Catherine M. Appleton

Dual-Modality Photoacoustic and Ultrasound Imaging System for Noninvasive Sentinel Lymph Node Detection in Patients with Breast Cancer

The detection of regional lymph node metastases is important in cancer staging as it guides the prognosis of the patient and the strategy for treatment. Sentinel lymph node biopsy (SLNB) is an accurate, less invasive alternative to axillary lymph node dissection. The sentinel lymph node hypothesis states that the pathological status of the axilla can be accurately predicted by determining the status of the first lymph nodes that drain from the primary tumor. Physicians use radio-labeled sulfur colloid and/or methylene blue dye to identify the SLN, which is most likely to contain metastatic cancer cells. However, the surgical procedure causes morbidity and associated expenses. To overcome these limitations, we developed a dual-modality photoacoustic and ultrasonic imaging system to noninvasively detect SLNs based on the accumulation of methylene blue dye. Ultimately, we aim to guide percutaneous needle biopsies and provide a minimally invasive method for axillary staging of breast cancer.

Pathologic Outcomes of Nonmalignant Papillary Breast Lesions Diagnosed at Imaging-guided Core Needle Biopsy

PURPOSE To determine the upstage rate from nonmalignant papillary breast lesions obtained at imaging-guided core needle biopsy (CNB) and if there are any clinical, imaging, or pathologic features that can be used to predict eventual upstaging to malignancy. MATERIALS AND METHODS This retrospective case review was institutional review board approved and HIPAA compliant, with a waiver of informed consent. A database search (from January 2001 to March 2010) was performed to find patients with a nonmalignant papillary breast lesion diagnosed at CNB. Of the resulting 128 patients, 86 (67%) underwent surgical excision; 42 (33%) patients were observed with imaging, for a median observation time of 4.1 years (range, 1.0-8.6 years). Chart review was performed to determine pertinent features of each case. RESULTS Fourteen of 128 patients were subsequently found to have malignancy at excision, for an upstage rate of 11%. Nine (7%) of the 128 patients were subsequently found to have atypia at excision. Comparisons between patients with upstaged lesions and patients whose lesions were not upstaged demonstrated patients with upstaged lesions to be slightly older (65 vs 56 years, P=.01), more likely to have a mass than calcifications at imaging (P=.03), and to have had less tissue obtained at biopsy (three vs five cores obtained, P=.02; 14- vs 9-gauge needle used, P<.01; no vacuum assistance used, P<.01). Most strongly predictive of eventual malignancy, however, was whether the interpreting pathologist qualified the benign diagnosis at CNB with additional commentary (P<.01). CONCLUSION Given the substantial upstage rate (11%) of papillary lesions diagnosed at imaging-guided CNB, surgical excision is an appropriate management decision; however, careful evaluation in concert with an expert breast pathologist may allow for observation in appropriately selected patients.

Positive margin rates following breast-conserving surgery for stage I–III breast cancer: palpable versus nonpalpable tumors

BACKGROUND Margin status is a significant risk factor for local recurrence. We sought to examine whether the method of tumor localization predicted the margin status and the need for re-excision for both nonpalpable and palpable breast cancer. METHODS We identified 358 consecutive breast cancer patients who were treated with breast-conserving therapy (BCT) from 1999 to 2006. Data included patient and tumor characteristics, method of localization (needle versus palpation), and pathologic outcomes. Descriptive statistics were used for data summary and data were compared using χ(2). RESULTS Of 358 patients undergoing BCT, 234 (65%) underwent needle localization for a nonpalpable tumor and 124 (35%) underwent a palpation-guided procedure. Patients undergoing palpation-guided procedures were younger and had larger tumors at a more advanced pathologic stage of disease than those undergoing needle localization procedures (P < 0.05 for each). Patient race, tumor grade, presence of lymphovascular invasion, biomarker profile, and nodal status were not significantly different between the two groups (P > 0.05). Overall, 137 patients (38%) had one or more positive margins: 90 of 234 (38%) who had a needle localization procedure and 47 of 124 (38%) who had a palpation-guided procedure (P > 0.05). The number of margins affected did not differ significantly between the two groups. CONCLUSION Although patients with palpable breast cancer had larger tumors than those with nonpalpable breast cancer, the incidence and number of positive margins was similar to those who had needle localization for nonpalpable tumors. Improved methods of localization are needed to reduce the rate of positive margins and the need for re-excision.

