance. METHODS: We extracted routine records from the English NHS Breast Screening Programme for readers examining between 1000 and 45,000 mammograms between April 2014 and March 2017. We measured the relationship between the volume of cases read and screening performance (cancer detection rate, recall rate, positive predictive value of recall (PPV) and discrepant cancers) using linear logistic regression. We also examined the effect of reader occupational group on performance. RESULTS: In total, 759 eligible mammography readers (445 consultant radiologists, 235 radiography advanced practitioners, 79 consultant radiographers) examined 6.1 million women's mammograms during the study period. PPV increased from 12.9 to 14.4 to 17.0% for readers examining 2000, 5000 and 10000 cases per year respectively. This was driven by decreases in recall rates from 5.8 to 5.3 to 4.5 with increasing volume read, and no change in cancer detection rate (from 7.6 to 7.6 to 7.7). There was no difference in cancer detection rate with reader occupational group. Consultant radiographers had higher recall rate and lower PPV compared to radiologists (OR 1.105, p = 0.012; OR 0.874, p = 0.002, unadjusted). CONCLUSION: Positive predictive value of screening increases with the total volume of cases examined per reader, through decreases in numbers of cases recalled with no concurrent change in numbers of cancers detected. KEY POINTS: • In the English Breast Screening Programme, readers who examined a larger number of cases per year had a higher positive predictive value, because they recalled fewer women for further tests but detected the same number of cancers. • Reader type did not affect cancer detection rate, but consultant radiographers had a higher recall rate and lower positive predictive value than consultant radiologists, although this was not adjusted for length of experience.

Position paper on screening for breast cancer by the European Society of Breast Imaging (EUSOBI) and 30 national breast radiology bodies from Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Israel, Lithuania, Moldova, The Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Spain, Sweden, Switzerland and Turkey.

EUSOBI and 30 national breast radiology bodies support mammography for population-based screening, demonstrated to reduce breast cancer (BC) mortality and treatment impact. According to the International Agency for Research on Cancer, the reduction in mortality is 40 % for women aged 50-69 years taking up the invitation while the probability of false-positive needle biopsy is <1 % per round and overdiagnosis is only 1-10 % for a 20-year screening. Mortality reduction was also observed for the age groups 40-49 years and 70-74 years, although with "limited evidence". Thus, we firstly recommend biennial screening mammography for average-risk women aged 50-69 years; extension up to 73 or 75 years, biennially, is a second priority, from 40-45 to 49 years, annually, a third priority. Screening with thermography or other optical tools as alternatives to mammography is discouraged. Preference should be given to population screening programmes on a territorial basis, with double reading. Adoption of digital mammography (not film-screen or phosphor-plate computer radiography) is a priority, which also improves sensitivity in dense breasts. Radiologists qualified as screening readers should be involved in programmes. Digital breast tomosynthesis is also set to become "routine mammography" in the screening setting in the next future. Dedicated pathways for high-risk women offering breast MRI according to national or international guidelines and recommendations are encouraged. KEY POINTS: • EUSOBI and 30 national breast radiology bodies support screening mammography. • A first priority is double-reading biennial mammography for women aged 50-69 years. • Extension to 73-75 and from 40-45 to 49 years is also encouraged. • Digital mammography (not film-screen or computer radiography) should be used. • DBT is set to become "routine mammography" in the screening setting in the next future.

Breast MRI: EUSOBI recommendations for women's information.

UNLABELLED: This paper summarizes information about breast MRI to be provided to women and referring physicians. After listing contraindications, procedure details are described, stressing the need for correct scheduling and not moving during the examination. The structured report including BI-RADS® categories and further actions after a breast MRI examination are discussed. Breast MRI is a very sensitive modality, significantly improving screening in high-risk women. It also has a role in clinical diagnosis, problem solving, and staging, impacting on patient management. However, it is not a perfect test, and occasionally breast cancers can be missed. Therefore, clinical and other imaging findings (from mammography/ultrasound) should also be considered. Conversely, MRI may detect lesions not visible on other imaging modalities turning out to be benign (false positives). These risks should be discussed with women before a breast MRI is requested/performed. Because breast MRI drawbacks depend upon the indication for the examination, basic information for the most important breast MRI indications is presented. Seventeen notes and five frequently asked questions formulated for use as direct communication to women are provided. The text was reviewed by Europa Donna-The European Breast Cancer Coalition to ensure that it can be easily understood by women undergoing MRI. KEY POINTS: • Information on breast MRI concerns advantages/disadvantages and preparation to the examination • Claustrophobia, implantable devices, allergic predisposition, and renal function should be checked • Before menopause, scheduling on day 7-14 of the cycle is preferred • During the examination, it is highly important that the patient keeps still • Availability of prior examinations improves accuracy of breast MRI interpretation.

