Non-sentinel Node Metastasis Research Articles

The predictive power of serum S-100B for non-sentinel node positivity in melanoma patients

BackgroundCompletion lymph node dissection (CLND) in sentinel node (SN) positive melanoma patients leads to substantial morbidity and costs, while only approximately 20% have a metastasis in non-sentinel nodes (NSNs). The aim of this study was to investigate if the biomarkers S-100B and Lactate Dehydrogenase (LDH) are associated with NSN positivity, to identify patients in whom CLND could safely be omitted. MethodsAll SN positive patients who underwent CLND at the University Medical Centre Groningen between January 2004 and January 2015 were analysed. Patient and tumor characteristics, and serum S-100B and LDH values measured the day before CLND were statistically tested for their association with NSN positivity. ResultsNSN positivity was found in 20.6% of the 107 patients undergoing CLND. Univariate analysis revealed male gender (p = 0.02), melanoma of the lower extremity (p = 0.05), Breslow thickness (p = 0.004), ulceration (p = 0.04), proportion of involved SNs (p = 0.045) and S-100B value (p = 0.01) to be associated with NSN positivity. LDH level was not significantly associated with positive NSNs (p = 0.39). In multivariable analysis, S-100B showed to have the strongest association with NSN positivity, within its reference interval of 0.20 μg/l (p = 0.02, odds ratio 5.71, 95% confidence interval 1.37–23.87). ConclusionIn this study, the preoperatively measured S-100B value is the strongest predictor for NSN positivity in patients planned for CLND. Fluctuations of the S-100B level within the reference interval might give important clues about residual tumor load. Although further validation will be needed, this new closer look of S-100B could be of value in patient selection for CLND in the future.

Prediction of additional lymph node involvement in breast cancer patients with positive sentinel lymph nodes.

Axillary lymph node dissection (ALND) has traditionally been the principal method for evaluating axillary lymph node status in breast cancer patients. In the past decades sentinel lymph nodes biopsy after lymphatic mapping has been used to stage the disease. The majority of sentinel lymph nodes (SLN) positive patients do not have additional metastases in non-sentinel nodes (non-SLN) after additional ALND. These patients are exposed to the morbidity of ALND without any benefit from additional axillary clearence. In the present study we would like to asses the criteria for selecting those patients, who have high risk for non-SLN metastases in the axilla in cases of positive SLN. In this retrospective analysis, clinical and pathologic data from 163 patients who underwent SLN biopsy followed by ALND were collected. Following clinical and pathological characteristics were analyzed to predict the likehood of non-SLN metastases: age, staging, histologic type and grading of the tumors, hormonal receptor status, HER-2 receptor status and Ki-67 protein, angioinvasion, metastases in SLN and non-SLN. Relative frequencies of individual characteristics between sample groups were statistically tested by Chi-square test at significance level p=0.5, when sample sizes in groups were small (≤5) by Fisher´s exact test. Metastasis in SLN were present in 67 (41%) of patients, 48 patients (29,4%) had metastasis also in non-SLN. The ratio between non-SLN positive / non-SLN negative lymph nodes in patients with positive SLN increases with the stage of the disease, the difference between values for the pT1c and pT2 stadium was statistically significant (p = 0.0296). The same applies to grading, but the differences were not significant (p>0.05). We could not find significant differences for angioinvasion of the tumor, probably for small number of patients with angioinvasion (p>0.05).Only the stage of the tumor was shown to be significant in predicting the metastasis in non-SLN in our group of breast cancer patients with positive SLN Nearly 80% of the patients of 70 years and older displayed no benefit from axillary staging, because of negative SLN as well as non-SLN, although thanks to the small sample size this was not astatistically significant result. Furthermore, current recommendations for axillary staging in breast cancer patients are discussed.

