Current options and future perspectives for breast margin assessment in clinical practice

Abstract Background: Ensuring negative margins at the time of breast conserving surgery for invasive breast cancer or ductal carcinoma in situ is necessary to minimize the chance of local recurrence and avoid re-excisions that cause patient concern and may delay adjuvant therapy. However, about 25% of women who have lumpectomy have a second surgery to remove residual disease, suggesting an ongoing need for improved methods of intraoperative margin assessment. This study aimed to perform a contemporary review of methods of intraoperative margin assessment during breast conservation surgery. Methods: A review of the scientific literature from 2009 to 2021 comprising 62 manuscripts of the current and proposed. intraoperative techniques for breast margin assessment during breast conservation surgery was conducted via PubMed and Google Scholar. The methods assessed were grouped into 10 categories based on the technology employed: bioimpedance/radiofrequency, high-resolution imaging, optical imaging, mass spectrometry, magnetic-resonance imaging, 2D/3D specimen CT, X-ray, multimodal optical microscopy, pharmacologic and pathological margin assessment. All technologies were reviewed for overall effectiveness in lowering re-excision rates derived from their respective advantages, limitations, sensitivity, and specificity. Results: Overall, 8 current and 7 technologies under development were assessed (Table 1). Frozen section and cytology yielded the highest diagnostic accuracy; however, these can be time-consuming, resource-intensive, and have limited sampling points. Conversely, 2D specimen CT provides rapid results but is limited by relatively low sensitivity. Future technologies such as optical coherence tomography showed promising results in demonstrating higher diagnostic accuracy for lumpectomy and margin shaves, but remain to be proven in clinical practice. Conclusion: Intraoperative margin assessments can lower final positive margins and subsequent re-excisions rates. A number of current and upcoming technologies that assess margin status range in their respective efficacies and limitations. There remains demand for improved margin assessment at the time of breast conserving surgery, but which technologies will become standard of care remains, at present, unclear. Table 1.Methods of intraoperative margin assessmentMethod:Brand:Sensitivity:Specificity:Source:Bioimpedence• ClearEdge™87.3%75.6%Dixon et al. 2016• MarginProbe75.2%70-87%Schanabel et al., 2014Cytology:• Imprint72%97%Esbona & Zhanhai 2012; Qui et al., 2018Frozen Section–83%95%Schmidt et al, 2020; Schwarz & Schmidt, 2020Mass Spectrometry• iKnife93.4-94.7%94.7-96.2%St. John et al., 2017• MasSpec Pen83-95%95-100%Garza et al., 2020Multimodal optical microscopy• fluorescence imaging combination withRCM/OCT subsystemTBDTBDScimone et al., 2021MRI• ClearSight™93%92%Moshe et al., 2016Optical Coherence Tomography (OCT)• OTIS™96%92%Mojahed et al., 2020; Schmidt et al. 2020Pharmacology• Bevacizumab98%79%Koch et al., 2017• Lumicell2-3D specimen CT• Mozart®93%78%Black et al., [poster]• Faxitron78.6-85.6%100%Emmadi & Wiley 2012; Bathla et al. 2011• MicroCT56%100%Qiu et al. 2018X-ray• XPCI83%83%Massimi et al. 2021 Citation Format: Huma Javaid, Ivan Marin, Jessica Montalvan, Logan Healy, Brian Menegaz, Cary Hsu, Eric Silberfein, Elizabeth Bonefas, Stacey A. Carter, Alastair M. Thompson. Current options and future perspectives for breast margin assessment in clinical practice [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-10.