Real-time, intraoperative detection of residual breast cancer in lumpectomy cavity walls using a novel cathepsin-activated fluorescent imaging system
Obtaining tumor-free surgical margins is critical to prevent recurrence in breast-conserving surgery but it remains challenging. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor.
Lumpectomy cavity walls and excised specimens of breast cancer lumpectomy patients were assessed with the LUM Imaging System (Lumicell, Inc., Wellesley MA) with and without intravenous LUM015, a cathepsin-activatable fluorescent agent. Fluorescence at potential sites of residual tumor was evaluated with a sterile hand-held probe, displayed on a monitor and correlated with histopathology.
Background autofluorescence was assessed in excised specimens from 9 patients who did not receive LUM015. In vivo lumpectomy cavities and excised specimens were then imaged in 15 women undergoing breast cancer surgery who received no LUM015, 0.5, or 1 mg/kg LUM015 (5 women per dose). Among these, 11 patients had invasive carcinoma with ductal carcinoma in situ (DCIS) and 4 had only DCIS. Image acquisition took 1 s for each 2.6-cm-diameter surface. No significant background normal breast fluorescence was identified. Elevated fluorescent signal was seen from invasive cancers and DCIS. Mean tumor-to-normal signal ratios were 4.70 ± 1.23 at 0.5 mg/kg and 4.22 ± 0.9 at 1.0 mg/kg (p = 0.54). Tumor was distinguished from normal tissue in pre-and postmenopausal women and readings were not affected by breast density. Some benign tissues produced fluorescent signal with LUM015.
The LUM Imaging System allows rapid identification of residual tumor in the lumpectomy cavity of breast cancer patients and may reduce rates of positive margins.
KeywordsImage-guided surgery Breast cancer Lumpectomy surgery Intraoperative tumor detection
This study was supported by NCI Grant 1R21CA173762-01. We gratefully acknowledge the Massachusetts General Hospital Translational Clinical Research Center and their NIH Grant #1UL1TR001102 for providing research nurse support. The clinical production of LUM015 was funded with federal funds from the National Cancer Institute, National Institutes of Health, under NCI’s Experimental Therapeutics Program (http://www.next.cancer.gov).
Compliance with ethical standards
Conflict of interest
Authors D. Strasfeld and J. Ferrer have received remuneration and stock ownership from Lumicell, Inc. All other authors declare that he/she have no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 1.Fisher B, Anderson S, John Bryant J et al (2002) Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347:1233–1241. https://doi.org/10.1056/NEJMoa022152 CrossRefPubMedGoogle Scholar
- 4.Clarke M, Collins R, Darby S et al. (2005) Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366:2087–2106CrossRefPubMedGoogle Scholar
- 14.Tang R, Buckley JM, Fernandez L, Aftreth O, Michaelson J, Saksena M, Coopey S, Specht M, Gadd M, Yagi Y, Rafferty E, Brachtel E, Smith BL (2013) Micro-computed tomography (Micro-CT): a novel method for intra-operative breast cancer specimen imaging. Breast Cancer Res Treat 139:311–316CrossRefPubMedGoogle Scholar
- 15.Tang R, Saksena M, Coopey SB, Fernandez L, Buckley JM, Lei L, Aftreth O, Koerner F, Michaelson J, Rafferty E, Brachtel E, Smith BL (2016) Intraoperative micro-computed tomography (micro-CT): a novel method for determination of primary tumour dimensions in breast cancer specimens. Br J Radiol 89(1058):20150581. https://doi.org/10.1259/bjr.20150581 CrossRefPubMedGoogle Scholar
- 16.Brachtel EF, Johnson NB, Huck AE, Rice-Stitt TL, Vangel MG, Smith BL, Tearney GJ, Kang D (2016) Spectrally encoded confocal microscopy for diagnosing breast cancer in excision and margin specimens. Lab Invest 96:459–467. https://doi.org/10.1038/labinvest.2015.158 CrossRefPubMedPubMedCentralGoogle Scholar
- 23.World Health Organization Classification of Tumours of the Breast, Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ (eds) (2012) International Agency for Research on Cancer, LyonGoogle Scholar
- 26.Sharma V, Shivalingaiah S, Peng Y et al (2012) Auto-fluorescence lifetime and light reflectance spectroscopy for breast cancer diagnosis: potential tools for intraoperative margin detection. Biomed Opt Express 3:1825–1840. https://doi.org/10.1364/BOE.3.001825 CrossRefPubMedPubMedCentralGoogle Scholar