Translating microcalcification biomarker information into the laboratory: A preliminary assessment utilizing core biopsies obtained from sites of mammographic calcification.

Rationale and objectives: The potential of breast microcalcification chemistry to provide clinically valuable intelligence is being increasingly studied. However, acquisition of crystallographic details has, to date, been limited to high brightness, synchrotron radiation sources. This study, for the first time, evaluates a laboratory-based system that interrogates histological sections containing microcalcifications. The principal objective was to determine the measurement precision of the laboratory system and assess whether this was sufficient to provide potentially clinical valuable information. Materials and methods: Sections from 5 histological specimens from breast core biopsies obtained to evaluate mammographic calcification were examined using a synchrotron source and a laboratory-based instrument. The samples were chosen to represent a significant proportion of the known breast tissue, mineralogical landscape. Data were subsequently analysed using conventional methods and microcalcification characteristics such as crystallographic phase, chemical deviation from ideal stoichiometry and microstructure were determined. Results: The crystallographic phase of each microcalcification (e.g., hydroxyapatite, whitlockite) was easily determined from the laboratory derived data even when a mixed phase was apparent. Lattice parameter values from the laboratory experiments agreed well with the corresponding synchrotron values and, critically, were determined to precisions that were significantly greater than required for potential clinical exploitation. Conclusion: It has been shown that crystallographic characteristics of microcalcifications can be determined in the laboratory with sufficient precision to have potential clinical value. The work will thus enable exploitation acceleration of these latent microcalcification features as current dependence upon access to limited synchrotron resources is minimized.

Outcome of pure mucocele-like lesions diagnosed on breast core biopsy.

AIM: Current guidelines recommend that mucocele-like lesions (MLL) of the breast diagnosed on needle core biopsy (NCB) should be categorized as a lesion of uncertain malignant potential (B3). However, data on the outcome of MLL diagnosed on NCB remains limited due to the rarity of this lesion. The aim of this study was to assess the outcome of pure MLL without atypia diagnosed on NCB using a large series of cases and a review of the literature to provide evidence that can guide management. METHODS AND RESULTS: Patients who underwent diagnostic excision biopsy after a core biopsy diagnosis of MLL without atypia were identified from several centres. Two of 54 patients (4%) with MLL without atypia on core biopsy had ductal carcinoma in situ in the subsequent excision specimen. This is similar to the rate in previous studies of 4% (four of 106). If there is atypia in the core biopsy, previous studies found that the frequency of malignancy is much higher at 21% (seven of 33). CONCLUSIONS: Our results provide evidence that pure MLL without atypia diagnosed on NCB is usually associated with a benign outcome.

Exploration of utility of combined optical photothermal infrared and Raman imaging for investigating the chemical composition of microcalcifications in breast cancer.

Microcalcifications play an important role in cancer detection. They are evaluated by their radiological and histological characteristics but it is challenging to find a link between their morphology, their composition and the nature of a specific type of breast lesion. Whilst there are some mammographic features that are either typically benign or typically malignant often the appearances are indeterminate. Here, we explore a large range of vibrational spectroscopic and multiphoton imaging techniques in order to gain more information about the composition of the microcalcifications. For the first time, we validated the presence of carbonate ions in the microcalcifications by O-PTIR and Raman spectroscopy at the same time, the same location and the same high resolution (0.5 µm). Furthermore, the use of multiphoton imaging allowed us to create stimulated Raman histology (SRH) images which mimic histological images with all chemical information. In conclusion, we established a protocol for efficiently analysing the microcalcifications by iteratively refining the area of interest.

Breast calcification micromorphology classification.

