R Wilson

Magnetic resonance imaging of the breast: Recommendations from the EUSOMA working group

The use of breast magnetic resonance imaging (MRI) is rapidly increasing. EUSOMA organised a workshop in Milan on 20-21st October 2008 to evaluate the evidence currently available on clinical value and indications for breast MRI. Twenty-three experts from the disciplines involved in breast disease management - including epidemiologists, geneticists, oncologists, radiologists, radiation oncologists, and surgeons - discussed the evidence for the use of this technology in plenary and focused sessions. This paper presents the consensus reached by this working group. General recommendations, technical requirements, methodology, and interpretation were firstly considered. For the following ten indications, an overview of the evidence, a list of recommendations, and a number of research issues were defined: staging before treatment planning; screening of high-risk women; evaluation of response to neoadjuvant chemotherapy; patients with breast augmentation or reconstruction; occult primary breast cancer; breast cancer recurrence; nipple discharge; characterisation of equivocal findings at conventional imaging; inflammatory breast cancer; and male breast. The working group strongly suggests that all breast cancer specialists cooperate for an optimal clinical use of this emerging technology and for future research, focusing on patient outcome as primary end-point.

The Clinical Effectiveness and Cost-Effectiveness of Different Surveillance Mammography Regimens After the Treatment for Primary Breast Cancer: Systematic Reviews, Registry Database Analyses and Economic Evaluation

BACKGROUND Following primary breast cancer treatment, the early detection of ipsilateral breast tumour recurrence (IBTR) or ipsilateral secondary cancer in the treated breast and detection of new primary cancers in the contralateral breast is beneficial for survival. Surveillance mammography is used to detect these cancers, but the optimal frequency of surveillance and the length of follow-up are unclear. OBJECTIVES To identify feasible management strategies for surveillance and follow-up of women after treatment for primary breast cancer in a UK setting, and to determine the effectiveness and cost-effectiveness of differing regimens. METHODS A survey of UK breast surgeons and radiologists to identify current surveillance mammography regimens and inform feasible alternatives; two discrete systematic reviews of evidence published from 1990 to mid 2009 to determine (i) the clinical effectiveness and cost-effectiveness of differing surveillance mammography regimens for patient health outcomes and (ii) the test performance of surveillance mammography in the detection of IBTR and metachronous contralateral breast cancer (MCBC); statistical analysis of individual patient data (West Midlands Cancer Intelligence Unit Breast Cancer Registry and Edinburgh data sets); and economic modelling using the systematic reviews results, existing data sets, and focused searches for specific data analysis to determine the effectiveness and cost-utility of differing surveillance regimens. RESULTS The majority of survey respondents initiate surveillance mammography 12 months after breast-conserving surgery (BCS) (87%) or mastectomy (79%). Annual surveillance mammography was most commonly reported for women after BCS or after mastectomy (72% and 53%, respectively). Most (74%) discharge women from surveillance mammography, most frequently 10 years after surgery. The majority (82%) discharge from clinical follow-up, most frequently at 5 years. Combining initiation, frequency and duration of surveillance mammography resulted in 54 differing surveillance regimens for women after BCS and 56 for women following mastectomy. The eight studies included in the clinical effectiveness systematic review suggest surveillance mammography offers a survival benefit compared with a surveillance regimen that does not include surveillance mammography. Nine studies were included in the test performance systematic review. For routine IBTR detection, surveillance mammography sensitivity ranged from 64% to 67% and specificity ranged from 85% to 97%. For magnetic resonance imaging (MRI), sensitivity ranged from 86% to 100% and specificity was 93%. For non-routine IBTR detection, sensitivity and specificity for surveillance mammography ranged from 50% to 83% and from 57% to 75%, respectively, and for MRI from 93% to 100% and from 88% to 96%, respectively. For routine MCBC detection, one study reported sensitivity of 67% and specificity of 50% for both surveillance mammography and MRI, although this was a highly select population. Data set analysis showed that IBTR has an adverse effect on survival. Furthermore, women experiencing a second tumour measuring >20 mm in diameter were at a significantly greater risk of death than those with no recurrence or those whose tumour was <10 mm in diameter. In the base-case analysis, the strategy with the highest net benefit, and most likely to be considered cost-effective, was surveillance mammography alone, provided every 12 months at a societal willingness to pay for a quality-adjusted life-year of either £20,000 or £30,000. The incremental cost-effectiveness ratio for surveillance mammography alone every 12 months compared with no surveillance was £4727. LIMITATIONS Few studies met the review inclusion criteria and none of the studies was a randomised controlled trial. The limited and variable nature of the data available precluded any quantitative analysis. There was no useable evidence contained in the Breast Cancer Registry database to assess the effectiveness of surveillance mammography directly. The results of the economic model should be considered exploratory and interpreted with caution given the paucity of data available to inform the economic model. CONCLUSIONS Surveillance is likely to improve survival and patients should gain maximum benefit through optimal use of resources, with those women with a greater likelihood of developing IBTR or MCBC being offered more comprehensive and more frequent surveillance. Further evidence is required to make a robust and informed judgement on the effectiveness of surveillance mammography and follow-up. The utility of national data sets could be improved and there is a need for high-quality, direct head-to-head studies comparing the diagnostic accuracy of tests used in the surveillance population. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Variations in compliance to quality indicators by age for 41,871 breast cancer patients across Europe: A European Society of Breast Cancer Specialists database analysis

