New imaging tools aim to cut repeat breast cancer surgery

Breast cancer remains the most common cancer affecting women worldwide, with more than 2.3 million women diagnosed every year and incidence continuing to climb. For early-stage disease, the treatment of choice is breast conserving surgery combined with radiotherapy, an approach that removes the tumour while preserving the appearance and function of the breast. Yet the operation itself rests on a strikingly imprecise foundation: surgeons must decide how much tissue to remove using little more than visual inspection and touch. In an opinion article published in Frontiers in Medical Engineering, surgeons and a pathologist from Imperial College London, Imperial College Healthcare NHS Trust and Harvard Medical School argue that a wave of emerging imaging technologies could finally bring microscopic precision to the operating theatre, potentially sparing thousands of women the trauma of a second operation.

The problem the authors describe is known as a positive margin. For breast conserving surgery to work, the edges of the excised specimen must be free of cancer, a state called a clear margin. In practice, margin status is only confirmed after the operation, when a pathologist examines the tissue under the microscope. Estimates based on what the surgeon can see and feel during surgery are simply not reliable enough. Depending on the study and the definition used, roughly 14 to 40 percent of women undergoing the procedure are found to have disease extending too close to the resection edge, requiring further surgery to ensure the cancer has been completely removed.

The consequences of margin positivity reach far beyond the operating schedule. Re-excision surgery has been shown to harm patient reported outcomes, including psychological wellbeing and satisfaction with the appearance of the breast. It is also financially inefficient: total treatment costs can rise by up to 24 percent per patient when a second operation is needed. A recent large systematic review and meta-analysis of more than one hundred thousand patients added clinical weight to the issue, showing that margins closer than one millimetre are associated with increased local and distant recurrence of the disease.

Part of the difficulty is that guidelines disagree on what counts as clear. The National Comprehensive Cancer Network in the United States accepts a no ink on tumour approach for invasive carcinoma, meaning cancer cells may touch the inked edge of the specimen, while recommending two millimetres as a preferred minimum for ductal carcinoma in situ, a non-invasive precursor lesion. The Association of Breast Surgery in the United Kingdom defines a clear margin as at least one millimetre for invasive disease and a two millimetre radial margin for DCIS. The European Society for Medical Oncology similarly accepts no ink on tumour for invasive cancer but recommends at least two millimetres for DCIS. These differing thresholds, along with variations in operative technique such as routine removal of additional cavity shave tissue and differences in tumour subtype, help explain the wide range of reported margin positivity rates.

Current intraoperative assessment tools fall short in different ways. Two-dimensional specimen mammography is user-friendly and integrates easily into surgical workflows, but the images it produces are of low resolution. A recent meta-analysis suggests it may achieve a pooled sensitivity of only 0.39 for margin assessment, and it cannot identify non-calcified lesions at all, while benign calcifications may sometimes be overinterpreted as malignant. Frozen section histology, in which tissue is rapidly frozen, sliced and stained for immediate microscopic review, has high sensitivity, but its main barriers are the lack of pathology availability and the increased operating time, which make it logistically prohibitive for many institutions.

Among the emerging technologies highlighted by the authors, three-dimensional tomosynthesis specimen radiography takes multiple radiographs of the excised specimen in one millimetre digital slices, allowing the specimen and its contents to be reconstructed in three dimensions. In a single-centre retrospective analysis, this approach was found to be superior to two-dimensional radiography because it enabled surgeons to visualise the orientation of margins and map areas needing additional excision at the index procedure, potentially lowering re-excision rates. Micro computed tomography goes further, providing real-time ex-vivo three-dimensional volumetric images that capture the whole specimen in detail, which can then be manipulated and sliced into any configuration to guide surgeons on where to excise additional tissue. Preliminary tissue studies demonstrated that Micro-CT detected margin positivity in up to 93 percent of cases deemed positive by histopathologists, though a systematic review of eight studies reported lower pooled figures, with sensitivity of 0.63 and specificity of 0.77. The main barriers to implementation remain the lack of clinical trial evidence and the need for image management systems to interpret the data.

