Breast Conserving Surgery Specimens Research Articles

Resection Ratios and Tumor Eccentricity in Breast-Conserving Surgery Specimens for Surgical Accuracy Assessment.

This study aims to evaluate several defined specimen parameters that would allow to determine the surgical accuracy of breast-conserving surgeries (BCS) in a representative population of patients. These specimen parameters could be used to compare surgical accuracy when using novel technologies for intra-operative BCS guidance in the future. Different specimen parameters were determined among 100 BCS patients, including the ratio of specimen volume to tumor volume (resection ratio) with different optimal margin widths (0 mm, 1 mm, 2 mm, and 10 mm). Furthermore, the tumor eccentricity [maximum tumor-margin distance - minimum tumor-margin distance] and the relative tumor eccentricity [tumor eccentricity ÷ pathological tumor diameter] were determined. Different patient subgroups were compared using Wilcoxon rank sum tests. When using a surgical margin width of 0 mm, 1 mm, 2 mm, and 10 mm, on average, 19.16 (IQR 44.36), 9.94 (IQR 18.09), 6.06 (IQR 9.69) and 1.35 (IQR 1.78) times the ideal resection volume was excised, respectively. The median tumor eccentricity among the entire patient population was 11.29 mm (SD = 3.99) and the median relative tumor eccentricity was 0.66 (SD = 2.22). Resection ratios based on different optimal margin widths (0 mm, 1 mm, 2 mm, and 10 mm) and the (relative) tumor eccentricity could be valuable outcome measures to evaluate the surgical accuracy of novel technologies for intra-operative BCS guidance.

The value of oestrogen receptor, progesterone receptor and keratins 5 and 14 immunohistochemistry in the evaluation of epithelial proliferations at cauterised margins in breast-conserving surgery specimens

In breast conservative surgery, it is sometimes difficult to decide whether the cauterised tissue at the inked margin represents normal / hyperplastic or neoplastic tissue. We retrospectively assessed the value of ER, PR, CK5 and CK14 IHC in clarifying the nature of cauterised tissues at the margins concerning 34 lesions of 23 patients. 27 cases belonged to lesions that could not be adequately classified on the basis of the HE stains. Two thirds of them could be classified as non-neoplastic or neoplastic and two thirds of the remaining could be favourised as neoplastic or non-neoplastic, with 3/27 cases remaining uncertain. All 4 IHC reactions were helpful in classifying the lesions in almost half of the cases. However, 3 or 4 immunostains were supportive of the classification in 19/27. The most useful stains were the keratins, generally demonstrating a matching pattern of cell labelling with CK5 and CK14. ER and PR were somewhat less useful in classifying uncertain lesions. Considering all the 27 questionable lesions, IHC with ER, PR, CK5 and CK14 clarified the lesions at the cauterised margins in 23 cases. Taken all these considerations into account, CK5, CK14, PR and ER IHC may help in distinguishing between cautery damaged neoplastic and non-neoplastic tissues. All four IHC may yield the best support for decision making, but CK5 and/or CK14 may be sufficient in their own. The essential approach is that the results must be interpreted with caution, in the context of the given patient’s disease, to avoid misinterpretations.

Abstract P1-09-08: Comparisons of aesthetic outcomes and prognosis of conventional breast conserving surgery, oncoplastic breast conserving surgery and breast conserving surgery plus immediate lipofilling in early breast cancer

