Breast cancer incidence and early diagnosis in a family history risk and prevention clinic: 33-year experience in 14,311 women.

PURPOSE: Women at increased familial breast cancer risk have been offered screening starting at an earlier age and increased frequency than national Screening Programmes for over 30 years. There are limited data on longer-term largescale implementation of this approach on cancer diagnosis. METHODS: Women at our institution at ≥ 17% lifetime breast cancer risk have been offered enhanced screening with annual mammography starting at age 35 or 5-years younger than youngest affected relative, with upper age limit 50 for moderate and 60 for high-risk. Breast cancer pathology, stage and receptor status were assessed as well as survival from cancer diagnosis by Kaplan-Meier analysis. RESULTS: Overall 14,311 women were seen and assessed for breast cancer risk, with 649 breast cancers occurring in 129,119 years follow up (post-prevalent annual incidence = 4.55/1000). Of 323/394 invasive breast cancers occurring whilst on enhanced screening, most were lymph-node negative (72.9%), T1 (≤ 20 mm, 73.2%) and stage-1 (61.4%), 126/394 stage2-4 (32%). 10-year breast cancer specific survival was 91.3% (95% CI 87.4-94.0) better than the 75.9% (95% CI 74.9-77.0) published for England in 2013-2017. As expected, survival was significantly better for women with screen detected cancers (p < 0.001). Ten-year survival was particularly good for those diagnosed ≤ 40 at 93.8% (n = 75; 95% CI 84.2-97.6). Women with lobular breast cancers had worse 10-year survival at 85.9% (95% CI 66.7-94.5). Breast cancer specific survival was good for 119 BRCA1/2 carriers with 20-year survival in BRCA1:91.2% (95% CI 77.8-96.6) and 83.8% (62.6-93.5) for BRCA2. CONCLUSIONS: Targeted breast screening in women aged 30-60 years at increased familial risk is associated with good long-term survival that is substantially better than expected from population data.

Safety and feasibility of breast lesion localization using magnetic seeds (Magseed): a multi-centre, open-label cohort study.

PURPOSE: Wire localization has several disadvantages, notably wire migration and difficulty scheduling the procedure close to surgery. Radioactive seed localization overcomes these disadvantages, but implementation is limited due to radiation safety requirements. Magnetic seeds potentially offer the logistical benefits and transcutaneous detection equivalence of a radioactive seed, with easier implementation. This study was designed to evaluate the feasibility and safety of using magnetic seeds for breast lesion localization. METHODS: A two-centre open-label cohort study to assess the feasibility and safety of magnetic seed (Magseed) localization of breast lesions. Magseeds were placed under radiological guidance into women having total mastectomy surgery. The primary outcome measure was seed migration distance. Secondary outcome measures included accuracy of placement, ease of transcutaneous detection, seed integrity and safety. RESULTS: Twenty-nine Magseeds were placed into the breasts of 28 patients under ultrasound guidance. There was no migration of the seeds between placement and surgery. Twenty-seven seeds were placed directly in the target lesion with the other seeds being 2 and 3 mm away. All seeds were detectable transcutaneously in all breast sizes and at all depths. There were no complications or safety issues. CONCLUSIONS: Magnetic seeds are a feasible and safe method of breast lesion localization. They can be accurately placed, demonstrate no migration in this feasibility study and are detectable in all sizes and depths of breast tissue. Now that safety and feasibility have been demonstrated, further clinical studies are required to evaluate the seed's effectiveness in wide local excision surgery.

A comparison of five methods of measuring mammographic density: a case-control study.

