Assessment for residual nodal disease after neoadjuvant chemotherapy with image-guided surgery.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 99-99
Author(s):  
Abigail Suzanne Caudle ◽  
Wei Tse Yang ◽  
Elizabeth Ann Mittendorf ◽  
Dalliah MaShon Black ◽  
Michael Gilcrease ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Needle Biopsy ◽  
Residual Disease ◽  
False Negative ◽  
False Negative Rate ◽  
Selective Removal ◽  
Breast Cancer Patients ◽  
Nodal Disease ◽  
Pathologic Evaluation ◽  
Axillary Lymphadenectomy

99 Background: Staging of breast cancer patients is enhanced by axillary ultrasound (US) and needle biopsy of abnormal lymph nodes (LN). When clips are placed in sampled metastatic LNs, they can be evaluated for nodal response to neoadjuvant chemotherapy (NCT). The goals of this study were to determine if pathologic changes in clipped LNs reflect nodal response to NCT and if targeted axillary dissection (TAD), which includes sentinel lymph node dissection (SLND) in addition to selective localization and removal of clipped LNs, could increase the accuracy of nodal assessment. Methods: This prospective study included patients with US-identified axillary metastases confirmed by needle biopsy with a clip placed in the sampled LN. After NCT, patients underwent axillary lymphadenectomy (ALND) with x-ray of the axillary contents to identify the clip-containing LN. In 38 patients, the clipped LN was selectively removed using wire (n=2) or I125seed localization (n=36) before ALND was performed. Five patients did not undergo ALND. The pathologic findings of the clipped LN were reported separately from the other nodes. Results: Ninety node positive patients were enrolled. Forty (44%) had a complete nodal response to NCT and 50 (56%) had residual disease. Pathologic evaluation of the clipped LN revealed metastases in 47/50 patients with residual disease, resulting in a false negative rate (FNR) of 6% (95% CI 1.3-16.6). In 52 patients who underwent SLND, the clipped LN was not a SLN in 23% (n=12). Thirty-one of these patients had residual disease; metastases were not seen in SLNs in 5 cases resulting in a FNR for SLND alone of 16% (95% CI 5.4-34). Evaluation of the clipped LN in addition to SLND improved the FNR to 3% (1/31, 95% CI 0.1-17). Thirty-one patients underwent TAD while an additional 7 had localization and selective removal of the clipped LN without SLND with one false negative result. Conclusions: US-guided marking of LNs with documented metastatic disease allows for their selective removal and improved pathologic evaluation for residual nodal disease. The FNR of SLND can be reduced by ensuring removal and evaluation of the clipped LN. TAD is technically feasible and allows for improved assessment of nodal response after NCT.

scholarly journals Improved Axillary Evaluation Following Neoadjuvant Therapy for Patients With Node-Positive Breast Cancer Using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection

2016 ◽  
Vol 34 (10) ◽  
pp. 1072-1078 ◽  
Author(s):  
Abigail S. Caudle ◽  
Wei T. Yang ◽  
Savitri Krishnamurthy ◽  
Elizabeth A. Mittendorf ◽  
Dalliah M. Black ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Axillary Dissection ◽  
Residual Disease ◽  
False Negative ◽  
False Negative Rate ◽  
Selective Removal ◽  
Nodal Basin ◽  
Pathologic Evaluation ◽  
Axillary Lymphadenectomy

Purpose Placing clips in nodes with biopsy-confirmed metastasis before initiating neoadjuvant therapy allows for evaluation of response in breast cancer. Our goal was to determine if pathologic changes in clipped nodes reflect the status of the nodal basin and if targeted axillary dissection (TAD), which includes sentinel lymph node dissection (SLND) and selective localization and removal of clipped nodes, improves the false-negative rate (FNR) compared with SLND alone. Methods A prospective study of patients with biopsy-confirmed nodal metastases with a clip placed in the sampled node was performed. After neoadjuvant therapy, patients underwent axillary surgery and the pathology of the clipped node was compared with other nodes. Patients undergoing TAD had SLND and selective removal of the clipped node using iodine-125 seed localization. The FNR was determined in patients undergoing complete axillary lymphadenectomy (ALND). Results Of 208 patients enrolled in this study, 191 underwent ALND, with residual disease identified in 120 (63%). The clipped node revealed metastases in 115 patients, resulting in an FNR of 4.2% (95% CI, 1.4 to 9.5) for the clipped node. In patients undergoing SLND and ALND (n = 118), the FNR was 10.1% (95% CI, 4.2 to 19.8), which included seven false-negative events in 69 patients with residual disease. Adding evaluation of the clipped node reduced the FNR to 1.4% (95% CI, 0.03 to 7.3; P = .03). The clipped node was not retrieved as an SLN in 23% (31 of 134) of patients, including six with negative SLNs but metastasis in the clipped node. TAD followed by ALND was performed in 85 patients, with an FNR of 2.0% (1 of 50; 95% CI, 0.05 to 10.7). Conclusion Marking nodes with biopsy-confirmed metastatic disease allows for selective removal and improves pathologic evaluation for residual nodal disease after chemotherapy.

