SLN-positive Breast Cancer Research Articles

Comparison of clinical characteristics between ACOSOG Z0011-eligible cohort and sentinel lymph node-positive breast cancer patients in Hong Kong.

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial resulted in de-escalation of axillary surgery among early-stage breast cancer patients with low-volume sentinel lymph node (SLN) disease undergoing breast-conserving surgery and radiation therapy. Nevertheless, the mastectomy rate in the Chinese population remains high. This study compared the clinical characteristics of the ACOSOG Z0011-eligible cohort with SLN-positive breast cancer patients in Hong Kong. This retrospective analysis of a prospectively maintained database at a university-affiliated breast cancer centre in Hong Kong was performed from June 2014 to May 2019. The database included all patients with clinical tumour (T) stage T1 or T2 invasive breast carcinoma, no palpable adenopathy, one or two positive SLNs on histological examination, and no prior neoadjuvant systemic treatment. Comparisons were made between the mastectomy and breast-conserving treatment groups in our cohort, along with the sentinel-alone arm in the ACOSOG Z0011 trial. One hundred and seventy-one patients met the inclusion criteria: 112 underwent mastectomy and 59 underwent breast-conserving treatment. Our mastectomy group had higher prevalences of T2 tumours (P<0.001), lymphovascular invasion (P<0.001), and SLN macrometastases (P=0.004) compared with the ACOSOG Z0011 cohort. However, in our patient population, mean pathological size slightly differed between the mastectomy and breast-conserving treatment groups (2.2 cm vs 1.8 cm; P=0.005). Other histopathological features were similar. This study demonstrated that clinicopathological features were comparable between SLN-positive breast cancer patients undergoing mastectomy and those undergoing breast-conserving treatment. Low-risk SLN-positive mastectomy patients may safely avoid completion axillary lymph node dissection.

Association between postoperative pathological results and non-sentinel nodal metastasis in breast cancer patients with sentinel lymph node-positive breast cancer

ObjectiveFor patients with 1–2 positive sentinel lymph nodes (SLN) identified by biopsy, the necessity of axillary lymph node dissection (ALND) remains a matter of debate. The primary aim of this study was to investigate the association between postoperative pathological factors and non-sentinel lymph node (NSLN) metastases in Chinese patients diagnosed with sentinel node-positive breast cancer.MethodsThis research involved a total of 280 individuals with SLN-positive breast cancer. The relationship between postoperative pathological variables and non-sentinel lymph node metastases was scrutinized using univariate, multivariate, and stratified analysis.ResultsAmong the 280 patients with a complete count of SLN positives, 126 (45.0%) exhibited NSLN metastasis. Within this group, 45 cases (35.71%) had 1 SLN positive, while 81 cases (64.29%) demonstrated more than 1 SLN positive. Multivariate logistic regression analysis revealed that HER2 expression status (OR 2.25, 95% CI 1.10–4.60, P = 0.0269), LVI (OR 6.08, 95% CI 3.31–11.14, P < 0.0001), and the number of positive SLNs (OR 4.17, 95% CI 2.35–7.42, P < 0.0001) were positively correlated with NSLNM.ConclusionIn our investigation, the risk variables for NSLN metastasis included LVI, HER2 expression, and the quantity of positive sentinel lymph nodes. However, further validation is imperative, including this institution, distinct institutions, and diverse patient populations.

Efficacy and safety comparison between axillary lymph node dissection with no axillary surgery in patients with sentinel node-positive breast cancer: a systematic review and meta-analysis

BackgroundThis systematic review and meta-analysis aimed to study the evidence on the efficacy and safety of omitting axillary lymph node dissection (ALND) for patients with clinically node-negative but sentinel lymph node (SLN)-positive breast cancer using all the available evidence.MethodsThe Embase, Medline, and Cochrane Library databases were searched through February 25, 2023. Original trials that compared only the sentinel lymph node biopsy (SLNB) with ALND as the control group for patients with clinically node-negative but SLN-positive breast cancer were included. The primary outcomes were axillary recurrence rate, total recurrence rate, disease-free survival (DFS), and overall survival (OS). Meta-analyses were performed to compare the odds ratio (OR) in rates and the hazard ratios (HR) in time-to-event outcomes between both interventions. Based on different study designs, tools in the revised Cochrane risk of bias tool were used for randomized trials and the risk of bias in nonrandomized studies of interventions to assess the risk of bias for each included article. Funnel plots and Egger's test were used for the publication’s bias assessment.ResultsIn total, 30 reports from 26 studies were included in the systematic review (9 reports of RCTs, 21 reports of retrospective cohort studies). According to our analysis, omitting ALND in patients with clinically node-negative but SLN-positive breast cancer had a similar axillary recurrence rate (OR = 0.95, 95% confidence interval (CI): 0.76–1.20), DFS (HR = 1.02, 95% CI: 0.89–1.16), and OS (HR = 0.97, 95% CI: 0.92–1.03), but caused a significantly lower incidence of adverse events and benefited in locoregional recurrence rate (OR = 0.76, 95% CI: 0.59–0.97) compared with ALND.ConclusionFor patients with clinically node-negative but SLN-positive breast cancer (no matter the number of the positive SLN), this review showed that SLNB alone had a similar axillary recurrence rate, DFS, and OS, but caused a significantly lower incidence of adverse events and showed a benefit for the locoregional recurrence compared with ALND. An OS benefit was found in the Macro subset that used SLNB alone versus complete ALND. Therefore, omitting ALND is feasible in this setting.Trial registrationCRD 42023397963

