Real-time intraoperative detection of breast cancer using near-infrared fluorescence imaging and Methylene Blue

Background

Despite recent developments in preoperative breast cancer imaging, intraoperative localization of tumor tissue can be challenging, resulting in tumor-positive resection margins during breast conserving surgery. Based on certain physicochemical similarities between Technetium(^99mTc)-sestamibi (MIBI), an SPECT radiodiagnostic with a sensitivity of 83–90% to detect breast cancer preoperatively, and the near-infrared (NIR) fluorophore Methylene Blue (MB), we hypothesized that MB might detect breast cancer intraoperatively using NIR fluorescence imaging.

Methods

Twenty-four patients with breast cancer, planned for surgical resection, were included. Patients were divided in 2 administration groups, which differed with respect to the timing of MB administration. N = 12 patients per group were administered 1.0 mg/kg MB intravenously either immediately or 3 h before surgery. The mini-FLARE imaging system was used to identify the NIR fluorescent signal during surgery and on post-resected specimens transferred to the pathology department. Results were confirmed by NIR fluorescence microscopy.

Results

20/24 (83%) of breast tumors (carcinoma in N = 21 and ductal carcinoma in situ in N = 3) were identified in the resected specimen using NIR fluorescence imaging. Patients with non-detectable tumors were significantly older. No significant relation to receptor status or tumor grade was seen. Overall tumor-to-background ratio (TBR) was 2.4 ± 0.8. There was no significant difference between TBR and background signal between administration groups. In 2/4 patients with positive resection margins, breast cancer tissue identified in the wound bed during surgery would have changed surgical management. Histology confirmed the concordance of fluorescence signal and tumor tissue.

Conclusions

This feasibility study demonstrated an overall breast cancer identification rate using MB of 83%, with real-time intraoperative guidance having the potential to alter patient management.     

Intraoperative Ultrasound and Oncoplastic Combined Approach: An Additional Tool for the Oncoplastic Surgeon to Obtain Tumor-Free Margins in Breast Conservative Surgery—A 2-Year Single-Center Prospective Study

BackgroundThe main goal of oncoplastic breast-conserving surgery (OBCS) is to obtain tumor-free resection margins after cancer excision with satisfactory cosmetic results. Positive tumor margins are associated with high rates of tumor recurrence requiring reoperation. The aim of this prospective clinical trial was to demonstrate the reliability of intraoperative ultrasound (IOUS) to obtain tumor-free resection margins in OBCS.Patients and MethodsBetween December 2016 and March 2018, data from 130 patients with by T1-2 breast cancer, either invasive or in situ, who underwent OBCS were prospectively collected. The oncoplastic surgeon performed IOUS in the operating theater to localize the lesion and mark its skin projection. Then specimens were examined to assess the presence of the lesion and margin adequacy. Definitive histologic reports were reviewed, with a focus on margin status.ResultsAll patients experienced oncoplastic approaches, and lesions were always found on the specimen at the histologic report. In 126 cases (97%), margins were considered adequate. In 17 cases (13%), IOUS showed positive margins, and resection was contextually enlarged. In 12 of these (9%), the pathologic report confirmed the need for enlarged resection. This study shows that IOUS-guided surgery can obtain a high percentage of tumor-free resection margins in OBCS without scheduling conflicts between radiology, nuclear, and surgery departments. Full cooperation between radiologists and oncoplastic surgeons is required to achieve high-standard oncologic and reconstructive outcomes.ConclusionIOUS represent an additional tool for the breast surgeon to improve margin-free management of neoplastic lesions, preventing reoperations in patients undergoing oncoplastic surgery.     