OBJECTIVE The aim of this study is to assess age-specific compliance to quality indicators (QIs) regarding the treatment of breast cancer as defined by European Society of Breast Cancer Specialists (EUSOMA) for patients across Europe. METHODS All patients entered into this study were affected by in situ or invasive breast cancer, diagnosed and treated between 2003 and 2012 at 27 Breast Units across Europe, who were entered into the EUSOMA database. Patients were categorised according to age; compliance to thirteen QIs was assessed for each age group and per time period (2003-2007 and 2008-2012). Compliance to QIs was tested by multivariable logistic regression models adjusted for breast unit, incidence year and tumour characteristics. RESULTS Overall, 41,871 patients with a mean age of 59.6years were available for analysis. The highest compliance was reached for patients aged 55-64years and in the time period 2008-2012, whilst the lowest compliance was observed for women aged over 74 or under 40years and in the earlier time period. In multivariable logistic regression models, a significant difference between age categories was shown for 12 out of 13 QIs (P<0.001). Compliance to the QIs for patients aged ⩾75years was significantly lower when compared to patients aged 55-64years for ten QIs, whilst for patients in the youngest age group this was true for seven QIs. CONCLUSION In conclusion, we found that among the 27 included breast units across Europe, compliance to QIs for breast cancer treatment is often lower in the youngest and oldest breast cancer patients, with a tendency to overtreatment in the youngest patients, and to under-treatment in the elderly.

The effect of EUSOMA certification on quality of breast cancer care

AIM OF THE STUDY The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast units to establish minimum standards and ensure specialist multidisciplinary care. In the present study we assess the impact of EUSOMA certification for all breast units for which sufficient information was available before and after certification. MATERIALS AND METHODS For 22 EUSOMA certified breast units data of 30,444 patients could be extracted from the EUSOMA database on the evolution of QIs before and after certification. RESULTS On the average of all units, the minimum standard of care was achieved for 12/13 QIs before and after EUSOMA certification (not met for DCIS receiving just one operation). There was a significant improvement of 5 QIs after certification. The proportion of patients with invasive cancer undergoing an axillary clearance containing >9 lymph nodes (91.5% vs 89.4%, p 0.003) and patients with invasive cancer having just 1 operation (83.1% vs 80.4%, p < 0.001) dropped, but remained above the minimum standard. The targeted standard of breast care was reached for the same 4/13 QIs before and after EUSOMA certification. CONCLUSION Although the absolute effect of EUSOMA certification was modest it further increases standards of care and should be regarded as part of a process aiming for excellence. Dedicated units already provide a high level of care before certification, but continuous monitoring and audit remains of paramount importance as complete adherence to guidelines is difficult to achieve.

Diffusion-weighted imaging of the high-risk breast: Apparent diffusion coefficient values and their relationship to breast density.

To document the apparent diffusion coefficient (ADC) of fibroglandular breast tissue in women at high‐risk of developing breast cancer and investigate the relationship between ADC and breast density.

