A comparison of the imaging features of pleomorphic and classical invasive lobular carcinoma.

PURPOSE: Pleomorphic invasive lobular carcinoma (pILC) is a distinct morphological variant of ILC with a poorer prognosis than classical ILC (cILC). The aim of this study was to ascertain whether the conventional imaging appearances of the two entities differ. METHODS: A single-center retrospective review of conventional imaging was undertaken in 150 consecutive patients with histopathologically confirmed ILC (38 pILC; 112 cILC) between April 2010 and July 2015. Mammographic and sonographic findings were evaluated using the BI-RADS lexicon by a radiologist blinded to pathology, and the findings in the two groups were compared. The degree of discrepancy between imaging and pathological sizing in the two groups was evaluated. RESULTS: Lesions were mammographically occult in 11% of pILC and 14% of cILC (p = 0.56). On mammography, skin or trabecular thickening and microcalcification were commoner in pILC than cILC (13% vs. 1%, p < 0.01; 25% vs. 5%, p < 0.01). Architectural distortion was more frequent in cILC than pILC (26% vs. 9%, p = 0.01). On ultrasound, pILC more frequently exhibited mixed echogenicity (28% vs. 13%; p = 0.04), skin thickening, subcutaneous or parenchymal edema (8% vs. 0%; p = 0.02), echogenic surrounding fat (33% vs. 9%; p < 0.01), and posterior acoustic enhancement (10% vs. 1%; p = 0.02) than cILC. CILC was more frequently manifested as a focal area of altered echogenicity (24% vs. 8%; p = 0.04). Mean elastography stiffness was higher for pILC (174.8 vs. 124.6 kPa; p = 0.02). Imaging-pathological size disparity was similar for both subtypes. CONCLUSION: There are differences in the imaging features between pILC and cILC which reflect the more aggressive nature of pILC.

Predicting the response to neoadjuvant chemotherapy. Can the addition of tomosynthesis improve the accuracy of contrast-enhanced spectral mammography? A comparison with breast MRI.

OBJECTIVES: Image monitoring is essential to monitor response to neoadjuvant chemotherapy (NACT). Whilst breast MRI is the gold-standard technique, evidence suggests contrast-enhanced spectral mammography (CESM) is comparable. We investigate whether the addition of digital breast tomosynthesis (DBT) to CESM increases the accuracy of response prediction. METHODS: Women receiving NACT for breast cancer were included. Imaging with CESM+DBT and MRI was performed post-NACT. Imaging appearance was compared with pathological specimens. Accuracy for predicting pathological complete response (pCR) and concordance with size of residual disease was calculated. RESULTS: Sixteen cancers in 14 patients were included, 10 demonstrated pCR. Greatest accuracy for predicting pCR was with CESM enhancement (accuracy: 81.3%, sensitivity: 100%, specificity: 57.1%), followed by MRI (accuracy: 62.5%, sensitivity: 44.4%, specificity: 85.7%). Concordance with invasive tumour size was greater for CESM enhancement than MRI, concordance-coefficients 0.70 vs 0.66 respectively. MRI demonstrated greatest concordance with whole tumour size followed by CESM+microcalcification, concordance coefficients 0.86 vs 0.69. DBT did not improve accuracy for prediction of pCR or residual disease size. CESM+DBT underestimated size of residual disease, MRI overestimated but no significant differences were seen (p>0.05). CONCLUSIONS: CESM is similar to MRI for predicting residual disease post-NACT. Size of enhancement alone demonstrates best concordance with invasive disease. Inclusion of residual microcalcification improves concordance with ductal carcinoma in situ. The addition of DBT to CESM does not improve accuracy. ADVANCES IN KNOWLEDGE: The addition ofDBT to CESM does not improve NACT response prediction. CESM enhancement has greatest accuracy for residual invasive disease, CESM+calcification has greater accuracy for residual in situ disease.

Contrast-enhanced digital breast tomosythesis and breast MRI to monitor response to neoadjuvant chemotherapy: patient tolerance and preference.