Abstract Background: Conventional breast conserving surgery (CBCS) considered as a confined alternative to mastectomy could lead to potentially breast deformities. Oncoplastic breast conserving surgery (OBCS) as well as breast conserving surgery (BCS) plus immediate lipofilling have been shown to be reliable techniques for maintaining the natural breast contours, however, few studies compared those three surgical options for oncological safety, complications and aesthetic outcomes in early breast cancer (EBC). Methods: We retrospectively reviewed the data of BC patients who underwent BCS between January 2017 and December 2021 from The First Affiliated Hospital of Chongqing Medical University. We included female patients who received BCS for unilateral stage 0-III BC. Those who had bilateral BC, incomplete surgical records, unfinished adjuvant therapy, multiple primary malignant tumors and lost to follow-up and were excluded. Patient-reported outcome measures (PROMs) were assessed using the BREAST-Q Version 2.0. We utilized a multivariable linear regression model to identify clinical factors correlated with the BREAST-Q score, and the log-rank test and Cox regression models were used to compare the survival difference between groups. Results: Of 268 patients, 90 (33.6%) underwent CBCS, 53 (19.8%) underwent OBCS and 125 (46.6%) underwent BCS plus immediate lipofilling. Patients in OBCS and BCS plus immediate lipofilling groups were younger than those in CBCS group (mean age: 43.9yrs vs 49.1yrs, P=0.001 and 45.7yrs vs 49.1yrs, P=0.008). The largest tumor size and heaviest BCS specimen were observed in the OBCS group compared with CBCS (mean tumor size: 23.4mm vs 17.3mm, P< 0.001 and median excised weight: 122.0g vs 36.5g, P< 0.001) and BCS plus immediate lipofilling group (mean tumor size: 23.4mm vs 17.4mm, P< 0.001 and median excised weight: 122.0g vs 37.0g, P< 0.001). It was balanced for pathological type, Ki-67, ER and PR expression between three groups. In the multivariable linear regression models, with the CBCS group as referent, either OBCS or BCS plus immediate lipofilling groups had a significantly higher score in satisfaction with breast (Estimate: 9.27, P=0.001 and Estimate: 13.08, P< 0.001) and psychosocial well-being (Estimate: 6.06, P=0.021 and Estimate: 9.34, P< 0.001). Additionally, sexual well-being was improved among patients receiving BCS plus immediate lipofilling (Estimate: 6.19, P=0.029). Nevertheless, patients in OBCS group harbored worse physical well-being compared with CBCS (Estimate: -15.89, P< 0.001). There was no significantly statistical difference among three groups on re-excision rate (P=0.721) and postoperative complications (P=0.663). After 37-month median follow-up, identical event-free survival (EFS) was revealed among three groups (HROBCS vs CBCS: 3.93; 95%CI, 0.78-19.81, P=0.098; HRBCS plus Lipofilling vs CBCS: 1.15, 95%CI, 0.28-4.67, P=0.847). Conclusion: This study demonstrated that OBCS as well as BCS plus immediate lipofilling shared equivalent oncological safety but better cosmetic outcomes and patient satisfaction when compared with CBCS for EBC patients, suggesting that further prospective randomized clinical trials are warranted to confirm our findings. Citation Format: JH Ren, Yuanyuan Wang, Xiang Zhang, Kang Wang, Renxi Tang, Ling Yang, Junge Gong, Jiawei Xu, Qing Li, WM Zhu, Qiao Cheng, Guosheng Ren, Hongyuan Li. Comparisons of aesthetic outcomes and prognosis of conventional breast conserving surgery, oncoplastic breast conserving surgery and breast conserving surgery plus immediate lipofilling in early breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-09-08.

Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscopy ‘Histolog® scanner’ for breast margin assessment in comparison with conventional specimen radiography

PurposeThe Histolog® Scanner (SamanTree Medical SA, Lausanne, Switzerland) is a large field-of-view confocal laser scanning microscope designed to allow intraoperative margin assessment by the production of histological images ready for assessment in the operating room. We evaluated the feasibility and the performance of the Histolog® Scanner (HS) to correctly identify infiltrated margins in clinical practice of lumpectomy specimens. It was extrapolated if the utilization of the HS has the potential to reduce infiltrated margins and therefore reduce re-operation rates in patients undergoing breast conserving surgery (BCS) due to a primarily diagnosed breast cancer including ductal carcinoma in situ. MethodsThis is a single-center, prospective, non-interventional, diagnostic pilot study including 50 consecutive patients receiving BCS. The complete surface of the specimen was scanned using the HS intraoperatively. The surgery and the intraoperative margin assessment of the specimen was performed according to the clinical routine consisting of conventional specimen radiography as well as the clinical impression of the surgeon. Three surgeons and an experienced pathologist assessed the scans produced by the HS for cancer cells on the surface. The potential of the HS to correctly identify involved margins was compared to the results of the conventional specimen radiography alone as well as the clinical routine. The histopathological report served as the gold standard. Results50 specimens corresponding to 300 surfaces were scanned by the HS. The mean sensitivity of the surgeons to identify involved margins with the HS was 37.5% ± 5.6%, the specificity was 75.2% ± 13.0%. The assessment of resection margins by the pathologist resulted in a sensitivity of 37.5% and a specificity of 81.0%, while the local clinical routine resulted in a sensitivity of 37.5% and a specificity of 78.2%. ConclusionAcquisition of high-resolution histological images using the HS was feasible in clinical practice. Sensitivity and specificity were comparable to clinical routine. With more specific training and experience on image interpretation and acquisition, the HS may have the potential to enable more accuracy in the margin assessment of BCS specimens.