Risk factors of non-sentinel lymph node metastasis and performance of MSKCC nomogramin breast cancer patients with metastatic sentinel lymph node

To study the factors influencing the non-sentinel lymph node(NSLN) status and to assess performance of Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram in predicting sentinel lymph node(SLN) metastases in a SLN positive Chinese breast cancer population. Data were collected from breast cancer patients who were diagnosed with pathological positive sentinel lymph node and received further axillary lymph node dissection(ALND) in Shanghai Ruijin Hospital from January 2011 to August 2014. MSKCC nomogram was used to calculate each patient's NSLN metastasis risk score. The receiver operator characteristic curve (ROC curve) and the area under the ROC curve (AUC) was used to assess the predictive accuracy of the model. Among the 1 147 patients who received sentinel biopsy, 150 SLN positive patients who received ALND were enrolled in this study. By univariate analysis, multifocal breast cancer (χ(2)=5.887, P=0.015), SLN+ /SLN ratio (χ(2)=6.683, P=0.010) and abnormal axillary lymph node displayed by ultrasound (χ(2)=7.736, P=0.005) were the influencing factors of NSLN metastases. By multivariate analysis, multifocal breast cancer (OR=7.25, 95% CI: 1.73 to 30.43, P=0.007), SLN+ /SLN ratio ≥ 0.5 (OR=2.564, 95% CI: 1.22 to 5.39, P=0.013) and abnormal axillary lymph node displayed by ultrasound (OR=2.471, 95% CI: 1.18 to 5.19, P=0.017) were the independent influencing factors of NSLN metastases. The AUC of MSKCC nomogram in this population was 0.677. For breast cancer patients with positive sentinel lymph node, multifocality, SLN+ /SLN ratio and axillary lymphadenopathy displayed by ultrasound is related to NSLN metastasis. MSKCC has low accuracy in predicting NSLN status of this population.

Risk of non-sentinel node metastases in patients with symptomatic cancers compared to screen-detected breast cancers

Background: Symptomatic breast cancers may be more aggressive as compared to screen-detected breast cancers. This could favor axillary lymph node dissection (ALND) in patients with symptomatic breast cancer and positive sentinel nodes.Method: We identified 955 patients registered in the Danish Breast Cancer Cooperative Group (DBCG) Database in 2008 – 2010 with micrometastases (773) or isolated tumor cells (ITC) (182) in the sentinel node. Patients were cross-checked in the Danish Quality Database of Mammography Screening and 481 patients were identified as screen-detected cancers. The remaining 474 patients were considered as having symptomatic cancers. Multivariate analyses of the risk of non-sentinel node metastases were performed including known risk factors for non-sentinel node metastases as well as method of detection.Results: 18% of the patients had metastases in non-sentinel nodes. This was evenly distributed between patients with symptomatic and screen-detected cancers; 18.5% vs 17.5% (OR 1.07; 95% CI 0.77–1.49; p = 0.69). In patients with micrometastases 21% had non-sentinel node metastases in the group with symptomatic cancers compared to 19% of patients with screen-detected cancers. This difference was not significant (OR 1.16; 95% CI 0.81–1.65, p = 0.43). Neither the multivariate analysis showed an increased risk of non-sentinel node metastases in patients with symptomatic cancers compared to screen-detected cancers (OR 1.12, CI 0.77–1.62, p = 0.55). In patients with ITCs 8% of patients with symptomatic cancers had non-sentinel node metastases compared to 13% of patients with screen-detected cancers. This difference was not significant (OR 0.58; 95% CI 0.22–1.54, p = 0.27). In the multivariate analysis, the risk of non-sentinel node metastases was still not significantly increased in patients with symptomatic cancers compared to screen-detected cancers (OR 0.45; 95% CI 0.16–1.27, p = 0.13).Conclusion: We did not find any clinically relevant difference in the risk of non-sentinel node metastases between patients with symptomatic and screen-detected cancers with micrometastases or ITC in the sentinel node.

The use of one-step nucleic acid amplification (OSNA) and tumor-related factors in the axillary management of breast cancer: A predictive model.

