Early detection of local recurrence has been shown to improve survival. What is unclear is how frequently mammography should be performed, how long surveillance should continue and how the answers to these questions vary with tumour pathology, patients age, and surgery type. Many of these questions are not directly answerable from the current literature. While some of these questions will be answered by the Mammo-50 study, evidence from local recurrence rates, tumour biology, and the lead time of mammography can be used to guide policy. Young age is the strongest predictor of local recurrence and given the short lead time of screening in women under 50, these women require annual mammography. Women over 50 with HER-2 positive and triple negative breast cancer have higher rates of local recurrence after breast conserving surgery than women with luminal cancers. Women with HER-2 positive and triple negative breast cancer also have a higher rate of recurrence in years 1-3 post surgery. Annual mammography in year 1-4 would appear justified. Women over 50 with luminal cancers have low rates of local recurrence and no early peak. Recurrence growth will be low due to tumour biology and hormone therapy. Biennial mammography after year 2 would seem appropriate. Women over 50 following mastectomy have no early peak in contralateral cancers so the frequency should be determined by the lead time of screening. This would suggest 2 yearly mammography for women aged 50-60 while 3 yearly mammography may suffice for women over 60.

PURPOSE:The aim of this study is to develop a pre-operative prognostic model based on known pre-operative factors.METHODS:A database of ultrasound (US) lesions undergoing biopsy documented US lesion size, stiffness, and patient source prospectively. Women with invasive cancer presenting between 2010 and 2015 were the study group. Breast and axillary core results and ER, PR and HER receptor status were collected prospectively. Assessment of US skin thickening, US distal enhancement and presence of chronic kidney disease (CKD) was performed retrospectively. Patient survival and cause of death were ascertained from computer records. Predictive models for (i) all-cause mortality (ACM) and (ii) breast cancer death (BCD) were built and then validated using bootstrap k-fold cross-validation. A comparison of predictive performance was made between a full cause-specific Cox model, a sub cause-specific Cox model, and a full Fine-Gray sub-distribution hazard model.RESULTS:1136 patients were included in the study. The median follow-up time was 6.2 years. 125 (11%) women died from breast cancer and 155 (14%) died from other causes. For the prediction of BCD, the cause-specific Cox sub-model performed the best. The time dependent AUC begins above 0.91 in year one to 3 reducing to 0.83 in year 6. The factors included in the Cox sub model were tumour size, skin thickening, source of detection, tumour grade, ER status, pre-operative nodal metastasis and CKD.CONCLUSION:We have shown that a model based on preoperative factors can predict BCD. Such prediction if externally validated and incorporating treatment data could be useful for treatment planning and patient counselling.

Several additional techniques are now widely available when performing handheld breast US which may be helpful in routine clinical practice and others which show research potential. These include various forms of elastography including strain and shear wave techniques and Doppler assessment of vascularity with and without contrast. The most useful technique is shear wave elastography (SWE) which allows quantitative and reproducible analysis of tissue stiffness. Cancers tend to be stiff and benign lesions soft. SWE can be used successfully to differentiate benign from malignant lesions, monitor neoadjuvant chemotherapy, and predict nodal metastasis and outcome. Superb vascular imaging is the most promising vascular modality and it may be useful in monitoring neoadjuvant chemotherapy and benign/malignant differentiation.

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.

Purpose The primary aim was to develop and validate a novel mammography positioning measure, specifically incorporating parameters which might relate to mammography pain. We then explored relationships between the new adverse positioning score and (1) pain; (2) patient and technique factors. Methods A 15-item instrument incorporating positioning features with potential to relate to mammography pain was developed. Participants’ mammograms (n = 310) were reviewed for presence of these features. Validity was investigated using the Rasch model. Scores produced by the resultant measure were investigated for associations with patients’ pain scores and relevant patient and technique factors, using Pearson correlation, analysis of variance, and multiple linear regression. Results Statistical indices within the Rasch measurement framework provided good evidence that the measure reflected a coherent construct of adverse positioning. Thus, the scores produced with the measurement instrument were valid for use in further statistical analysis. There is, however, scope for improvement of the measure’s discriminatory properties. Adverse positioning scores were higher for greater breast volumes (r = 0.12, p=.0391) and body mass index (BMI) (r = 0.13, p=.0349), and varied by mammographer (F(11,298) 2.38, p = .0078). The relationships with BMI and mammographer persisted in regression modelling. No relationship was found between adverse positioning and pain. Conclusions Evidence from Rasch analysis suggests that this novel measure is valid for quantifying a coherent “adverse positioning” construct in mammography. Adverse positioning scores varied by mammographer and were related to higher patient BMI but not to mammography pain. The measure warrants expansion, further refinement, and testing in larger studies.

