Non-sentinel lymph node metastases risk factors in patients with breast cancer with one or two sentinel lymph node macro-metastases
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SUBMITTER: Xu L
PROVIDER: S-EPMC10641163 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
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Project description:BackgroundIndividualized decisions are required in early-stage breast cancer patients. We aimed to establish a novel model for predicting non-sentinel lymph node (SLN) metastases in patients with positive SLNs, using preoperative and intraoperative characteristics and inflammatory indicators.MethodsThe data of 489 patients with invasive breast cancer were retrospectively collected from Xuanwu Hospital between 2014 and 2021. Among them, 96 patients with at least one positive SLN were used to build the predictive model. Univariate and multivariate analyses were performed to identify the risk factors of non-SLN metastases. A nomogram was developed using these risk factors and was validated by calibration curves. The area under the receiver operating characteristics curve (AUC) and decision curve analyses (DCA) were used to compare our novel nomogram with the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. Cross-validation was performed for further internal validation of the predictive model. External validation was conducted using another treatment group (n=46 patients) in Xuanwu Hospital.ResultsNon-SLN metastases occurred in 42 of the 83 patients with positive SLNs (50.6%). Multivariate stepwise logistic regression indicated that the risk factors were age (P=0.032), number of positive SLNs (P=0.020), number of negative SLNs (P=0.011), resected tumor size (P=0.038), and monocyte count (P=0.012). A predictive model was developed and virtualized by nomogram using these five risk factors. The AUC of our nomogram was 0.867, which was significantly higher than that of the MSKCC model. DCA also showed a superior clinical value for our novel nomogram. After 10-fold cross-validation with 400 times repetitions, the AUC of our model was still 0.830. External validation of our model showed an AUC of 0.727. The model was well-calibrated in the internal and external validation series.ConclusionsA five-factor nomogram was developed for predicting non-SLN metastases in early-stage breast cancer patients. This novel tool exhibited good accuracy and could assist clinicians with intraoperative decisions in breast cancer patients with positive SLNs.
| S-EPMC10333765 | biostudies-literature
Project description:BackgroundThe rate of breast-conserving surgery is very low in China, compared with that in developed countries; most breast cancer patients receive mastectomy. It is great important to explore the possibility of omitting axillary lymph node dissection (ALND) in early-stage breast cancer patients with 1 or 2 positive sentinel lymph nodes (SLNs) in China. The aim of this study was to develop a nomogram based on elastography for the prediction of the risk of non-SLN (NSLN) metastasis in early-stage breast cancer patients with 1 or 2 positive SLNs.MethodsA total of 601 breast cancer patients were initially recruited. According to the inclusion and exclusion criteria, 118 early-stage breast cancer patients with 1 or 2 positive SLNs were finally enrolled and were assigned to the training cohort (n=82) and the validation cohort (n=36), respectively. In the training cohort, the independent predictors were screened by logistic regression analysis and then were used to conducted the nomogram for the prediction of NSLN metastasis in early-stage breast cancer patients with 1 or 2 positive SLNs. The calibration curves, concordance index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and Decision curve analysis (DCA) were used to verified the performance of the nomogram.ResultsThe multivariable analysis showed that the enrolled patients with positive HER2 expression (OR=6.179, P=0.013), Ki67≥14% (OR=8.976, P=0.015), larger lesion size (OR=1.038, P=0.045), and higher Emean (OR=2.237, P=0.006) were observed to be the independent factors of NSLN metastasis. Based on the above four independent predictors, a nomogram was conducted to predict the risk of the NSLN metastasis in early-stage breast cancer patients with 1 or 2 positive SLNs. The nomogram showed good discrimination in the prediction of NSLN metastasis, with bias-corrected C-index of 0.855 (95% CI, 0.754-0.956) and 0.853 (95% CI, 0.724-0.983) in the training and validation cohorts, respectively. Furthermore, the AUC was 0.877 (95%CI: 0.776- 0.978) and 0.861 (95%CI: 0.732-0.991), respectively, indicating a good performance of the nomogram. The calibration curve suggested a satisfactory agreement between the predictive and actual risk in both the training (χ2 = 11.484, P=0.176, HL test) and validation (χ2 = 6.247, p = 0.620, HL test) cohorts, and the obvious clinical nets were revealed by DCA.ConclusionsWe conducted a satisfactory nomogram model to evaluate the risk of NSLN metastasis in early-stage breast cancer patients with 1 or 2 SLN metastases. This model could be considered as an ancillary tool to help such patients to be selectively exempted from ALND.