Near-infrared fluorescence sentinel lymph node mapping in breast cancer: a multicenter experience

Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has the potential to improve the sentinel lymph node (SLN) procedure by facilitating percutaneous and intraoperative identification of lymphatic channels and SLNs. Previous studies suggested that a dose of 0.62 mg (1.6 mL of 0.5 mM) ICG is optimal for SLN mapping in breast cancer. The aim of this study was to evaluate the diagnostic accuracy of NIR fluorescence for SLN mapping in breast cancer patients when used in conjunction with conventional techniques. Study subjects were 95 breast cancer patients planning to undergo SLN procedure at either the Dana-Farber/Harvard Cancer Center (Boston, MA, USA) or the Leiden University Medical Center (Leiden, the Netherlands) between July 2010 and January 2013. Subjects underwent the standard-of-care SLN procedure at each institution using ⁹⁹Technetium-colloid in all subjects and patent blue in 27 (28 %) of the subjects. NIR fluorescence-guided SLN detection was performed using the Mini-FLARE imaging system. SLN identification was successful in 94 of 95 subjects (99 %) using NIR fluorescence imaging or a combination of both NIR fluorescence imaging and radioactive guidance. In 2 of 95 subjects, radioactive guidance was necessary for initial in vivo identification of SLNs. In 1 of 95 subjects, NIR fluorescence was necessary for initial in vivo identification of SLNs. A total of 177 SLNs (mean 1.9, range 1–5) were resected: 100 % NIR fluorescent, 88 % radioactive, and 78 % (of 40 nodes) blue. In 2 of 95 subjects (2.1 %), SLNs-containing macrometastases were found only by NIR fluorescence, and in one patient this led to upstaging to N1. This study demonstrates the safe and accurate application of NIR fluorescence imaging for the identification of SLNs in breast cancer patients, but calls into question what technique should be used as the gold standard in future studies.     

An operational near-infrared fluorescence imaging system prototype for large animal surgery

Near-infrared (NIR) fluorescence imaging has the potential to revolutionize human cancer surgery by providing sensitive, specific, and real-time intraoperative visualization of normal and disease processes. We have previously introduced the concept of a low-cost, safe, and easy-to-use NIR fluorescence imaging system that permits the surgeon to "see" surgical anatomy and NIR fluorescence simultaneously, non-invasively, with high spatial resolution, in real-time, and without moving parts. In this study, we present an operational prototype designed specifically for use during large animal surgery. Such a system serves as a foundation for future clinical studies. We discuss technical considerations, and provide details of the implementation of subsystems related to excitation light, light collection, computer, and software. Using the prototype, and the clinically available NIR fluorophore indocyanine green, we demonstrate vascular imaging in 35 kg pigs. Cancer-specific applications of this imaging system include image-guided cancer resection with real-time assessment of surgical margins, image-guided sentinel lymph node mapping, intraoperative mapping of tumor and normal vasculature, image-guided avoidance of critical structures such as nerves, and intraoperative detection of occult metastases in the surgical field. Taken together, this study describes an optical imaging system engineered for eventual translation to the clinic.     

Molecular imaging with a fluorescent antibody targeting carbonic anhydrase IX can successfully detect hypoxic ductal carcinoma in situ of the breast

Ductal carcinoma in situ (DCIS) of the breast is difficult to remove completely during surgery as it is not palpable and can therefore require re-excision. Real-time visualization of DCIS using near-infrared fluorescent probes could help the surgeon during surgery as well as the pathologist post-operatively to distinguish the tumor from healthy tissue. As hypoxia-induced necrosis is a common phenomenon in DCIS, we investigated the molecular imaging of DCIS using a fluorescent antibody targeting a hypoxia marker, carbonic anhydrase IX (CAIX), in a preclinical mouse model. A monoclonal antibody against human CAIX was fluorescently labeled with the near-infrared dye IRDye800CW and characterized in vitro. An in vivo study was performed in SCID/Beige mice that were orthotopically transplanted with human breast cancer cells mimicking human DCIS (MCF10DCIS) and MCF10DCIS stably expressing CAIX. A clinically approved fluorescence imaging system was used to monitor probe uptake and to determine tumor-to-normal tissue ratios (TNR). Mean in vivo TNR of CAIX-transduced (CAIX+) tumors was 7.5 ± 0.5. Mean in vivo TNR of DCIS tumors with hypoxic areas reached a plateau level at 48 h after injection of 2.1 ± 0.1 (mean ± SEM) compared to 1.7 ± 0.1 in DCIS without hypoxic areas. Mean intra-operative TNR of DCIS tumors with necrotic regions was higher than that of DCIS tumors without necrotic regions 96 h after injection—2.9 ± 0.1 and 1.5 ± 0.1, respectively—while the TNR of CAIX+ tumors was 11.2 ± 1.0. Specific tumor uptake of MabCAIX-IRDye800CW was confirmed by a biodistribution assay, and immunofluorescence imaging on tumor sections showed specific uptake in hypoxic tumor regions, with higher contrast than conventional chromagen-based immunohistochemistry. Molecular fluorescence imaging with MabCAIX-IRDye800CW can be successfully used to detect hypoxic DCIS before and during surgery to facilitate radical resection. Furthermore, it allows for sensitive CAIX-specific immunofluorescence microscopy of tumor sections, thereby introducing the concept of molecular fluorescence pathology.     