MRI-Based Radiomics Nomogram: Prediction of Axillary Non-Sentinel Lymph Node Metastasis in Patients With Sentinel Lymph Node-Positive Breast Cancer.

BackgroundOvertreatment of axillary lymph node dissection (ALND) may occur in patients with axillary positive sentinel lymph node (SLN) but negative non-SLN (NSLN). Developing a magnetic resonance imaging (MRI)-based radiomics nomogram to predict axillary NSLN metastasis in patients with SLN-positive breast cancer could effectively decrease the probability of overtreatment and optimize a personalized axillary surgical strategy.MethodsThis retrospective study included 285 patients with positive SLN breast cancer. Fifty five of them had metastatic NSLNs and 230 had non-metastatic NSLNs. MRI-based radiomic features of primary tumors were extracted and MRI morphologic findings of the primary tumor and axillary lymph nodes were assessed. Four models, namely, a radiomics signature, an MRI-clinical nomogram, and two MRI-clinical-radiomics nomograms were established based on MRI morphologic findings, clinicopathologic characteristics, and MRI-based radiomic features to predict the NSLN status. The optimal predictors in each model were selected using the 5-fold cross-validation (CV) method. Their predictive performances were determined by the receiver operating characteristic (ROC) curves analysis. The area under the curves (AUCs) of different models was compared by the Delong test. Their discrimination capability, calibration curve, and clinical usefulness were also assessed.ResultsThe 5-fold CV analysis showed that the AUCs ranged from 0.770 to 0.847 for the radiomics signature, from 0.720 to 0.824 for the MRI-clinical nomogram, from 0.843 to 0.932 for the MRI-clinical-radiomics nomogram. The optimal predictive factors in the radiomics signature, MRI-clinical nomogram, and MRI-clinical-radiomics nomogram were one texture feature of diffusion-weighted imaging (DWI), two clinicopathologic features together with one MRI morphologic finding, and the DWI-based texture feature together with the two clinicopathologic features plus the one MRI morphologic finding, respectively. The MRI-clinical-radiomics nomogram with CA 15-3 included achieved the highest AUC compared with the radiomics signature (0.868 vs. 0.806, P <0.001) and MRI-clinical nomogram (0.868 vs. 0.761; P <0.001). In addition, the MRI-clinical-radiomics nomogram without CA 15-3 showed a higher performance than that of the radiomics signature (AUC, 0.852 vs. 0.806, P = 0.016) and the MRI-clinical nomogram (AUC, 0.852 vs. 0.761, P = 0.007). The MRI-clinical-radiomics nomograms showed good discrimination and good calibration. Decision curve analysis demonstrated that the MRI-clinical-radiomics nomograms were clinically useful.ConclusionThe MRI-clinical-radiomics nomograms developed in our study showed high predictive performance, which can be used to predict the axillary NSLN status in SLN-positive breast cancer patients before surgery.

Abstract P3-20-05: Trends of axillary treatment in sentinel node-positive breast cancer patients undergoing amputation