| S-EPMC10277680 | biostudies-literature
Project description:BackgroundPatients with breast cancer presenting with single lymph node metastasis (from a sentinel node) experience prolonged survival compared to patients with multiple lymph node metastases (≥3). However, little information is available on the genetic and immunological characteristics of breast cancer metastases within the regional lymph nodes as they progress from the sentinel lymph node (SLN) downstream to multiple regional lymph nodes (MLNs).MethodsGenomic profiling was performed using a next-generation sequencing panel covering 520 cancer-related genes in the primary tumour and metastatic lymph nodes of 157 female patients with breast cancer. We included primary tumours, metastatic lymph nodes and adjacent clinically normal lymph nodes (20 patients from the SLN group and 28 patients from the MLNs group) in the whole transcriptome analysis.FindingsThe downstream metastatic lymph nodes (P = 0.029) and the primary breast tumours (P = 0.011) had a higher frequency of PIK3CA mutations compared to the SLN metastasis. We identified a distinct group of 14 mutations from single sentinel node metastasis and a different group of 15 mutations from multiple nodal metastases. Only 4 distinct mutations (PIK3CA, CDK4, NFKBIA and CDKN1B) were conserved in metastases from both lymph node settings. The tumour mutational burden (TMB) was significantly lower in single nodal metastasis compared to the paired primary breast cancer (P = 0.0021), while the decline in TMB did not reach statistical significance in the MLNs group (P = 0.083). In the gene set enrichment analysis, we identified 4 upregulated signatures in both primary tumour and nodal metastases from the MLNs group, including 3 Epithelial-mesenchymal transition(EMT) signatures and 1 angiogenesis signature. Both the CD8/Treg ratio and the CD8/EMT ratio were significantly higher in adjacent normal lymph nodes from patients with a single metastasis in the SLN compared with samples from the MLNs group (P = 0.045 and P = 0.023, respectively). This suggests that the immune defence from the MLNs patients might have a less favourable microenvironment, thus permitting multiple lymph nodes metastasis.InterpretationSingle lymph node metastases and multiple lymph node metastases have significant differences in their molecular profiles and immune profiles. The findings are associated with more aggressive tumour characteristics and less favourable immune charactoristics in patients with multiple nodal metastases compared to those with a single metastasis in the sentinel node.FundingThis work was supported by funds from High-level Hospital Construction Project (DFJH201921), the National Natural Science Foundation of China (81902828 and 82002928), the Fundamental Research Funds for the Central Universities (y2syD2192230), and the Medical Scientific Research Foundation of Guangdong Province (B2019039).
| S-EPMC8399410 | biostudies-literature
Project description:BackgroundCurrent practice is to perform a completion axillary lymph node dissection (ALND) for breast cancer patients with tumor-involved sentinel lymph nodes (SLNs), although fewer than half will have non-sentinel node (NSLN) metastasis. Our goal was to develop new models to quantify the risk of NSLN metastasis in SLN-positive patients and to compare predictive capabilities to another widely used model.MethodsWe constructed three models to predict NSLN status: recursive partitioning with receiver operating characteristic curves (RP-ROC), boosted Classification and Regression Trees (CART), and multivariate logistic regression (MLR) informed by CART. Data were compiled from a multicenter Northern California and Oregon database of 784 patients who prospectively underwent SLN biopsy and completion ALND. We compared the predictive abilities of our best model and the Memorial Sloan-Kettering Breast Cancer Nomogram (Nomogram) in our dataset and an independent dataset from Northwestern University.Results285 patients had positive SLNs, of which 213 had known angiolymphatic invasion status and 171 had complete pathologic data including hormone receptor status. 264 (93%) patients had limited SLN disease (micrometastasis, 70%, or isolated tumor cells, 23%). 101 (35%) of all SLN-positive patients had tumor-involved NSLNs. Three variables (tumor size, angiolymphatic invasion, and SLN metastasis size) predicted risk in all our models. RP-ROC and boosted CART stratified patients into four risk levels. MLR informed by CART was most accurate. Using two composite predictors calculated from three variables, MLR informed by CART was more accurate than the Nomogram computed using eight predictors. In our dataset, area under ROC curve (AUC) was 0.83/0.85 for MLR (n = 213/n = 171) and 0.77 for Nomogram (n = 171). When applied to an independent dataset (n = 77), AUC was 0.74 for our model and 0.62 for Nomogram. The composite predictors in our model were the product of angiolymphatic invasion and size of SLN metastasis, and the product of tumor size and square of SLN metastasis size.ConclusionWe present a new model developed from a community-based SLN database that uses only three rather than eight variables to achieve higher accuracy than the Nomogram for predicting NSLN status in two different datasets.