Breast-Conserving Surgery after Neoadjuvant Chemotherapy Using a Three-Dimensional-Printed Surgical Guide Based on Supine Magnetic Resonance Imaging: A Case Report

Tumor localization in patients receiving neoadjuvant chemotherapy (NACT) is challenging because substantial therapeutic remission of the original tumor after NACT is often noted. Currently, there is no guidance device that allows for an accurate estimation of the resection range in breast-conserving surgery after NACT. To increase the accuracy of tumor resection, we used a 3-dimensional-printed breast surgical guide based on magnetic resonance imaging (MRI) in the supine position for a breast cancer patient who underwent breast-conserving surgery after NACT. Using this device, the breast tumor with apparent therapeutic changes after NACT on imaging was successfully removed with clear resection margins by identifying the original tumor site in the affected breast. Irrespective of whether the residual tumor area after NACT is well defined, it is possible to confirm and target the tumor area on pre-NACT MRI using this device.     

Outcomes in breast cancer patients relative to margin status after treatment with breast-conserving surgery and radiation therapy: the University of Pennsylvania experience

Purpose: To evaluate the significance of final microscopic resection margin status on treatment outcomes in women with early breast cancer who are treated with breast-conserving surgery and definitive breast irradiation.

Methods and Materials: An analysis was performed of 1021 consecutive women with clinical Stage I or II invasive carcinoma of the breast treated with breast-conserving surgery and definitive breast irradiation. Complete gross excision of tumor was performed in all cases, and an axillary staging procedure was performed to determine pathologic axillary lymph node status. The 1021 patients were divided into four groups based on the final microscopic margin from the tumor excision or from the re-excision if performed. These four groups were: (a) 518 patients with negative margins; (b) 124 patients with focally positive margins; (c) 96 patients with focally close margins (≤ 2 mm); and (d) 283 patients with unknown margins.

Results: Local failure was not significantly different in patients with negative, focally positive, focally close or unknown final pathologic margins of resection at 8 years (8% vs. 10% vs. 17% vs. 16%, respectively, p = 0.21). The 8-year outcome also was not different among the four groups for overall survival (86% vs. 83% vs. 88% vs. 81%, respectively, p = 0.13), cause-specific survival (89% vs. 86% vs. 88% vs. 83%, respectively, p = 0.14), no evidence of disease survival (81% vs. 73% vs. 86% vs. 77%, respectively, p = 0.09), and freedom from distant metastases (85% vs. 75% vs. 86% vs. 79%, respectively, p = 0.08).

Conclusion: These results demonstrate that selected patients with focally positive or focally close microscopic resection margins can be treated with breast-conserving surgery and definitive breast irradiation with 8-year local control rates and survival rates that are similar to those seen in breast-conservation patients with negative or unknown final resection margins.     

Proof-of-Concept Study of 3-D–Printed Mold–Guided Breast-Conserving Surgery in Breast Cancer Patients

Purpose

In this proof-of-concept study, we proposed 3-D–printed mold–guided breast-conserving surgery (BCS) in breast cancer patients.