Abstract Objectives: To evaluate patterns of care in axillary treatment of Dutch patients - who were diagnosed with stage I-IV primary invasive breast cancer, underwent amputation and were found positive by sentinel lymph node biopsy (SLNB) - in the years following the publication of the American College for Surgeons Oncology Group (ACOSOG)-Z0011 and After Mapping of the Axilla: Radiotherapy Or Surgery (AMAROS) trials. Methods: Data from females diagnosed between January 1st 2009 and December 31st 2018 were obtained from the Netherlands Cancer Registry (NKR). Trends in completion axillary lymph node dissection (cALND), administration of adjunctive radiotherapy and, inversely, of omission of any kind of axillary treatment, were revealed by descriptive analyses on SNL positive patients. Results: Of 28,070 cT1-4 breast cancer patients undergoing amputation with SLNB from 2009 up until 2018, 10,706 were diagnosed as SLN positive. In the latter, the frequency of subsequent cALND went down significantly from 78% in 2009 to 10% in 2018 (P &amp;lt; 0.001), while adjunctive radiotherapy increased from 4% to 49% (P &amp;lt; 0.001). Omission of any additional local treatment increased from 18% to 41% (P &amp;lt; 0.001). In N1 patients cALND decreased from 57% to 13% (P &amp;lt; 0.001) and was mostly replaced by radiotherapy, increasing from 2% to 70% (P &amp;lt; 0.001). In N1mi and N0i+ patients, cALND decreased to less than 1% of cases in 2018, while radiotherapy increased from 4% to 40% and 8% to 13% (P &amp;lt; 0.001), respectively. Conclusion: In SLN positive breast cancer patients undergoing breast amputation, cALND had become rare 10 years following the AMAROS and Z0011 trial results. While radiotherapy mostly replaced cALND in the vast majority of N1 patients, less than half of N1mi and only a tenth of N0i+ patients received radiotherapy as the only adjunctive axillary treatment by the end of 2018. Citation Format: Eline EF Verreck, Julia van Steenhoven, Anne Kuijer, Marissa van Maaren, Sabine Siesling, Thijs van Dalen. Trends of axillary treatment in sentinel node-positive breast cancer patients undergoing amputation [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-20-05.

POZİTİF SENTİNEL LENF DÜĞÜMÜ OLAN MEME KANSERLİ HASTALARDA TAMAMLAYICI AKSİLLER DİSEKSIYON GEREKLİLİĞİNİN NOMOGRAM YÖNTEMLERİNİN DEĞERLENDİRİLMESİYLE BELİRLENMESİ

AIM: Our aim was to evaluate the efficacies of different nomogram approaches, including the Memorial Sloan Kettering Cancer Centre (MSKCC), Stanford University, Tenon Hospital, Cambridge University and TR methods, in patients operated for breast cancer.&#x0D; MATERIAL AND METHOD: The study included 60 breast cancer patients who were operated on for breast cancer at Ankara Numune Training and Research Hospital, A2 General Surgery Clinic, between 2007 and 2012. All patients were sentinel lymph node (SLN)-positive and had undergone axillary lymph node dissection (ALND). Five different scoring systems were applied retrospectively to these 60 patients. Receiver operating characteristics (ROC) curves were created for the nomograms and the area under the curve (AUC) sensitivity and specificity results were calculated.&#x0D; RESULTS: Twenty-two patients (37%) had axillary non-SLN metastases. AUC values of MSKCC, Stanford, Cambridge, Tenon and TR nomogram were calculated as 0.646, 0.644, 0.62, 0.595, and 0.66, respectively. A significant difference was found between the groups with and without non-SLN metastasis in terms of SLN metastasis size (p = 0.013).&#x0D; CONCLUSION: The MSKCC, Stanford, Cambridge, Tenon, and TR nomogram models were found to have insufficient power to discriminate between patients with and without non-SLN metastases in patients with SLN-positive breast cancer (AUC values

Impact of Axillary Dissection Among Patients With Sentinel Node-Positive Breast Cancer Undergoing Mastectomy.

Results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial supports omission of completion axillary lymph node dissection (CLND) after breast-conservation surgery with a positive sentinel lymph node biopsy (SLNB). We hypothesized that CLND also does not impact outcomes in women with clinically node-negative (cN0), pathologically node-positive breast cancer undergoing mastectomy. A single-institution retrospective review was performed of patients with SLN-positive breast cancer treated from July 1999 through May 2018. Clinicopathologic and outcome data were collected. Patients with SLNBs were compared with those receiving SLNB and CLND. The Kruskal-Wallis, chi-square, and Fisher exact tests were used to assess for differences between continuous and categorical variables. The log-rank test was used for time-to-event analyses, and Cox proportional hazards models were fit for locoregional and distant recurrence and overall survival (OS). Of 329 patients with SLN-positive breast cancer undergoing mastectomy, 60% had CLND (n=201). Median age at diagnosis was 53 years (interquartile range [IQR], 46-62 years). The median number of SLNs sampled was 3 (IQR, 2-4), and the median number of positive SLNs was 1 (IQR, 1-2). Patients receiving CLND had higher tumor grades (P=.02) and a higher proportion of hormone receptor negativity (estrogen receptor, 19%; progesterone receptor, 27%; both P=.007). A total of 44 patients (22%) had increased N stage after CLND. Median follow-up was 51 months (IQR, 29-83 months). No association was found between CLND and change in OS and locoregional or distant recurrence. Completion of postmastectomy radiotherapy was associated with improved OS (P=.04). CLND is not significantly correlated with reduced recurrence or improved OS among patients who have cN0, SLN-positive breast cancer treated with mastectomy. CLND was significantly correlated with receipt of adjuvant systemic therapy. Completion of postmastectomy radiotherapy was associated with improved OS.