| S-EPMC2311316 | biostudies-literature
Project description:BackgroundThe initial results of the SINODAR-ONE randomized clinical trial reported that patients with T1-2 breast cancer and one to two macrometastatic sentinel lymph nodes treated with breast-conserving surgery, sentinel lymph node biopsy only, and adjuvant therapy did not present worse 3-year survival, regional recurrence, or distant recurrence rates compared with those treated with axillary lymph node dissection. To extend the recommendation of axillary lymph node dissection omission even in patients treated with mastectomy, a sub-analysis of the SINODAR-ONE trial is presented here.MethodsPatients with T1-2 breast cancer and no more than two metastatic sentinel lymph nodes undergoing mastectomy were analysed. After sentinel lymph node biopsy, patients were randomly assigned to receive either axillary lymph node dissection followed by adjuvant treatment (standard arm) or adjuvant treatment alone (experimental arm). The primary endpoint was overall survival. The secondary endpoint was recurrence-free survival.ResultsA total of 218 patients were treated with mastectomy; 111 were randomly assigned to the axillary lymph node dissection group and 107 to the sentinel lymph node biopsy-only group. At a median follow-up of 33.0 months, there were three deaths (two deaths in the axillary lymph node dissection group and one death in the sentinel lymph node biopsy-only group). There were five recurrences in each treatment arm. No axillary lymph node recurrence was observed. The 5-year overall survival rates were 97.8 and 98.7 per cent in the axillary lymph node dissection treatment arm and the sentinel lymph node biopsy-only treatment arm, respectively (P = 0.597). The 5-year recurrence-free survival rates were 95.7 and 94.1 per cent in the axillary lymph node dissection treatment arm and the sentinel lymph node biopsy treatment arm, respectively (P = 0.821).ConclusionIn patients with T1-2 breast cancer and one to two macrometastatic sentinel lymph nodes treated with mastectomy, the overall survival and recurrence-free survival rates of patients treated with sentinel lymph node biopsy only were not inferior to those treated with axillary lymph node dissection. To strengthen the conclusion of the trial, the enrolment of patients treated with mastectomy was reopened as a single-arm experimental study.Registration numberNCT05160324 (http://www.clinicaltrials.gov).
| S-EPMC10492188 | biostudies-literature
Project description:BackgroundSentinel lymph node metastasis (SLNM) is a critical factor in the prognosis and treatment planning for breast cancer (BC), as it indicates the potential spread of cancer to other parts of the body. The accurate prediction and diagnosis of SLNM are essential for improving clinical outcomes and guiding treatment decisions.ObjectiveThis study aimed to construct a Lasso regression model by integrating multimodal ultrasound (US) techniques, including US, shear wave elastography (SWE), and contrast-enhanced ultrasound (CEUS), to improve the predictive accuracy of sentinel lymph node metastasis in breast cancer and provide more precise guidance for clinical treatment.ResultsA total of 253 eligible samples were screened, of which 148 were group benign and 105 were group malignant. There were statistically significant differences (p < 0.05) between group malignant patients in terms of age, palpable mass, body mass index, distance to nipple, maximum diameter, blood flow, microcalcification, 2D border, 2D morphology, and 2D uniformity and group benign. The Lasso regression model was useful in the diagnosis of benign and malignant nodules with an AUC of 0.966 and in diagnosing SLNM with an AUC of 0.832.ConclusionIn this study, we successfully constructed and validated a Lasso regression model based on the multimodal ultrasound technique for predicting whether SLNM occurs in BCs, showing high diagnostic accuracy.
| S-EPMC11411459 | biostudies-literature
Project description:BackgroundOne-step nucleic acid amplification (OSNA) for cytokeratin 19 messenger RNA is an intraoperative diagnostic procedure for the detection of lymph node metastasis.ObjectiveThis study aimed to construct intraoperative nomograms using OSNA for the prediction of non-sentinel lymph node (NSLN) metastasis and four or more axillary lymph node (ALN) metastases.MethodsOf the 4736 breast cancer patients (T1-3, N0) who underwent sentinel lymph node (SLN) biopsy and had SLNs examined intraoperatively with OSNA, 623 with SLN metastasis treated with completion ALN dissection (cALND) were retrospectively analyzed, and were randomly divided into training (n = 312) and validation (n = 311) sets.ResultsOf the clinicopathological parameters available preoperatively and intraoperatively, the multivariate analysis of the training set revealed that clinical tumor size and total tumor load (TTL) determined by OSNA were significantly associated with NSLN metastasis, and that clinical tumor size, number of macrometastatic SLNs, and TTL were significantly associated with four or more ALN metastases. Nomograms for NSLN metastasis and four or more ALN metastases were constructed using these parameters, and their area under the receiver operating characteristic curve (AUC) of the validation set were both 0.70, with a diagnostic accuracy similar to that of previously reported postoperative nomograms.ConclusionsWe constructed intraoperative nomograms using OSNA for the prediction of NSLN metastasis and four or more ALN metastases. These nomograms are as accurate as the conventional postoperative nomograms and might be helpful for decision making regarding the indication for cALND or the choice of adjuvant chemotherapeutic regimens and radiation field.
