Huong T. Le-Petross

Sentinel Lymph Node Surgery After Neoadjuvant Chemotherapy in Patients With Node-Positive Breast Cancer The ACOSOG Z1071 (Alliance) Clinical Trial

IMPORTANCE Sentinel lymph node (SLN) surgery provides reliable nodal staging information with less morbidity than axillary lymph node dissection (ALND) for patients with clinically node-negative (cN0) breast cancer. The application of SLN surgery for staging the axilla following chemotherapy for women who initially had node-positive cN1 breast cancer is unclear because of high false-negative results reported in previous studies. OBJECTIVE To determine the false-negative rate (FNR) for SLN surgery following chemotherapy in women initially presenting with biopsy-proven cN1 breast cancer. DESIGN, SETTING, AND PATIENTS The American College of Surgeons Oncology Group (ACOSOG) Z1071 trial enrolled women from 136 institutions from July 2009 to June 2011 who had clinical T0 through T4, N1 through N2, M0 breast cancer and received neoadjuvant chemotherapy. Following chemotherapy, patients underwent both SLN surgery and ALND. Sentinel lymph node surgery using both blue dye (isosulfan blue or methylene blue) and a radiolabeled colloid mapping agent was encouraged. MAIN OUTCOMES AND MEASURES The primary end point was the FNR of SLN surgery after chemotherapy in women who presented with cN1 disease. We evaluated the likelihood that the FNR in patients with 2 or more SLNs examined was greater than 10%, the rate expected for women undergoing SLN surgery who present with cN0 disease. RESULTS Seven hundred fifty-six women were enrolled in the study. Of 663 evaluable patients with cN1 disease, 649 underwent chemotherapy followed by both SLN surgery and ALND. An SLN could not be identified in 46 patients (7.1%). Only 1 SLN was excised in 78 patients (12.0%). Of the remaining 525 patients with 2 or more SLNs removed, no cancer was identified in the axillary lymph nodes of 215 patients, yielding a pathological complete nodal response of 41.0% (95% CI, 36.7%-45.3%). In 39 patients, cancer was not identified in the SLNs but was found in lymph nodes obtained with ALND, resulting in an FNR of 12.6% (90% Bayesian credible interval, 9.85%-16.05%). CONCLUSIONS AND RELEVANCE Among women with cN1 breast cancer receiving neoadjuvant chemotherapy who had 2 or more SLNs examined, the FNR was not found to be 10% or less. Given this FNR threshold, changes in approach and patient selection that result in greater sensitivity would be necessary to support the use of SLN surgery as an alternative to ALND. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00881361.

Inflammatory Breast Cancer: The Disease, the Biology, the Treatment

Inflammatory breast cancer (IBC) is a rare and aggressive form of invasive breast cancer accounting for 2.5% of all breast cancer cases. It is characterized by rapid progression, local and distant metastases, younger age of onset, and lower overall survival compared with other breast cancers. Historically, IBC is a lethal disease with less than a 5% survival rate beyond 5 years when treated with surgery or radiation therapy. Because of its rarity, IBC is often misdiagnosed as mastitis or generalized dermatitis. This review examines IBCs unique clinical presentation, pathology, epidemiology, imaging, and biology and details current multidisciplinary management of the disease, which comprises systemic therapy, surgery, and radiation therapy. CA Cancer J Clin 2010.

Cortical Morphologic Features of Axillary Lymph Nodes as a Predictor of Metastasis in Breast Cancer: In Vitro Sonographic Study

OBJECTIVE The purpose of this study was in vitro sonographic-pathologic correlation of findings in dissected axillary lymph nodes from breast cancer patients undergoing axillary lymph node dissection and classification of the sonographic appearance of the nodes on the basis of cortical morphologic features to facilitate early recognition of metastatic disease. MATERIALS AND METHODS High-resolution sonography was used for in vitro examination of 171 lymph nodes from 19 axillae in 18 patients with unknown nodal status who underwent axillary lymph node dissection for early infiltrating breast cancer. The images were evaluated by two blinded observers, and discordant readings were referred to a third blinded observer. Each lymph node was classified as one of types 1-6 according to cortical morphologic features. Types 1-4 were considered benign, ranging from hyperechoic with no visible cortex to thickened generalized hypoechoic cortical lobulation. Type 5 (focal hypoechoic cortical lobulation) and type 6 (hypoechoic node with absent hilum) nodes were considered metastatic. The reference standard for metastatic disease was histopathologic evaluation of sectioned nodes by a single pathologist blinded to sonographic findings. Largest nodal diameter also was measured. RESULTS Interobserver agreement was 77% for classification of nodal morphology (types 1-6) and 88% for characterization of a node as benign or malignant. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of cortical shape in prediction of metastatic involvement of axillary nodes were 77%, 80%, 36%, 96%, and 80%. Type 4 nodes had the most false-negative findings (four of 36). Node size ranged from 0.2 to 3.8 cm, and subcentimeter nodes of all types were detected. CONCLUSION In breast cancer, axillary lymph nodes can be classified according to cortical morphologic features. Predominantly hyperechoic nodes (types 1-3) can be considered benign. Generalized cortical lobulation (type 4) is uncommonly a false-negative finding, but metastasis, if present, is invariably detected at sentinel node mapping. The presence of asymmetric focal hypoechoic cortical lobulation (type 5) or a completely hypoechoic node (type 6) should serve as a guideline for universal performance of fine-needle aspiration for preoperative staging of breast cancer. This classification, when verified with larger samples, may serve as a useful clinical guideline if proven with results of in vivo studies.