The ACR/Society of Breast Imaging Resident and Fellowship Training Curriculum for Breast Imaging, Updated

The education committees of the ACR Commission on Breast Imaging and the Society of Breast Imaging have revised the resident and fellowship training curriculum to reflect the current state of breast imaging in the United States. The original curriculum, created by the Society of Breast Imaging in 2000, had been updated only once before, in 2006. Since that time, a number of significant changes have occurred in the way mammography is acquired, how adjunctive breast imaging methods are used, and how pathology is assessed. This curricular update is meant to reflect these and other changes and to offer guidance to educators and trainees in preparing those interested in providing breast imaging services.

Successful Completion of the Pilot Phase of a Randomized Controlled Trial Comparing Sentinel Lymph Node Biopsy to No Further Axillary Staging in Patients with Clinical T1-T2 N0 Breast Cancer and Normal Axillary Ultrasound

BACKGROUND Axillary surgery is not considered therapeutic in patients with clinical T1-T2 N0 breast cancer. The importance of axillary staging is eroding in an era in which tumor biology, as defined by biomarker and gene expression profile, is increasingly important in medical decision making. We hypothesized that axillary ultrasound (AUS) is a noninvasive alternative to sentinel lymph node biopsy (SLNB), and AUS could replace SLNB without compromising patient care. STUDY DESIGN Patients with clinical T1-T2 N0 breast cancer and normal AUS were eligible for enrollment. Subjects were randomized to no further axillary staging (arm 1) vs SLNB (arm 2). Descriptive statistics were used to describe the results of the pilot phase of the randomized controlled trial. RESULTS Sixty-eight subjects were enrolled in the pilot phase of the trial (34 subjects in arm 1, no further staging; 32 subjects in arm 2, SLNB; and 2 subjects voluntarily withdrew from the trial). The median age was 61 years (range 40 to 80 years) in arm 1 and 59 years (range 31 to 81 years) in arm 2, and there were no significant clinical or pathologic differences between the arms. Median follow-up was 17 months (range 1 to 32 months). The negative predictive value (NPV) of AUS for identification of clinically significant axillary disease (>2.0 mm) was 96.9%. No axillary recurrences have been observed in either arm. CONCLUSIONS Successful completion of the pilot phase of the randomized controlled trial confirms the feasibility of the study design, and provides prospective evidence supporting the ability of AUS to exclude clinically significant disease in the axilla. The results provide strong support for a phase 2 randomized controlled trial.

Recent trends in adherence to continuous screening for breast cancer among Medicare beneficiaries

OBJECTIVE The aim of this study is to examine recent trends in adherence to continuous screening, especially the rate of subsequent screening mammography following an initial screening before and after the U.S. Preventive Services Task Force (USPSTF) revised its guidelines on breast cancer in November 2009. METHODS We retrospectively analyzed Medicare fee-for-service claims data to: 1) compare rate of subsequent screening mammography over 27 month periods for 317,150 women screened in either 2004 or 2009; and 2) examine patterns of subsequent screening by age and race. RESULTS When adjusted for age, race, state of residence, county-level covariates, and clustered on ordering provider, the rate of subsequent screening decreased in 2009 relative to 2004 (OR=0.75; 95% CI: 0.74-0.76). Adjusted odds ratios are similar for alternative follow-up windows (15 months, 0.71; 24 months, 0.70; 30 months 0.75). The decline was mostly attributable to women 75 and older who are now less likely to return for a subsequent screening. Although USPSTF guidelines call for 24 months, approximately half of women continue screening at 12-month intervals in both cohorts. CONCLUSIONS The rate of subsequent screening mammography has declined after 2009. Older women seem to follow the revised USPSTF guideline, but confusion by physicians and patients about competing guidelines may be contributing to these findings.

Which Imaging Modality Is Superior for Prediction of Response to Neoadjuvant Chemotherapy in Patients with Triple Negative Breast Cancer

Background and Objectives. Triple negative breast cancer (TNBC) has been shown to be generally chemosensitive. We sought to investigate the utility of mammography (MMG), ultrasonography (US), and breast magnetic resonance imaging (MRI) in predicting residual disease following neoadjuvant chemotherapy for TNBC. Methods. We identified 148 patients with 151 Stage I–III TNBC treated with neoadjuvant chemotherapy. Residual tumor size was estimated by MMG, US, and/or MRI prior to surgical intervention and compared to the subsequent pathologic residual tumor size. Data were compared using chi-squared test. Results. Of 151 tumors, 44 (29%) did not have imaging performed prior to surgical treatment. Thirty-eight (25%) tumors underwent a pathologic complete response (pCR), while 113 (75%) had residual invasive disease. The imaging modality was accurate to within 1 cm of the final pathologic residual disease in 74 (69%) cases and within 2 cm in 94 (88%) cases. Groups were similar with regards to patient age, race, tumor size and grade, and clinical stage (P > 0.05). Accuracy to within 1 cm was the highest for US (83%) and the lowest for MMG (56%) (P < 0.05). Conclusions. Breast US and MRI were more accurate than MMG in predicting residual tumor size following neoadjuvant chemotherapy in patients with TNBC. None of the imaging modalities were predictive of a pCR.