scholarly journals Identification of sentinel lymph nodes using contrast-enhanced ultrasound in breast cancer patients who underwent neoadjuvant chemotherapy.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 59-59
Author(s):  
Xiufeng Wu ◽  
Lina Tang ◽  
Yi Zeng ◽  
Xia Chen
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
False Negative ◽  
False Negative Rate ◽  
Breast Cancer Patients ◽  
Identification Rate ◽  
Contrast Enhanced ◽  
Sensitivity Specificity

59 Background: The aim of this prospective study was to evaluate the feasibility of contrast-enhanced ultrasonography (CEUS) for the identification of sentinel lymph node (SLN) in breast cancer patients with cN0 following neoadjuvant chemotherapy (NAC). Methods: Patients with cN0 following NAC (n=66) received a periareolar injection of SonoVue followed by ultrasound (US) to identify contrast-enhanced SLN before surgery. All patients underwent axillary lymph node dissection for verification of axillary node status after the SLN biopsy. The identification rate, sensitivity, specificity, accuracy, false negative rate, negative predictive value, positive predictive value was recorded. Results: In almost all cases, the SLNs were easily identified with an identification rate of 98.5 % (65/66). Compared with pathological diagnosis, sensitivity, specificity, accuracy, and false negative rate of CEUS for SLN diagnosis were 66.7%, 95.8%, 78.8%, and 14.3% respectively. Conclusions: Identification of SLN by CEUS is a technically feasible method with an identification rate as high as 98.5%. [Table: see text][Table: see text]

Axillary management in T1-3N1M0 breast cancer patients with needle biopsy proven nodal metastases at presentation after neoadjuvant chemotherapy (ATNEC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS600-TPS600
Author(s):  
Amit Goyal ◽  
Sophie Cramp ◽  
Duncan Wheatley ◽  
Andrea Marshall ◽  
Shama Puri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Needle Biopsy ◽  
Nodal Metastases ◽  
Breast Cancer Patients ◽  
Nodal Disease ◽  
Sentinel Nodes ◽  
Axillary Treatment ◽  
Dual Tracer

TPS600 Background: Neoadjuvant chemotherapy (NACT) results in eradication of cancer in the axillary nodes in 40% to 70% of patients. This raises questions about the benefit of further axillary treatment in those patients with no evidence of residual nodal disease (ypN0) after NACT. Methods: Design: ATNEC is a phase 3, randomised (1:1), multi-centre trial, with embedded economic evaluation, comparing standard axillary treatment (axillary lymph node dissection [ALND] or axillary radiotherapy [ART]) with no further axillary treatment in T1-3N1M0 breast cancer patients with needle biopsy proven axillary nodal metastases, who after NACT have no residual nodal disease (ypN0) on dual tracer sentinel node biopsy (SNB) and removal of at least 3 nodes (sentinel nodes and marked involved node). Stratification: Institution, type of surgery (breast conserving surgery vs mastectomy), receptor status (triple negative vs HER2 positive vs ER positive and/or PR positive and HER2 negative). Inclusion criteria are: Age ≥ 18, Male or female, T1-3N1M0 breast cancer at diagnosis (pre-NACT), FNA or core biopsy confirmed axillary nodal metastases at presentation, ER and HER2 status evaluated on primary tumour, received standard NACT as per local guidelines, ultrasound of the axilla at completion of NACT, dual tracer SNB after NACT and at least 3 nodes removed (sentinel nodes and marked node), no evidence of nodal metastases post NACT (ypN0). Exclusion criteria are: bilateral invasive breast cancer, SNB prior to NACT, marked node not removed except where at least one node removed shows evidence of down-staging with complete pathological response e.g. fibrosis/scarring and at least 3 nodes removed, previous ipsilateral axillary surgery, previous cancer within last 5 years or concomitant malignancy except basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, in situ or stage 1 melanoma, contra- or ipsilateral in situ breast cancer. Aims: To assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy - who after NACT have no residual nodal disease on SNB (ypN0) - is non-inferior to axillary treatment in terms of disease free survival, and reduces the risk of lymphoedema at 5 years. Statistical methods: All analyses will be carried out on an intention-to-treat basis to preserve randomisation, avoid bias from exclusions and preserve statistical power. Radiotherapy quality assurance: Study has in-built radiotherapy QA programme that will be co-ordinated by National Radiotherapy Trials QA (RTTQA) group. Target accrual: 1900. Trial status: Recruiting. Number of sites: 100. Clinical trial information: NCT04109079.

