CESAR: Contrast Enhanced mammography versus magnetic reSonace imaging for Assessing Response to neoadjuvant chemotherapy

Research question: Is contrast enhanced mammography (CEM) non-inferior to breast magnetic resonance imaging (MRI) for assessing the response to NACT in patients with breast cancer.

Background: As the use of NACT increases together with a drive to de-escalate the extent of surgery, it is essential that accurate imaging is available to all women undergoing NACT to guide best possible treatment. Whilst breast MRI is considered the gold standard technique it can be difficult to access in an appropriate timeframe and is contraindicated or poorly tolerated by some patients.

Emerging evidence suggests that CEM may offer a potential alternative that is quicker, cheaper and preferred by patients. However, there is no robust evidence to support its use for this indication. Despite the paucity of evidence, there is a rapid uptake of CEM throughout the UK and it is increasingly being used as a pragmatic choice.

Aims and Objectives: To demonstrate non-inferiority of CEM compared to MRI for sizing of residual disease as compared with the gold standard of post-surgical pathology. Size of residual disease encompasses pathological response and allows a more detailed assessment of imaging accuracy.

Methods: A multicentre prospective paired imaging cohort study. We will invite people aged over 18-years scheduled to receive NACT for invasive breast cancer.

The primary outcome is the absolute differences between tumour size measurements from each imaging technique (CEM and MRI) and surgical pathology. Secondary outcomes are the comparative accuracy of CEM and MRI for determining pCR, diagnostic accuracy of the pre-treatment imaging for identifying multifocality and patient preference and acceptability of the two techniques.

Given the outcome measure is continuous with paired data, a sample size of 150 patients would be sufficient to demonstrate non inferiority using a paired t test with a limit of 10mm, 90% power and a 2.5% one sided significance level, assuming the correlation between measurements is 0.6, standard deviation is no more than 20mm with a mean difference of 5mm or less, allowing for 10% dropout.

A non-inferiority design is considered most appropriate for this study because of the established advantages of CEM over MRI in terms of accessibility, cost, speed and patient preference. This will provide sufficient evidence to establish whether CEM is an accurate alternative to MRI in this setting, and drive policy change.

Timeline for delivery: The duration is intended to be 3-years, with 2-years of that consisting of the recruitment period.

Impact and Dissemination: If the proposed study demonstrates that CEM is non-inferior to MRI for monitoring response to NACT it will guide change in clinical practice supported by clinical guidelines with worldwide implications.

We will share a summary of the results with relevant national organisations and present the results through breast specific national and international conferences.

Members of the PPI group will help to ensure that the findings are written in an accessible way and shared with their networks. We will publish the results in peer-reviewed journals and present them at relevant medical conferences.