Abstract P3-03-30: Validity and safety of omission of axillary lymph node dissection among sentinel lymph node-positive breast cancer patients treated with mastectomy

Abstract Background:American College of Surgeons Oncology Group Z0011 trial showed that axillary lymph node dissection (ALND) had no impact on recurrence and survival in patients with positive sentinel lymph node (SLN) after breast-conserving surgery. However, it is still unknown if the omission of ALND can be applicable to patients treated with mastectomy. The aim of this study wasto evaluate whether ALND could be safely omitted for patients with SLN–positive breast cancer after mastectomy. Methods: From a prospective database of 296 patients with clinically node-negative breast cancer who underwent mastectomy and sentinel lymph node biopsy (SLNB) from March 2006 to December 2016, 81 patients who had positive SLNs were selected. Patient characteristics and prognosis were compared between SLN-positive patients with and without ALND. Patients treated with neoadjuvant chemotherapy were excluded from the analysis. Lymphatic mapping was performed using a combined method of blue dye and radioisotope. Results: The median age of entire patients was 57.0 (range: 32-85) years and the median tumor size was 2.5 (range: 0.6-7.9) cm. Of 81 patients, 23 (28.4%) patients omitted ALND. Patients with SLNB alone were more likely to have smaller SLN involvements (p&amp;lt;0.001): micrometastasis was identified in 13 (56.5%) patients in SLNB-alone group and 9 (15.5%) patients in ALND group. The number of positive SLN was comparable between SLNB-alone (median: 1.0, range: 1-6) and ALND groups (median: 1.0, range: 1-5) (p=0.063). There was no significant difference in characteristics including age, tumor size and tumor subtypes between the two groups. Post-mastectomy radiotherapy was performed in 5 (21.7%) patients with SLNB alone and 16 (27.6%) patients with ALND (p=0.588). The majority of patients with macrometastatic SLN received adjuvant chemotherapy in both groups (83.3% vs. 75.5%, p=0.562). Twenty (87.0%) and 51 (87.9%) patients received adjuvant endocrine therapy in SLNB-alone and ALND group, respectively (p=0.584). After a median follow-up of 54.7 months, no axillary recurrence was observed in both groups and 5-year disease-free survival was not significantly different between the two groups (75.0% vs. 88.8%, p=0.489). Lymphedema was observed significantly more often after ALND than after SLNB (22.4% vs. 4.3%, p=0.045). Conclusions: These data suggested that ALND could be safely omitted in SLN-positive breast cancer patients treated with mastectomy and appropriate systemic therapy. Citation Format: Matsumoto A, Umemoto Y, Jinno H. Validity and safety of omission of axillary lymph node dissection among sentinel lymph node-positive breast cancer patients treated with mastectomy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-30.

A new model to predict risk of nonsentinel lymph node status in Chinese sentinel lymph node-positive patients after neoadjuvant chemotherapy.

There is no previous predictive model to assess risk of nonsentinel lymph node metastases (NSLN) in sentinel lymph node (SLN)-positive breast cancer patients after neoadjuvant chemotherapy (NAT). Our goal was to develop a new predictive model for SLN-positive patients after NAT, and validate this new model. A series of 513 patients with metastases in SLN who received NAT were used to evaluate factors affecting NSLN status. Logistic regression analysis was performed to develop a predictive model, which was validated by a subsequent prospective 138 patients. There were 115 (22.4%) patients with metastases in NSLN followed by axillary lymph node dissection (ALND). Multivariate analysis indicated that tumor (T) stage, number of positive SLN,micrometastases, extracapsular extension (ECE), and clinical response of primary tumor after NAT were significant independent predictors for the NSLN metastases. Area under the curve (AUC) of the model was 0.795 (95% CI, 0.734-0.861). When applied to the prospective series, the model accurately predicted the risk of NSLN disease, AUC was 0.772 (95% CI, 0.653-0.845). We present a new predictive model to assess the risk of NSLN status in Chinese SLN-positive breast cancer patients after NAT. The predictive model performed well in prospective validation but needs to be further studied in external center patients before application to clinical use.