61 Background: Recent trends in surgical practice advocate selective use of axillary nodal clearance (ANC) following sentinel lymph node biopsy (SNB) in the treatment of breast cancer. We aimed to determine the effectiveness of one-step nucleic acid amplification (OSNA) using CK19 mRNA copy number and tumor-related factors in predicting non-sentinel axillary nodal involvement, in order to formulate local guidelines for ANC. Methods: Patients due to have SNB at our institution for invasive breast cancer as well as selected patients with high grade ductal carcinoma in situ with negative assessment of the axilla on pre-operative imaging were included. Alternate slices of each node were sent for assessment by either OSNA or Histopathology. Immediate ANC was performed if OSNA was positive. The CK19 mRNA copy number, the total tumor load (summation of m RNA copy number of positive nodes,TTL), the total nodal status at ANC and tumor characteristics including grade, tumor size and lymphovascular invasion (LVI) for each patient were determined. A model of risk probability was constructed using TTL and tumor related factors. Results: 664 nodes were examined from 425 patients who had SNB performed between 2011 and 2014. After excluding 8 patients who did not meet the study criteria, 648 nodes from 417 patients were included for analysis. The concordance between OSNA and histology was 91.4%; positive predictive value (PPV) and negative predictive value (NPV) was 77% and 97% respectively. Patients with TTL less than 1400 did not have additional non sentinel lymph node involvement. TTL (p<0.01), and presence of LVI (p<0.05) were predictive for additional nodal involvement. The risk model identified all patients with more than 2 positive nodes as requiring ANC. All patients with non-sentinel node metastases at ANC were selected. Conclusions: OSNA is a sensitive and reliable intraoperative method for the detection of sentinel node metastases. Our study has shown it can also be used to predict the presence of non-sentinel metastases. Patients deemed high risk may be offered immediate ANC while axillary surgery in other groups may be omitted or be decision-based on risk stratification.

Evaluation of the Probability of Non-sentinel Lymph Node Metastasis in Breast Cancer Patients with Sentinel Lymph Node Metastasis using Two Different Methods.

The aim of this retrospective clinical study was to evaluate the accuracy and feasibility of two different clinical scales, namely the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and Tenon's axillary scoring system, which were developed for predicting the non-sentinel lymph node (NSLN) status in our breast cancer patients. The medical records of patients who were diagnosed with breast cancer between January 2010 and November 2013 were reviewed. Those who underwent sentinel lymph node biopsy (SLNB) for axillary staging were recruited for the study, and patients who were found to have positive SLNB and thus were subsequently subjected to axillary lymph node dissection (ALND) were also included. Patients who had neoadjuvant therapy, who had clinically positive axilla, and who had stage 4 disease were excluded. Patients were divided into two groups. Group 1 included those who had negative NSLNs, whereas Group 2 included those who had positive NSLNs. The following data were collected: age, tumor size, histopathological characteristics of the tumor, presence of lymphovascular invasion, presence of multifocality, number of negative and positive NSLNs, size of metastases, histopathological method used to define metastases, and receptor status of the tumor. The score of each patient was calculated according to the MSKCC nomogram and Tenon's axillary scoring system. Statistical analysis was conducted to investigate the correlation between the scores and the involvement of NSLNs. The medical records of patients who were diagnosed with breast cancer and found to have SLNB for axillary staging was reviewed. Finally, 50 patients who had positive SLNB and thus were subsequently subjected to ALND were included in the study. There were 17 and 33 patients in Groups 1 and 2, respectively. Both the MSKCC nomogram and Tenon's axillary scoring system were demonstrated to be significantly accurate in the prediction of the involvement of NSLNs (p<0.05 for each). Among all the parameters, the only one that was found to be correlated with the risk of NSLN involvement was the presence of lymphovascular invasion. The MSKCC nomogram and Tenon's axillary scoring system both seem to be reliable tools for the assessment of NSLN status in SLNB-positive breast cancer in our breast cancer population. Nevertheless, the omission of ALNB in SLNB-positive breast cancer cannot be yet recommended because of the lack of long-term results of current nomograms and scoring systems.