OBJECTIVE: Contrast-enhanced digital breast tomosynthesis (CE-DBT) is a novel imaging technique, combining contrast-enhanced spectral mammography and tomosynthesis. This may offer an alternative imaging technique to breast MRI for monitoring of response to neoadjuvant chemotherapy. This paper addresses patient experience and preference regarding the two techniques. METHODS: Conducted as part of a prospective pilot study; patients were asked to complete questionnaires pertaining to their experience of CE-DBT and MRI following pre-treatment and end-of-treatment imaging. Questionnaires consisted of eight questions answered on a categorical scale, two using a visual analogue scale (VAS), and a question to indicate preference of imaging technique. Statistical analysis was performed with Wilcoxon signed rank test and McNemar test for related samples using SPSS v. 25. RESULTS: 18 patients were enrolled in the pilot study. Matched CE-DBT and MRI questionnaires were completed after 22 patient episodes. Patient preference was indicated after 31 patient episodes. Overall, on 77% of occasions patients preferred CE-DBT with no difference between pre-treatment and end-of-treatment imaging. Overall experience (p = 0.008), non-breast pain (p = 0.046), anxiety measured using VAS (p = 0.003), and feeling of being put at ease by staff (p = 0.023) was better for CE-DBT. However, more breast pain was experienced during CE-DBT when measured on both VAS (p = 0.011) and categorical scale (p = 0.021). CONCLUSION: Our paper suggests that patients prefer CE-DBT to MRI, adding further evidence in favour of contrast-enhanced mammographic techniques. ADVANCES IN KNOWLEDGE: Contrast mammographic techniques offer an alternative, more accessible imaging technique to breast MRI. Whilst other studies have addressed patient experience of contrast-enhanced spectral mammography, this is the first study to directly explore patient preference for CE-DBT over MRI in the setting of neoadjuvant chemotherapy, finding that overall, patients preferred CE-DBT despite the relatively long breast compression.

Changes and tracking of mammographic density in relation to Pike's model of breast tissue aging: a UK longitudinal study.

Percent mammographic density (PMD) is a strong marker of breast cancer risk. It may be a correlate of the rate of breast tissue aging, as proposed by Pike to explain breast cancer age-incidence. We examined longitudinal changes in PMD in 645 breast screening attendees in London, UK, in which each had between 2 and 5 screens spanning 3-12 years at ages 50-65 years and compare these to Pike's model. Within-woman PMD declined during these ages, with a slowing rate of decline. Annual rates of decline were 1.4% (95% confidence interval: 1.2-1.6), 0.7% (0.6-0.9) and 0.1% (-0.2 to 0.4) at ages 50, 57 and 64. Dense area declined similarly, but the absolute magnitude of the rate of increase of nondense area was almost double that of dense area. PMD dropped by 2.4% (1.4-3.4) on menopausal transition and increased by 2.4% (1.4-3.5) with the use of hormone therapy. Higher body mass index, greater parity and being Afro-Caribbean or South Asian ethnicities were associated with lower PMD, but did not affect rate of change of PMD at these ages. Within-woman rank correlation of PMD was 0.80 for readings taken 9 years apart. Effects of menopause and parity and the lack of effect of menarche on age-specific PMD at these ages are consistent with the predicted determinants in Pike's model. A high degree of tracking of PMD indicates that at ages 50-65 years high-risk women could be identified by a single early screen at age older than 50.

Sex steroids, growth factors and mammographic density: a cross-sectional study of UK postmenopausal Caucasian and Afro-Caribbean women.

INTRODUCTION: Sex steroids, insulin-like growth factors (IGFs) and prolactin are breast cancer risk factors but whether their effects are mediated through mammographic density, one of the strongest risk factors for breast cancer, is unknown. If such a hormonal basis of mammographic density exists, hormones may underlie ethnic differences in both mammographic density and breast cancer incidence rates. METHODS: In a cross-sectional study of 270 postmenopausal Caucasian and Afro-Caribbean women attending a population-based breast screening service in London, UK, we investigated whether plasma biomarkers (oestradiol, oestrone, sex hormone binding globulin (SHBG), testosterone, prolactin, leptin, IGF-I, IGF-II and IGF binding protein 3 (IGFBP3)) were related to and explained ethnic differences in mammographic percent density, dense area and nondense area, measured in Cumulus using the threshold method. RESULTS: Mean levels of oestrogens, leptin and IGF-I:IGFBP3 were higher whereas SHBG and IGF-II:IGFBP3 were lower in Afro-Caribbean women compared with Caucasian women after adjustment for higher mean body mass index (BMI) in the former group (by 3.2 kg/m(2) (95% confidence interval (CI): 1.8, 4.5)). Age-adjusted percent density was lower in Afro-Caribbean compared with Caucasian women by 5.4% (absolute difference), but was attenuated to 2.5% (95% CI: -0.2, 5.1) upon BMI adjustment. Despite ethnic differences in biomarkers and in percent density, strong ethnic-age-adjusted inverse associations of oestradiol, leptin and testosterone with percent density were completely attenuated upon adjustment for BMI. There were no associations of IGF-I, IGF-II or IGFBP3 with percent density or dense area. We found weak evidence that a twofold increase in prolactin and oestrone levels were associated, respectively, with an increase (by 1.7% (95% CI: -0.3, 3.7)) and a decrease (by 2.0% (95% CI: 0, 4.1)) in density after adjustment for BMI. CONCLUSIONS: These findings suggest that sex hormone and IGF levels are not associated with BMI-adjusted percent mammographic density in cross-sectional analyses of postmenopausal women and thus do not explain ethnic differences in density. Mammographic density may still, however, be influenced by much higher premenopausal hormone levels.