BACKGROUND: High mammographic density is associated with both risk of cancers being missed at mammography, and increased risk of developing breast cancer. Stratification of breast cancer prevention and screening requires mammographic density measures predictive of cancer. This study compares five mammographic density measures to determine the association with subsequent diagnosis of breast cancer and the presence of breast cancer at screening. METHODS: Women participating in the "Predicting Risk Of Cancer At Screening" (PROCAS) study, a study of cancer risk, completed questionnaires to provide personal information to enable computation of the Tyrer-Cuzick risk score. Mammographic density was assessed by visual analogue scale (VAS), thresholding (Cumulus) and fully-automated methods (Densitas, Quantra, Volpara) in contralateral breasts of 366 women with unilateral breast cancer (cases) detected at screening on entry to the study (Cumulus 311/366) and in 338 women with cancer detected subsequently. Three controls per case were matched using age, body mass index category, hormone replacement therapy use and menopausal status. Odds ratios (OR) between the highest and lowest quintile, based on the density distribution in controls, for each density measure were estimated by conditional logistic regression, adjusting for classic risk factors. RESULTS: The strongest predictor of screen-detected cancer at study entry was VAS, OR 4.37 (95% CI 2.72-7.03) in the highest vs lowest quintile of percent density after adjustment for classical risk factors. Volpara, Densitas and Cumulus gave ORs for the highest vs lowest quintile of 2.42 (95% CI 1.56-3.78), 2.17 (95% CI 1.41-3.33) and 2.12 (95% CI 1.30-3.45), respectively. Quantra was not significantly associated with breast cancer (OR 1.02, 95% CI 0.67-1.54). Similar results were found for subsequent cancers, with ORs of 4.48 (95% CI 2.79-7.18), 2.87 (95% CI 1.77-4.64) and 2.34 (95% CI 1.50-3.68) in highest vs lowest quintiles of VAS, Volpara and Densitas, respectively. Quantra gave an OR in the highest vs lowest quintile of 1.32 (95% CI 0.85-2.05). CONCLUSIONS: Visual density assessment demonstrated a strong relationship with cancer, despite known inter-observer variability; however, it is impractical for population-based screening. Percentage density measured by Volpara and Densitas also had a strong association with breast cancer risk, amongst the automated measures evaluated, providing practical automated methods for risk stratification.

Mammographic density and breast cancer risk in breast screening assessment cases and women with a family history of breast cancer.

BACKGROUND: Mammographic density has been shown to be a strong independent predictor of breast cancer and a causative factor in reducing the sensitivity of mammography. There remain questions as to the use of mammographic density information in the context of screening and risk management, and of the association with cancer in populations known to be at increased risk of breast cancer. AIM: To assess the association of breast density with presence of cancer by measuring mammographic density visually as a percentage, and with two automated volumetric methods, Quantra™ and VolparaDensity™. METHODS: The TOMosynthesis with digital MammographY (TOMMY) study of digital breast tomosynthesis in the Breast Screening Programme of the National Health Service (NHS) of the United Kingdom (UK) included 6020 breast screening assessment cases (of whom 1158 had breast cancer) and 1040 screened women with a family history of breast cancer (of whom two had breast cancer). We assessed the association of each measure with breast cancer risk in these populations at enhanced risk, using logistic regression adjusted for age and total breast volume as a surrogate for body mass index (BMI). RESULTS: All density measures showed a positive association with presence of cancer and all declined with age. The strongest effect was seen with Volpara absolute density, with a significant 3% (95% CI 1-5%) increase in risk per 10 cm3 of dense tissue. The effect of Volpara volumetric density on risk was stronger for large and grade 3 tumours. CONCLUSIONS: Automated absolute breast density is a predictor of breast cancer risk in populations at enhanced risk due to either positive mammographic findings or family history. In the screening context, density could be a trigger for more intensive imaging.

Three-dimensional segmentation of breast masses from digital breast tomosynthesis images.