Trends in axillary treatment for breast cancer patients undergoing sentinel lymph node biopsy as determined by a questionnaire from the Japanese Breast Cancer Society

Sentinel lymph node biopsy (SLNB) alone has been compared with SLNB followed by axillary lymph node dissection (ALND) in sentinel lymph node (SLN)-positive breast cancer patients in randomized phase III trials: the addition of ALND did not further improve the patient's outcome. However, there is still some controversy, regarding the clinical application of SLNB alone. To identify the optimal axillary treatment in the era of SLNB, the Japanese Breast Cancer Society conducted a group study of SLNB in 2014. A questionnaire on axillary surgery and radiation therapy was sent to 432 Japanese institutes in December 2014, and 309 (72%) completed the questionnaire. SLNB was performed at 98% of the institutes, and 77% offered irradiation for cancer treatment. Regarding breast-conserving surgery (BCS), SLNB alone was indicated at 41% of the institutes in the cases of SLN with micrometastases. However, in the cases of SLN with macrometastases, ALND was performed at 64%. The proportion of ALND seemed to be higher in total mastectomy than in BCS regardless of the SLN-positive status. In the cases of SLN with micrometastases, the radiation field was localized in the conserved breast at about half of the institutes. On the other hand, in the cases of SLN with macrometastases, it was extended to axillary and/or supraclavicular lesions beyond the conserved breast at about 70% of the institutes. Japanese breast physicians were conservative with respect to the omission of ALND in SLN-positive breast cancer, especially in the cases of SLN with macrometastases.

Comparison of five different popular scoring systems to predict nonsentinel lymph node status in patients with metastatic sentinel lymph nodes: a tertiary care center experience.

Sentinel lymph node biopsy (SLNB) is the current standard of care for breast cancers with no clinically palpable axillary lymph nodes. Almost 50 % of sentinel lymph node positive patients have negative non-sentinel nodes and undergo non-therapeutic axillary dissection. Five different scoring systems, reported in the literature, were compared for their predictive ability of non-SLN involvement in patients with SLN positive breast cancer. 242 patients who underwent breast surgery and SLNB were included in the study. Of these, 70 who were confirmed to have SLN metastasis and received complementary ALND and constituted the final study population. The nomograms (MSKCC, M.D. Anderson Cancer Center, Tenon model, Stanford and Turkish) were statistically compared for their prediction of non-SLN metastasis (95 % confidence interval). We have determined only two clinicopathologic (multifocality and size of the primary tumor) situations which have a statistically significant association between SLN metastasis with using a multivariate logistic regression analysis. Multifocality (P = 0.001) and size of the primary tumor (P = 0.001) were associated with a higher probability of-SLN metastasis. No predictive model was constructed that showed good area under the curve (AUC) discrimination in the validation series. Currently published predictive models lack accuracy when applied to a different population. Multi-institutional heterogenic population studies are important to determine the exact combination of scoring systems and/or nomograms.

A Dutch Prediction Tool to Assess the Risk of Additional Axillary Non–Sentinel Lymph Node Involvement in Sentinel Node-Positive Breast Cancer Patients

BackgroundMultiple predictive systems have previously been developed to identify the sentinel lymph node (SLN)-positive patients at low risk of additional axillary non-SLN involvement and for whom completion axillary lymph node dissection (ALND) could be avoided. However, previous studies showed that these tools had poor performance in Dutch patients with breast cancer, probably owing to variations in pathology settings and differences in population characteristics. The aim of the present study was to develop a predictive tool for the risk of non-SLN involvement in a Dutch population with SLN-positive breast cancer. Materials and MethodsThe data from 513 patients with SLN-positive breast cancer at 10 participating hospitals, who had undergone ALND from January 2007 to December 2008 were studied. The uni- and multivariable associations of predictors for non-SLN metastases were analyzed, and a predictive model was developed. The discriminatory ability of the model was measured by the area under the receiver operating characteristic curve (AUC) and the agreement between predicted probabilities and observed frequencies was visualized by a calibration plot. ResultsA predictive model was developed that included the 2 strongest predictors: the size of the SLN metastases in millimeters and the presence of a negative sentinel lymph node. The model showed good discriminative ability (AUC, 0.75) and good calibration over the complete range of predicted probabilities. ConclusionWe have developed a tool to predict additional non-SLN metastases in Dutch patients with SLN-positive breast cancer that is easy to use in daily clinical breast cancer practice.