Identification and Resection of Clipped Node Decreases the False-negative Rate of Sentinel Lymph Node Surgery in Patients Presenting With Node-positive Breast Cancer (T0-T4, N1-N2) Who Receive Neoadjuvant Chemotherapy: Results From ACOSOG Z1071 (Alliance).

Background:The American College of Surgeons Oncology Group Z1071 trial reported a false-negative rate (FNR) of 12.6% with sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy in women presenting with node-positive breast cancer. One proposed method to decrease the FNR is clip placement in the positive node at initial diagnosis with confirmation of clipped node resection at surgery. Methods:Z1071 was a multi-institutional trial wherein women with clinical T0–T4,N1–N2,M0 breast cancer underwent SLN surgery and axillary dissection (ALND) after neoadjuvant chemotherapy. In cases with a clip placed in the node, the clip location at surgery (SLN or ALND) was evaluated. Results:A clip was placed at initial node biopsy in 203 patients. In the 170 (83.7%) patients with cN1 disease and at least 2 SLNs resected, clip location was confirmed in 141 cases. In 107 (75.9%) patients where the clipped node was within the SLN specimen, the FNR was 6.8% (confidence interval [CI]: 1.9%–16.5%). In 34 (24.1%) cases where the clipped node was in the ALND specimen, the FNR was 19.0% (CI: 5.4%–41.9%). In cases without a clip placed (n = 355) and in those where clipped node location was not confirmed at surgery (n = 29), the FNR was 13.4% and 14.3%, respectively. Conclusions:Clip placement at diagnosis of node-positive disease with removal of the clipped node during SLN surgery reduces the FNR of SLN surgery after neoadjuvant chemotherapy. Clip placement in the biopsy-proven node at diagnosis and evaluation of resected specimens for the clipped node should be considered when conducting SLN surgery in this setting.

Axillary Ultrasound After Neoadjuvant Chemotherapy and Its Impact on Sentinel Lymph Node Surgery: Results From the American College of Surgeons Oncology Group Z1071 Trial (Alliance)

PURPOSE The American College of Surgeons Oncology Group Z1071 trial reported a 12.6% false-negative rate (FNR) for sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in cN1 disease. Patients were not selected for surgery based on response, but a secondary end point was to determine whether axillary ultrasound (AUS) after NAC after fine-needle aspiration cytology can identify abnormal nodes and guide patient selection for SLN surgery. PATIENTS AND METHODS Patients with T0-4, N1-2, M0 breast cancer underwent AUS after neoadjuvant chemotherapy. AUS images were centrally reviewed and classified as normal or suspicious lymph nodes. AUS findings were tested for association with pathologic nodal status and SLN FNR. The impact of AUS results to select patients for SLN surgery to reduce the FNR was assessed. RESULTS Postchemotherapy AUS images were reviewed for 611 patients. One hundred thirty (71.8%) of 181 AUS-suspicious patients were node positive at surgery compared with 243 (56.5%) of 430 AUS-normal patients (P < .001). Patients with AUS-suspicious nodes had a greater number of positive nodes and greater metastasis size (P < .001). The SLN FNR was not different based on AUS results; however, using a strategy where only patients with normal AUS undergo SLN surgery would potentially reduce the FNR in Z1071 patients with ≥ two SLNs removed from 12.6% to 9.8% when preoperative AUS results are considered as part of SLN surgery. CONCLUSION AUS is recommended after chemotherapy to guide axillary surgery. An FNR of 9.8% with the combination of AUS and SLN surgery would be acceptable for the adoption of SLN surgery for women with node-positive breast cancer treated with neoadjuvant chemotherapy.

Retrospective Study of 18F-FDG PET/CT in the Diagnosis of Inflammatory Breast Cancer: Preliminary Data

Our objective was to retrospectively evaluate 18F-FDG PET/CT in the initial staging of inflammatory breast cancer (IBC). Methods: The institutional review board waived informed consent and approved this study, which was compliant with the Health Insurance Portability and Accountability Act. The cases of 41 women with a mean age of 50 y (range, 25–71 y) and newly diagnosed IBC who underwent 18F-FDG PET/CT at diagnosis were retrospectively reviewed. All PET/CT images were analyzed visually and semiquantitatively by 2 physicians. The maximum standardized uptake value in the primary breast, regional nodes (axillary, subpectoral, supraclavicular, internal mammary), and extranodal regions was documented. The accuracy of PET/CT image interpretation was assessed by histopathologic analysis, if available; concurrent or subsequent imaging findings (contrast-enhanced CT, contrast-enhanced MRI, sonography, or PET/CT follow-up); or clinical follow-up. Results: All patients presented with unilateral IBC. PET/CT showed hypermetabolic uptake in the skin in all patients, in the affected breast in 40 (98%), in the ipsilateral axillary nodes in 37 (90%), and in the ipsilateral subpectoral nodes in 18 (44%). Twenty patients (49%) were found to have distant metastases at staging, 7 (17%) of whom were not known to have metastases before undergoing PET/CT. Disease sites included bone, liver, contralateral axilla, lung, chest wall, pelvis, and the subpectoral, supraclavicular, internal mammary, mediastinal, and abdominal nodes. Conclusion: PET/CT should be considered in the initial staging of IBC, as the technique provided valuable information on locoregional and distant disease in this preliminary retrospective study.