Assessing Resection Margin Status in Breast-conserving Surgery Specimens: Comparison Among Gross Evaluation, Frozen Section Analysis, and Permanent Section Diagnosis in 725 Patients With Breast Cancer.

An accurate evaluation of resection margin (RM) is critical in breast-conserving surgery (BCS) as negative RM status is critical for successful local control. We compared gross and microscopic methods for RM evaluation and analyzed their concordances. Gross evaluation (GE), frozen section analysis (FSA), and permanent section diagnosis (PSD) were compared for specimens from 725 breast cancer patients. The RM was grossly involved in 74 cases (10.2%). The sensitivity and specificity of GE were 22.9% and 96.1%, respectively. FSA revealed positive RM in 290 cases (40.0%), with high sensitivity (86.7%) and specificity (83.1%). With PSD, 240 cases (33.1%) showed RM involvement. Discordant results between gross and microscopic methods were observed in 104 cases (14.3%). Our observations of the low sensitivity of GE, high discordance rate between gross and microscopic methods, and high sensitivity and specificity of FSA support the necessity of intraoperative FSA for assessing RM status during BCS.

Assessment of pathological biopsy and safety margin of specimens from breast cancer patients with breast conversing surgery

Breast-conserving surgery (BCS) has now become one of the optimal surgical choices for early invasive breast cancer. The pathological diagnosis of margin in breast-conserving specimen is very important. There is no acknowledge on the approaches of pathological biopsy and safety margin diagnosis of breast conserving surgery. This paper will compare the biopsy and diagnosis methods of breast-conserving surgery specimens between Tianjin Medical University Cancer Institute and Hospital in China and MD Anderson Cancer Center in the United States. We summarize our biopsy method and diagnostic criteria to explore how to accurately evaluate the margin of breast-conserving surgery specimen from a pathological point of view, and to escort a successful breast-conserving surgery.

Combined total internal reflection AF spectral-imaging and Raman spectroscopy for fast assessment of surgical margins during breast cancer surgery.

The standard treatment for breast cancer is surgical removal mainly through breast-conserving surgery (BCS). We developed a new technique based on auto-fluorescence (AF) spectral imaging and Raman spectroscopy for fast intraoperative assessment of excision margins in BCS. A new wide-field AF imaging unit based on total internal reflection (TIR) was combined with a Raman spectroscopy microscope equipped with a 785 nm laser. The wavelength of the AF excitation was optimized to 365 nm in order to maximize the discrimination of adipose tissue. This approach allows for the non-adipose regions of tissue, which are at a higher risk of containing a tumor, to be targeted more efficiently by the Raman spectroscopy measurements. The integrated TIR-AF-Raman was tested on small tissue samples as well as fresh wide local excisions, delivering the analysis of the entire cruciate surface of BCS specimens (5.1 × 7.6 cm2) in less than 45 minutes and also providing information regarding the location of the tumor in the specimen. Full automation of the instrument and selection of a faster translation stage would allow for the measurement of BCS specimens within an intraoperative time scale (20 minutes). This study demonstrates that the TIR-AF Raman microscope represents a feasible step towards the development of a technique for intraoperative assessment of large WLE within intraoperative timescales.

Biophotonic technologies for assessment of breast tumor surgical margins-A review.

Breast conserving surgery (BCS) offering similar surgical outcomes as mastectomy while retaining breast cosmesis is becoming increasingly popular for the management of early stage breast cancers. However, its association with reoperation rates of 20% to 40% following incomplete tumor removal warrants the need for a fast and accurate intraoperative surgical margin assessment tool that offers cellular, structural and molecular information of the whole specimen surface to a clinically relevant depth. Biophotonic technologies are evolving to qualify as such an intraoperative tool for clinical assessment of breast cancer surgical margins at the microscopic and macroscopic scale. Herein, we review the current research in the application of biophotonic technologies such as photoacoustic imaging, Raman spectroscopy, multimodal multiphoton imaging, diffuse optical imaging and fluorescence imaging using medically approved dyes for breast cancer detection and/or tumor subtype differentiation toward intraoperative assessment of surgical margins in BCS specimens, and possible challenges in their route to clinical translation.