Validation of Memorial Sloan–Kettering Cancer Center nomogram for prediction of non-sentinel lymph node metastasis in sentinel lymph node positive breast cancer patients an international comparison

BackgroundCurrent guidelines for breast cancer treatment recommend completion axillary lymph node dissection (CALND) following in case of positive sentinel lymph node (SLN) metastasis, which only in 35%–70% shows additional nodal metastases. Several nomograms and scoring systems have been created to predict the risk of metastasis in non-SLNs. The aim of the study was to identify individual patient risk for non-sentinel lymph node metastasis by validating with MSKCC nomogram and to evaluate the variability within a group of SLN-positive breast cancer patients with the final goal of avoiding unnecessary CALND. Patients and methodsWe retrospectively evaluated 1496 primary breast cancer patients. 324 women with a positive SLN who underwent CALND were identified. The predictive accuracy was measured and compared with the MSKCC nomogram by the area under the receiver operating characteristic curve. Receiver operating characteristic (ROC) curve was drawn on the basis of the sensitivity and specificity, and the area under the curve (AUC) was calculated. ResultsAt least one metastatic non-SLN were identified in 88/324 (27.2%) patients. Tumor size, tumor type, tumor grade, number of positive SLNs and number of negative SLNs were significantly associated with non-SLN status in multivariate analyses. The MSKCC nomogram showed an AUC value of 0.738 (95% confidence interval = 0.682–0.793) after the validation for our collectives. ConclusionsThe MSKCC nomogram showed a good prediction for the non-SLN metastasis and performed adequately in our patient collective. Therefore, for the use of nomogram, validation with other populations of patients is strongly suggested.

A support vector machine model for predicting non-sentinel lymph node status in patients with sentinel lymph node positive breast cancer

This study aimed to investigate the accuracy and feasibility of support vector machine (SVM) modeling in predicting non-sentinel lymph node (NSLN) status in patients with SLN-positive breast cancer. Clinicopathological data were collected from 201 cases with sentinel lymph node biopsy breast cancer and included patient age, tumor size, histological type and grade, vascular invasion, estrogen receptor status, progesterone receptor status, CerbB2 status, size and number of positive SLNs, number of negative SLNs, and positive SLN membrane invasion. Feature vector selection was based on a combination of statistical filtration and model-dependent screening. The arbitrary combination with the smallest p value for SVM input was selected, the predicative results of the model were evaluated by a 10-fold cross validation, and a training model was established. Using SLN-positive patients as a double-blind test set, 85 patients were input into the model to analyze its sensitivity and specificity. The combination with the highest cross-validation accuracy was selected for the SVM model and consisted of the following: the number and size of positive SLNs, the number of negative SLNs, and the membrane invasion of positive SLNs. The training accuracy of the model established with the four variables was 92 %, and its cross-validation veracity was 87.6 %. The accuracy of an 85-patient double-blind test of the SVM model was 91.8 %. In conclusion, this SVM model is an accurate and feasible method for the prediction of NSLN status in SLN-positive breast cancer and is conducive to guide clinical treatment.

Validation of Three Breast Cancer Nomograms and a New Formula for Predicting Non-sentinel Lymph Node Status

The aim of the study was to evaluate the available breast nomograms (MSKCC, Stanford, Tenon) to predict non-sentinel lymph node metastasis (NSLNM) and to determine variables for NSLNM in SLN positive breast cancer patients in our population. We retrospectively reviewed 170 patients who underwent completion axillary lymph node dissection between Jul 2008 and Aug 2010 in our hospital. We validated three nomograms (MSKCC, Stanford, Tenon). The likelihood of having positive NSLNM based on various factors was evaluated by use of univariate analysis. Stepwise multivariate analysis was applied to estimate a predictive model for NSLNM. Four factors were found to contribute significantly to the logistic regression model, allowing design of a new formula to predict non-sentinel lymph node metastasis. The AUCs of the ROCs were used to describe the performance of the diagnostic value of MSKCC, Stanford, Tenon nomograms and our new nomogram. After stepwise multiple logistic regression analysis, multifocality, proportion of positive SLN to total SLN, LVI, SLN extracapsular extention were found to be statistically significant. AUC results were MSKCC: 0.713/Tenon: 0.671/Stanford: 0.534/DEU: 0.814. The MSKCC nomogram proved to be a good discriminator of NSLN metastasis in SLN positive BC patients for our population. Stanford and Tenon nomograms were not as predictive of NSLN metastasis. Our newly created formula was the best prediction tool for discriminate of NSLN metastasis in SLN positive BC patients for our population. We recommend that nomograms be validated before use in specific populations, and more than one validated nomogram may be used together while consulting patients.

Does the Rapid Acceptance of ACOSOG Z0011 Compromise Selection of Systemic Therapy?

