The value of prognostic ultrasound features of breast cancer in different molecular subtypes with a focus on triple negative disease.

The ultrasound (US) features of breast cancer have recently been shown to have prognostic significance. We aim to assess these features according to molecular subtype. 1140 consecutive US visible invasive breast cancers had US size and mean stiffness by shearwave elastography (SWE) recorded prospectively. Skin thickening (> 2.5 mm) overlying the cancer on US and the presence of posterior echo enhancement were assessed retrospectively while blinded to outcomes. Cancers were classified as luminal, triple negative (TN) or HER2 + ve based on immunohistochemistry and florescent in-situ hybridization. The relationship between US parameters and breast cancer specific survival (BCSS) was ascertained using Kaplan-Meier survival curves and ROC analysis. At median follow-up 6.3 year, there were 117 breast cancer (10%) and 132 non-breast deaths (12%). US size was significantly associated with BCSS all groups (area under the curve (AUC) 0.74 in luminal cancers, 0.64 for TN and 0.65 for HER2 + ve cancers). US skin thickening was associated most strongly with poor prognosis in TN cancers (53% vs. 80% 6 year survival, p = 0.0004). Posterior echo enhancement was associated with a poor BCSS in TN cancers (63% vs. 82% 6 year survival, p = 0.02). Mean stiffness at SWE was prognostic in the luminal and HER2 positive groups (AUC 0.69 and 0.63, respectively). In the subgroup of patients with TN cancers receiving neo-adjuvant chemotherapy posterior enhancement and skin thickening were not associated with response. US skin thickening is a poor prognostic indicator is all 3 subtypes studied, while posterior enhancement was associated with poor outcome in TN cancers.

Are baseline mammographic and ultrasound features associated with metastasis free survival in women receiving neoadjuvant chemotherapy for invasive breast cancer?

OBJECTIVES: To identify associations between baseline ultrasound (US) and mammographic features and metastasis free survival (MFS) in women receiving neo-adjuvant chemotherapy (NACT) for breast cancer. METHODS: The data were collected as part of an ethically approved prospective study. Women with invasive breast cancer receiving NACT who were metastasis free at diagnosis were included. Baseline US and mammography were performed. Imaging was assessed by an experienced breast radiologist who was blinded to outcomes. US imaging features documented included posterior effect, skin thickening, size and stiffness using shear wave elastography (SWE). The mammographic features documented were spiculation and microcalcification. The development of metastatic disease was ascertained from computer records. Statistical analysis was performed using Kaplan Meier survival curves and Receiver Operator Characteristic (ROC) analysis. RESULTS: 171 women with 172 cancers were included in the study and 55 developed metastatic disease. Mean follow-up was 6.0 years. Women with mammographic calcification had significantly poorer metastasis free survival (MFS) compared to women without calcification (p = 0.043, 6 yr MFS 50 % vs 69 %). Women bearing cancer with distal shadowing had poorer MFS than women without shadowing (p = 0.025, 6 yr MFS 47 % vs. 73 %). Women with US skin thickening had poorer MFS compared to women without skin thickening (p = 0.032, 6 yr MFS 52 % vs. 68 %). Mammographic spiculation, US size and stiffness at SWE had no significant association with MFS. CONCLUSION: We have identified mammographic and US features associated with MFS in women receiving NACT. Such information may be useful when counselling patients about the benefits and risks of NACT.

Digital breast tomosynthesis: sensitivity for cancer in younger symptomatic women.

OBJECTIVE: Full-field digital mammography (FFDM) has limited sensitivity for cancer in younger women with denser breasts. Digital breast tomosynthesis (DBT) can reduce the risk of cancer being obscured by overlying tissue. The primary study aim was to compare the sensitivity of FFDM, DBT and FFDM-plus-DBT in women under 60 years old with clinical suspicion of breast cancer. METHODS: This multicentre study recruited 446 patients from UK breast clinics. Participants underwent both standard FFDM and DBT. A blinded retrospective multireader study involving 12 readers and 300 mammograms (152 malignant and 148 benign cases) was conducted. RESULTS: Sensitivity for cancer was 86.6% with FFDM [95% CI (85.2-88.0%)], 89.1% with DBT [95% CI (88.2-90%)], and 91.7% with FFDM+DBT [95% CI (90.7-92.6%)]. In the densest breasts, the maximum sensitivity increment with FFDM +DBT over FFDM alone was 10.3%, varying by density measurement method. Overall specificity was 81.4% with FFDM [95% CI (80.5-82.3%)], 84.6% with DBT [95% CI (83.9-85.3%)], and 79.6% with FFDM +DBT [95% CI (79.0-80.2%)]. No differences were detected in accuracy of tumour measurement in unifocal cases. CONCLUSIONS: Where available, DBT merits first-line use in the under 60 age group in symptomatic breast clinics, particularly in women known to have very dense breasts. ADVANCES IN KNOWLEDGE: This study is one of very few to address the accuracy of DBT in symptomatic rather than screening patients. It quantifies the diagnostic gains of DBT in direct comparison with standard digital mammography, supporting informed decisions on appropriate use of DBT in this population.

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.

Pre-operative stromal stiffness measured by shear wave elastography is independently associated with breast cancer-specific survival.

