Breast Cancer Surgery Procedure Publications

2017
Stephanie M Wong, Rachel A Freedman, Yasuaki Sagara, Fatih Aydogan, William T Barry, and Mehra Golshan. 3/2017. “Growing Use of Contralateral Prophylactic Mastectomy Despite no Improvement in Long-term Survival for Invasive Breast Cancer.” Ann Surg, 265, 3, Pp. 581-9.Abstract
OBJECTIVE: To update and examine national temporal trends in contralateral prophylactic mastectomy (CPM) and determine whether survival differed for invasive breast cancer patients based on hormone receptor (HR) status and age. METHODS: We identified women diagnosed with unilateral stage I to III breast cancer between 1998 and 2012 within the Surveillance, Epidemiology, and End Results registry. We compared characteristics and temporal trends between patients undergoing breast-conserving surgery, unilateral mastectomy, and CPM. We then performed Cox proportional-hazards regression to examine breast cancer-specific survival (BCSS) and overall survival (OS) in women diagnosed between 1998 and 2007, who underwent breast-conserving surgery with radiation (breast-conserving therapy), unilateral mastectomy, or CPM, with subsequent subgroup analysis stratifying by age and HR status. RESULTS: Of 496,488 women diagnosed with unilateral invasive breast cancer, 59.6% underwent breast-conserving surgery, 33.4% underwent unilateral mastectomy, and 7.0% underwent CPM. Overall, the proportion of women undergoing CPM increased from 3.9% in 2002 to 12.7% in 2012 (P < 0.001). Reconstructive surgery was performed in 48.3% of CPM patients compared with only 16.0% of unilateral mastectomy patients, with rates of reconstruction with CPM rising from 35.3% in 2002 to 55.4% in 2012 (P < 0.001). When compared with breast-conserving therapy, we found no significant improvement in BCSS or OS for women undergoing CPM (BCSS: HR 1.08, 95% confidence interval 1.01-1.16; OS: HR 1.08, 95% confidence interval 1.03-1.14), regardless of HR status or age. CONCLUSIONS: The use of CPM more than tripled during the study period despite evidence suggesting no survival benefit over breast conservation. Further examination on how to optimally counsel women about surgical options is warranted.
Melissa A Mallory, Yasuaki Sagara, Fatih Aydogan, Stephen Desantis, Jagadeesan Jayender, Diana Caragacianu, Eva Gombos, Kirby G. Vosburgh, Ferenc A Jolesz, and Mehra Golshan. 2017. “Feasibility of Intraoperative Breast MRI and the Role of Prone Versus Supine Positioning in Surgical Planning for Breast-Conserving Surgery.” Breast J, 23, 6, Pp. 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.
Shinn-Huey S Chou, Eva C Gombos, Sona A Chikarmane, Catherine S Giess, and Jagadeesan Jayender. 2017. “Computer-Aided Heterogeneity Analysis in Breast MR Imaging Assessment of Ductal Carcinoma In Situ: Correlating Histologic Grade and Receptor Status.” J Magn Reson Imaging, 46, 6, Pp. 1748-59.Abstract

PURPOSE: To identify breast MR imaging biomarkers to predict histologic grade and receptor status of ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: Informed consent was waived in this Health Insurance Portability and Accountability Act-compliant Institutional Review Board-approved study. Case inclusion was conducted from 7332 consecutive breast MR studies from January 1, 2009, to December 31, 2012. Excluding studies with benign diagnoses, studies without visible abnormal enhancement, and pathology containing invasive disease yielded 55 MR-imaged pathology-proven DCIS seen on 54 studies. Twenty-eight studies (52%) were performed at 1.5 Tesla (T); 26 (48%) at 3T. Regions-of-interest representing DCIS were segmented for precontrast, first and fourth postcontrast, and subtracted first and fourth postcontrast images on the open-source three-dimensional (3D) Slicer software. Fifty-seven metrics of each DCIS were obtained, including distribution statistics, shape, morphology, Renyi dimensions, geometrical measure, and texture, using the 3D Slicer HeterogeneityCAD module. Statistical correlation of heterogeneity metrics with DCIS grade and receptor status was performed using univariate Mann-Whitney test. RESULTS: Twenty-four of the 55 DCIS (44%) were high nuclear grade (HNG); 44 (80%) were estrogen receptor (ER) positive. Human epidermal growth factor receptor-2 (HER2) was amplified in 10/55 (18%), nonamplified in 34/55 (62%), unknown/equivocal in 8/55 (15%). Surface area-to-volume ratio showed significant difference (P < 0.05) between HNG and non-HNG DCIS. No metric differentiated ER status (0.113 < p ≤ 1.000). Seventeen metrics showed significant differences between HER2-positive and HER2-negative DCIS (0.016 < P < 0.050). CONCLUSION: Quantitative heterogeneity analysis of DCIS suggests the presence of MR imaging biomarkers in classifying DCIS grade and HER2 status. Validation with larger samples and prospective studies is needed to translate these results into clinical applications. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017.