Completion Lymph Node Dissection Based on Risk of Nonsentinel Metastasis in Cutaneous Melanoma of the Head and Neck.

Theoretically, completion lymph node dissection (CNLD) should have the lowest benefit in the absence of nonsentinel lymph node (NSLN) metastases. For this reason, substantial research efforts have attempted to define specific criteria that are associated with a low-enough risk of NSLN positivity so that CLND can be deferred. Our objectives were (1) to identify features associated with low risk of NSLN positivity in sentinel lymph node-positive cutaneous melanoma of the head and neck (CMHN) and (2) to analyze the effect of CLND on 5-year disease-specific survival (DSS) among subgroups stratified by risk of NSLN metastasis. Retrospective analysis of population-based data. SEER database. Patients with sentinel lymph node-positive CMHN were categorized according to lymph node treatment following sentinel lymph node biopsy (SLNB): 210 underwent CLND and 140 deferred. Clinicopathologic characteristics and survival were compared between SLNB+CLND and SLNB-only groups. Survival analyses were stratified by age and characteristics associated with NSLN positivity. Minimal tumor thickness and nonulceration were associated with lowest risk of positive NSLN (P < .025). In the subgroup with the lowest risk of metastasis, patients aged <60 years who underwent CLND+SLNB had markedly better DSS than those receiving SLNB only (>90% vs <25%; P < .0025). Paradoxically, in subgroups with a higher risk of NSLN metastasis, DSS was similar whether CLND was performed or not (P > .25). Selecting patients for CLND according to risk of NSLN metastasis may be a suboptimal strategy for improving DSS. We believe that CLND should not be withheld on the basis of "low risk" features in CMHN.

Validation of Six Nomograms for Predicting Non-sentinel Lymph Node Metastases in a Dutch Breast Cancer Population.

BackgroundThe usefulness of axillary lymph node dissection (ALND) in patients with positive sentinel nodes (SN) is still an ongoing debate. Several nomograms have been developed for predicting non-sentinel lymph node metastases (NSLNM). We validated six nomograms using data from 10 years of breast cancer surgery in our hospital.MethodsWe retrospectively analyzed all patients with a proven breast malignancy and a SN procedure between 2001 and 2011 in our hospital.ResultsData from 1084 patients were reviewed; 260 (24 %) had a positive SN. No patients with isolated tumor cells, 6 patients (8 %) with micrometastases, and 65 patients (41 %) with macrometastases had additional axillary NSLNM. In 2 patients (3 %) with micrometastases, the ALND influenced postoperative treatment. In the group of patients with macrometastases tumor size >2 cm, extranodal growth and having no negative SNs were predictors of NSLNM. The revised MD Anderson Cancer Center and Helsinki nomograms performed the best, with an area under the curve value of 0.78.ConclusionsALND could probably be safely omitted in most patients with micrometastases but is still indicated in patients with macrometastases, especially in patients with tumor size >2 cm, extranodal growth, and no negative SNs. The revised MD Anderson Cancer Center and Helsinki nomograms were the most predictive in our patient group.

Peritumoral D2-40 Chalkley score independently predicts metastases and survival in patients with cutaneous malignant melanoma.

Many observational studies investigated the prognostic significance of angiogenesis and lymphangiogenesis in patients with melanoma. However, the obtained results are rather contradictory, probably due to the lack of the consensus methodology. To investigate the prognostic significance of angiogenesis and lymphangiogenesis-related parameters in patients with melanoma, we performed a retrospective investigation following the consensus recommendations for angiogenesis and lymphangiogenesis quantification in solid tumors and reporting recommendations for tumor marker (REMARK) criteria for reporting the results. Blood and lymphatic vessel Chalkley scores, endothelial cell proliferation fractions and microvessel densities were quantified using a double immunostaining for endothelial marker CD34 or lymphendothelial marker D240 and the proliferation marker Ki-67 in 196 patients with melanoma. These parameters were evaluated separately for peritumoral (PT) and intratumoral areas and were correlated with outcome. In multivariate analysis PT D240 Chalkley score was identified as a strongest predictor for sentinel lymph node metastases, non-sentinel lymph node metastases, distant metastases, disease free survival and overall survival in patients with melanoma. If additional studies corroborate our findings, we believe that the inclusion of PT D240 Chalkley counts to the routine pathology examination of melanoma samples would provide additional information for identifying high-risk patients.