Cancerous residue in breast-conserving surgery

Local tumor extension was studied using a continuous series of multiple blocks of mastectomy specimens to assess malignancy remaining after breast-conserving surgery for early-stage breast cancer. In this study, 183 cases were chosen, consisting of 6 noninvasive ductal carcinoma cases and 177 invasive ductal carcinoma cases. The histopathology in 59 (32%) of the 183 cases corresponded to that showing extensions of more than 2.6 cm from the tumor margin. These wide extensions were also seen in 17% of breast cancers with a tumor size of less than 2 cm. The incidence of wide extension was higher in younger patients with cases of noninvasive ductal carcinoma. Extension to the nipple-areola was seen in 14% of cases with a tumor size of less than 2 cm. Breast cancers with multicentric development accounted for 3% of those with a tumor size under 2 cm. These findings suggest that if lumpectomy is performed with a margin of 2 cm for tumors with a size of 2 cm or less, a cancerous residue would be found in the surgical margin of 15–20% of the cases. The actual incidence was 23% of cases after breast-conserving treatment in our study. On the basis of the data, breast-conserving treatment with only local resection of the primary lesion showed cancerous residue such as intraductal cancerous extension in about 20% of cases. Therefore, it was concluded that, as part of breast-conserving therapy of early-stage breast cancer, radiation therapy of the whole breast should be performed after surgery with clear margins to Control local recurrence. © 1993 Wiley-Liss, Inc.     

彩色多普勒超声引导下亚甲蓝边界定位法在乳腺癌保乳手术中的应用价值

目的探讨术前彩色多普勒超声引导下应用亚甲蓝定位肿瘤边界在乳腺癌保乳手术中的效果。方法收集2015年5月至2017年12月拟行保乳手术的乳腺癌患者120例,随机分为观察组和对照组各60例。观察组术前在彩色多普勒超声引导下行亚甲蓝定位,对照组采用传统手术方法。所有标本切除后进行病理检查,统计两组切缘情况。从精准性及微创性两方面比较两种方法的手术效果。结果观察组中,3例(5.0%)最大切缘>2 cm,57例(95.0%)最大切缘≤2 cm;对照组中,31例(51.7%)最大切缘>2 cm,29例(48.3%)最大切缘≤2 cm。两组比较差异有统计学意义(P=0.000)。观察组6例(10.0%)患者的手术标本镜下切缘阳性,54例(90.0%)切缘阴性;对照组15例(25.0%)镜下切缘阳性,45例(75.0%)切缘阴性。两组比较差异有统计学意义(P=0.031)。观察组和对照组分别有2例和3例在行二次扩切后切缘仍为阳性,改行乳腺全切手术。结论采用术前彩色多普勒超声引导下亚甲蓝定位肿瘤边界指导乳腺癌保乳手术的方法较常规方法在手术精准性及微创性两方面均有优势。     

Intraoperative detection and removal of microscopic residual sarcoma using wide‐field imaging

BACKGROUND:

The goal of limb‐sparing surgery for a soft tissue sarcoma of the extremity is to remove all malignant cells while preserving limb function. After initial surgery, microscopic residual disease in the tumor bed will cause a local recurrence in approximately 33% of patients with sarcoma. To help identify these patients, the authors developed an in vivo imaging system to investigate the suitability of molecular imaging for intraoperative visualization.

METHODS:

A primary mouse model of soft tissue sarcoma and a wide field‐of‐view imaging device were used to investigate a series of exogenously administered, near‐infrared (NIR) fluorescent probes activated by cathepsin proteases for real‐time intraoperative imaging.

RESULTS:

The authors demonstrated that exogenously administered cathepsin‐activated probes can be used for image‐guided surgery to identify microscopic residual NIR fluorescence in the tumor beds of mice. The presence of residual NIR fluorescence was correlated with microscopic residual sarcoma and local recurrence. The removal of residual NIR fluorescence improved local control.

CONCLUSIONS:

The authors concluded that their technique has the potential to be used for intraoperative image‐guided surgery to identify microscopic residual disease in patients with cancer. Cancer 2012. © 2012 American Cancer Society.     