Comparison of Dixon Sequences for Estimation of Percent Breast Fibroglandular Tissue

Objectives To evaluate sources of error in the Magnetic Resonance Imaging (MRI) measurement of percent fibroglandular tissue (%FGT) using two-point Dixon sequences for fat-water separation. Methods Ten female volunteers (median age: 31 yrs, range: 23–50 yrs) gave informed consent following Research Ethics Committee approval. Each volunteer was scanned twice following repositioning to enable an estimation of measurement repeatability from high-resolution gradient-echo (GRE) proton-density (PD)-weighted Dixon sequences. Differences in measures of %FGT attributable to resolution, T1 weighting and sequence type were assessed by comparison of this Dixon sequence with low-resolution GRE PD-weighted Dixon data, and against gradient-echo (GRE) or spin-echo (SE) based T1-weighted Dixon datasets, respectively. Results %FGT measurement from high-resolution PD-weighted Dixon sequences had a coefficient of repeatability of ±4.3%. There was no significant difference in %FGT between high-resolution and low-resolution PD-weighted data. Values of %FGT from GRE and SE T1-weighted data were strongly correlated with that derived from PD-weighted data (r = 0.995 and 0.96, respectively). However, both sequences exhibited higher mean %FGT by 2.9% (p < 0.0001) and 12.6% (p < 0.0001), respectively, in comparison with PD-weighted data; the increase in %FGT from the SE T1-weighted sequence was significantly larger at lower breast densities. Conclusion Although measurement of %FGT at low resolution is feasible, T1 weighting and sequence type impact on the accuracy of Dixon-based %FGT measurements; Dixon MRI protocols for %FGT measurement should be carefully considered, particularly for longitudinal or multi-centre studies.

Metastatic Breast Cancer in a Young Adult Man After Total-Body Irradiation for Acute Lymphoblastic Leukemia

Case Report A 27-year-old man presented with a tender, hard, swollen lump in his right breast and eversion of his right nipple. He had been assessed, with clinical examination and an ultrasound scan, the previous year for bilateral breast swelling and diagnosed with gynecomastia, which was treated conservatively. He had a history of acute lymphoblastic leukemia (ALL) at age 7; that was treated initially with chemotherapy followed by allogenic bone marrow transplant and total-body irradiation (TBI) four years later as a result of a relapse. He received a total dose of 12 Gy with boosts to the brain and spine. Figure 1 shows the histology from the bone marrow trephine performed at that time. The section illustrates B-cell common ALL with complete replacement of marrow by a monomorphic lymphoblastic infiltrate and no evidence of cytoplasmic granules. Clinical examination revealed a hard mass that lay centrally in the right breast and a prominent everted nipple. Ultrasound showed a heterogenous 24-mm malignant mass containing flecks of calcification with associated vascularity in the right retroareolar region (U5; Fig 2) with normal axillary lymph nodes. Mammography showed a 30-mm malignant mass within the right breast with associated pleomorphic calcification and scattered indeterminate calcifications on the left (right M5, left M3; Fig 3A, mediolateral oblique projection, and 3B, craniocaudal projection). Ultrasound-guided core biopsy of the lesion confirmed the presence of a grade 2 invasive ductal carcinoma, which showed high expression of estrogen and progesterone receptors but weak expression of HER2 (Fig 4). Polysomy of chromosome 17 was also noted. The left breast calcifications were not sampled but appeared pleomorphic and suggested the presence of ductal carcinoma in situ. Before treatment of his breast cancer, the patient went to France, where he suffered an accidental fall that led to severe back pain. A computed tomography scan performed after his admission to hospital showed vertebral collapse of T11 and, to a lesser degree, L1 impinging on the spinal cord as the sagittal reformats of Figure 5 demonstrate. Areas of lucency were also noted throughout the axial skeleton and were highly suspicious for metastatic disease as shown on an axial section through the sacrum (Fig 6). He underwent a spinal stabilization procedure and, on his return to the United Kingdom, had a Tcm bone scan, which showed multiple foci of intense abnormal uptake of tracer in the left hemipelvis, spine, ribs, and cranium and confirmed the presence of extensive osteoblastic bone metastases (Fig 7; LT, left; RT, right; ANT, anterior; POST, posterior). He has received 20 Gy of radiotherapy to his spine from T10 to L2 in five fractions to optimize local control and prevent future cord compression. His disease is being managed medically with tamoxifen and zoledronic acid and has demonstrated a good clinical response; the tumor in the right breast is barely palpable.

Investigating the influence of flip angle and k-space sampling on dynamic contrast-enhanced MRI breast examinations.