Are baseline ultrasound and mammographic features associated with rates of pathological completes response in patients receiving neoadjuvant chemotherapy for breast cancer?

BACKGROUND: Increasing numbers of breast cancer patients receive neoadjuvant chemotherapy (NACT). We seek to investigate whether baseline mammographic and ultrasound features are associated with complete pathological response (pCR) after NACT. METHODS: A database of NACT patients was reviewed. Baseline imaging parameters assessed were ultrasound: posterior effect; echo pattern; margin and lesion diameter; mammography: spiculation and microcalcification. Core biopsy grade and immunophenotype were documented. Data were analysed for the whole study group and by immunophenotype. RESULTS: Of the 222 cancers, 83 (37%) were triple negative (TN), 61 (27%) ER positive/HER-2 negative and 78 (35%) HER-2 positive. A pCR occurred in 46 of 222 cancers (21%). For the whole group, response was associated with high core biopsy grade (grade 3 vs. grade 1 or 2) (26% vs. 9%, p = 0.0044), absence of posterior shadowing on ultrasound (26% vs. 10%, p <  0.001) and the absence of mammographic spiculation (26 vs. 6%, p <  0.001). Within the HER-2 positive group; the absence of shadowing and spiculation remained highly associated with pCR, in addition to small ultrasound size (AUC = 0.71, p < 0.001) and the absence of microcalcification (39% vs. 21%, p < 0.02). On multivariable analysis absence of spiculation and core grade remained significant for the whole cohort, size and absence of spiculation remained significant for HER-2 positive tumours. No feature predicted pCR in TN tumours. CONCLUSION: A pCR is less likely when there is mammographic spiculation. Small ultrasound size is associated with pCR in HER-2 positive tumours. These findings may be helpful when discussing NACT and surgical options with patients. TRIAL REGISTRATION: UK Clinical Trials Gateway: registration number 16712.

Breast MRI and tumour biology predict axillary lymph node response to neoadjuvant chemotherapy for breast cancer.

BACKGROUND: In patients who have had axillary nodal metastasis diagnosed prior to neoadjuvant chemotherapy for breast cancer, there is little consensus on how to manage the axilla subsequently. The aim of this study was to explore whether a combination of breast magnetic resonance imaging (MRI) assessed response and primary tumour pathology factors could identify a subset of patients that might be spared axillary node clearance. METHODS: A retrospective data analysis was performed of patients with core biopsy-proven axillary nodal metastasis prior to commencement of neoadjuvant chemotherapy (NAC) who had subsequent axillary node clearance (ANC) at definitive breast surgery. Breast tumour and axillary response at MRI before, during and on completion of NAC, core biopsy tumour grade, tumour type and immunophenotype were correlated with pathological response in the breast and the number of metastatic nodes in the ANC specimens. RESULTS: Of 87 consecutive patients with MRI at baseline, interim and after neoadjuvant chemotherapy who underwent ANC at time of breast surgery, 33 (38%) had no residual macrometastatic axillary disease, 28 (32%) had 1-2 metastatic nodes and 26 (30%) had more than 2 metastatic nodes. Factors that predicted axillary nodal complete response were MRI complete response in the breast (p < 0.0001), HER2 positivity (p = 0.02) and non-lobular tumour type (p = 0.015). CONCLUSION: MRI assessment of breast tumour response to NAC and core biopsy factors are predictive of response in axillary nodes, and can be used to guide decision making regarding appropriate axillary surgery.

Ethnic variations in mammographic density: a British multiethnic longitudinal study.

It is not known whether the 20-30% lower breast cancer incidence rates in first-generation South Asian and Afro-Caribbean women relative to Caucasian women in the United Kingdom are reflected in mammographic density. The authors conducted a United Kingdom population-based multiethnic study of mammographic density at ages 50-64 years in 645 women. Data on breast cancer risk factors were obtained using a questionnaire/telephone interview. Threshold percent density was assessed on 5,277 digitized mammograms taken in 1995-2004 and was analyzed using multilevel models. Both ethnic minorities were characterized by more protective breast cancer risk factor distributions than Caucasians, such as later menarche, shorter stature, higher parity, earlier age at first birth, and less use of hormone therapy, but they had a higher mean body mass index; the last four factors were associated with lower mammographic density. Age-adjusted percent mammographic densities in Afro-Caribbeans and South Asians were 5.6% (95% confidence interval (CI): 3.5, 7.5) and 5.9% (95% CI: 3.6, 8.0) lower, respectively, than in Caucasians. Lower densities were partly attributed to higher body mass index, less use of hormone therapy, and a protective reproductive history, but these factors did not account entirely for ethnic differences, since fully adjusted mean densities were 1.3% (95% CI: -1.3, 3.7) and 3.8% (95% CI: 1.1, 6.3) lower, respectively. Ethnic differences in mammographic density are consistent with those for breast cancer risk.