The acceptance of sentinel lymph node (SLN) biopsy as standard care in cN0 breast cancer is one of the great success stories in contemporary surgical oncology and is supported by the results of at least 69 observational studies, 7 randomized trials, and extensive literature covering all aspects of the procedure. The logical next question in the evolution of axillary staging is to ask whether all SLNpositive patients require axillary lymph node dissection (ALND), and it is clear that for many American surgeons they do not. In a retrospective study from the National Cancer Data Base, Bilimoria et al. report on 97,314 SLNpositive patients treated nationwide between 1998 and 2006. They show 23 % of patients with SLN macrometastases ([2 mm, pN1) and 55 % with SLN micrometastases (0.2–2 mm, pN1mi) did not have ALND, yet for both pN1 and pN1mi SLN disease, axillary local recurrence and 5-year relative survival were the same with or without ALND. These suggestive results are of course subject to selection bias, but are confirmed by ACOSOG Z0011, a unique and visionary prospective trial that randomized 813 SLNpositive patients with clinical stage T1-2N0 breast cancer to ALND vs no further surgery. All patients were SLNpositive by routine H&E (not immunohistochemical) staining, and all had breast conservation including wholebreast RT. Patients with 3 or more positive SLN (or with matted nodes) were excluded, and formal axillary RT was not allowed. Additional positive nodes were found in 27 % of the patients who had ALND, but at 6 years’ follow-up there were no differences between the ALND and noALND arms in local (3.6 % vs 1.9 %), regional (0.5 % vs 0.9 %), or overall locoregional recurrence (4.1 % vs 2.8 %), nor were there any differences in disease-free or overall survival. Over the last 2 years many institutions and surgeons in the United States (and to a lesser extent in Europe and worldwide) have found the results of Z0011 to be persuasive and practice-changing, incorporating into their treatment guidelines a policy of ‘‘no-ALND’’ for SLN-positive patients who meet the Z0011 selection criteria. In this issue of the Annals, Montemurro and colleagues ask whether the growing acceptance of Z0011 may have been premature. Among 321 of their own SLN-positive breast cancer patients who matched the Z0011 selection criteria, all of whom had ALND, they ask how often the results of ALND were sufficient to change the systemic therapy. In their study design, 2 medical oncologists retrospectively reviewed each patient’s chart twice, first making a recommendation for systemic therapy based on SLN status alone, and then incorporating the results of the ALND. They found that the information gained from the ALND changed the recommended treatment in 16 % of patients, most of them ER-positive/her2-negative (luminal A and B) and most in the direction of ‘‘ACT’’ (doxorubicin, cyclophosphamide, and paclitaxel) chemotherapy. They conclude by suggesting that to avoid undertreatment ALND may be appropriate for some, if not all, SLNpositive patients meeting the Z0011 criteria. Their argument deserves serious consideration, but I do not share their concerns, for the following reasons. First, the subtext of their study is the hypothesis that there are node-positive patients who do not require chemotherapy. This is expressed obliquely in the 2011 St. Gallen Consensus document: ‘‘the Panel did not believe that node positivity per se was an indication for use of chemotherapy, though a strong majority would use it if more than 3 lymph nodes were involved.’’ This fits with the authors’ observation that ALND changed therapy primarily by finding additional positive nodes in those SLNSociety of Surgical Oncology 2012

57P Validation of Three Breast Cancer Nomograms for Predicting the Non-Sentinel Lymph Node Metastases and a New Formula for Predicting Non-Sentinel Lymph Node Status. (Second Study from Turkey-First Unicenter Study)

ABSTRACT Introduction Patients who have positive SLNB should undergo to axillary lymph node dissection (ALND), about 40-70% of them have no nonsentinel lymph node (NSLN) metastasis. Purpose The aim of the study is to evaluate the available breast nomograms (MSKCC,Stanford,Tenon) to predict non-sentinel lymph node metastasis (NSLNM) and to determine the variables on NSLNM in the SLN positive breast Cancer (BC) patients in the our population. Method We retrospectively reviewed BC patients who underwent SLN biopsy. One hundred and seventy SLN biopsy positive patients who had completion axillary lymph node dissection were evaluated. We described two groups; group one NSLN negative (70 patients), group two NSLN positive (100 patients). Four factors were found to contribute significantly to the logistic regression model. After multiple logistic regression analysis of significant parameters, we designed a new formula to predict non-sentinel lymph node metastasis, based on the multivariate analysis. The areas under (AUC) the receiver operating characteristic curve (ROC) were used to describe the performance of the diagnostic value of nomograms and our new nomogram. Results After stepwise multiple logistic regression analysis four parameters found statistically significant. AUC results for each nomograms: MSKCC: 0,713 / Tenon: 0,671 / Stanford: 0,534 / DEU: 0,814. Conclusion The MSKCC nomogram was good discriminator of NSLN metastasis in SLN positive BC patients for our population. A newly created formula depending on four factors (Multifocality, LVI, proportion of positive SLN among total SLN, SLN extracapsular extention) is the best prediction toll for discriminate of NSLN metastasis in SLN positive BC patients for our population. Disclosure All authors have declared no conflicts of interest.