2016
Eva C Gombos, Jagadeesan Jayender, Danielle M Richman, Diana L Caragacianu, Melissa A Mallory, Ferenc A Jolesz, and Mehra Golshan. 2016. “Intraoperative Supine Breast MR Imaging to Quantify Tumor Deformation and Detection of Residual Breast Cancer: Preliminary Results.” Radiology, 281, 3, Pp. 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.
Melissa Anne Mallory, Katya Losk, Kristen Camuso, Stephanie Caterson, Suniti Nimbkar, and Mehra Golshan. 2016. “Does "Two is Better Than One" Apply to Surgeons? Comparing Single-Surgeon Versus Co-surgeon Bilateral Mastectomies.” Ann Surg Oncol, 23, 4, Pp. 1111-6.Abstract
BACKGROUND: Bilateral mastectomies (BM) are traditionally performed by single surgeons (SS); a co-surgeon (CS) technique, where each surgeon concurrently performs a unilateral mastectomy, offers an alternative approach. We examined differences in general surgery time (GST), overall surgery time (OST), and patient complications for BM performed by CS and SS. METHODS: Patients undergoing BM with tissue expander reconstruction (BMTR) between January 2010 and May 2014 at our center were identified through operative case logs. GST (incision to end of BM procedure), reconstruction duration (RST) (plastic surgery start to end of reconstruction) and OST (OST = GST + RST) was calculated. Patient age, presence/stage of cancer, breast weight, axillary procedure performed, and 30-day postoperative complications were extracted from medical records. Differences in GST and OST between CS and SS cases were assessed with a t test. A multivariate linear regression was fit to identify factors associated with GST. RESULTS: A total of 116 BMTR cases were performed [CS, n = 67 (57.8 %); SS, n = 49 (42.2 %)]. Demographic characteristics did not differ between groups. GST and OST were significantly shorter for CS cases, 75.8 versus 116.8 min, p < .0001, and 255.2 versus 278.3 min, p = .005, respectively. Presence of a CS significantly reduces BMTR time (β = -38.82, p < .0001). Breast weight (β = 0.0093, p = .03) and axillary dissection (β = 28.69, p = .0003) also impacted GST. CONCLUSIONS: The CS approach to BMTR reduced both GST and OST; however, the degree of time savings (35.1 and 8.3 %, respectively) was less than hypothesized. A larger study is warranted to better characterize time, cost, and outcomes of the CS-approach for BM.
2015
Eva C Gombos, Jayender Jagadeesan, Danielle M Richman, and Daniel F Kacher. 2015. “Magnetic Resonance Imaging-Guided Breast Interventions: Role in Biopsy Targeting and Lumpectomies.” Magn Reson Imaging Clin N Am, 23, 4, Pp. 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.
Lester Chee Hao Leong, Eva C Gombos, Jayender Jagadeesan, and Stephanie Man Chung Fook-Chong. 2015. “MRI kinetics with volumetric analysis in correlation with hormonal receptor subtypes and histologic grade of invasive breast cancers.” AJR Am J Roentgenol, 204, 3, Pp. W348-56.Abstract
OBJECTIVE. The aim of this study was to assess whether computer-assisted detection-processed MRI kinetics data can provide further information on the biologic aggressiveness of breast tumors. MATERIALS AND METHODS. We identified 194 newly diagnosed invasive breast cancers presenting as masses on contrast-enhanced MRI by a HIPAA-compliant pathology database search. Computer-assisted detection-derived data for the mean and median peak signal intensity percentage increase, most suspicious kinetic curve patterns, and volumetric analysis of the different kinetic patterns by mean percentage tumor volume were compared against the different hormonal receptor (estrogen-receptor [ER], progesterone-receptor [PR], ERRB2 (HER2/neu), and triple-receptor expressivity) and histologic grade subgroups, which were used as indicators of tumor aggressiveness. RESULTS. The means and medians of the peak signal intensity percentage increase were higher in ER-negative, PR-negative, and triple-negative (all p ≤ 0.001), and grade 3 tumors (p = 0.011). Volumetric analysis showed higher mean percentage volume of rapid initial enhancement in biologically more aggressive ER-negative, PR-negative, and triple-negative tumors compared with ER-positive (64% vs 53.6%, p = 0.013), PR-positive (65.4% vs 52.5%, p = 0.001), and nontriple-negative tumors (65.3% vs 54.6%, p = 0.028), respectively. A higher mean percentage volume of rapid washout component was seen in ERRB2-positive tumors compared with ERRB2-negative tumors (27.5% vs 17.9%, p = 0.020). CONCLUSION. Peak signal intensity percentage increase and volume analysis of the different kinetic patterns of breast tumors showed correlation with hormonal receptor and histologic grade indicators of cancer aggressiveness. Computer-assisted detection-derived MRI kinetics data have the potential to further characterize the aggressiveness of an invasive cancer.
2014
David Calligaris, Diana Caragacianu, Xiaohui Liu, Isaiah Norton, Christopher J Thompson, Andrea L Richardson, Mehra Golshan, Michael L Easterling, Sandro Santagata, Deborah A Dillon, Ferenc A Jolesz, and Nathalie YR Agar. 2014. “Application of Desorption Electrospray Ionization Mass Spectrometry Imaging in Breast Cancer Margin Analysis.” Proc Natl Acad Sci U S A, 111, 42, Pp. 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.

Jagadaeesan Jayender, Sona Chikarmane, Ferenc A Jolesz, and Eva Gombos. 2014. “Automatic Segmentation of Invasive Breast Carcinomas from Dynamic Contrast-Enhanced MRi using Time Series Analysis.” J Magn Reson Imaging, 40, 2, Pp. 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.

Mehra Golshan, Yasuaki Sagara, Barbara Wexelman, Fatih Aydogan, Stephen Desantis, H Elise Min, Kirby Vosburgh, Jayender Jagadeesan, Diana Caragacianu, Eva Gombos, and Ferenc Andras Jolesz. 2014. “Pilot Study to Evaluate Feasibility of Image-Guided Breast-Conserving Therapy in the Advanced Multimodal Image-Guided Operating (AMIGO) Suite.” Ann Surg Oncol, 21, 10, Pp. 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.