Breast Cancer Surgery

For patients with early stage breast carcinoma, the ability to achieve complete tumor resection with breast conservation therapy (BCT) remains imperfect despite advances in surgical, pathologic and imaging techniques. The goal of BCT is to remove a patient’s breast cancer with negative surgical margins while achieving a cosmetically acceptable result. The presence or absences of malignant cells on the edge or close to the edge of a lumpectomy specimen is called the surgical margin, and it serves as a marker of residual disease in the breast. 

Currently re-excision rates to achieve clear margins in the United States range between 15-40%. The negative impacts of re-excision include delays in the completion of adjuvant therapies, increased infection rates, increased health care costs, increased mastectomy rates and negative psychological impacts on the patients. The principle of clear margins is imperative since presence of positive margins is associated with increased loco-regional recurrence, and the failure to maintain local control is associated with a decrease in long-term breast cancer specific survival.

In AMIGO, we are studying the use of novel intraoperative mass spectrometry and magnetic resonance imaging (MRI) as methods to detect residual cancer in the hopes of reducing the rates of re-excision for breast cancer patients. AMIGO enables surgeons to incorporate existing and novel imaging technologies including intraoperative MRI and mass spectrometry, to efficiently and precisely guide treatment — before, during, and after surgery — without the patient or medical team ever leaving the operating room.

It is our hypothesis that utilizing intra-procedural mass spectrometry and breast MRI will allow for improved visualization and characterization of tumors and breast-tumor biomarkers that will be effective in assessing tumor margins and areas of residual disease. Ultimately we hope that implementation of these advanced imaging technologies during breast surgery will allow surgeons to achieve more precise excisions and successful first-surgery clear margin rates, ultimately hopefully avoiding the need for further operations.

Mehra Golshan MD FACS
Distinguished Chair in Surgical Oncology

If you are a patient and would like to learn about the offerings of AMIGO, please visit the BWH AMIGO page.

Review the clinical trial here.

Study Contact:
Stephen (Dan) DeSantis 

 

Breast Conserving Surgery Workflow in AMIGO

Diagnostic Imaging. 3D volume rendered MIP images showing the main mass and satellites. The presence of satellite tumors poses a difficulty in ensuring complete tumor resection.
Diagnostic Imaging. Color overlay by a Computer-aided software over the rapidly enhancing mass (invasive ductal cancer).
initial breast MRI
Preoperative. In the AMIGO operating room the patient is placed under general anesthesia. A contrast enhanced 3D MRI then is performed while the patient is in supine position. In this case, an MRI is performed before and after contrast injection, delineating the tumor boundaries in relationship to fixed landmarks. Upon completion of the preprocedural MRI, the MRI machine leaves the room and the images are evaluated.
breast intraop prep
Intraoperative. The woman's breast is then prepared and draped in standard sterile fashion. Through palpation, the tumor is identified and surgical incisions marked.
breast intraop openingIntraoperative. As part of the lymph node evaluation procedure, marcaine and 2cc of 1% methylene blue diluted with 3cc of saline are injected. The breast is then massaged to distribute the methylene blue to the lymphatics before beginning the incision between the pectorals and latissimus muscles, below the marked line.
breast resectionIntraoperative. The methylene blue renders the sentinel lymph nodes detectable. The lymph nodes sent to pathology for evaluation. After the lumpectomy is performed, the resected tumor is sent to pathology.
breast temp closingIntraoperative. The lumpectomy cavity is temporarily closed with a nylon suture.
breast saline injectionIntraoperative. Before completing closure, the lumpectomy cavity is filled with exact volume of resected tumor and a 1cm margin. Finally, the incision is covered.
Breast PostPostoperative. Immediately post-surgery, a second MRI scan (again, with contrast) is obtained while the patient is on the operating table. The purpose of this MRI is to examine the saline filled cavity to identify areas of enhancement that may be suspicious for residual carcinoma. Following the imaging, the MRI scanner leaves the operating room. A radiologist compares the resected tumor to an MRI of the second breast for possible areas of residual tissue. On the left side, the preoperative images are shown; on the right side, the new images are displayed.
Postoperative. Post-surgical post-contrast MRI showing the saline cavity filled with saline.
Postoperative. 3D volume rendered image showing the surgical cavity.
breast reexision
Re-excision. If suspicious remaining tissue is detected on the MRI images, the breast is reopened and the residual tumor removed.