Correlation of X-ray diffraction signatures of breast tissue and their histopathological classification.

This pilot study examines the correlation of X-ray diffraction (XRD) measurements with the histopathological analysis of breast tissue. Eight breast cancer samples were investigated. Each sample contained a mixture of normal and cancerous tissues. In total, 522 separate XRD measurements were made at different locations across the samples (8 in total). The resulting XRD spectra were subjected to principal component analysis (PCA) in order to determine if there were any distinguishing features that could be used to identify different tissue components. 99.0% of the variation between the spectra were described by the first two principal components (PC). Comparing the location of points in PC space with the classification determined by histopathology indicated correlation between the shape/magnitude of the XRD spectra and the tissue type. These results are encouraging and suggest that XRD could be used for the intraoperative or postoperative classification of bulk tissue samples.

Shear wave elastography of breast cancer: Sensitivity according to histological type in a large cohort.

PURPOSE: To define the shear wave elastography (SWE) characteristics of breast cancer histological types by size in a large cohort. METHODS: Consecutive patients with US visible masses underwent SWE. All those with confirmed invasive breast cancer were included in the study. Histologic type was ascertained from core biopsy and surgical resection specimens. For each type, mean and median values for Emean and Emax were ascertained. Commoner tumour types were further analysed by invasive size. The significance of differences was established using the Chi-square test. RESULTS: 1137 tumours constituted the study group. The proportion of tumours with Emean below 50 kPa was higher in tubular cancers (23%) compared to ductal carcinomas of no specific type (DNST) (6%) (p < 0.001). Emax below 80 kPa was seen in 34% of tubular cancers compared to 16% of DNST (p < 0.002). Emean and Emax for lobular, mucinous, papillary and metaplastic cancers were not different from those of DNST. There were no significant differences in Emean or Emax between tumour types once broken down according to invasive size. CONCLUSIONS: Most breast cancer histological types have similar SWE characteristics. The exception is tubular cancer which has significantly lower stiffness than other histologic types, accounted for largely by their small size.

Computerised tomography in the staging of Hodgkin's disease and non-Hodgkin's lymphoma.

The last 25 years have seen major changes in the imaging investigation and subsequent management of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL); accurate staging is vital for prognostication and treatment in both, and particularly in HD. The choice of imaging modality for staging depends on its accuracy, impact on clinical decision-making, and availability. Modern CT scanners fulfil most of the desired criteria. The advent of CT scanning, along with the development of ever more effective chemotherapeutic regimens, has resulted in the virtual demise of bipedal lymphangiography (LAG) as a staging tool in patients with lymphoma. It has rendered superfluous a battery of other tests that were in routine use. This contribution reviews the evidence for the use of CT in preference to LAG. CT accurately depicts nodal enlargement above and below the diaphragm, has variable sensitivity for intra-abdominal visceral involvement and is generally outstanding in depicting the extent of disease, especially extranodal extension. Despite the advances in CT technology, there are still areas where CT performs less well (e.g. disease in normal-sized lymph nodes, splenic and bone marrow infiltration). The influence of technical factors, such as the use of intravenous contrast medium, is discussed. In some instances, CT is not the imaging modality of choice and the place of newer techniques such as MRI and endoscopic ultrasound will be reviewed.

MR evaluation of normal retroperitoneal and pelvic lymph nodes.

PURPOSE: To establish guidelines for normal retroperitoneal and pelvic lymph node size at magnetic resonance imaging (MRI) by correlation with computed tomographic (CT) and lymphangiographic (LAG) data. MATERIALS AND METHODS: Twelve patients previously studied with pre- and post-LAG CT to determine normal pelvic lymph node size [ 1 ] were examined with MRI. All were on surveillance for stage I testicular tumour (minimum follow-up 10 years). Three observers recorded blind the site, size and number of nodes in the retroperitoneum and pelvis at 11 sites. The results were validated with previous CT imaging. RESULTS: Eight hundred and fifteen nodes in 12 patients were visible on the MRI initially, and a further 44 nodes were identified after comparison with post-LAG CT. More nodes were seen on MRI than on CT. The 95th centile values for maximum short axis diameter (MSAD) of pelvic lymph nodes were common iliac and obturator 4 mm, external and internal iliac 5 mm and hypogastric 6 mm. In the retroperitoneum the 95th centile MSAD values were retrocrural, high left para-aortic, paracaval and interaortocaval 3 mm, post-caval 4 mm and low left para-aortic 5 mm. CONCLUSION: MRI criteria for normal retroperitoneal and pelvic lymph node size are defined. Adoption of these recommendations may improve the sensitivity of MRI for the detection of nodal metastases.