Assessment of three-dimensional (3-D) morphology and volume of breast masses is important for cancer diagnosis, staging, and treatment but cannot be derived from conventional mammography. Digital breast tomosynthesis (DBT) provides data from which 3-D mass segmentation could be obtained. Our method combined Gaussian mixture models based on intensity and a texture measure indicative of in-focus structure, gray-level variance. Thresholding these voxel probabilities, weighted by distance to the estimated mass center, gave the final 3-D segmentation. Evaluation used 40 masses annotated twice by a consultant radiologist on in-focus slices in two diagnostic views. Human intraobserver variability was assessed as the overlap between repeated annotations (median 77% and range 25% to 91%). Comparing the segmented mass outline with probability-weighted ground truth from these annotations, median agreement was 68%, and range was 7% to 88%. Annotated and segmented diameters correlated well with histological mass size (both Spearman's rank correlations [Formula: see text]). The volumetric segmentation demonstrated better agreement with tumor volumes estimated from pathology than volume derived from radiological annotations (95% limits of agreement [Formula: see text] to 11 ml and [Formula: see text] to 41 ml, respectively). We conclude that it is feasible to assess 3-D mass morphology and volume from DBT, and the method has the potential to aid breast cancer management.

A randomised trial of screening with digital breast tomosynthesis plus conventional digital 2D mammography versus 2D mammography alone in younger higher risk women.

INTRODUCTION: Digital breast tomosynthesis (DBT) has been shown to increase invasive cancer detection rates at screening compared to full field digital (2D) mammography alone, and some studies have reported a reduction in the screening recall rate. No prospective randomised studies of DBT have previously been published. This study compares recall rates with 2D mammography with and without concurrent DBT in women in their forties with a family history of breast cancer undergoing incident screening. MATERIALS AND METHODS: Asymptomatic women aged 40-49 who had previously undergone mammography for an increased risk of breast cancer were recruited in two screening centres. Participants were randomised to screening with 2D mammography only at the first study screen followed a year later by screening with 2D plus DBT, or vice versa. Recall rates were compared using an intention to treat analysis. Reading performance was analysed for the larger centre. RESULTS: 1227 women were recruited. 1221 first screens (604 2D, 617 2D+DBT) and 1124second screens (558 2D+DBT, 566 2D) were analysed. Eleven women had screen-detected cancers: 5 after 2D, 6 after 2D+DBT. The false positive recall rates were 2.4% for 2D and 2.2% for 2D+DBT (p=0.89). There was a significantly greater reduction between rounds in the number of women with abnormal reads who were not recalled after consensus/arbitration with 2D+DBT than 2D (p=0.023). CONCLUSION: The addition of DBT to 2D mammography in incident screening did not lead to a significant reduction in recall rate. DBT may increase reader uncertainty until DBT screening experience is acquired.

Does Reader Performance with Digital Breast Tomosynthesis Vary according to Experience with Two-dimensional Mammography?

Purpose To assess whether individual reader performance with digital breast tomosynthesis (DBT) and two-dimensional (2D) mammography varies with number of years of experience or volume of 2D mammograms read. Materials and Methods After written informed consent was obtained, 8869 women (age range, 29-85 years; mean age, 56 years) were recruited into the TOMMY trial (A Comparison of Tomosynthesis with Digital Mammography in the UK National Health Service Breast Screening Program), an ethically approved, multicenter, multireader, retrospective reading study, between July 2011 and March 2013. Each case was read prospectively for clinical assessment and to establish ground truth. A retrospective reading data set of 7060 cases was created and randomly allocated for independent blinded review of (a) 2D mammograms, (b) DBT images and 2D mammograms, and (c) synthetic 2D mammograms and DBT images, without access to previous examinations. Readers (19 radiologists, three advanced practitioner radiographers, and two breast clinicians) who had 3-25 (median, 10) years of experience in the U.K. National Health Service Breast Screening Program and read 5000-13 000 (median, 8000) cases per annum were included in this study. Specificity was analyzed according to reader type and years and volume of experience, and then both specificity and sensitivity were analyzed by matched inference. The median duration of experience (10 years) was used as the cutoff point for comparison of reader performance. Results Specificity improved with the addition of DBT for all readers. This was significant for all staff groups (56% vs 68% and 49% vs 67% [P < .0001] for radiologists and advanced practitioner radiographers, respectively; 46% vs 55% [P = .02] for breast clinicians). Sensitivity was improved for 19 of 24 (79%) readers and was significantly higher for those with less than 10 years of experience (91% vs 86%; P = .03) and those with total mammographic experience of fewer than 80 000 cases (88% vs 86%; P = .03). Conclusion The addition of DBT to conventional 2D screening mammography improved specificity for all readers, but the gain in sensitivity was greater for readers with less than 10 years of experience.