Predicting Non-sentinel Lymph Node Metastasis in a Chinese Breast Cancer Population with 1-2 Positive Sentinel Nodes: Development and Assessment of a New Predictive Nomogram.

We have developed a new nomogram to predict the probability of a patient with 1-2 metastatic sentinel lymph nodes (SLNs) to present further axillary disease. Data were collected from 480 patients who were diagnosed with 1-2 positive lymph nodes and thus underwent axillary lymph node dissection between March 2005 and June 2011. Clinical and pathological features of the patients were assessed with multivariable logistic regression. The Shanghai Cancer Center Non-SLN nomogram (SCC-NSLN) was created from the logistic regression model. This new model was subsequently applied to 481 patients from July 2011 to December 2013. The predictive accuracy of the SCC-NSLN nomogram was measured by calculating the area under the receiver operating characteristic curve (AUC). Based on the results of the univariate analysis, the variables that were significantly associated with the incidence of non-SLN metastasis in an SLN-positive patient included lymphovascular invasion, neural invasion, the number of positive SLNs, the number of negative SLNs, and the size of SLN metastasis (P < 0.05). Using multivariate analysis, lymphovascular invasion, the number of positive SLNs, the number of negative SLNs, and the size of SLN metastasis were identified as independent predictors of non-SLN metastasis. The SCC-NSLN nomogram was then developed using these four variables. The new model was accurate and discriminating on both the modeling and validation groups (AUC: 0.7788 vs 0.7953). The false-negative rates of the SCC-NSLN nomogram were 3.54 and 9.29 % for the predicted probability cut-off points of 10 and 15 % when applied to patients who have 1-2 positive SLNs. The SCC-NSLN nomogram could serve as an acceptable clinical tool in clinical discussions with patients. The omission of ALND might be possible if the probability of non-SLN involvement is <10 and <15 % in accordance with the acceptable risk determined by medical staff and patients.

Breast cancer metastasis burden in sentinel nodes analysed using one-step nucleic acid amplification predicts axillary nodal status

BackgroundIn breast cancer patients undergoing sentinel lymph node biopsy (SLNB) analysis using one-step nucleic acid amplification (OSNA), clarity is required as to the risk factors for non-sentinel lymph node (NSLN) involvement upon axillary lymph node dissection (ALND). This study aims to identify these factors, including categorising by extent of sentinel node positivity: solitary positive node (solitary), multiple nodes with some positive (multiple incomplete positive), or multiple nodes all of which are positive (multiple all positive). MethodsWe conducted a cohort study using prospectively collected data on 856 SLNBs analysed using OSNA, from patients with cT1-3 clinically node-negative invasive breast cancer. ALND was performed for 289 positive SLNBs. ResultsNSLN metastases were identified in 73 (25.3%) ALNDs. Significant factors for NSLN involvement on multivariate analysis were: SLNB macrometastases (cytokeratin-19 mRNA count >5000 copies/μl) (adj.OR = 3.01; 95% CI, 1.61–5.66; p = 0.0006), multiple all positive vs. multiple incomplete positive SLNB (adj.OR = 2.92; 95% CI, 1.38–6.19; p = 0.0050), and undergoing mastectomy (adj.OR = 1.89; 95% CI, 1.00–3.55; p = 0.0486). Amongst multiple incomplete positive SLNBs, an 8.8% NSLN risk was identified when only micrometastases were present. ConclusionExtent of sentinel lymph node positivity measured using OSNA predicts NSLN metastasis risk, aiding decisions surrounding axillary treatment.