| S-EPMC6097722 | biostudies-literature
Project description:The incidence of malignant melanoma has increased over the past 25 years in the UK, but death rates have remained fairly constant. The 5-year survival rate ranges from 20% to 95%, depending on disease stage. Risks are greater in white populations and in people with higher numbers of skin naevi. We conducted a systematic overview, aiming to answer the following clinical question: What is the evidence for performing a sentinel lymph node biopsy in people with malignant melanoma with clinically uninvolved lymph nodes? We searched: Medline, Embase, The Cochrane Library and other important databases up to October 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). At this update, searching of electronic databases retrieved 221 studies. After deduplication and removal of conference abstracts, 99 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 58 studies and the further review of 41 full publications. Of the 41 full articles evaluated, one systematic review and three RCTs were added at this update. We performed a GRADE evaluation for two PICO combinations. In this systematic overview, we evaluated the evidence for performing sentinel lymph node biopsy in people with malignant melanoma with clinically uninvolved lymph nodes.
| S-EPMC4720216 | biostudies-literature
Project description:Introduction: Best surgical approach of axillary staging remains controversial in locally recurrent breast cancer. We evaluated the reliability of repeat sentinel lymph node biopsy (reSLNB) in patients with ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) with sentinel lymph node biopsy (SLNB) in terms of identification rate (IR) and false negative rate (FNR). To address the FNR, we identified patients who underwent sequential axillary lymph node dissection (ALND) after reSLNB. Methods: A systematic search of PubMed, EMBASE, and Cochrane Library were conducted to identify patient-level data from articles. We searched for data of patients who underwent BCS with SLNB for primary breast cancer and who underwent sequential ALND after reSLNB due to local recurrence. Patients data was also identified by the same criteria at two institutions. Results: In total, 197 peer-reviewed publications were obtained, of which 20 included patients who met the eligibility criteria. Data from 464 patients were collected. From the two institutions, 31 patients were identified. A total of 495 patients were pooled. The IR of reSLNB was 71.9% (356/495). To address the FNR of reSLNB, 171 patients who underwent ALND after reSLNB were identified. The FNR and accuracy of reSLNB were 9.4% (5/53) and 97.1% (165/170), respectively. Conclusion: Our pooled data analysis showed that the FNR of reSLNB is lower than 10%, indicating that this operation is a reliable axillary surgery in patients with IBTR after they underwent BCS.
| S-EPMC7538804 | biostudies-literature
Project description:BackgroundPrediction of non-sentinel lymph node (SLN) status after primary systemic therapy (PST) may allow tailored axillary staging. The aim of this analysis was to compare established nomograms from i) the primary operative (n = 6) and ii) the neoadjuvant (n = 1) setting with an optimized nomogram to predict non-SLN status in patients after PST.Methods181 patients converting from cN1 prior to PST to ycN0 but found to have a histologically positive SLN in the SENTINA trial were analyzed. Established models were applied. An optimized model was compiled using univariate and subsequent multivariable logistic regression (backward selection, likelihood ratio test).ResultsArea-under-the-curve (AUC) values from the primary operative models showed sufficient performance (0.82-0.71). For the neoadjuvant model, the AUC was found to be inferior to prior analyses (0.66) but within published confidence intervals. The SENTINA nomogram comprised the diameter of the largest lymph node (p = 0.006, odds ratio (OR) = 1.19), tumor size prior to PST (p = 0.085, OR = 1.31), and number of all positive SLN (p = 0.083, OR = 2.04). This model was validated using a separate cohort of arm C (n = 168, AUC 0.79, 95% confidence interval 0.74-0.85).ConclusionWe validated 7 models of prediction of non-SLN among patients showing axillary conversion through PST. Our own 'SENTINA nomogram' yielded AUC values comparable to previous nomograms.
| S-EPMC6381911 | biostudies-literature