The impact of using weight estimated from mammographic images vs self-reported weight on breast cancer risk calculation.

Personalised breast screening requires assessment of individual risk of breast cancer, of which one contributory factor is weight. Self-reported weight has been used for this purpose, but may be unreliable. We explore the use of volume of fat in the breast, measured from digital mammograms. Volumetric breast density measurements were used to determine the volume of fat in the breasts of 40,431 women taking part in the Predicting Risk Of Cancer At Screening (PROCAS) study. Tyrer-Cuzick risk using self-reported weight was calculated for each woman. Weight was also estimated from the relationship between self-reported weight and breast fat volume in the cohort, and used to re-calculate Tyrer-Cuzick risk. Women were assigned to risk categories according to 10 year risk (below average <2%, average 2-3.49%, above average 3.5-4.99%, moderate 5-7.99%, high ≥8%) and the original and re-calculated Tyrer-Cuzick risks were compared. Of the 716 women diagnosed with breast cancer during the study, 15 (2.1%) moved into a lower risk category, and 37 (5.2%) moved into a higher category when using weight estimated from breast fat volume. Of the 39,715 women without a cancer diagnosis, 1009 (2.5%) moved into a lower risk category, and 1721 (4.3%) into a higher risk category. The majority of changes were between below average and average risk categories (38.5% of those with a cancer diagnosis, and 34.6% of those without). No individual moved more than one risk group. Automated breast fat measures may provide a suitable alternative to self-reported weight for risk assessment in personalized screening.

Increased peri-ductal collagen micro-organization may contribute to raised mammographic density.

BACKGROUND: High mammographic density is a therapeutically modifiable risk factor for breast cancer. Although mammographic density is correlated with the relative abundance of collagen-rich fibroglandular tissue, the causative mechanisms, associated structural remodelling and mechanical consequences remain poorly defined. In this study we have developed a new collaborative bedside-to-bench workflow to determine the relationship between mammographic density, collagen abundance and alignment, tissue stiffness and the expression of extracellular matrix organising proteins. METHODS: Mammographic density was assessed in 22 post-menopausal women (aged 54-66 y). A radiologist and a pathologist identified and excised regions of elevated non-cancerous X-ray density prior to laboratory characterization. Collagen abundance was determined by both Masson's trichrome and Picrosirius red staining (which enhances collagen birefringence when viewed under polarised light). The structural specificity of these collagen visualisation methods was determined by comparing the relative birefringence and ultrastructure (visualised by atomic force microscopy) of unaligned collagen I fibrils in reconstituted gels with the highly aligned collagen fibrils in rat tail tendon. Localised collagen fibril organisation and stiffness was also evaluated in tissue sections by atomic force microscopy/spectroscopy and the abundance of key extracellular proteins was assessed using mass spectrometry. RESULTS: Mammographic density was positively correlated with the abundance of aligned periductal fibrils rather than with the abundance of amorphous collagen. Compared with matched tissue resected from the breasts of low mammographic density patients, the highly birefringent tissue in mammographically dense breasts was both significantly stiffer and characterised by large (>80 µm long) fibrillar collagen bundles. Subsequent proteomic analyses not only confirmed the absence of collagen fibrosis in high mammographic density tissue, but additionally identified the up-regulation of periostin and collagen XVI (regulators of collagen fibril structure and architecture) as potential mediators of localised mechanical stiffness. CONCLUSIONS: These preliminary data suggest that remodelling, and hence stiffening, of the existing stromal collagen microarchitecture promotes high mammographic density within the breast. In turn, this aberrant mechanical environment may trigger neoplasia-associated mechanotransduction pathways within the epithelial cell population.