Radioguided Intraoperative Margins Evaluation (RIME): Preliminary results of a new technique to aid breast cancer resection

Aims

Women undergoing breast-conserving surgery for cancer can present residual disease. We have developed a technique called Radioguided Intraoperative Margins Evaluation (RIME) that uses a radiopharmaceutical to distinguish normal and cancer tissues. The aim of this study was to assess whether RIME is a feasible technique, and if it could help in breast cancer resection with free margins, minimizing residual disease.

Methods

Twenty-three breast cancer patients programmed for mastectomy were selected. Before surgery, the patients were submitted to scintimammography with ^99mTc-sestamibi to estimate the optimal time to begin radioguided surgery. Twenty patients were submitted to magnetic resonance imaging (MRI), to evaluate skin, deep fascia and to detect other tumor foci. At the beginning of the surgery, the same dose of ^99mTc-sestamibi was intravenously injected into patients. Tumor resection was performed under guidance of a gamma-probe, characterizing the RIME technique. Finally, modified radical mastectomy was performed. Tumor and residual breast were histopathologically examined.

Results

The RIME technique was successfully performed in all patients. The principal tumor was removed by this technique and provided 82.6% of histologically free margins (mean margins, 4.8 mm). Additionally, 47.8% of patients were without residual disease. The mean size of residual carcinoma was 3.67 mm and generally located near the tumor bed (<1.5 cm). There was no significant association between presence of residual disease and tumor size or margin status.

Conclusion

RIME is a feasible technique that could help tumor resection with free margins; however, it seems to be limited for small carcinoma foci.     

Oncoplastic approaches to partial mastectomy: an overview of volume-displacement techniques

Oncoplastic surgery refers to several surgical techniques by which segments of malignant breast tissue are removed to achieve wide surgical margins while the remaining glandular tissue is transposed to achieve the best possible cosmetic outcome. We summarise the general approach to oncoplastic lumpectomy for surgeons who recognise the limitations of standard lumpectomy for large breast cancers, and review different cancer distributions in the breast and their associated imaging characteristics. Full-thickness fibroglandular excision of the mass and surrounding breast tissue allows resection with wide surgical margins. Subsequent breast-flap advancement (mastopexy) results in closure of the resulting surgical defect with good or excellent cosmetic closure. These approaches can improve both the aesthetic outcome of breast cancer resections and the likelihood of surgeons obtaining wide surgical margins in preparation for breast-conserving radiotherapy. Advanced volume-displacement techniques, which are based on the key principles of breast reductive surgery, can greatly increase the options for breast conservation in complex cancer cases.     

A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation

The determination of brain tumor margins both during the presurgical planning phase and during surgical resection has long been a challenging task in the therapy of brain tumor patients. Using a model of gliosarcoma with stably green fluorescence protein-expressing 9L glioma cells, we explored a multimodal (near-infrared fluorescent and magnetic) nanoparticle as a preoperative magnetic resonance imaging contrast agent and intraoperative optical probe. Key features of nanoparticle metabolism, namely intracellular sequestration by microglia and the combined optical and magnetic properties of the probe, allowed delineation of brain tumors both by preoperative magnetic resonance imaging and by intraoperative optical imaging. This prototypical multimodal nanoparticle has unique properties that may allow radiologists and neurosurgeons to see the same probe in the same cells and may offer a new approach for obtaining tumor margins.     

Preclinical evaluation of near‐infrared (NIR) fluorescently labeled cetuximab as a potential tool for fluorescence‐guided surgery