INTRODUCTION: With the increased use of neoadjuvant therapy for breast cancer, there is a need for pre-operative prediction of prognosis. We aimed to assess the prognostic value of tumour stiffness measured by ultrasound shear wave elastography (SWE). METHODS: A consecutive cohort of patients with invasive breast cancer underwent breast ultrasound (US) including SWE. The following were recorded prospectively: US diameter, stiffness at SWE, presentation source, core biopsy grade, oestrogen receptor (ER) status and pre-operative nodal status. Breast cancer-specific survival (BCSS) was analysed with regard to US size and stiffness, tumour grade on core biopsy, ER status, presentation mode and pre-operative nodal status. Analysis used Cox proportional hazards regression. RESULTS: Of the 520 patients, 42 breast cancer and 53 non-breast cancer deaths were recorded at mean follow-up of 5.4 years. Hazard ratios (HR) for tertiles of stiffness were 1, 4.8 and 8.1 (P = 0.0001). HR for 2 groups based on US size < or ≥ 20 mm were 1 and 5.1 (P < 0.0001). HR for each unit increase in tumour grade on core biopsy was 3.9 (P < 0.0001). The HR for ER positivity compared to ER negativity was 0.21 (P < 0.001). BCSS was also associated with presentation mode and pre-operative nodal status. In a multivariable model, stiffness, US size and ER status were independently associated with BCSS. CONCLUSION: Multiple pre-operative factors including stromal stiffness at SWE have independent prognostic significance. A larger dataset with longer follow-up could be used in the future to construct a pre-operative prognostic model to guide treatment decisions.

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.

PET-CT evaluation of solitary pulmonary nodules: correlation with maximum standardized uptake value and pathology.

PURPOSE: 18-fluorine fluorodeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography (PET-CT) has an established role for the characterization of solitary pulmonary nodules (SPN). Visual assessment of nodule morphology, together with maximum standardized uptake value (SUVmax), is used to estimate likelihood of malignancy. We correlated SUVmax value with pathology of SPN and assessed diagnostic accuracy in differentiating malignant from benign nodule, using 2.5 as threshold SUVmax. METHODS: Retrospective review of PET-CT scans for SPN characterization between April 2008 and June 2011 was performed. Only cases with pathological verification were included. RESULTS: A total of 641 PET-CTs were performed for SPN characterization and staging; 186 patients (77 males, 109 females) with pathological confirmation were included, and 158 (85 %) nodules were malignant: adenocarcinomas (n = 66), squamous cell carcinomas (n = 40), and metastases (n = 20) were the commonest. 28 lesions (15 %) were benign, including granuloma/chronic inflammation (n = 8), infection (n = 7), and hamartomas (n = 5). Using cutoff SUVmax of 2.5, the accuracy of PET-CT in diagnosing malignant SPN is 81.2 %, with sensitivity 86.7 %, specificity 50 %, PPV 90.7 %, and NPV 40 %. The likelihood of malignancy increases with SUVmax. Nevertheless, even with SUVmax <2.5, there is a 62 % chance that a nodule is malignant. CONCLUSIONS: Although PET-CT is useful in diagnostic workup of SPN, it cannot replace "gold standard" tissue diagnosis.

Imaging of solitary pulmonary nodule-a clinical review.

Current widespread use of cross-sectional imaging has led to exponential rise in detection of solitary pulmonary nodules (SPNs). Whilst large numbers of these are benign 'incidentalomas', lung cancers presenting as SPNs are often early disease, which have good prognosis. Therefore, there is rising demand and expectation for more accurate, non-invasive, diagnostic tests to characterize SPNs, aiming to avoid missed or delayed diagnosis of lung cancer. There are wide differential diagnoses of benign and malignant lesions that manifest as SPNs. On conventional imaging, the morphological features supporting benignity include stable small nodule size, smooth demarcated margins, and calcifications. Lack of significant contrast enhancement is also more suggestive of benign nodules. With improved understanding of tumor biology, for instance neo-vascularization and increased vascular permeability, imaging techniques such as dynamic contrast-enhanced computed tomography (CT) provide details on contrast uptake and wash-out kinetics, which is more closely reflecting the physiological and pathological phenomena. Positron emission tomography (PET) using 18fluorine-fluoro-deoxyglucose ((18)F-FDG) is a well-established functional imaging technique, for which one of the most common indications is differentiating between benign and malignant SPNs. Combined PET-CT integrates the anatomical, morphological and metabolic aspects in a single examination, improving overall diagnostic accuracy. Semi-quantitative analysis in FDG-PET imaging is based on measurement of maximum standardized uptake values (SUVmax). SUVmax analysis may become more useful as an assessment of tumor biology in future risk stratification models for cancers. Dual-time point FDG-PET imaging, dual-energy CT, perfusion CT, magnetic resonance (MR) imaging using dynamic contrast enhancement or diffusion-weighted imaging (DWI) techniques, are among the growing armamentarium for diagnostic imaging of SPNs. Provided there is no unacceptably high procedural or operative risk, tissue diagnosis by resection or percutaneous biopsy of SPN should be advocated in those patients identified as at moderate or high risk of malignancy, based on clinical stratification.