Randomized controlled trial of stereotactic 11-G vacuum-assisted core biopsy for the diagnosis and management of mammographic microcalcification.

OBJECTIVE: To compare the accuracy of 11-G vacuum-assisted biopsy (VAB) with 14-G core needle biopsy (CNB) to diagnose mammographic microcalcification (MM) and effect on surgical outcomes. METHODS: Following ethical approval, VAB and CNB (control) were compared in a randomized prospective study for first-line diagnosis of MM and subsequent surgical outcomes in two breast-screening units. Participants gave written informed consent. Exclusions included comorbidity precluding surgery, prior ipsilateral breast cancer and lesions >40 mm requiring mastectomy as first surgical procedure. The final pathological diagnosis was compared with the initial biopsy result. Quality-of-life (QOL) questionnaires were administered at baseline, 2, 6 and 12 months. 110 participants were required to show a 25% improvement in diagnosis with VAB compared with CNB (90% power). RESULTS: Eligibility was assessed for 787 cases; 129 females recalled from the National Health Service breast screening programme were randomized. Diagnostic accuracy of VAB was 86% and that of CNB was 84%. Using VAB, 2/14 (14.3%) cases upgraded from ductal carcinoma in situ to invasion at surgery and 3/19 (15.8%) using CNB. Following VAB 7/16 (44%) cases required repeat surgery vs 7/24 (29%) after CNB. Both groups recorded significant worsening of functional QOL measures and increased breast pain at follow-up. CONCLUSION: VAB and CNB were equally accurate at diagnosing MM, and no significant differences in surgical outcomes were observed. ADVANCES IN KNOWLEDGE: The first randomized controlled study of VAB for diagnosis of microcalcification using digital mammography showed no difference in diagnostic accuracy of VAB and CNB, or in the proportion of participants needing repeat non-operative biopsy or second therapeutic operation to treat malignancy.

Mammographic density adds accuracy to both the Tyrer-Cuzick and Gail breast cancer risk models in a prospective UK screening cohort.

INTRODUCTION: The Predicting Risk of Cancer at Screening study in Manchester, UK, is a prospective study of breast cancer risk estimation. It was designed to assess whether mammographic density may help in refinement of breast cancer risk estimation using either the Gail model (Breast Cancer Risk Assessment Tool) or the Tyrer-Cuzick model (International Breast Intervention Study model). METHODS: Mammographic density was measured at entry as a percentage visual assessment, adjusted for age and body mass index. Tyrer-Cuzick and Gail 10-year risks were based on a questionnaire completed contemporaneously. Breast cancers were identified at the entry screen or shortly thereafter. The contribution of density to risk models was assessed using odds ratios (ORs) with profile likelihood confidence intervals (CIs) and area under the receiver operating characteristic curve (AUC). The calibration of predicted ORs was estimated as a percentage [(observed vs expected (O/E)] from logistic regression. RESULTS: The analysis included 50,628 women aged 47-73 years who were recruited between October 2009 and September 2013. Of these, 697 had breast cancer diagnosed after enrolment. Median follow-up was 3.2 years. Breast density [interquartile range odds ratio (IQR-OR) 1.48, 95 % CI 1.34-1.63, AUC 0.59] was a slightly stronger univariate risk factor than the Tyrer-Cuzick model [IQR-OR 1.36 (95 % CI 1.25-1.48), O/E 60 % (95 % CI 44-74), AUC 0.57] or the Gail model [IQR-OR 1.22 (95 % CI 1.12-1.33), O/E 46 % (95 % CI 26-65 %), AUC 0.55]. It continued to add information after allowing for Tyrer-Cuzick [IQR-OR 1.47 (95 % CI 1.33-1.62), combined AUC 0.61] or Gail [IQR-OR 1.45 (95 % CI 1.32-1.60), combined AUC 0.59]. CONCLUSIONS: Breast density may be usefully combined with the Tyrer-Cuzick model or the Gail model.