Optoacoustic characterization of breast conserving surgery specimens – A pilot study

In this pilot study, we tested an ultrasound-guided optoacoustic tomography (US-OT) two-dimensional (2D) array scanner to understand the optoacoustic patterns of excised breastconserving surgery (BCS) specimens. We imaged 14 BCS specimens containing malignant tumors at eight wavelengths spanning 700−1100 nm. Spectral unmixing across multiple wavelengths allowed for visualizing major intrinsic chromophores in the breast tissue including hemoglobin and lipid up to a depth of 7 mm. We identified less/no lipid signals within the tumor and intense deoxy-hemoglobin (Hb) signals on the rim of the tumor as unique characteristics of malignant tumors in comparison to no tumor region. We also observed continuous broad lipid signals as features of negative margins and compromised lipid signals interrupted by vasculature as features of positive margins. These differentiating patterns can form the basis of US-OT to be explored as an alternate, fast and efficient intraoperative method for evaluation of tumor resection margins.

Diagnostic Accuracy of Quantitative Micro-Elastography for Margin Assessment in Breast-Conserving Surgery.

Inadequate margins in breast-conserving surgery (BCS) are associated with an increased likelihood of local recurrence of breast cancer. Currently, approximately 20% of BCS patients require repeat surgery due to inadequate margins at the initial operation. Implementation of an accurate, intraoperative margin assessment tool may reduce this re-excision rate. This study determined, for the first time, the diagnostic accuracy of quantitative micro-elastography (QME), an optical coherence tomography (OCT)-based elastography technique that produces images of tissue microscale elasticity, for detecting tumor within 1 mm of the margins of BCS specimens. Simultaneous OCT and QME were performed on the margins of intact, freshly excised specimens from 83 patients undergoing BCS and on dissected specimens from 7 patients undergoing mastectomy. The resulting three-dimensional images (45 × 45 × 1 mm) were coregistered with postoperative histology to determine tissue types present in each scan. Data from 12 BCS patients and the 7 mastectomy patients served to build a set of images for reader training. One hundred and fifty-four subimages (10 × 10 × 1 mm) from the remaining 71 BCS patients were included in a blinded reader study, which resulted in 69.0% sensitivity and 79.0% specificity using OCT images, versus 92.9% sensitivity and 96.4% specificity using elasticity images. The quantitative nature of QME also facilitated development of an automated reader, which resulted in 100.0% sensitivity and 97.7% specificity. These results demonstrate high accuracy of QME for detecting tumor within 1 mm of the margin and the potential for this technique to improve outcomes in BCS. SIGNIFICANCE: An optical imaging technology probes breast tissue elasticity to provide accurate assessment of tumor margin involvement in breast-conserving surgery.

Three-dimensional mapping of the attenuation coefficient in optical coherence tomography to enhance breast tissue microarchitecture contrast.

Effective intraoperative tumor margin assessment is needed to reduce re-excision rates in breast-conserving surgery (BCS). Mapping the attenuation coefficient in optical coherence tomography (OCT) throughout a sample to create an image (attenuation imaging) is one promising approach. For the first time, three-dimensional OCT attenuation imaging of human breast tissue microarchitecture using a wide-field (up to ~45 × 45 × 3.5 mm) imaging system is demonstrated. Representative results from three mastectomy and one BCS specimen (from 31 specimens) are presented with co-registered postoperative histology. Attenuation imaging is shown to provide substantially improved contrast over OCT, delineating nuanced features within tumors (including necrosis and variations in tumor cell density and growth patterns) and benign features (such as sclerosing adenosis). Additionally, quantitative micro-elastography (QME) images presented alongside OCT and attenuation images show that these techniques provide complementary contrast, suggesting that multimodal imaging could increase tissue identification accuracy and potentially improve tumor margin assessment.