Media Coverage

  1. Amigo Innovative Breast Cancer Surgery. Nexstar Broadcasting, Inc.- August 14, 2013
  2. New Operating Room at BWH Helps Breast Cancer Patients Avoid Multiple Surgeries. CBS Boston - December 7, 2012
  3. Reducing Repeat Surgeries After Breast Cancer. BWH Health Hub – January, 2013
  4. The Fine Line Between Breast Cancer and Normal Tissue. MedicalPress – September, 2014

Select Publications

Mallory MA, Sagara Y, Aydogan F, Desantis S, Jayender J, Caragacianu D, Gombos E, Vosburgh KG, Jolesz FA, Golshan M. Feasibility of Intraoperative Breast MRI and the Role of Prone Versus Supine Positioning in Surgical Planning for Breast-Conserving Surgery. Breast J. 2017;23 (6) :713-7.Abstract
We assessed the feasibility of supine intraoperative MRI (iMRI) during breast-conserving surgery (BCS), enrolling 15 patients in our phase I trial between 2012 and 2014. Patients received diagnostic prone MRI, BCS, pre-excisional supine iMRI, and postexcisional supine iMRI. Feasibility was assessed based on safety, sterility, duration, and image-quality. Twelve patients completed the study; mean duration = 114 minutes; all images were adequate; no complications, safety, or sterility issues were encountered. Substantial tumor-associated changes occurred (mean displacement = 67.7 mm, prone-supine metric, n = 7). We have demonstrated iMRI feasibility for BCS and have identified potential limitations of prone breast MRI that may impact surgical planning.
Gombos EC, Jayender J, Richman DM, Caragacianu DL, Mallory MA, Jolesz FA, Golshan M. Intraoperative Supine Breast MR Imaging to Quantify Tumor Deformation and Detection of Residual Breast Cancer: Preliminary Results. Radiology. 2016;281 (3) :720-9.Abstract
Purpose To use intraoperative supine magnetic resonance (MR) imaging to quantify breast tumor deformation and displacement secondary to the change in patient positioning from imaging (prone) to surgery (supine) and to evaluate residual tumor immediately after breast-conserving surgery (BCS). Materials and Methods Fifteen women gave informed written consent to participate in this prospective HIPAA-compliant, institutional review board-approved study between April 2012 and November 2014. Twelve patients underwent lumpectomy and postsurgical intraoperative supine MR imaging. Six of 12 patients underwent both pre- and postsurgical supine MR imaging. Geometric, structural, and heterogeneity metrics of the cancer and distances of the tumor from the nipple, chest wall, and skin were computed. Mean and standard deviations of the changes in volume, surface area, compactness, spherical disproportion, sphericity, and distances from key landmarks were computed from tumor models. Imaging duration was recorded. Results The mean differences in tumor deformation metrics between prone and supine imaging were as follows: volume, 23.8% (range, -30% to 103.95%); surface area, 6.5% (range, -13.24% to 63%); compactness, 16.2% (range, -23% to 47.3%); sphericity, 6.8% (range, -9.10% to 20.78%); and decrease in spherical disproportion, -11.3% (range, -60.81% to 76.95%). All tumors were closer to the chest wall on supine images than on prone images. No evidence of residual tumor was seen on MR images obtained after the procedures. Mean duration of pre- and postoperative supine MR imaging was 25 minutes (range, 18.4-31.6 minutes) and 19 minutes (range, 15.1-22.9 minutes), respectively. Conclusion Intraoperative supine breast MR imaging, when performed in conjunction with standard prone breast MR imaging, enables quantification of breast tumor deformation and displacement secondary to changes in patient positioning from standard imaging (prone) to surgery (supine) and may help clinicians evaluate for residual tumor immediately after BCS. (©) RSNA, 2016 Online supplemental material is available for this article.
Gombos EC, Jagadeesan J, Richman DM, Kacher DF. Magnetic Resonance Imaging-Guided Breast Interventions: Role in Biopsy Targeting and Lumpectomies. Magn Reson Imaging Clin N Am. 2015;23 (4) :547-61.Abstract
Contrast-enhanced breast MR imaging is increasingly being used to diagnose breast cancer and to perform biopsy procedures. The American Cancer Society has advised women at high risk for breast cancer to have breast MR imaging screening as an adjunct to screening mammography. This article places special emphasis on biopsy and operative planning involving MR imaging and reviews use of breast MR imaging in monitoring response to neoadjuvant chemotherapy. Described are peer-reviewed data on currently accepted MR imaging-guided procedures for addressing benign and malignant breast diseases, including intraoperative imaging.
Calligaris D, Caragacianu D, Liu X, Norton I, Thompson CJ, Richardson AL, Golshan M, Easterling ML, Santagata S, Dillon DA, et al. Application of Desorption Electrospray Ionization Mass Spectrometry Imaging in Breast Cancer Margin Analysis. Proc Natl Acad Sci U S A. 2014;111 (42) :15184-9.Abstract