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

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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. ADVANCES IN KNOWLEDGE: One-view DBT may be adequate in assessing soft-tissue abnormalities seen only on one FFDM view.

Accuracy of Digital Breast Tomosynthesis for Depicting Breast Cancer Subgroups in a UK Retrospective Reading Study (TOMMY Trial).

PURPOSE: To compare the diagnostic performance of two-dimensional (2D) mammography, 2D mammography plus digital breast tomosynthesis (DBT), and synthetic 2D mammography plus DBT in depicting malignant radiographic features. MATERIALS AND METHODS: In this multicenter, multireader, retrospective reading study (the TOMMY trial), after written informed consent was obtained, 8869 women (age range, 29-85 years; mean, 56 years) were recruited from July 2011 to March 2013 in an ethically approved study. From these women, a reading dataset of 7060 cases was randomly allocated for independent blinded review of (a) 2D mammography images, (b) 2D mammography plus DBT images, and (c) synthetic 2D mammography plus DBT images. Reviewers had no access to results of previous examinations. Overall sensitivities and specificities were calculated for younger women and those with dense breasts. RESULTS: Overall sensitivity was 87% for 2D mammography, 89% for 2D mammography plus DBT, and 88% for synthetic 2D mammography plus DBT. The addition of DBT was associated with a 34% increase in the odds of depicting cancer (odds ratio [OR] = 1.34, P = .06); however, this level did not achieve significance. For patients aged 50-59 years old, sensitivity was significantly higher (P = .01) for 2D mammography plus DBT than it was for 2D mammography. For those with breast density of 50% or more, sensitivity was 86% for 2D mammography compared with 93% for 2D mammography plus DBT (P = .03). Specificity was 57% for 2D mammography, 70% for 2D mammography plus DBT, and 72% for synthetic 2D mammography plusmDBT. Specificity was significantly higher than 2D mammography (P < .001in both cases) and was observed for all subgroups (P < .001 for all cases). CONCLUSION: The addition of DBT increased the sensitivity of 2D mammography in patients with dense breasts and the specificity of 2D mammography for all subgroups. The use of synthetic 2D DBT demonstrated performance similar to that of standard 2D mammography with DBT. DBT is of potential benefit to screening programs, particularly in younger women with dense breasts. (©) RSNA, 2015.

The TOMMY trial: a comparison of TOMosynthesis with digital MammographY in the UK NHS Breast Screening Programme--a multicentre retrospective reading study comparing the diagnostic performance of digital breast tomosynthesis and digital mammography with digital mammography alone.

