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.
Highlights
Axillary lymph node (ALN) status is an important independent prognostic factor for early breast cancer, as it is predictive of disease-free survival and overall survival[1,2,3]
Accurate identification of metastasis to the ALN preoperatively is essential for staging and planning of treatment regimens, including neoadjuvant chemotherapy (NAC)[4], postmastectomy radiation, and consideration of reconstruction[5,6,7]
The standard staging of the axilla preoperatively in women presenting with clinically negative lymph nodes is important since it will allow patients to be triaged to axillary lymph node dissection with a positive test result, or to sentinel lymph node biopsy (SLNB) with a negative test result[12]
Summary
Axillary lymph node (ALN) status is an important independent prognostic factor for early breast cancer, as it is predictive of disease-free survival and overall survival[1,2,3]. Postmastectomy radiation is recommended for select breast cancer patients with more than one involved lymph node since it has been shown to improve disease-free survival and overall survival[9,10,11]. Large clinical studies have reported that SLNB has a lower morbidity rate than axillary lymph node dissection, but similar accuracy[14,15,16,17]. Several studies have provided strong support that preoperative ultrasoundguided fine needle aspiration (FNA) cytology can evaluate suspicious lymph nodes with accuracy in women with breast cancer[19,20,21]. A test with a high level of sensitivity and specificity for accurate determination of a suspicious lymph node as benign or positive for cancer to assist with the further staging of breast cancer is urgently needed.
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