Assessment of Genetic Aberrations in Plasma Cells Using a Sequential Morphology (Phenotype)/FISH (Genotype) Approach Significantly Improves the Detection of Residual Disease in Post Treatment Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1549-1549
Author(s):  
Marilyn L. Slovak ◽  
Victoria Bedell ◽  
Kristen Pagel ◽  
Lawrence Weiss ◽  
David Smith ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Residual Disease ◽  
False Negative ◽  
False Negative Rate ◽  
Molecular Cytogenetics ◽  
Post Treatment ◽  
Pcr Analysis ◽  
Image Analyzer ◽  
Novel Approach

Abstract Multiple myeloma (MM) is a B cell malignancy characterized by clonal expansion of plasma cells. Many MM patients achieve a complete remission by conventional criteria; yet most patients relapse as a consequence of residual disease. Current approaches for the measurement of minimal residual disease (MRD) in bone marrow (BM) are based on morphologic assessment of BM aspirate and biopsy, flow cytometry, immunohistochemistry, molecular (PCR) studies, conventional cytogenetics (CC) and fluorescence in situ hybridization (FISH) analyses. Morphologic assessment of MRD is often difficult due to the fact that normal plasma cells may also be present in the BM. Genetic factors have emerged as significant prognostic factors in MM; however, CC studies are hampered by the low proliferative nature of the malignant cells. FISH analyses have detected clonal abnormalities of -13/del(13q), 14q32/IGH, del(17p), and hyperdiploidy (+5,+9,+15) in >80% of newly diagnosed MM cases; yet, detection of these abnormalities post treatment by the standard FISH approach has proven to be very difficult in samples with less than 20% BM involvement. PCR-based approaches are sensitive but suffer a critically high false-negative rate. In this study, we investigated 137 post treatment samples collected from 101 MM patients (31 patients with multiple studies), all showing < 20% BM involvement, using a sequential May-Grünwald Giemsa (MGG) (morphology)/FISH approach to determine the plasma cell genotype (target or T-FISH). Cytospin slides were made using 200 μl of BM and stained with MGG for morphologic classification on a Duet™ Image Analyzer (Bioview Ltd., Rehovot, Israel). After identifying and mapping the plasma cells, the slides were destained and hybridized with one of four FISH probe sets corresponding to the chromosome aberrations listed above. The T-FISH results were correlated with CC, BM pathology, which quantified the percentage of plasma cells in the BM aspirate, and BIOMED-2 PCR analysis for IGH (FR1, 2 and 3) and IGK gene rearrangements (InVivoScribe Technologies, San Diego, CA). T-FISH identified MM aberrations in 123 of 137 (89.8%) samples, a finding significantly higher than the 50/83 (60.2%) positive cases detected by combined molecular IGH and IGK PCR studies (two-sided Fisher’s Exact p < 0.0001). T-FISH aberrations observed were IGH in 77 samples, del(13q)/-13 in 48, hyperdiploidy in 37, hypodiploidy in 6, and del(17p) in 4, with 42 samples showing more than one abnormality. Only 10 samples showed clonal karyotypic aberrations by CC; an additional 3 samples showed a “presumed” stemline with only one abnormal cell (9.5%). A comparison with the percentage of plasma cells in the BM smears showed T-FISH detected residual disease in all 48 samples with ≥6 % plasma cells, 14 of 15 hemodilute samples, one smoldering MM sample and 82.2% (60/73) of the samples with 1–5% plasma cells. Our data indicate T-FISH is a quick, universally applicable, and robust assay to quantitate neoplastic plasma cells regardless of treatment status, making it the most sensitive molecular assay currently available to monitor a patient’s clinical course. Furthermore, the T-FISH molecular cytogenetics strategy provides a novel approach to monitor both traditional and targeted therapies in low proliferative malignancies by their underlying genetic abnormalities.