The purpose of this article is to provide raw data and measure-validation data pertaining to a co-submission published in European Journal of Radiology and entitled: Development and validation of a novel measure of adverse patient positioning in mammography. This Data in Brief article serves not only to provide greater detail than its companion article but also as an educational worked example of the Rasch measurement framework. Rasch measurement is a form of modern psychometric technique and our articles provide the first known example of its use in the evaluation of clinical radiological image quality. The data consist of observations of mammographic images, plus limited participant parameters relevant to the measure validation process. Also provided are validation indices produced by subjecting the primary data to Rasch analysis. An expert observer generated the primary data by reviewing mammographic images to judge the presence or absence of a set of features developed through theory and consultation with other experts. The validation data were generated through Rasch analysis, performed using Winsteps® software, which mathematically models the probability of having a correct response (or a present feature in this dataset) to an item in a given measurement instrument (e.g. questionnaire), as a function of the participant's ability/position on the underlying construct under study. The data can be reused by anyone wishing to learn and practice psychometric validation techniques. They can also form a basis for researchers wishing to build on our preliminary measure for the assessment of mammographic clinical image quality.

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.

Background: There is a lack of evidence or consensus amongst surgeons on optimum frequency or duration of follow-up including mammography for breast cancer patients aged 50 years and older at diagnosis. Mammo-50 aims to provide sound cost-benefit evidence whilst investigating alternative methods of follow-up.

AIM:To identify the breast cancer specific survival (BCSS) associated with nodal metastasis identified by axillary core biopsy (ACB), and by sentinel node biopsy (SNB) compared with node negative patients. A further aim was to assess the prognostic effects of axillary ultrasound (US) features and amount of tumour in ACB specimens. METHODS:Consecutive patients with cancer were identified from a database of US lesions undergoing breast biopsy. The three study groups were: a) those with metastasis identified by ACB, b) those undergoing immediate surgery with positive SNB and c) those undergoing immediate surgery with a negative SNB. US features and the amount of tumour in the ACB specimen were assessed by review of US images and pathological reports. BCSS was assessed using Kaplan Meier survival curves. RESULTS:967 patients were included, with mean follow-up of 6.0 yrs. There were 90 breast cancer deaths: 26% of those with a positive ACB, 11% with a positive SNB and 4% of those with a negative SNB. BCSS was significantly different between the groups (p < 0.001) with hazard ratio, compared with the negative SNB group, of 7.8 (95% CI 4.4-13.7) for patients with positive ACB and 2.5 (95% CI 1.3-4.6) for positive SNB. Axillary US findings and assessment of the amount of tumour in the ACB did not influence survival. CONCLUSION:This study suggests that women with a positive ACB have a worse BCSS compared to those with a positive SNB. This should be borne in mind when systemic therapy is being considered.

Our aim is to assess whether the poor breast cancer specific survival (BCSS) seen in women with breast cancer and impaired renal function can be explained by associations with other prognostic factors. The study group was a consecutive series of patients undergoing breast ultrasound (US) who had invasive breast cancer (n = 1171). All women had their US diameter and mean stiffness (kPa) at shear wave elastography (SWE) recorded. The core biopsy grade and receptor status were noted. Core biopsy of abnormal axillary nodes and the patient referral source was also noted. Survival including cause of death was ascertained. Comorbidities at diagnosis were recorded. Patients were divided into those with a GFR<60 (“renal group”), those with other comorbidities and those with none. BCSS was assessed using Kaplan–Meier survival curves and Cox proportional hazards regression. One thousand, one hundred and forty-one patients constituted the study group. 107 (9%) patients had impaired renal function, 182 (16%) had other comorbidities while 852 (75%) had no comorbidities. Mean follow-up was 5.8 years. 109 breast cancer and 122 non-breast cancer deaths occurred. BCSS in the renal group was significantly worse than the other groups. Women with renal comorbidity were older, more likely to present symptomatically, have a pre-operative diagnosis of axillary metastases, and have larger and stiffer cancers. Cox proportional hazards regression showed that renal impairment maintained independent significance. The poor BCSS in women with impaired renal function is partially explained by advanced tumour stage at presentation. However, impaired renal function maintains an independent prognostic effect.

Abstract 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.

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).

Citation for published version (APA): Evans, A., Whelehan, P., Thompson, A., Purdie, C., Jordan, L., Macaskill, J., Henderson, S., & Vinnicombe, S. (2018). Identification of pathological complete response after neoadjuvant chemotherapy for breast cancer: comparison of greyscale ultrasound, shear wave elastography, and MRI. Clinical Radiology, 73(10), 910.e1910.e6. https://doi.org/10.1016/j.crad.2018.05.030