Preoperative breast MRI features associated with positive or close margins in breast-conserving surgery

PurposeTo determine preoperative magnetic resonance imaging (MRI) features associated with positive or close margins in patients with breast cancer who underwent breast-conserving surgery (BCS). Materials and methodsA retrospective review identified 249 patients with invasive ductal carcinoma (IDC) who underwent preoperative MRI and BCS as a primary procedure between 2008 and 2010. The MR images were reviewed for descriptions of findings with no new interpretations made. Margins were defined as positive (tumor touching the inked specimen margin), close (<2 mm tumor-free margin), or negative (≥2 mm tumor-free margin). Multivariate logistic regression analysis was performed to evaluate imaging and clinical factors predictive of positive or close margins. ResultsOf the 249 patients, 83 (33.3%) had positive or close margins and 166 (66.7%) had negative margins on the initial BCS specimen. Multivariate analysis showed that multifocal disease (odds ratio, 4.8; 95% CI, 1.9–12.2; p = 0.001), nonmass enhancement lesion (odds ratio, 3.0; 95% CI, 1.5–6.2, p = 0.003), greater background parenchymal enhancement (odds ratio, 2.5; 95% CI, 1.1–5.6; p = 0.023), larger lesion size (odds ratio, 1.3; 95% CI, 1.0–1.7, p = 0.032), and presence of ductal carcinoma in situ on needle biopsy (odds ratio, 2.4; 95% CI, 1.3–4.6; p = 0.008) were independent predictors of positive or close margins. ConclusionsMultifocal disease, nonmass enhancement lesion, or greater background parenchymal enhancement on preoperative breast MRI were significantly associated with positive or close margins. Identifying these MRI features before surgery can be helpful to reduce the reoperation rate in BCS.

Abstract P6-02-03: Interpretation schema for optical coherence tomography images in breast tissue

Abstract Purpose Optical coherence tomography (OCT) is an attractive technology for surgical imaging because it permits the real-time visualization of microscopic tissue morphology with a handheld probe without the need for exogeneous agents, tissue manipulation, ionizing radiation, or histological processing. While initial studies have shown that OCT is an effective margin-evaluation tool for breast conserving surgery (BCS), image interpretation and feature identification have not been directly studied. In this work, breast pathologies were assessed with a handheld OCT probe and the images were compared to histology. Methods Mastectomy and BCS specimens from 26 women were imaged with a handheld OCT probe, and histology slides from the same region were digitally photographed. OCT and histology images from the same region were paired by selecting the best structural matches. Because image characteristics in OCT are akin to those in ultrasound, descriptive OCT image feature terminology similar to that of ultrasound was developed. Each of these characteristics was used to select and describe OCT-histology image matches. Results In total, 2880 OCT images were acquired from 26 breast specimens, and 48 matching OCT-histology image pairs were identified. These matched image pairs illustrate tissue types including adipose tissue, dense fibrosis, fibroadipose tissue, blood vessels, regular and hyperplastic ducts and lobules, cysts, fibroadenoma, IDC, ILC, DCIS, calcifications, and biopsy cavities. Differentiation between pathologies was achieved by considering feature boundaries, interior appearance, posterior shadowing or enhancement, and overall morphologic patterns. Conclusions This is the first work to systematically catalog the features of breast OCT images. The results indicate that OCT can be used to identify important structures and distinguish between benign and malignant breast pathologies. Citation Format: Yemul KS, Zysk AM, Richardson AL, Tangella KV, Jacobs LK. Interpretation schema for optical coherence tomography images in breast tissue [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-02-03.

Interpretation of Optical Coherence Tomography Images for Breast Tissue Assessment.

Initial studies have shown that optical coherence tomography (OCT) is an effective margin-evaluation tool for breast-conserving surgery, but methods for the interpretation of breast OCT images have not been directly studied. In this work, breast pathologies were assessed with a handheld OCT probe. OCT images and corresponding histology were used to develop guidelines for the identification of breast tissue features in OCT images. Mastectomy and breast-conserving surgery specimens from 26 women were imaged with a handheld OCT probe. During standard pathology specimen dissection, representative 1-cm × 1-cm tissue regions were grossly identified, assessed with OCT, inked for orientation and image-matching purposes, and processed. Histology slides corresponding to the OCT image region were digitally photographed. OCT and histology images from the same region were paired by selecting the best structural matches. In total, 2880 OCT images were acquired from 26 breast specimens (from 26 patients) and 48 matching OCT-histology image pairs were identified. These matched image pairs illustrate tissue types including adipose tissue, dense fibrosis, fibroadipose tissue, blood vessels, regular and hyperplastic ducts and lobules, cysts, cyst, fibroadenoma, invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, calcifications, and biopsy cavities. Differentiation between pathologies was achieved by considering feature boundaries, interior appearance, posterior shadowing or enhancement, and overall morphologic patterns. This is the first work to systematically catalog the critical features of breast OCT images. The results indicate that OCT can be used to identify and distinguish between benign and malignant features in human breast tissue.