Distinguishing tumor from normal glandular breast tissue is an important step in breast-conserving surgery. Because this distinction can be challenging in the operative setting, up to 40% of patients require an additional operation when traditional approaches are used. Here, we present a proof-of-concept study to determine the feasibility of using desorption electrospray ionization mass spectrometry imaging (DESI-MSI) for identifying and differentiating tumor from normal breast tissue. We show that tumor margins can be identified using the spatial distributions and varying intensities of different lipids. Several fatty acids, including oleic acid, were more abundant in the cancerous tissue than in normal tissues. The cancer margins delineated by the molecular images from DESI-MSI were consistent with those margins obtained from histological staining. Our findings prove the feasibility of classifying cancerous and normal breast tissues using ambient ionization MSI. The results suggest that an MS-based method could be developed for the rapid intraoperative detection of residual cancer tissue during breast-conserving surgery.

Golshan M, Sagara Y, Wexelman B, Aydogan F, Desantis S, Elise Min H, Vosburgh K, Jagadeesan J, Caragacianu D, Gombos E, et al. Pilot Study to Evaluate Feasibility of Image-Guided Breast-Conserving Therapy in the Advanced Multimodal Image-Guided Operating (AMIGO) Suite. Ann Surg Oncol. 2014;21 (10) :3356-7.Abstract

BACKGROUND: The rate of reexcision in breast-conserving surgery remains high, leading to delay in initiation of adjuvant therapy, increased cost, increased complications, and negative psychological impact to the patient.1 (-) 3 We initiated a phase 1 clinical trial to determine the feasibility of the use of intraoperative magnetic resonance imaging (MRI) to assess margins in the advanced multimodal image-guided operating (AMIGO) suite. METHODS: All patients received contrast-enhanced three-dimensional MRI while under general anesthesia in the supine position, followed by standard BCT with or without wire guidance and sentinel node biopsy. Additional margin reexcision was performed of suspicious margins and correlated to final pathology (Fig. 1). Feasibility was assessed via two components: demonstration of safety and sterility and acceptable duration of the operation and imaging; and adequacy of intraoperative MRI imaging for interpretation and its comparison to final pathology. Fig. 1 Schema of AMIGO trial RESULTS: Eight patients (mean age 48.5 years), 4 with stage I breast cancer and 4 with stage II breast cancer, were recruited. All patients underwent successful BCT in the AMIGO suite with no AMIGO-specific complications or break in sterility during surgery. The mean operative time was 113 min (range 93-146 min). CONCLUSIONS: Our experience with AMIGO suggests that it is feasible to use intraoperative MRI imaging to evaluate margin assessment in real time. Further research is required to identify modalities that will lead to a reduction in reexcision in breast cancer therapy.

Jayender J, Chikarmane S, Jolesz FA, Gombos E. Automatic Segmentation of Invasive Breast Carcinomas from Dynamic Contrast-Enhanced MRi using Time Series Analysis. J Magn Reson Imaging. 2014;40 (2) :467-75.Abstract

PURPOSE: To accurately segment invasive ductal carcinomas (IDCs) from dynamic contrast-enhanced MRI (DCE-MRI) using time series analysis based on linear dynamic system (LDS) modeling. MATERIALS AND METHODS: Quantitative segmentation methods based on black-box modeling and pharmacokinetic modeling are highly dependent on imaging pulse sequence, timing of bolus injection, arterial input function, imaging noise, and fitting algorithms. We modeled the underlying dynamics of the tumor by an LDS and used the system parameters to segment the carcinoma on the DCE-MRI. Twenty-four patients with biopsy-proven IDCs were analyzed. The lesions segmented by the algorithm were compared with an expert radiologist's segmentation and the output of a commercial software, CADstream. The results are quantified in terms of the accuracy and sensitivity of detecting the lesion and the amount of overlap, measured in terms of the Dice similarity coefficient (DSC). RESULTS: The segmentation algorithm detected the tumor with 90% accuracy and 100% sensitivity when compared with the radiologist's segmentation and 82.1% accuracy and 100% sensitivity when compared with the CADstream output. The overlap of the algorithm output with the radiologist's segmentation and CADstream output, computed in terms of the DSC was 0.77 and 0.72, respectively. The algorithm also shows robust stability to imaging noise. Simulated imaging noise with zero mean and standard deviation equal to 25% of the base signal intensity was added to the DCE-MRI series. The amount of overlap between the tumor maps generated by the LDS-based algorithm from the noisy and original DCE-MRI was DSC = 0.95. CONCLUSION: The time-series analysis based segmentation algorithm provides high accuracy and sensitivity in delineating the regions of enhanced perfusion corresponding to tumor from DCE-MRI.