High Intersystem Variability for the Prediction of Additional Axillary Non-Sentinel Lymph Node Involvement in Individual Patients with Sentinel Node-Positive Breast Cancer

To compare the outcomes of the available systems that predict the risk of non-sentinel lymph node (non-SLN) metastasis and to evaluate the variability within a group of SLN-positive breast cancer patients. Predicted probabilities and scores for non-SLN metastasis were calculated with nine predictive systems for 120 SLN-positive patients who underwent a completion axillary lymph node dissection. The number of patients was calculated that were considered low risk or had a probability of ≤ 10% by at least one of the systems. For each nomogram, a box plot was constructed. All patients with a predicted probability of ≤ 10% according to the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram were selected, and a comparison was made with the probabilities predicted by the other systems. Nearly two-thirds (64.2%, n = 77) of patients with SLN-positive breast cancer were allocated to a low-risk or low-probability group by at least one of the predictive systems. No patients were uniformly classified as low risk by all nine prediction models. At the group level, a considerable variation in the distribution of the predicted probabilities was observed. At the individual level, calculation of the predicted probabilities for the selected patients who were considered low risk (≤ 10%) according to the MSKCC nomogram, showed even larger variations, ranging from 4 to 94%. This study shows that there is an unacceptably high variability in individual predictions when the predictive systems that are currently available are used to predict non-SLN metastasis in patients with SLN-positive breast cancer.

Paradigm shift in axilla surgery for breast cancer patients treated with sentinel node biopsy

Sentinel node biopsy (SNB) is a standard technique for the diagnosis of regional lymph node metastases in clinically node-negative breast cancer patients. In the case of pathologically negative sentinel lymph nodes (SLN), axillary lymph node dissection (ALND) can be avoided. Recent clinical studies on SNB in breast cancer were reviewed regarding the pathological and molecular diagnosis of SLN, the tools used to predict non-SLN metastases, the prognostic significance of isolated tumor cells (ITC) and micrometastases (MIC), and axilla surgery. ITC or MIC in SLN was associated with worse survival in patients treated with SNB alone or SNB followed by ALND. However, this effect was limited and adjuvant therapy improved survival. If T1 and one SLN-positive breast cancer patients are treated with whole-breast irradiation and adjuvant therapy, additional ALND may not be necessary. SNB without ALND can be adopted for patients with a small number of SLN metastases. Although the lack of apparent regional lymph node recurrence, similar to tumor dormancy, cannot be fully explained, ALND should be performed in cases that are highly suspected to be non-SLN metastases.

A 10-Year Trend Analysis of Sentinel Lymph Node Frozen Section and Completion Axillary Dissection for Breast Cancer: Are These Procedures Becoming Obsolete?

Recent results from the ACOSOG Z0011 trial question the use of intraoperative frozen section (FS) during sentinel lymph node (SLN) biopsy and the role of axillary dissection (ALND) for SLN-positive breast cancer patients. Here we present a 10-year trend analysis of SLN-FS and ALND in our practice. We reviewed our prospective SLN database over 10years (1997-2006, 7509 SLN procedures) for time trends and variation between surgeons in the use of SLN-FS and ALND in patients with cN0 invasive breast cancer. Use of SLN-FS decreased from 100% to 62% (P<0.0001) and varied widely by surgeon (66% to 95%). There were no statistically significant trends in the performance of ALND for patients with SLN metastases detected by FS (n=1370, 99-99%) or routine hematoxylin and eosin (H&E) (n=333; 69-77%), but only for those detected by serial section H&E with or without immunohistochemistry (n=438; 73-48%; P=0.0054) or immunohistochemistry only (n=294; 48-28%; P<0.0001). These trends coincided with an increase in the proportion of completion versus immediate ALND (30-40%; P=0.0710). Over 10years, we have observed a diminishing rate of SLN-FS and, for patients with low-volume SLN metastases, fewer ALND, trends that suggest a more nuanced approach to axillary management. If the Z0011 selection criteria had been applied to our cohort, 66% of SLN-FS (4159 of 6327) and 48% of ALND (939 of 1953) would have been avoided, sparing 13% of all patients the morbidity of ALND.