Micro-computed tomography enables rapid surgical margin assessment during breast conserving surgery (BCS): correlation of whole BCS micro-CT readings to final histopathology

BackgroundRoughly 23% of breast conserving surgery (BCS) patients undergo a second re-excision procedure due to pathologically positive surgical margins. We investigated the feasibility and potential value of micro-Computed Tomography (micro-CT) as a surgical margin guidance tool during BCS.MethodsA cohort of 32 BCS specimens was prospectively imaged with a pre-clinical micro-CT system upon arrival in the surgical pathology laboratory. Reconstructed micro-CT scans were evaluated retrospectively by an experienced breast radiologist, who provided binary determinations whether lesions extended to the specimen margin. These readings were then compared to the final pathological diagnosis and to 2D specimen radiography readings.ResultsOf the 32 specimens imaged, 28 had malignant and four had benign pathological diagnoses. Overall five (four malignant, one benign) of the 32 specimens had lesion tissue extending to the margin. For all 32 specimens, micro-CT reconstructions were calculated (< 4 min. acquisition + reconstruction time) and each specimen was volumetrically analyzed by a radiologist. Of the 28 malignant specimen readings, 18 matched the final pathological diagnosis [64%, 95 CI (47%–81%)], with a negative predictive value of 89% [95 CI (74%–96%)]. Micro-CT readings revealed changes in the tumor location and margin status as compared to single-projection radiography readings.ConclusionsMicro-CT scanning of BCS specimens enabled margin status assessment over the entirety of the surgical surface in a clinically relevant time frame, provided additional spatial information over single-projection radiography, and may be a potentially useful BCS guidance tool.

Effect of formalin fixation on volume of breast conserving surgery specimens

Effect of formalin fixation on volume of breast conserving surgery specimens

Abstract P4-03-05: Wide-field optical coherence tomography (WF-OCT) for near real-time, point-of-care assessment of margin status in breast-conserving surgery specimens: Results of a feasibility study at a high-volume single-centre

Abstract Wide-Field Optical Coherence Tomography (WF-OCT) is a non-destructive, non-contact light imaging modality capable of label-free visualization of the internal microscopic architecture of breast tissue specimens. Its unique combination of high-resolution imaging in near real-time with tissue penetration depths approaching 2-mm makes it a promising imaging modality for obtaining detailed surgical margin status in breast-conserving surgery (BCS) specimens. A prototype WF-OCT imaging platform developed by Perimeter Medical Imaging, Inc. (Toronto, Canada) has permitted fully-automated, dynamically-focused visualization of margin widths around the intact surfaces of freshly excised BCS specimens. Herein are reported the results of a feasibility study at a high-volume single-centre evaluating the routine use of WF-OCT for sampling of surgical margin status in BCS specimens at the point-of-care. Methods: Women with biopsy confirmed breast cancer and scheduled for primary BCS were recruited at Princess Margaret Cancer Centre (Toronto, Canada). Standard medical care was not altered. Freshly excised BCS specimens including all lumpectomy samples were imaged by WF-OCT immediately prior to standard histological processing. The system acquired dynamically-focused, hemispherical coverage over two contra-lateral surfaces of the intact BCS specimen within the time constraints of the cold ischemic time window. High-resolution (10 μm) images of the tissue surface down to a 1 to 2-mm depth were obtained. Blinded assessments were performed on image data sets by two clinical readers (surgeon and radiologist) trained on a validated and unrelated data set correlating OCT images with histology slides. The readers were first asked to independently assess margin status using only blinded pre- and intra-operative knowledge (without OCT). Upon completion, the readers were provided OCT images of all scanned surface and similarly asked to assess the margin status with the additional OCT information. These assessments were subsequently evaluated by a breast pathologist comparing the OCT images and corresponding histopathology sections. The added utility of WF-OCT imaging information for margin prediction was studied. Results: [Pending study completion in August 2015]. Through accurate correlation with the histopathologic gold standard, OCT demonstrated capability to differentiate tissue microstructures, including: distinctive patterns for adipose tissue, fibrous stroma, breast lobules and ducts, cysts and microcysts, as well as in-situ and invasive carcinomas. Implications: The fully-automated WF-OCT imaging platform can integrate conveniently into standard pathological processing workflows to provide comprehensive sampling of surgical margin status in BCS specimens at the point-of-care. Clinical readers from surgical and radiological backgrounds can be trained to competently interpret WF-OCT images of BCS specimens for accurate prediction margin status. The implementation of WF-OCT at the point-of-care for routine surgical margin assessments will be further explored in future clinical trials. Citation Format: Valic MS, Leong WL, Done SJ, Wilson BC, Kulkarni S, McCready DR, Niu CJ, Atachia Y, Munro EA, Rempel D. Wide-field optical coherence tomography (WF-OCT) for near real-time, point-of-care assessment of margin status in breast-conserving surgery specimens: Results of a feasibility study at a high-volume single-centre. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-03-05.

