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.

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.

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.

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.