Rationale and Objectives To retrospectively investigate the effect of flip angle (FA) and k-space sampling on the performance of dynamic contrast-enhanced (DCE-) magnetic resonance imaging (MRI) breast sequences. Materials and Methods Five DCE-MRI breast sequences were evaluated (10°, 14°, and 18° FAs; radial or linear k-space sampling), with 7–10 patients in each group (n = 45). All sequences were compliant with current technical breast screening guidelines. Contrast agent (CA) uptake curves were constructed from the right mammary artery for each examination. Maximum relative enhancement, Emax, and time-to-peak enhancement, Tmax, were measured and compared between protocols (analysis of variance and Mann–Whitney). For each sequence, calculated values of maximum relative enhancement, Ecalc, were derived from the Bloch equations and compared to Emax. Fat suppression performance (residual bright fat and chemical shift artifact) was rated for each examination and compared between sequences (Fisher exact tests). Results Significant differences were identified between DCE-MRI sequences. Emax increased significantly at higher FAs and with linear k-space sampling (P < .0001; P = .001). Radial protocols exhibited greater Tmax than linear protocols at FAs of both 14° (P = .025) and 18° (P < .0001), suggesting artificially flattened uptake curves. Good correlation was observed between Ecalc and Emax (r = 0.86). Fat suppression failure was more pronounced at an FA of 18° (P = .008). Conclusions This retrospective approach is validated as a tool to compare and optimize breast DCE-MRI sequences. Alterations in FA and k-space sampling result in significant differences in CA uptake curve shape which could potentially affect diagnostic interpretation. These results emphasize the need for careful parameter selection and greater standardization of breast DCE-MRI sequences.

Quantitative evaluation of contrast agent uptake in standard fat‐suppressed dynamic contrast‐enhanced MRI examinations of the breast

Purpose To propose a method to quantify T1 and contrast agent uptake in breast dynamic contrast‐enhanced (DCE) examinations undertaken with standard clinical fat‐suppressed MRI sequences and to demonstrate the proposed approach by comparing the enhancement characteristics of lobular and ductal carcinomas. Methods A standard fat‐suppressed DCE of the breast was performed at 1.5 T (Siemens Aera), followed by the acquisition of a proton density (PD)‐weighted sequence, also fat suppressed. Both sequences were characterized with test objects (T1 ranging from 30 ms to 2,400 ms) and calibration curves were obtained to enable T1 calculation. The reproducibility and accuracy of the calibration curves were also investigated. Healthy volunteers and patients were scanned with Ethics Committee approval. The effect of B0 field inhomogeneity was assessed in test objects and healthy volunteers. The T1 of breast tumors was calculated at different time points (pre‐, peak‐, and post‐contrast agent administration) for 20 patients, pre‐treatment (10 lobular and 10 ductal carcinomas) and the two cancer types were compared (Wilcoxon rank‐sum test). Results The calibration curves proved to be highly reproducible (coefficient of variation under 10%). T1 measurements were affected by B0 field inhomogeneity, but frequency shifts below 50 Hz introduced only 3% change to fat‐suppressed T1 measurements of breast parenchyma in volunteers. The values of T1 measured pre‐, peak‐, and post‐contrast agent administration demonstrated that the dynamic range of the DCE sequence was correct, that is, image intensity is approximately directly proportional to 1/T1 for that range. Significant differences were identified in the width of the distributions of the post‐contrast T1 values between lobular and ductal carcinomas (P < 0.05); lobular carcinomas demonstrated a wider range of post‐contrast T1 values, potentially related to their infiltrative growth pattern. Conclusions This work has demonstrated the feasibility of fat‐suppressed T1 measurements as a tool for clinical studies. The proposed quantitative approach is practical, enabled the detection of differences between lobular and invasive ductal carcinomas, and further enables the optimization of DCE protocols by tailoring the dynamic range of the sequence to the values of T1 measured.

Breast imaging for aesthetic surgery: British Society of Breast Radiology (BSBR), Association of Breast Surgery Great Britain & Ireland (ABS), British Association of Plastic Reconstructive and Aesthetic Surgeons (BAPRAS)

This is an overview of the guidelines for breast imaging before and after aesthetic (cosmetic) breast surgery, which includes but is not limited to implants, lipomodelling and mammoplasty procedures. The guidelines are based on a review of the literature and consensus of breast imaging and aesthetic breast surgery specialists. 1. Pre-aesthetic surgery 2. Post-aesthetic surgery If breast imaging or breast assessment is required, it should be performed in a designated breast facility with access to specialist breast imaging and a complete breast multidisciplinary team in accordance with national guidelines and recommendations.