REI-EXCISE is a multicentre, prospective, non-randomised feasibility study, aimed to evaluate the diagnostic accuracy of rapid ionisation mass spectroscopy using an iKnife device. The iKnife will collect vapour, a by-product of surgery, which will pass through the mass spectrometer machine for analysis in order to evaluate what is "normal" and what is "cancerous" breast tissue.

There is an urgent need to address high rates of close or positive margins and re-operative breast cancer surgery, which commonly results from the inability of the surgeon to rapidly and reliably evaluate resection margin status intra-operatively.

This study therefore seeks to address this problem by aiming to develop a method for near real time, in vivo intra-operative tissue classification that may be used by breast surgeons as an intelligent knife (or "iKnife") to better guide oncological margin control. The method known as Rapid Evaporative Ionisation Mass Spectrometry (REIMS) technology uses mass spectrometric and chemometric analysis of the tissue specific ionic content of the surgical diathermy smoke plume for the rapid identification of dissected breast tissues.

There are no additional treatment interventions as part of REI-EXCISE. The main study procedures are breast conserving surgery using the REIMS iKnife for mass spectral analysis of each surgical margin and correlation between the results of a software recognition algorithm that capitalised on the spectral data (i.e. iKnife margin = positive / negative) with conventional histopathological assessment. False positive iKnife data will be further interrogated with digital droplet polymerase chain reaction and imprint cytology assessment.

Inclusion Criteria:

• BCS for ductal carcinoma in situ (B5a)
• BCS for invasive ductal carcinoma (B5b)
• BCS for invasive lobular carcinoma (B5b)
• B3 lesions undergoing surgical excision

Exclusion Criteria:

• Pregnant or lactating
• 18 years or younger
• Diagnostic excision biopsy for classical lobular carcinoma in situ (LCIS) (current practice is that classical LCIS at a surgical resection margin would not mandate wider excision)

Or if the patient is diagnosed with

• Non-epithelial breast tumour (phyllodes, lymphoma)

Note on patients receiving Neo-adjuvant Chemotherapy (NACT):

Patients selecting to receive NACT will be eligible for participation. However, the data for patients receiving NACT will be analysed separately as a pre-planned subgroup and these patients will not contribute data to the n=35 patients with positive margins required for this feasibility trial. Data from NACT cases have not been used to generate the validated multispectral database since eccentric fibrosis made the histological analysis more complex, which limited the number of patients in whom tissue was available for research.

Patients undergoing breast conserving surgery (BCS) for invasive or non-invasive breast cancer.

There is no upper age limit. We believe that older adults represent a group for whom multiple operations could represent a significant perioperative risk and therefore might stand to benefit from iKnife as much if not more so than younger patients. The lower age limit is 18 for the purposes of adequate informed consent to take part in this trial. A breast cancer diagnosis in adolescence is extremely rare.

Final versions of the anonymised databases and data files will be made available to the wider research community including other groups interested in breast cancer margin technologies and clinical applications / translation of mass spectroscopy.

Imperial College London retains copyright of the databases and data files. As part of the registration process users must agree to the conditions in the Data User Agreement including: restrictions against attempting to identify participants; destruction of data after analysis; reporting responsibilities (i.e. any publication arising as a result of sharing of the data will need to acknowledge the project PIs: Zoltan Takats & Daniel Leff and Cancer Research United Kingdom as the funder); respecting the embargo period regarding publication; proper acknowledgment of the data resource and restrictions on sharing with third parties. A Data User Agreement must be signed before access to the data is permitted.

6 months after study completion

Researchers will be able to access data upon a written request to the project PIs (Zoltan Takats & Daniel Leff).