The feasibility of a randomised controlled trial for the axillary management of a select group of invasive breast cancer patients: SLNB vs. no-SLNB.

BACKGROUND: The results of ZOO11 have shaken our thinking and approach for the axillary management of small invasive breast cancers where the incidence and burden of axillary metastasis would be much less than that of ZOO11 population. The traditional approach of sentinel lymph node biopsy (SLNB) for "all invasive cancers" is challenged because of the diminishing role of axillary lymph nodes (ALNs) status in guiding the adjuvant systemic therapy. Certainly this raises the question of whether SLNB can be avoided in a select group of patients without compromising clinical outcomes. The aim of this study was to identify such a group of patients in whom SLNB is no longer required. METHOD: Patients with breast cancers ≤2 cm in size and clinically negative axilla who underwent breast conserving surgery (BCS) and SLNB were identified. Patients were divided into different groups; incidence of ALNs metastasis, further non-SLNs metastasis and a total number of tumour positive ALNs of ≥4 were determined. RESULTS: A total of 194 patients met the criteria; incidence of tumour positive SLNs, further non-SLNs metastasis and a total number of tumour positive ALNs of ≥4 varied between different groups and was 9.3-15.5 %, 0-35 % and 0-2.6 %, respectively. Patients with T1b, grade 1-2 tumours had less than 5 % risk of ALNs macrometastasis. CONCLUSION: It is possible to identify a group of patients whose burden of axillary disease is acceptably low enough that SLNB can be avoided. Feasibility of a non-inferiority randomised controlled trial (RCT) in a select group of patients with or without SLNB has been explored to compare the distant disease free, disease free and overall survival and axillary relapse rate (ARR).

An independent assessment of the 7 nomograms for predicting the probability of additional axillary nodal metastases after positive sentinel lymph node biopsy in a cohort of British patients with breast cancer.

INTRODUCTION: Axillary lymph node dissection (ALND) is currently the recommended procedure in patients with tumor-positive sentinel lymph node biopsy (SLNB). A significant proportion of patients with positive SLNs will not have any additional metastases in nonsentinel lymph nodes (NSLNs). Predictive nomograms could identify a subgroup of patients with low or high risk of further disease in whom completion ALND can be avoided or recommended. The aim of this study was to assess the accuracy of the currently available 7 nomograms in a cohort of British patients with breast cancer. PATIENTS AND METHODS: A total of 138 patients with positive SLNs who underwent completion ALND were identified. Data were then used to calculate the probability of further metastases in NSLNs predicted by the 7 nomograms that are currently in use: the MSKCC (Memorial Sloan Kettering Cancer Center), Cambridge, Turkish, Stanford, MDACC (University of Texas MD Anderson Cancer Center), Tenon, and MOU (Masarykuv onkologický ústav, Masaryk Memorial Cancer Institute) models. The area under the receiver operating characteristic (ROC) curve (AUC) was calculated for each nomogram. RESULTS: Of the 138 patients, 54 (41%) had additional metastases in NSLNs. AUC values for the MSKCC, Cambridge, Turkish, Stanford, MDACC, Tenon, and MOU models are 0.68, 0.68, 0.70, 0.69, 0.56, 0.63, and 0.74, respectively. CONCLUSION: The MOU nomogram was more predictive than the other nomograms, with a better AUC value and false-negative rate. None of the models were able to achieve AUC value ≥ 0.80 in a cohort of British patients with breast cancer.

International multicenter tool to predict the risk of four or more tumor-positive axillary lymph nodes in breast cancer patients with sentinel node macrometastases.

Recently, many centers have omitted routine axillary lymph node dissection (ALND) after metastatic sentinel node biopsy in breast cancer due to a growing body of literature. However, existing guidelines of adjuvant treatment planning are strongly based on axillary nodal stage. In this study, we aim to develop a novel international multicenter predictive tool to estimate a patient-specific risk of having four or more tumor-positive axillary lymph nodes (ALN) in patients with macrometastatic sentinel node(s) (SN). A series of 675 patients with macrometastatic SN and completion ALND from five European centers were analyzed by logistic regression analysis. A multivariate predictive model was created and validated internally by 367 additional patients and then externally by 760 additional patients from eight different centers. All statistical tests were two-sided. Prevalence of four or more tumor-positive ALN in each center's series (P = 0.010), number of metastatic SNs (P < 0.0001), number of negative SNs (P = 0.003), histological size of the primary tumor (P = 0.020), and extra-capsular extension of SN metastasis (P < 0.0001) were included in the predictive model. The model's area under the receiver operating characteristics curve was 0.766 in the internal validation and 0.774 in external validation. Our novel international multicenter-based predictive tool reliably estimates the risk of four or more axillary metastases after identifying macrometastatic SN(s) in breast cancer. Our tool performs well in internal and external validation, but needs to be further validated in each center before application to clinical use.