The high rate of recurrence in patients with pancreatic ductal adenocarcinoma (PDAC) could be reduced by supporting the surgeons in discriminating healthy from diseased tissues with intraoperative fluorescence‐guidance. Here, we studied the suitability of Cetuximab, a therapeutic monoclonal antibody targeting the human epidermal growth factor receptor (EGFR), near‐infrared (NIR) fluorescently labeled as a new tool for fluorescence‐guided surgery. Distribution and binding of systemically injected Cetuximab Alexa Fluor 647 conjugate (Cetux‐Alexa‐647) and the co‐injected control human IgG Alexa Fluor 750 conjugate (hIgG‐Alexa‐750) was studied over 48 h by NIR fluorescence imaging in mice bearing human orthotopic AsPC‐1 and MIA PaCa‐2 PDAC tumors. Cetux‐Alexa‐647, but not the control hIgG‐Alexa‐750 fluorescence, was specifically detected in vivo in both primary pancreatic tumors with maximum fluorescence intensities at 24 h, and in metastases of AsPC‐1 tumors as small as 1 mm. Lifetime analysis and NIR fluorescence microscopy of tumor sections confirmed the binding specificity of Cetux‐Alexa‐647 to PDAC cells. Comparable results were obtained with Cetuximab conjugated to Alexa Fluor 750 dye (Cetux‐Alexa‐750). Fluorescence‐guided dissection, performed 24 h after injection of Cetuximab conjugated to IRDye 800CW (Cetux‐800CW), enabled a real‐time delineation of AsPC‐1 tumor margins, and small metastases. Odyssey scans revealed that only the vital part of the tumor, but not the necrotic part was stained with Cetux‐800CW. NIR fluorescently labeled Cetuximab may be a promising tool that can be applied for fluorescence‐guided surgery to visualize tumor margins and metastatic sites in order to allow a precise surgical resection.     

Feasibility of intraoperative radiation therapy for early breast cancer in Japan: a single-center pilot study and literature review

Background

Intraoperative radiation therapy (IORT) is under evaluation in breast-conserving surgery because the feasibility of the IORT procedure including transportation of the patient under general anesthesia is not well established. Thus, this prospective single-center study aimed to test the feasibility of IORT at a single dose of 21 Gy in Japanese breast cancer patients.

Methods

The primary endpoint was early toxicity; the secondary endpoint was late toxicity. Patients with histologically or cytologically proven primary early breast cancer were eligible. Inclusion criteria were as follows: (1) T < 2.5 cm; (2) desire for breast-conserving surgery; (3) age >50 years; (4) surgical margin >1 cm; (5) intraoperative pathologically free margins; and (6) sentinel node negative. Exclusion criteria were (1) contraindications to radiation therapy; (2) past radiation therapy for the same breast or chest; (3) extensive intraductal component; and (4) a tumor located in the axillary tail of the breast. All patients gave written informed consent. Partial resection was performed with at least a margin of 1 cm around the tumor. The patient was transported from the surgical suite to the radiation room. Radiation (Clinac^® 21EX, Varian Medical Systems, Inc.) at 21 Gy was delivered directly to the mammary gland. Toxicity was evaluated with the Common Terminology Criteria for Adverse Events V4.0.

Results

Five patients were enrolled in this pilot study and received 21 Gy. Follow-up ranged from 7.8 to 11.0 months (median 10.2). Intraoperative transportation to the radiation room during the surgical procedure under general anesthesia was performed safely in all patients. Treatment-related toxicities within 3 months were deep connective tissue fibrosis (grade 1, n = 3) and pain (grade 1, n = 3). There was no case of wound infection, wound dehiscence, or soft tissue necrosis. Overall, there was no severe adverse event.

Conclusions

The procedure was tolerated very well in this first group of Japanese female patients treated with IORT, as was the case with European women. A longer follow-up is needed for the evaluation of any potential late side effects or recurrences. A phase II study is now being conducted for the next group of patients (UMIN000003578).     

Breast-conserving surgery and selective adjuvant radiation therapy for stage I and II breast cancer.