OBJECTIVES: The importance of consistent terminology in describing the appearance of breast calcifications in mammography is well recognised. Imaging of calcifications using electron microscopy is a globally growing field of research. We therefore suggest that the time is ripe to develop a lexicon of terms for classifying the micromorphology of breast calcifications. METHODS: Calcifications within a wide range of histological sections of breast tissue, both benign and malignant, were imaged by Scanning Electron Microscopy (SEM). These images were examined, and the micromorphology of calcifications present was grouped to create a classification system. RESULTS: Based on the appearance of the calcifications observed, we propose five main categories for classification of the micromorphology of breast calcifications, namely, Dense Homogenous, Punctulate, Banded, Spongy and Aggregate. CONCLUSIONS: Use of the descriptive categories outlined here will help to ensure consistency and comparability of published observations on the micromorphology of breast calcifications. ADVANCES IN KNOWLEDGE: This is the first time a lexicon and classification system has been proposed for the micromorphology of breast calcifications, as observed by scanning electron microscopy of histological sections. This will facilitate comparability of observed relationships between micromorphology, mammographic appearance, chemistry and pathology.

The Relationship between Mammography Readers' Real-Life Performance and Performance in a Test Set-based Assessment Scheme in a National Breast Screening Program.

Purpose: To compare an individual's Personal Performance in Mammographic Screening (PERFORMS) score with their Breast Screening Information System (BSIS) real-life performance data and determine which parameters in the PERFORMS scheme offer the best reflection of BSIS real-life performance metrics. Materials and Methods: In this retrospective study, the BSIS real-life performance metrics of individual readers (n = 452) in the National Health Service Breast Screening Program (NHSBSP) in England were compared with performance in the test set-based assessment scheme over a 3-year period from 2013 to 2016. Cancer detection rate (CDR), recall rate, and positive predictive value (PPV) were calculated for each reader, for both real-life screening and the PERFORMS test. For each metric, real-life and test set versions were compared using a Pearson correlation. The real-life CDR, recall rate, and PPV of outliers were compared against other readers (nonoutliers) using analysis of variance. Results: BSIS real-life CDRs, recall rates, and PPVs showed positive correlations with the equivalent PERFORMS measures (P < .001, P = .002, and P < .001, respectively). The mean real-life CDR of PERFORMS outliers was 7.2 per 1000 women screened and was significantly lower than other readers (nonoutliers) where the real-life CDR was 7.9 (P = .002). The mean real-life screening PPV of PERFORMS outliers was 0.14% and was significantly lower than the nonoutlier group who had a mean PPV of 0.17% (P = .006). Conclusion: The use of test set-based assessment schemes in a breast screening program has the potential to predict and identify poor performance in real life.© RSNA, 2020Keywords: Breast, ScreeningSee also the commentary by Thigpen and Rapelyea in this issue.

Breast ultrasound: recommendations for information to women and referring physicians by the European Society of Breast Imaging.

This article summarises the information that should be provided to women and referring physicians about breast ultrasound (US). After explaining the physical principles, technical procedure and safety of US, information is given about its ability to make a correct diagnosis, depending on the setting in which it is applied. The following definite indications for breast US in female subjects are proposed: palpable lump; axillary adenopathy; first diagnostic approach for clinical abnormalities under 40 and in pregnant or lactating women; suspicious abnormalities at mammography or magnetic resonance imaging (MRI); suspicious nipple discharge; recent nipple inversion; skin retraction; breast inflammation; abnormalities in the area of the surgical scar after breast conserving surgery or mastectomy; abnormalities in the presence of breast implants; screening high-risk women, especially when MRI is not performed; loco-regional staging of a known breast cancer, when MRI is not performed; guidance for percutaneous interventions (needle biopsy, pre-surgical localisation, fluid collection drainage); monitoring patients with breast cancer receiving neo-adjuvant therapy, when MRI is not performed. Possible indications such as supplemental screening after mammography for women aged 40-74 with dense breasts are also listed. Moreover, inappropriate indications include screening for breast cancer as a stand-alone alternative to mammography. The structure and organisation of the breast US report and of classification systems such as the BI-RADS and consequent management recommendations are illustrated. Information about additional or new US technologies (colour-Doppler, elastography, and automated whole breast US) is also provided. Finally, five frequently asked questions are answered. TEACHING POINTS: • US is an established tool for suspected cancers at all ages and also the method of choice under 40. • For US-visible suspicious lesions, US-guided biopsy is preferred, even for palpable findings. • High-risk women can be screened with US, especially when MRI cannot be performed. • Supplemental US increases cancer detection but also false positives, biopsy rate and follow-up exams. • Breast US is inappropriate as a stand-alone screening method.