Generation of anatomically realistic numerical phantoms for photoacoustic and ultrasonic breast imaging

Abstract. Photoacoustic computed tomography (PACT) and ultrasound computed tomography (USCT) are emerging modalities for breast imaging. As in all emerging imaging technologies, computer-simulation studies play a critically important role in developing and optimizing the designs of hardware and image reconstruction methods for PACT and USCT. Using computer-simulations, the parameters of an imaging system can be systematically and comprehensively explored in a way that is generally not possible through experimentation. When conducting such studies, numerical phantoms are employed to represent the physical properties of the patient or object to-be-imaged that influence the measured image data. It is highly desirable to utilize numerical phantoms that are realistic, especially when task-based measures of image quality are to be utilized to guide system design. However, most reported computer-simulation studies of PACT and USCT breast imaging employ simple numerical phantoms that oversimplify the complex anatomical structures in the human female breast. We develop and implement a methodology for generating anatomically realistic numerical breast phantoms from clinical contrast-enhanced magnetic resonance imaging data. The phantoms will depict vascular structures and the volumetric distribution of different tissue types in the breast. By assigning optical and acoustic parameters to different tissue structures, both optical and acoustic breast phantoms will be established for use in PACT and USCT studies.

Utility of breast MRI for evaluation of residual disease following excisional biopsy.

BACKGROUND Because benign postoperative changes may overlap those of malignancy, the utility of breast MRI following an excisional biopsy is unclear. We sought to investigate the ability of MRI to predict residual disease following an excisional biopsy for breast cancer. MATERIALS AND METHODS We reviewed 93 patients who underwent surgical treatment for stage 0-III breast cancer at our institution from January 2005 to May 2008. All patients had previously undergone excisional biopsy with subsequent MRI. Patient, tumor, and treatment characteristics were collected. Descriptive statistics were utilized for data summary and data were compared using Fishers exact or χ(2) tests. RESULTS The mean age of the 84 patients who had additional surgery following MRI was 51 ± 7 y. Thirteen (15%) patients had only postoperative changes on MRI; six had residual disease on final pathology. Of 71 patients with MRI findings suspicious for residual disease, 54 (76%) had pathologic confirmation, while 17 (24%) had only benign pathology. The sensitivity and specificity of MRI following excisional biopsy were 90% and 29%, respectively. Overall, 49 (58%) of the 84 patients underwent mastectomy, including 11 of 24 (46%) with negative final pathology. Patient age, tumor size, tumor grade, biomarker profile, nodal status, and MRI findings were not predictive of surgical treatment type (P > 0.05). CONCLUSION Although excisional biopsy decreases the specificity of breast MRI, its sensitivity remains high. Nearly 50% of patients with a suspicious MRI and negative final pathology underwent mastectomy, suggesting that additional biopsy of all suspicious MRI findings is necessary to avoid surgical overtreatment.

A Dual-Modality Photoacoustic and Ultrasound Imaging System for Noninvasive Sentinel Lymph Node Detection: Preliminary Clinical Results

Sentinel lymph node biopsy (SLNB) has emerged as an accurate, less invasive alternative to axillary lymph node dissection, and it has rapidly become the standard of care for patients with clinically node-negative breast cancer. The sentinel lymph node (SLN) hypothesis states that the pathological status of the axilla can be accurately predicted by determining the status of the first (i.e., sentinel) lymph nodes that drain from the primary tumor. Physicians use radio-labeled sulfur colloid and/or methylene blue dye to identify the SLN, which is most likely to contain metastatic cancer cells. However, the surgical procedure causes morbidity and associated expenses. To overcome these limitations, we developed a dual-modality photoacoustic and ultrasound imaging system to noninvasively detect SLNs based on the accumulation of methylene blue dye. Ultimately, we aim to guide percutaneous needle biopsies and provide a minimally invasive method for axillary staging of breast cancer. The system consists of a tunable dye laser pumped by a Nd:YAG laser, a commercial ultrasound imaging system (Philips iU22), and a multichannel data acquisition system which displays co-registered photoacoustic and ultrasound images in real-time. Our clinical results demonstrate that real-time photoacoustic imaging can provide sensitive and specific detection of methylene blue dye in vivo. While preliminary studies have shown that in vivo detection of SLNs by using co-registered photoacoustic and ultrasound imaging is feasible, further investigation is needed to demonstrate robust SLN detection.