P116. Effects of trastuzumab treatment on the patterns of survival and metastasis in Her-2 positive breast cancers

P116. Effects of trastuzumab treatment on the patterns of survival and metastasis in Her-2 positive breast cancers

P114. Acellular dermal matrix versus latissimus dorsi breast reconstruction: An investigation of the costs

P114. Acellular dermal matrix versus latissimus dorsi breast reconstruction: An investigation of the costs

Abstract P2-01-17: Total tumoral load as a prediction tool of non-sentinel node metastases in patients with early breast cancer and positive sentinel lymph node assesed by OSNA

Abstract Background: Total tumoral load (TTL) in the sentinel lymph nodes (SLN) assessed by the OSNA assay is a new variable that is able to predict the likelihood of more axillary metastasis. Compared with the number of positive SLNs, the TTL is independent of the number of metastatic SLNs and a better predictor of further nodal metastasis. Although establishing specific cutoff-points of the TTL can be questionable because they may change in the future and increasingly become more patient specific, we have seen that TTL &amp;lt;15.000 could be a good cut off by its high negative predictive value (NPV). Changes in practice have been occurred after the ACOSOG Z0011 trial and nowadays, patients with ≤ 2 positive SLNs may spare an axillary lymph node dissection (ALND) with no impact on the oncological outcome. In the Z0011, 27% of patients had additional non-SLN metastasis in the cALND. The objective of this study was to compare two methods of SLN metastatic burden, the TTL and the number of positive SLNs, for predicting non-SLN metastasis in patients with positive SLNs by OSNA. Methods: This is a retrospective cohort study of 145 consecutive patients with cT1-T2 invasive breast cancer with ultrasonographically node-negative treated between April 2010 to April 2013, where there is at least one positive SLN assesed by OSNA. We design a prediction tool based on the TTL results determined by OSNA to calculate the likelihood of not finding more positive non-SLN (http://www.vhebron.net/es/calculadora-risc-metastasi-2). Our group have demonstrated that TTL=15.000 could be a good cut off by its high NPV and sensitivity, 85.5% and 76.7%, respectively. Results: A total 325 SLNs were removed with a mean of 2.24. The type of SLN metastasis were macrometastasis in 85 patients (58.6%) and micrometastasis in 60 patients (41.4%). When considering patients with number of positive SLNs, of 109 patients with ≤2 positives SLNs and an cALND, 17 patients (22%) had non-SLN metastasis; and of 5 patients with ≥3 SLN, four (80%) had non-SLN metastasis. Taking the TTL results, of 51 patients with TTL &amp;lt;15.000 copies/µL with cALND (90.2% with one positive SLN), 7 patients (14%) had non-SLN metastasis, were a media of 2.2 extra non-SLN metastasis. Of 55 patients with TTL ≥15.000 copies/µL (with 1 or 2 positives SLNs) with cALND, 20 patients (36%) had non-SLN metastasis and there were a media of 2.5 non-SLN metastasis (range 1-8). Of 34 patients (62%) with one positive SLN with TTL ≥15.000 copies/µL, 12 patients (35%) had non-SLN metastasis; and of 21 patients with two positive SLN with TTL ≥15.000 copies/µL, eight patients (38%) had non-SLN metastasis. Conclusion: The total tumor load obtained by OSNA predicts non-SLN metastasis independent of the number of positive SLNs. The assess of the TTL in our cohort of patients show that patients with one or two positives SLNs with high TTL had high likelihood of non-SLN metastasis greater than 27% of Z0011 criteria. Prospective studies are needed to determine the clinical impact of this variable in patients outcome in the management of patients with SLN assesed by OSNA. Citation Format: Martin Espinosa-Bravo, Francesc Pérez-Ceresuela, Sebastian Diaz-Botero, Vicente Peg, Isabel T Rubio. Total tumoral load as a prediction tool of non-sentinel node metastases in patients with early breast cancer and positive sentinel lymph node assesed by OSNA [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-17.