BACKGROUND: Digital breast tomosynthesis (DBT) is a three-dimensional mammography technique with the potential to improve accuracy by improving differentiation between malignant and non-malignant lesions. OBJECTIVES: The objectives of the study were to compare the diagnostic accuracy of DBT in conjunction with two-dimensional (2D) mammography or synthetic 2D mammography, against standard 2D mammography and to determine if DBT improves the accuracy of detection of different types of lesions. STUDY POPULATION: Women (aged 47-73 years) recalled for further assessment after routine breast screening and women (aged 40-49 years) with moderate/high of risk of developing breast cancer attending annual mammography screening were recruited after giving written informed consent. INTERVENTION: All participants underwent a two-view 2D mammography of both breasts and two-view DBT imaging. Image-processing software generated a synthetic 2D mammogram from the DBT data sets. RETROSPECTIVE READING STUDY: In an independent blinded retrospective study, readers reviewed (1) 2D or (2) 2D + DBT or (3) synthetic 2D + DBT images for each case without access to original screening mammograms or prior examinations. Sensitivities and specificities were calculated for each reading arm and by subgroup analyses. RESULTS: Data were available for 7060 subjects comprising 6020 (1158 cancers) assessment cases and 1040 (two cancers) family history screening cases. Overall sensitivity was 87% [95% confidence interval (CI) 85% to 89%] for 2D only, 89% (95% CI 87% to 91%) for 2D + DBT and 88% (95% CI 86% to 90%) for synthetic 2D + DBT. The difference in sensitivity between 2D and 2D + DBT was of borderline significance (p = 0.07) and for synthetic 2D + DBT there was no significant difference (p = 0.6). Specificity was 58% (95% CI 56% to 60%) for 2D, 69% (95% CI 67% to 71%) for 2D + DBT and 71% (95% CI 69% to 73%) for synthetic 2D + DBT. Specificity was significantly higher in both DBT reading arms for all subgroups of age, density and dominant radiological feature (p < 0.001 all cases). In all reading arms, specificity tended to be lower for microcalcifications and higher for distortion/asymmetry. Comparing 2D + DBT to 2D alone, sensitivity was significantly higher: 93% versus 86% (p < 0.001) for invasive tumours of size 11-20 mm. Similarly, for breast density 50% or more, sensitivities were 93% versus 86% (p = 0.03); for grade 2 invasive tumours, sensitivities were 91% versus 87% (p = 0.01); where the dominant radiological feature was a mass, sensitivities were 92% and 89% (p = 0.04) For synthetic 2D + DBT, there was significantly (p = 0.006) higher sensitivity than 2D alone in invasive cancers of size 11-20 mm, with a sensitivity of 91%. CONCLUSIONS: The specificity of DBT and 2D was better than 2D alone but there was only marginal improvement in sensitivity. The performance of synthetic 2D appeared to be comparable to standard 2D. If these results were observed with screening cases, DBT and 2D mammography could benefit to the screening programme by reducing the number of women recalled unnecessarily, especially if a synthetic 2D mammogram were used to minimise radiation exposure. Further research is required into the feasibility of implementing DBT in a screening setting, prognostic modelling on outcomes and mortality, and comparison of 2D and synthetic 2D for different lesion types. STUDY REGISTRATION: Current Controlled Trials ISRCTN73467396. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 4. See the HTA programme website for further project information.

MRI breast screening in high-risk women: cancer detection and survival analysis.

Women with a genetic predisposition to breast cancer tend to develop the disease at a younger age with denser breasts making mammography screening less effective. The introduction of magnetic resonance imaging (MRI) for familial breast cancer screening programs in recent years was intended to improve outcomes in these women. We aimed to assess whether introduction of MRI surveillance improves 5- and 10-year survival of high-risk women and determine the accuracy of MRI breast cancer detection compared with mammography-only or no enhanced surveillance and compare size and pathology of cancers detected in women screened with MRI + mammography and mammography only. We used data from two prospective studies where asymptomatic women with a very high breast cancer risk were screened by either mammography alone or with MRI also compared with BRCA1/2 carriers with no intensive surveillance. 63 cancers were detected in women receiving MRI + mammography and 76 in women receiving mammography only. Sensitivity of MRI + mammography was 93 % with 63 % specificity. Fewer cancers detected on MRI were lymph node positive compared to mammography/no additional screening. There were no differences in 10-year survival between the MRI + mammography and mammography-only groups, but survival was significantly higher in the MRI-screened group (95.3 %) compared to no intensive screening (73.7 %; p = 0.002). There were no deaths among the 21 BRCA2 carriers receiving MRI. There appears to be benefit from screening with MRI, particularly in BRCA2 carriers. Extended follow-up of larger numbers of high-risk women is required to assess long-term survival.