Influence of mammographic parenchymal pattern in screening-detected and interval invasive breast cancers on pathologic features, mammographic features, and patient survival.

OBJECTIVE: The aim of our study was to assess the effect of mammographic parenchymal pattern on patient survival, mammographic features, and pathologic features of breast cancer in a screened population. MATERIALS AND METHODS: We classified the parenchymal pattern (according to BI-RADS) of 759 screened women who presented with a screening-detected (n = 455) or interval (n = 304) invasive breast cancer. Pathologic details (tumor size, histologic grade, lymph node stage, vascular invasion, and histologic type) and mammographic appearances were recorded. Breast cancer-specific survival was ascertained, with a median follow-up of 9.0 years. RESULTS: An excess of interval cancers was seen in women with dense breasts (p < 0.0001). Screening-detected (but not interval) tumors were significantly smaller in fatty breasts (p = 0.014). Tumor grade, lymph node stage, vascular invasion, and histologic type did not vary significantly with mammographic parenchymal pattern in screening-detected or interval cancers. Screening-detected cancers in fatty breasts were more likely to appear as indistinct (p = 0.003) or spiculated (p = 0.002) masses in contrast to cancers in dense breasts, which more commonly appeared as architectural distortions (p < 0.0001). No significant breast cancer-specific survival difference was seen by mammographic parenchymal pattern for screening-detected cancers (p = 0.75), interval cancers (p = 0.82), or both groups combined (p = 0.12). CONCLUSION: The prognosis of screened women presenting with breast cancer is unrelated to dense mammographic parenchymal pattern despite an excess of interval cancers and larger screening-detected tumors in this group. These data support the mammographic screening of women with dense parenchymal patterns.

Is mammographic spiculation an independent, good prognostic factor in screening-detected invasive breast cancer?

OBJECTIVE: The aim of this study was to review the prognostic significance of pathologic and radiologic factors for screening-detected invasive breast cancers of any size. MATERIALS AND METHODS: The patient group was a consecutive series of 470 screening-detected invasive breast cancers that were diagnosed between 1988 and 1998. Data regarding tumor type, grade, maximum invasive diameter, lymph node status, and the presence or absence of vascular invasion were recorded, as were the mammographic features of the lesion. Survival was ascertained from hospital records and a cancer registry. Differences in survival were assessed using Kaplan-Meier survival curves with a log-rank test for difference. The significance of any correlations was assessed using the chi-square test and the chi-square test for trend. Multivariate analysis used a Cox proportional hazards model. RESULTS: At univariate analysis, large invasive size, the presence of definite vascular invasion, high histologic grade, and nodal involvement were associated with poorer breast-cancer-specific survival. Mammographic spiculation (the presence of either a spiculated mass or distortion) was associated with more prolonged breast-cancer-specific survival. The presence or absence of mammographic comedo calcification did not influence breast-cancer-specific survival. In a Cox multivariate analysis that included those factors significant in univariate analysis, size, grade, nodal stage, and mammographic spiculation maintained their prognostic significance. CONCLUSION: Mammographic spiculation is an independent, good prognostic factor for screening-detected invasive breast cancer. The mechanism of how mammographic spiculation confers a beneficial prognostic effect is not clear.

Imaging overview of metaplastic carcinomas of the breast: a large study of 71 cases.

OBJECTIVE:: To review the clinical presentation, baseline imaging features, surgical management and final surgical pathology of metaplastic carcinoma of the breast. METHODS:: A total of 71 cases were identified over a 10-year period from two major UK breast cancer institutions. Imaging at diagnosis including mammography, ultrasound, MRI and CT scans and histological diagnosis were reviewed. Follow-up data including local and systemic recurrence were retrieved. RESULTS:: Of the 71 cases, 60 (84.5%) cases presented with a palpable lump. 60 (84.5%) cases showed a mass on mammography, of whom 47 (78.3%) cases were ill defined and 17.0% cases showed calcifications associated with a mass lesion. All 71 cases were seen as a mass on ultrasound. The imaging score was R3 or R4 in 26 cases and R5 in 47 cases. 16 patients underwent MRI with most (93.8%) showing a solid mass with central necrosis. No metastatic disease was seen in the 13 patients who underwent staging CT. Despite having a larger size, 50% of the cases successfully underwent breast conservative surgery. Positive axillary lymph nodes were seen in 11 (15.5%) cases. CONCLUSION:: In this series, metaplastic cancers were palpable in 85% cases, tended to be large at the time of presentation and imaging showed characteristics of malignancy. Only 11 (15.5%) cases had nodal involvement. ADVANCES IN KNOWLEDGE:: Metaplastic carcinomas are often palpable and of large size at the time of presentation. Metaplastic carcinomas raise the concern for malignancy on mammography and ultrasound, warranting further biopsy. Metaplastic carcinomas tend to be grade 3 and triple receptor negative.