Abstract 218: The new and rapid technique of detecting breast cancer cells using new fluorescent probe ‘gGlu-HMRG’ and its clinical application

Abstract Method After spraying with gGlu-HMRG reagent to the samples, we took images within 5 minutes and analyzed the fluorescence intensity of them. Comparing the changes of fluorescence intensity and pathological evaluations, we examined how this fluorescent method could reflect the pathological status in resected breast tissues (n = 108 from 36 cases), margins of breast conserving surgery specimens (n = 7 from 5 cases) and axillary lymph nodes (n = 149 from 38 cases). Result 1. The sensitivity and specificity were 92% and 94% respectively for binary classification (normal / abnormal) of various breast tissues. 2. We could detect all malignant lesions in the surface of surgical margins of breast conserving surgery specimens. Additionally, we could detect large tumor-free lesions as fluorescent negative regions. 3. The sensitivity and specificity were 97% and 79% respectively for diagnosing metastatic and non-metastatic axillary lymph nodes. Discussion and conclusion It was well feasible to distinguish breast tumor tissues from normal surrounding tissues by this new method. Since it is simple and non-tissue-destructive, it could be readily adopted in the clinical setting. We anticipate that it will reduce costs and the burden on histopathology services in the intraoperative pathological diagnosis of breast conserving surgery and sentinel lymph node biopsy. This technical innovation enable us to visualize tumor cells in the body intraoperatively and evolve the cancer surgery that needs the complete resection of cancer cells. *1 Urano, Y. et al. Rapid cancer detection by topically spraying a γ-glutamyltranspeptidase-activated fluorescent probe. Sci. Trans. Med. 3, 110ra119 (2011). Citation Format: Yoshiaki Shinden, Hiroki Ueo, Taro Tobo, Ayako Ganachi, Hisateru Komatsu, Sho Nambara, Tomoko Saito, Masami Ueda, Hidenari Hirata, Shotaro Sakimura, Yuki Takano, Ryutaro Uchi, Tomohiro Iguchi, Hidetoshi Eguchi, Keishi Sugimachi, Yoko Kubota, Yuichiro Kai, Yuko Kijima, Shoji Natsugoe, Hiraki Ueo, Yasuteru Urano, Koshi Mimori. The new and rapid technique of detecting breast cancer cells using new fluorescent probe ‘gGlu-HMRG’ and its clinical application. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 218. doi:10.1158/1538-7445.AM2015-218

Abstract P1-16-05: Intra-operative imaging of surgical margins in breast conserving surgery using localized tissue dielectric response