Predictors of non-sentinel lymph node (non-SLN) metastasis in patients with sentinel lymph node (SLN) metastasis in endometrial cancer

ObjectivesThe aim of this study was to determine the risk of metastasis in the remaining non-SLNs when the SLN is positive and to identify the factors that can predict this risk. MethodsWe reviewed all patients who underwent primary surgery for endometrial carcinoma with lymphadenectomy and SLN mapping (November 2010–November 2013) in our center. SLNs were ultra-staged on final pathology. ResultsA total of 268 patients were included. Overall, 43/268 patients (16%) were found to have SLN metastasis: macro-metastasis in 24 patients, micro-metastasis in 7 and ITC in 12. Non-SLN metastases were found in 15 of the 43 patients (34.8%) with positive SLN. Size of the SLN metastasis was the only factor associated with an increased likelihood of non-SLN metastasis (p=0.005). When the size of the SLN metastasis was ≤2mm, the risk of having another positive lymph node was only 5%, conversely, when the size of the SLN metastasis was >2mm, the risk of having another positive lymph node was 60.8% (p<0.0001). Histologic type, grade, depth of myometrial invasion, LVSI, cervical stromal invasion and CA-125 were not predictive. ConclusionWhen the SLN is positive, the risk of metastasis in the remaining non-SLNs was 34.8%. Size of the metastasis within the SLN was the only factor that could predict the risk of non-SLN metastasis; 2mm seems to be the cutoff size below which the risk of non-SLN metastasis is low.

Predictors of non-sentinel lymph node metastasis in patients with positive sentinel lymph node (SLN) in endometrial cancer

histology (Grade 3, Type I vs. Type II), depth of invasion, and lymphovascular space invasion. Group B cases were older (65.5 ± 9.2 vs. 63.0 ± 10.9 years, P= 0.02) and had more pelvic LNs harvested (26.4 ± 10.5 vs. 18.8 ± 8.5, P b 0.0001). Aortic LN yields were identical (9.0 ± 5.6 vs. 9.0 ± 6.0). More pelvic LN metastases were detected in Group B (30.3% vs. 13.6%, P b 0.0001). Group B had more Stage IIIC1 cases (19.3% vs. 6.0%, P b 0.0001), fewer Stage IIIA cases (0.8% vs. 6.6%, P b 0.01), more GOG high-risk cases (32.8% vs. 19.8%, P b 0.01), fewer low-risk cases (21.8% vs. 36.3%, P b 0.01), and more patients receiving combination chemotherapy + radiation (28.6% vs. 16.3%, P b 0.003). A total of 18/36 (50%) Group B cases with LNmetastases were isolated to the SLN, and 12/18 (66.7%) of these were micrometastases or isolated tumor cells that were missed on hematoxylin-and-eosin pathology. These 12 upstaged cases would have been considered GOG low-risk (n= 4), low-intermediate risk (n= 2), and high-intermediate risk (n= 6) without SLN mapping. Conclusions: This study suggests that compared to traditional pelvic lymphadenectomy, the addition of SLN mapping identifies more pelvic lymph node metastases and shifts GOG lowand intermediate-risk cases to high-risk cases, possibly resulting in administration of more postoperative chemotherapy and radiation therapy.

Histological examination of sentinel lymph nodes: significance of macrometastasis, micrometastasis, and isolated tumor cells

Sentinel lymph node biopsy has been started in 1990s and has become one of the standard diagnostic procedures used to treat patients with early breast cancer in this century. In Japan, for the microscopic diagnosis of metastasis to sentinel lymph nodes, intraoperative frozen section diagnosis is widely used in combination with subsequent permanent section diagnosis of the residual specimens. Metastatic foci to sentinel lymph nodes have been classified into macrometastasis, micrometastasis, and isolated tumor cells in 2002, and the definition of isolated tumor cells was modified in 2010. Clinical significance of occult sentinel lymph node metastases, being mostly composed of micrometastasis and isolated tumor cells, has been clarified in terms of predictive factors for non-sentinel lymph node metastasis and patient prognosis by large-scale retrospective studies and prospective randomized clinical trials. In the present review, clinical implications of micrometastases and isolated tumor cells in sentinel lymph nodes and the methods for pathological examination of SLN metastases employed in these studies were overviewed.