Phase contrast Micro-CT adds a refinement that makes small lesions stand out in a way not possible with conventional radiology. By applying a mask that selects refracted rays, the technology produces rapid three-dimensional images in which the size, shape and detail of breast cancers captured are comparable to the gold standard of histological examination. Preliminary studies estimate its sensitivity for intraoperative margin assessment at 1.6 times that of conventional two-dimensional imaging. Optical coherence tomography takes a different route, using low coherence interferometry to achieve high resolution visualisation of tissue, typically one to fifteen micrometres axially and ten to twenty micrometres laterally, reaching two to three millimetres in depth in real time. This makes it suitable for assessing breast cancer margins intraoperatively, with ongoing studies demonstrating its value. However, thicker tissue samples requiring deeper penetration may not be fully assessed, and additional training for image interpretation by pathologists remains a clinical barrier.

Two further modalities exploit light in distinctive ways. Cerenkov luminescence imaging detects the faint Cerenkov radiation emitted by decaying radiotracers such as fluorodeoxyglucose, which is injected intravenously before surgery. Because the tracer accumulates in areas of high metabolic activity, cancerous cells glow, allowing precise tumour localisation that is particularly useful for smaller or impalpable tumours and for residual disease. Intraoperatively, the technology provides real-time imaging of the excised specimen, and first-in-human feasibility studies have applied it safely without exposing theatre staff to high radiation levels. Residual radiotracer signal at the margin suggests incomplete resection, prompting further tissue removal. Limitations include false negatives in tumours with low glucose metabolism and the challenge of timing the injection to provide the optimal operating window. Confocal fluorescence microscopy, meanwhile, combines laser excitation, spatial pinhole filtering and fluorescence to achieve optical sectioning of operative specimens, generating high-resolution cellular images of the specimen surface likened to frozen section or histopathology without having to physically fix or slice the tissue. Surgeons can differentiate normal and malignant breast tissue with high accuracy, and current studies such as the SHIELD trial are investigating whether commercial confocal scanners reduce the risk of positive margins, though high costs, regulatory approval and training requirements keep clinical implementation some distance away.

The authors propose that intraoperative margin assessment should be viewed as a continuous, multidisciplinary and dynamic decision-making process rather than a single test. In their vision, surgeons would formulate a margin management strategy before surgery, considering tumour biology, localisation technique and planned radiotherapy. During the operation, two-dimensional or three-dimensional specimen radiography would serve as an initial screening tool, with advanced high-resolution modalities selectively applied to verify margin integrity at the microscopic level. Based on predefined threshold criteria, the surgical team could promptly decide whether to perform additional excision or cavity sampling. After surgery, imaging findings would be correlated with final histopathology at review meetings to refine interpretation algorithms and standardise evaluation protocols. Through this closed-loop model, intraoperative imaging would be transformed from isolated tools into integral components of increasingly precise and individualised breast conserving surgery.

With a growing number of women worldwide undergoing breast conserving surgery, the authors argue it is imperative that more accurate intraoperative imaging technologies are comprehensively evaluated and systematically integrated into surgical practice. Many barriers to implementation remain, from missing clinical trial evidence to unresolved questions of cost, training and workflow, underscoring the need for continued research and development. The special collection introduced by this opinion article will delve into the development and translational progress of each novel imaging modality in turn, aiming to determine diagnostic accuracy and implementation plans for improving precision in breast conserving surgery, and ultimately to reduce the number of women who must return to the operating theatre for a second attempt at clear margins.

Subject of Research: Enhancing precision in breast conserving surgery: introduction to emerging imaging technologies

Article Title: Enhancing precision in breast conserving surgery: introduction to emerging imaging technologies

Article References: Enhancing precision in breast conserving surgery: introduction to emerging imaging technologies. (n.d.). https://doi.org/10.3389/fmede.2026.1734520

Image Credits: AI Generated

DOI: 10.3389/fmede.2026.1734520

Keywords: Enhancing, precision, breast, conserving, surgery, introduction, emerging, imaging, technologies, scientific research