HER2 evaluation process for neoadjuvant targeted therapies in breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3034-3034
Author(s):  
Yoshio Mizuno ◽  
Naoko Takeda ◽  
Junichi Yamada ◽  
Hiroaki Abe ◽  
Yuko Inoue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Targeted Therapies ◽  
False Negative ◽  
Fish Analysis ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Surgical Specimen ◽  
Amplification Ratio ◽  
Her2 Testing

3034 Background: Treatment with a combination of HER2-targeted therapies has emerged as an addition of trastuzumab to neoadjuvant chemotherapy regimens in breast cancer patients and it goes on increasing. For clinical HER2 determination, immunohistochemical (IHC) analysis is an attractive method and all IHC 2+ cases are categorized as equivocal and should be reflexed to fluorescence in situ hybridization (FISH) testing. However, research in recent years with respect to false-negative cases for HER2 testing have been reported, and it comes to the question of what considering the indication for trastuzumab in the neoadjuvant chemotherapy. To clarify these controversial points in applying the results of HER2 testing in the clinical setting, we performed a retrospective analysis of core needle biopsy (CNB) and surgical specimen results. Methods: 422 patients underwent primary operations for early breast cancer at Tokyo-West Tokushukai Hospital (Tokyo, Japan) from October 2008 to December 2012. Among these patients, 262 patients who received CNB prior to operation were enrolled. Those patients who received preoperative chemotherapy or had DCIS were excluded. With regard to diagnostic criteria, HER2 positivity was defined as either 3+ by IHC or FISH analysis amplification ratio of ≥2.2. In addition, if in any cases which CNB samples or surgical specimens showed HER2-positive had defined true HER2-positive cases, we assessed the false-negative results of the HER2 test via IHC using CNB samples and surgical specimens. Results: In a matched cohort of 262 patients, 59 cases showed HER2-positive (five cases were CNBs negative to surgical specimens positive, 14 cases were CNBs positive to surgical specimens negative, and 40 cases were both positive). If we decide for selection of trastuzumab target cases by CNBs only, we make mistakes in indications of trastuzumab for five (8.5%) of 59 HER2-positive cases who were CNBs negative to surgical specimens positive. Conclusions: There are quite a few cases show false negatives for HER2 testing in CNB samples. In cases of considering the indication for trastuzumab in the neoadjuvant chemotherapy, even if the CNB samples resulted in negative, we consider that retesting with FISH analysis should be carried out.

Genomic profiling of residual tumor after neoadjuvant chemotherapy for breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12106-e12106
Author(s):  
Masaya Hattori ◽  
Padma Sheila Rajagopal ◽  
Lise Sveen ◽  
Galina Khramtsova ◽  
Toshio Yoshimatsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Tissue Bank ◽  
Residual Tumor ◽  
Cancer Tissue ◽  
Genomic Profiling ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Metastatic Recurrence

e12106 Background: Patients who have residual disease after neoadjuvant chemotherapy (NAC) have a higher risk of metastatic recurrence. Residual disease likely includes therapy-resistant subclones of breast cancer cells, which untreated lead to metastases. The aim of this study was to identify additional adjuvant therapies based on genomic profiling of residual disease post NAC therapy. Methods: Next-generation sequencing of tumor samples from patients (pts) with residual invasive breast cancer after NAC was performed using a Tempus xT, 595 gene panel on matched tumor-normal samples. All samples were obtained from the University of Chicago Breast Cancer tissue bank. Clinical information was obtained from electronic health records and the cancer registry. Results: Of 23 evaluable patients enriched for African Americans, 65% were HER2-positive, 22% TNBC and 13% ER+/HER2-. At a median follow up of 2.9 years, 8 pts (35%) have recurred and 8 were dead. We identified 119 clinically actionable variants in 22 tumors, and the most commonly altered genes were TP53 (18 alterations, 74% of cases), ERBB2 (8, 26%), PIK3CA (7, 30%), CDK4 (4, 17%), MCL1 (4, 17%), and MDM2 (4, 17%). Of significance, 67% of HER2-positive pts had no detectable ERBB2 copy number gain in the residual tumor. 78% of pts had at least one potential druggable target according to CIViC and/or OncoKB: 19 variants in HER2-positive, 8 in HER2-negative. The mean estimated tumor mutation burden (TMB) was 4.34 m/MB (range: 0-26.7), and 13% were considered TMB-high ( > 9 m/MB). No patients had high-microsatellite instability type residual tumors. Conclusions: Many potentially targetable alterations reside in residual disease of both HER2-positive and -negative breast cancer after NAC. Post-NAC treatment targeting these harbored alterations and post-NAC immunotherapy could have impact on the prognosis of breast cancer patients who have residual disease after NAC. [Table: see text]

MRI accuracy in residual disease evaluation in breast cancer patients treated with neoadjuvant chemotherapy

2006 ◽  
Vol 61 (11) ◽  
pp. 946-953 ◽  
Author(s):  
P. Belli ◽  
M. Costantini ◽  
C. Malaspina ◽  
A. Magistrelli ◽  
G. LaTorre ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Residual Disease ◽  
Breast Cancer Patients
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