Abstract INTRODUCTION: Breast conserving surgery (BCS) removes the tumor with a surrounding margin of normal breast tissue, and to reduce local recurrence clear margins are needed. Involved margins identified by pathology several days later require a second operation. Between 20-40% of BCS patients require re-excision. There is a clear unmet clinical need for effective and efficacious intra-operative, real time assessment of breast tumor margins. The handheld, battery operated TOUCH Imaging device displays spatially resolved images of margins based on tissue spectral dielectric response. This novel imaging device enables surgeons to assess in real-time the status of the excised tissue margins. AIM: To determine the efficacy and safety of TOUCH Imaging device as used by surgeons during BCS and its health economics. METHOD: The 1st study of the TOUCH Imaging device was run in the USA with freshly excised breast tissue as part of BCS. The study was run in the pathology lab to determine the efficacy and safety of using the device. The efficacy was determined by surgeons interpretation of device generated margin images compared with permanent section pathology. A follow up study in the UK is currently underway. Surgeons were trained to use the device in the operating room on freshly excised tissue. The imaging was performed after the surgery was completed with no subsequent intervention. The margins were scored as clear or positive and the localization of the abnormality was marked using special ink for specific pathology attention. In the learning phase 18 BCS cases were performed. The main study is being run in two phases and is currently underway. Phase-1 aimed to determine the accuracy of the device when used by individual surgeons in real time had been completed. Analysis is on the way, and phase-2 will start following the confirmation of device accuracy and will involve using the device to direct intra-operatively which margins require further excision. Phase 2 will provide insight to the potential health economics of using the TOUCH Imaging device. RESULTS: Data from the first study in the USA on 50 BCS specimens, imaging 214 distinct margins are shown in the table. The sensitivity of the device is high; the false negative rate low, the specificity and false positive rates are satisfactory. TOUCH Compared to Permanent Section Pathology Positive PathologyNegative PathologyPositive TOUCH66 ( 30.8%)50 (23.4%))Negative TOUCH5 ( 2.3%)93 ( 43.5%) % (95% CI)% (90% CI)Sensitivity92.96 (84.33, 97.67)92.96 ( 85.76, 97.18)Specificity65.03 (56.62, 72.81)65.03 (57.93, 71.66)False Positive Rate34.97 ( 27.19, 43.38)34.97 (28.34, 42.07)False negative Rate7.04 ( 2.33, 15.67)7.04 ( 2.82, 14.24) The training study in the UK on 18 BCS specimen results showed 50% True Positive, 39% True Negative, 11% False Positive, 6% False Negative rates. There were 5 cases (28%) of positive margins &amp;lt; 1 mm and the device images identified 4 with 1 case (6%) being missed. Results from the ongoing study will be presented. CONCLUSIONS: • The TOUCH Imaging device is safe and efficacious. • It is easy for surgeons to use in the operating room. • This device has the potential to reduce BCS re-operation rate. Citation Format: J Michael Dixon, Lorna Renshaw, Oliver Young, Dhananjay Kulkarni, Talha Saleem, Moshe Sarfaty, Ramaswamy Sreenivasam, Catherine Kusnick, Jeremy Thomas. Intra-operative imaging of surgical margins in breast conserving surgery using localized tissue dielectric response [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-16-05.

Use of an Intraoperative Ultrasonography-Guided Localization and Tissue Fixation Device Demonstrates Less Margin Positivity During Breast-Conserving Surgery for Invasive Breast Cancer Than Standard Preoperative Needle-Wire Localization: A Retrospective Comparative Analysis in a Consecutively Treated Case Series

PurposeTo retrospectively compare 2 methods of pre-resection, image-guided tumor localization—preoperative needle-wire localization (PNWL) and intraoperative ultrasonography-guided localization and tissue fixation (IUGLTF)—for patients with invasive breast cancer at the time of breast-conserving surgery (BCS). Patients and MethodsWe identified 118 cases in which image-guided localization was required for nonpalpable and questionably palpable tumors from a series of 204 consecutive invasive breast cancers treated by BCS. We defined a positive margin as tumor at the inked surface. We defined a close margin as tumor within 1 mm or less of the inked surface. ResultsOf those 118 cases requiring pre-resection, image-guided localization, 54 patients underwent PNWL and 64 underwent IUGLTF placement. A positive margin was identified in 6 of 54 (11.1%) undergoing PNWL compared with 1 of 64 (1.6%) undergoing IUGLTF (P = .046). A positive or close margin was identified in 9 of 54 (16.7%) undergoing PNWL compared with 3 of 64 (4.7%) undergoing IUGLTF (P = .032). The mean volume and mean weight of the BCS specimens were not different in the 2 groups. ConclusionBased on the finding of less margin positivity associated with the IUGLTF technique than the PNWL technique, we believe that the use of an IUGLTF device by surgeons during BCS could be highly advantageous in the surgical management of nonpalpable and questionably palpable invasive breast cancers.