Accuracy of GE digital breast tomosynthesis vs supplementary mammographic views for diagnosis of screen-detected soft-tissue breast lesions.

OBJECTIVE: To compare the accuracy of standard supplementary views and GE digital breast tomosynthesis (DBT) for assessment of soft-tissue mammographic abnormalities. METHODS: Women recalled for further assessment of soft-tissue abnormalities were recruited and received standard supplementary views (typically spot compression views) and two-view GE DBT. The added value of DBT in the assessment process was determined by analysing data collected prospectively by radiologists working up the cases. Following anonymization of cases, there was also a retrospective multireader review. The readers first read bilateral standard two-view digital mammography (DM) together with the supplementary mammographic views and gave a combined score for suspicion of malignancy on a five-point scale. The same readers then read bilateral standard two-view DM together with two-view DBT. Pathology data were obtained. Differences were assessed using receiver operating characteristic analysis. RESULTS: The study population was 342 lesions in 322 patients. The final diagnosis was malignant in 113 cases (33%) and benign/normal in 229 cases (67%). In the prospective analysis, the performance of two-view DM plus DBT was at least equivalent to the performance of two-view DM and standard mammographic supplementary views-the area under the curve (AUC) was 0.946 and 0.922, respectively, which did not reach statistical significance. Similar results were obtained for the retrospective review-AUC was 0.900 (DBT) and 0.873 (supplementary views), which did not reach statistical significance. CONCLUSION: The accuracy of GE DBT in the assessment of screen detected soft-tissue abnormalities is equivalent to the use of standard supplementary mammographic views. ADVANCES IN KNOWLEDGE: The vast majority of evidence relating to the use of DBT has been gathered from research using Hologic equipment. This study provides evidence for the use of the commercially available GE DBT system demonstrating that it is at least equivalent to supplementary mammographic views in the assessment of soft-tissue screen-detected abnormalities.

Nottingham Clinico-Pathological Response Index (NPRI) after neoadjuvant chemotherapy (Neo-ACT) accurately predicts clinical outcome in locally advanced breast cancer.

PURPOSE: There is a need to identify more sensitive clinicopathologic criteria to assess the response to neoadjuvant chemotherapy (Neo-ACT) and guide subsequent adjuvant therapy. EXPERIMENTAL DESIGN: We performed a clinicopathologic assessment of 426 patients who had completed Neo-ACT for locally advanced breast cancer (LABC) with a median follow-up of 70 months. Patients were divided into a training set treated with anthracycline combination chemotherapy (n = 172); an internal validation set treated with anthracycline and taxane (n = 129); and an external validation set treated with anthracycline with or without taxane (n = 125). RESULTS: A multivariate Cox regression model demonstrated the absence of fibrosis, presence of lymphovascular invasion, increasing number of lymph node metastases, and administration of hormone therapy were significantly associated with short breast cancer-specific survival (BCSS) and disease-free survival (DFS); Ps < 0.01, while reduction of tumor size was associated with DFS (P = 0.022). Nottingham Clinico-Pathological Response Indexes (NPRI) were calculated, and four prognostic groups (NPRI-PG) were identified. Patients in prognostic group 2 (NPRI-PG2) for BCSS (66 of 172; 38.4%) have the same prognosis as those who achieved pathologic complete response (pCR; NPRI-PG1; 15%). Receiver-operating characteristic (ROC) curves indicated that the NPRI outperformed the currently used prognostic factors and adding the NPRI improved their performance as a predictor for both BCSS (area under the curve [AUC], 0.88) and DFS (AUC, 0.87). CONCLUSIONS: The NPRI predicts BCSS and DFS, with a higher sensitivity than pCR. The NPRI can also improve the sensitivity and specificity of clinicopathologic response as a study endpoint, for assessing response to Neo-ACT, and can serve as a valuable tool for the discovery of future predictive molecular markers.