Effectiveness of alternating mammography and magnetic resonance imaging for screening women with deleterious BRCA mutations at high risk of breast cancer.

Magnetic resonance imaging (MRI) has been used to supplement screening mammography and clinical breast examination (CBE) in women who are at high risk of developing breast cancer. In this study, the authors investigated the efficacy of alternating screening mammography and breast MRI every 6 months in women who had a genetically high risk of developing breast cancer.

Fast spin‐echo triple‐echo dixon (fTED) technique for efficient T2‐weighted water and fat imaging

Previously published fast spin‐echo (FSE) implementations of a Dixon method for water and fat separation all require multiple scans and thus a relatively long scan time. Further, the minimum echo spacing (esp), a time critical for FSE image quality and scan efficiency, often needs to be increased in order to bring about the required phase shift between the water and fat signals. This work proposes and implements a novel FSE triple‐echo Dixon (fTED) technique that can address these limitations. In the new technique, three raw images are acquired in a single FSE scan by replacing each frequency‐encoding gradient in a conventional FSE with three consecutive gradients of alternating polarity. The timing of the three gradients is adjusted by selecting an appropriate receiver bandwidth (RBW) so that the water and fat signals for the three corresponding echoes have a relative phase shift of −180°, 0°, and 180°, respectively. A fully automated postprocessing algorithm is then used to generate separate water‐only and fat‐only images for each slice. The technique was implemented with and without parallel imaging. We demonstrate that the new fTED technique enables both uniform water/fat separation and fast scanning with uncompromised scan parameters, including applications such as T2‐weighted separate water and fat imaging of the abdomen during breath‐holding. Magn Reson Med 58:103–109, 2007.

Earlier age of onset of BRCA mutation‐related cancers in subsequent generations

Women who are diagnosed with a deleterious mutation in either breast cancer (BRCA) gene have a high risk of developing breast and ovarian cancers at young ages. In this study, the authors assessed age at diagnosis in 2 generations of families with known mutations to investigate for earlier onset in subsequent generations.

Abstract S2-1: The role of sentinel lymph node surgery in patients presenting with node positive breast cancer (T0-T4, N1-2) who receive neoadjuvant chemotherapy – results from the ACOSOG Z1071 trial

Background: The utility of sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in patients presenting with node-positive breast cancer has not been determined. The American College of Surgeons Oncology Group (ACOSOG) Z0171 trial was designed to evaluate SLN surgery after NAC in women presenting with node positive disease. Methods: ACOSOG Z1071 enrolled women with clinical T0-4, N1-2, M0 breast cancer receiving NAC. At the time of surgery, all patients were to undergo SLN surgery followed by axillary lymph node dissection (ALND). The primary endpoint was false negative rate (FNR) in women with cN1 disease with 2 or more SLNs reviewed. Positive SLNs were defined as metastases >0.2mm on HE 52 pts (48 cN1) had no SLN identified and had ALND; 11 underwent ALND only (all cN1), and 2 pts had SLN only (both cN1). In patients with SLN and ALND, the SLN identification rate was 92.5% (92.7% in cN1, 90% in cN2). SLN correctly identified nodal status in 84% of the 695 pts [258 of pathologically node negative and 327 of pathologically node positive; cN1: 83.8% (549/655), cN2: 90.0% (36/40)]. Of the 643 pts with a SLN identified there was a complete pathologic response in 40.3% (40.3 % for cN1 and 50% for cN2). Of the pts with a positive SLN, the SLN was the only site of disease in 40%. For pts with cN1 disease with 2+ SLNs identified with residual nodal disease, the SLN FNR was 12.8%. In pts with dual tracer technique the FNR was 11.1%. There were no FN results among pts with cN2 disease with 2+ SLNs reviewed. Of the 40 pts with a false negative SLN of the 528 cN1 patients with 2+ SLNs examined, the number of positive nodes at ALND was 1 (50.0%); 2 (25%); 3 (10.0%) and 4–9 (15.0%). Conclusions: NAC resulted in eradication of lymph node disease in 40% of node positive breast cancer patients. SLN surgery after NAC in node positive breast cancer pts correctly identified nodal status in 84% of all patients and was associated with a FNR of 12.8%. The FNR of SLN is higher than the prespecified study endpoint of 10%. Further analysis of factors associated with FNR such as clinical response, histological findings and axillary ultrasound findings is warranted prior to widespread use of SLN in these patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S2-1.