In this report we update our experience with selective adjuvant radiotherapy (XRT) following breast-conserving surgery (BCS) for early breast cancer. Of 150 evaluable private breast cancer patients treated by BCS since 1975, 83 were offered the option of foregoing adjuvant XRT because their primary disease met four pathological criteria: primary tumor less than or equal to 2.5 cm; adequate resection margins; no intramammary vascular, lymphatic, or perineural invasion by tumor; and minimal or no associated in situ cancer. Of the 67 patients who chose not to have XRT, four have developed local (breast) tumour recurrence at 80 months' median follow-up (5-year local recurrence rate 6.4% by Kaplan-Meier analysis). These findings are discussed in light of other series in which patients were carefully selected for BCS without XRT, and the observations of large randomized trials and unselected series of patients. We conclude that adjuvant XRT is not always necessary following BCS. The most valuable contribution of XRT to breast-conserving therapy is that a much larger proportion of breast cancer patients can be considered for conservative locoregional surgery than would otherwise be reasonable.     

Local control by breast-conserving surgery with nipple resection

Local control was compared between patients who had undergone breast-conserving therapy with and without nipple resection. We explored whether there was any difference in local control between the two treatment methods for patients with early breast cancer. A total of 333 women with breast cancer, who had undergone breast-conserving therapy between 1991 and 2002, were included in this study. Surgery consisted of a wide local excision of the primary tumor with a 2-cm free margin as the minimum distance. When the tumor was located under the nipple or close to the nipple, breast-conserving surgery with nipple resection was selected. A total of 320 patients received breast-conserving surgery without nipple resection and radiation therapy (BCT) and 13 patients breast-conserving surgery with nipple resection and radiation therapy (BCT-NR). There were no significant differences in age, tumor size, nodal status, clinical stage, ER status, histological type or surgical margin status between the two groups. The surgical margin was positive in 55 (17.2%) out of 320 patients in the BCT group and in one (7.7%) out of 13 patients in the BCT-NR group. There was no significant difference in the breast-free survival between the two groups. In conclusion, breast-conserving surgery with nipple resection and radiation therapy may be the treatment of choice for early breast cancer patients with the tumor located under the nipple or very close to the areola.     

Review: Breast-conserving treatment: Controversies and consensus

Although breast-conserving therapy (BCT) is an accepted alternative for the treatment of breast cancer, numerous controversies surround the selection criteria and the treatment details. A review of the literature revealed that patient selection is of critical importance. However, there is disagreement over the relative importance of some of the criteria for patient selection. A wide excision is preferable to a less complete excision (tumorectomy) or a more radical excision (quadrantectomy). Accurate assessment of surgical margins is important. The risk of local recurrence may be diminished if a re-excision is performed to obtain tumor-free margins. However, the suitability and practicality of the techniques used to assess the resection margins have been questioned. Radiotherapy is an integral part of BCT. Surgery alone remains an investigational approach. Axillary dissection remains a reliable method of assessing nodal status and treating regional disease. © 1996 Wiley-Liss, Inc.     

Accuracy of ultrasound-guided breast-conserving surgery in the determination of adequate surgical margins

The goal of this study was to assess the size of the ultrasound-measured margin associated with an adequate surgical margin during breast-conserving surgery (BCS). The study was designed as a prospective cohort study. Patients with primary invasive breast cancer undergoing BCS were included. The ultrasound-measured surgical margins were compared with the pathological margins. 147 patients were eligible for analysis. 21 (14.3 %) patients had close or positive resection margins and 13 (8.8 %) underwent a second operation. Small excision volume, multifocality, postmenopausal status, high grade tumor-associated intraductal component, and invasion of lymph vessels and lymph nodes were associated with increased risk of positive excision margins. In the study cohort, 882 Ultrasonography (US) margins were measured and a good correlation to the pathological margins was observed. Overestimation of the US-measured margins relative to the pathological margins was increased with younger age, premenopausal status, and intraductal component. The estimated positive and negative predictive values, sensitivity and specificity were 81.0, 96.2, 48.4, and 99.1 %, respectively. We found that a sonographically estimated margin of ≥4 mm was associated with an adequate pathological margin of ≥1 mm in 100 % of tumors that did not have a high grade intraductal component. However, this was not applicable for tumor-associated high grade intraductal component where a US margin of 14 mm was associated with clear pathological margins in 100 % of cases. Intraoperative ultrasonography is a safe and feasible method to obtain clear surgical margins by BCS.