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Automated and rapid detection of cancer in suspicious axillary lymph nodes in patients with breast cancer.

ABSTRACT: Preoperative staging of suspicious axillary lymph nodes (ALNs) allows patients to be triaged to ALN dissection or to sentinel lymph node biopsy (SLNB). Ultrasound-guided fine needle aspiration (FNA) and cytology of ALN is moderately sensitive but its clinical utility relies heavily on the cytologist's experience. We proposed that the 5-h automated GeneXpert system-based prototype breast cancer detection assay (BCDA) that quantitatively measures DNA methylation in ten tumor-specific gene markers could provide a facile, accurate test for detecting cancer in FNA of enlarged lymph nodes. We validated the assay in ALN-FNA samples from a prospective study of patients (N = 230) undergoing SLNB. In a blinded analysis of 218 evaluable LN-FNAs from 108 malignant and 110 benign LNs by histology, BCDA displayed a sensitivity of 90.7% and specificity of 99.1%, achieving an area under the ROC curve, AUC of 0.958 (95% CI: 0.928-0.989; P < 0.0001). Next, we conducted a study of archival FNAs of ipsilateral palpable LNs (malignant, N = 72, benign, N = 53 by cytology) collected in the outpatient setting prior to neoadjuvant chemotherapy (NAC). Using the ROC-threshold determined in the prospective study, compared to cytology, BCDA achieved a sensitivity of 94.4% and a specificity of 92.5% with a ROC-AUC = 0.977 (95% CI: 0.953-1.000; P < 0.0001). Our study shows that the automated assay detects cancer in suspicious lymph nodes with a high level of accuracy within 5 h. This cancer detection assay, scalable for analysis to scores of LN FNAs, could assist in determining eligibility of patients to different treatment regimens.

SUBMITTER: Li J

PROVIDER: S-EPMC8263765 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: Lymph node status is one of the decisive prognostic factors in breast cancer. Chemotherapy targeting regional lymphatic tissues has emerged as a promising therapy for the treatment of malignancies with a high tendency to disseminate lymphatically. The present study determined the drug concentrations in axillary lymph nodes after lymphatic chemotherapy (LC) in patients with breast cancer and compared the results with those receiving intravenous chemotherapy (VC) to investigate whether LC could improve the accumulation of anticancer drug in regional lymph nodes. METHODS: Sixty patients with breast carcinoma confirmed by preoperative puncture-biopsy were divided into two groups at random. The LC group (n = 30) received a subcutaneous injection of 4 ml of carboplatin-activated carbon suspension, containing 20 mg of carboplatin, adjacent to the primary tumour. The VC group (n = 30) received an intravenous administration of an equal dose of aqueous carboplatin. At 1, 12, 24, 36 and 48 hours after administration, modified radical mammectomies were performed on 12 patients at each time point, with 6 from each group. Axillary lymph nodes were removed for pathological examination. The platinum concentrations in nodes were determined by Zeeman atomic absorption spectrometry. RESULTS: A total of 275 axillary lymph nodes were resected, with 154 in the LC group and 121 in the VC group. Of the 275 lymph nodes, 136 (49.5%) from 23 patients (38.3%) had histopathologically detected metastases. At 1, 12, 24, 36 and 48 hours after injection, the carboplatin concentrations in the LC group were 11.82 +/- 3.50, 23.58 +/- 7.34, 18.22 +/- 4.93, 16.70 +/- 5.15 and 14.62 +/- 4.29 microg/g (means +/- SD), respectively, whereas those in the VC group were 0.06 +/- 0.02, 0.11 +/- 0.05, 0.10 +/- 0.02, 0.05 +/- 0.02 and 0 microg/g, respectively. Significant differences were found in each corresponding comparison (P < 0.001). Lymph node metastasis was uncorrelated with drug concentration (P > 0.05). CONCLUSION: LC can effectively and continuously improve the drug concentrations in axillary lymph nodes in patients with breast cancer, in comparison with VC.