T-stage and positive sentinel nodes ratio are the useful factors to predict non-sentinel node metastasis in breast cancer patients with macro-metastasis in the sentinel node

IntroductionCurrent guidelines recommend completion axillary lymph node dissection (cALND) in case of a sentinel lymph node (SN) metastasis larger than 2 mm (macrometastasis). However in many patients of those, the non-sentinel lymph nodes (NSN) contain no further metastasis, indicating that axillary lymph node dissection provides no benefit. To identify cases who could have undergone omission of the ALND with confidence, we have retrospectively evaluated the predictive factors of NSN metastasis with positive macrometastasis in the SN. MethodsThis study was based on a retrospective database of 420 patients who underwent sentinel lymph node biopsy (SNB) for breast cancer, of whom 61 patients had SN macrometastasis intra- and postoperatively. We examined predictive factors of NSN involvement in 51 cases of these 61 patients who underwent cALND. All clinical and histological variables were analyzed according to NSN status, by using Mann–Whitney U test, univariate and multivariate logistic regression model. ResultsT stage and the proportion of involved SNs among all identified SNs (SN ratio) were correlated with NSN metastasis. Univariate and multivariate analysis showed that T stage and SN ratio were the independent predictive factor of NSN metastasis. The area under ROC curve for SN ratio was 0.71. The best cut off value of SN ratio was 0.667. Negative predictive value to NSN metastasis in cases with both T2 and more than 0.667 of SN ratio was 85.7%. ConclusionIn patients with invasive breast cancer and macrometastasis of SN, T stage and SN ratio were useful for prediction of NSN metastasis.

Extranodal Extension on Sentinel Lymph Node Dissection: Why should we Treat it Differently?

American College of Surgeons Oncology Group Z0011 concluded that axillary lymph node dissection (ALND) may be avoided in selected patients with breast cancer with limited axillary nodal metastasis on sentinel lymph node dissection (SLND). However, patients with extranodal extension (ENE) were excluded to the follow existing standard of care, which is completion ALND. The significance of ENE detected on SLND is not well defined. Our objective was to determine the impact of ENE found on SLND on nonsentinel lymph node (NSLN) metastasis, recurrence, and overall mortality. We evaluated patients with breast cancer treated at a tertiary cancer center from 2005 to 2012. SLND was performed in 655 patients. Of those, 478 of 655 (73.0%) patients had no SLN metastases, 124 of 655 (18.9%) had SLN metastases without ENE (SLN-ENE), and 53 of 655 (8.1%) had SLN metastases with ENE (SLN+ENE). Of patients undergoing ALND, NSLN metastasis was detected in 37 of 84 (44.0%) of patients in the SLN-ENE group and 26 of 45 (57.8%) patients in the SLN+ENE group (P = 0.14). On adjusted analyses, ENE was associated with increased disease recurrence (odds ratio [OR], 5.48; 95% confidence interval [CI], 1.23 to 24.48; P = 0.03) as well as increased overall mortality (OR, 8.16; 95% CI, 1.72 to 38.63; P = 0.01). In conclusion, ENE is associated with increased overall axillary nodal burden, disease recurrence, and overall mortality.

Association between non-sentinel lymph node metastasis and clinicopathological factors in sentinel lymph node metastasis positive breast cancer

Koyama, Yu MD, PhD; Hasegawa, Miki MD; Tatsuda, Kumiko MD; Sakata, Jun MD; Kobayashi, Takashi; Minagawa, Masahiro MD; Kosugi, Shin-Ichi MD, PhD; Wakai, Toshifumi MD, PhD Author Information