Project description:PurposeObesity associated fat infiltration of organ systems is accompanied by organ dysfunction and poor cancer outcomes. Obese women demonstrate variable degrees of fat infiltration of axillary lymph nodes (LNs), and they are at increased risk for node-positive breast cancer. However, the relationship between enlarged axillary nodes and axillary metastases has not been investigated. The purpose of this study is to evaluate the association between axillary metastases and fat-enlarged axillary nodes visualized on mammograms and breast MRI in obese women with a diagnosis of invasive breast cancer.MethodsThis retrospective case-control study included 431 patients with histologically confirmed invasive breast cancer. The primary analysis of this study included 306 patients with pre-treatment and pre-operative breast MRI and body mass index (BMI) > 30 (201 node-positive cases and 105 randomly selected node-negative controls) diagnosed with invasive breast cancer between April 1, 2011, and March 1, 2020. The largest visible LN was measured in the axilla contralateral to the known breast cancer on breast MRI. Multivariate logistic regression models were used to assess the association between node-positive status and LN size adjusting for age, BMI, tumor size, tumor grade, tumor subtype, and lymphovascular invasion.ResultsA strong likelihood of node-positive breast cancer was observed among obese women with fat-expanded lymph nodes (adjusted OR for the 4th vs. 1st quartile for contralateral LN size on MRI: 9.70; 95% CI 4.26, 23.50; p < 0.001). The receiver operating characteristic curve for size of fat-enlarged nodes in the contralateral axilla identified on breast MRI had an area under the curve of 0.72 for predicting axillary metastasis, and this increased to 0.77 when combined with patient and tumor characteristics.ConclusionFat expansion of axillary lymph nodes was associated with a high likelihood of axillary metastases in obese women with invasive breast cancer independent of BMI and tumor characteristics.

Project description:Nodal ultrasonography with needle biopsy of abnormal lymph nodes helps to define the extent of breast cancer before neoadjuvant chemotherapy. A clip can be placed to designate lymph nodes with documented metastases. Targeted axillary dissection or selective removal of lymph nodes known to contain metastases (clip-containing nodes) as well as sentinel lymph nodes (SLNs) may provide more accurate assessment of the pathologic response after neoadjuvant chemotherapy.To determine the feasibility of image-guided localization and resection of lymph nodes containing known metastases.This prospective feasibility trial performed at MD Anderson Cancer Center, Houston, Texas, included 12 patients with axillary nodal metastases confirmed by results of fine-needle aspiration biopsy who had a clip placed in the lymph node targeted for biopsy from December 1, 2012, through November 30, 2013.Preoperative targeting of the clip-containing lymph node under ultrasonographic guidance consisting of wire localization in 2 patients and placement of radioactive iodine I 125 (125I)-labeled seeds in 10 patients. Surgeons removed the localized lymph node before completion axillary lymph node dissection and used radiography of the specimen to confirm removal of the clip-containing lymph node and seed.Confirmation of the removal of the clip-containing lymph node.Image-guided localization and selective removal were successful in all 12 patients. Five patients underwent SLN dissection in addition to removal of the clip-containing lymph node. Placement of 125I seeds did not interfere with lymphoscintigraphy or intraoperative identification of SLNs. In 4 of the 5 patients (80%), the clip-containing lymph node was one of the SLNs. Ten patients completed neoadjuvant chemotherapy before surgery. Of the 9 patients who underwent lymph node dissection, 4 (44%) had residual nodal disease after chemotherapy; all had disease identified in the clip-containing lymph node.Axillary lymph nodes marked with a clip can be localized and selectively removed to accomplish targeted axillary dissection, which is technically possible after chemotherapy and is easily performed with other axillary surgery, such as SLN dissection. The ability to add selective removal of the clip-containing lymph nodes to SLN dissection may identify patients for limited nodal surgery after chemotherapy with increased accuracy for determining residual disease compared with SLN identification alone.

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Automated and rapid detection of cancer in suspicious axillary lymph nodes in patients with breast cancer.

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