Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial

On Behalf Of The Senomac Trialists’ Group ,Jana De Boniface,Roger Olofsson Bagge,Yvette Andersson,Malin Sund,Hemming Johansson,Johan Ahlgren,Dan Lundstedt,Jan Frisell,Lisa Rydén,Leif Bergkvist

doi:10.1186/s12885-017-3361-y

On Behalf Of The Senomac Trialists’ Group , Jana De Boniface + Show 9 more

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https://doi.org/10.1186/s12885-017-3361-y

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Abstract

BackgroundThe role of axillary lymph node dissection (ALND) has increasingly been called into question among patients with positive sentinel lymph nodes. Two recent trials have failed to show a survival difference in sentinel node-positive breast cancer patients who were randomized either to undergo completion ALND or not. Neither of the trials, however, included breast cancer patients undergoing mastectomy or those with tumors larger than 5 cm, and power was debatable to show a small survival difference.MethodsThe prospective randomized SENOMAC trial includes clinically node-negative breast cancer patients with up to two macrometastases in their sentinel lymph node biopsy. Patients with T1-T3 tumors are eligible as well as patients prior to systemic neoadjuvant therapy. Both breast-conserving surgery and mastectomy, with or without breast reconstruction, are eligible interventions. Patients are randomized 1:1 to either undergo completion ALND or not by a web-based randomization tool. This trial is designed as a non-inferiority study with breast cancer-specific survival at 5 years as the primary endpoint. Target accrual is 3500 patients to achieve 80% power in being able to detect a potential 2.5% deterioration of the breast cancer-specific 5-year survival rate. Follow-up is by annual clinical examination and mammography during 5 years, and additional controls after 10 and 15 years. Secondary endpoints such as arm morbidity and health-related quality of life are measured by questionnaires at 1, 3 and 5 years.DiscussionSeveral large subgroups of breast cancer patients, such as patients undergoing mastectomy or those with larger tumors, have not been included in key trials; however, the use of ALND is being questioned even in these groups without the support of high-quality evidence. Therefore, the SENOMAC Trial will investigate the need of completion ALND in case of limited spread to the sentinel lymph nodes not only in patients undergoing any breast surgery, but also in neoadjuvantly treated patients and patients with larger tumors.Trial registrationNCT 02240472, retrospective registration date September 14, 2015 after trial initiation on January 31, 2015.

Highlights

The role of axillary lymph node dissection (ALND) has increasingly been called into question among patients with positive sentinel lymph nodes
Aims and endpoints The main aim of this study is to evaluate whether it is safe to refrain from completion ALND in individuals with breast cancer and Sentinel node (SN) macrometastasis
A review by Schmidt-Hansen et al [33] identified only three prospective randomized trials comparing SN-biopsy with or without completion ALND in patients with SN metastases, reporting on a total of 2020 patients. This said, two of these three trials did exclusively include cases of SN-micrometastasis (AATRM 048/13/2000 and International Breast Cancer Study Group (IBCSG)-23-01) and the third trial (ACOSOG Z0011) included only 430 patients with SNmacrometastases while the remaining 301 patients had SN-micrometastases only; the size of SN-metastasis was not reported on the 125 patients left in the intent-to-treat sample (N = 856)

Summary

Methods

This prospective multicenter non-inferiority trial randomizes breast cancer patients with macrometastasis in at most two sentinel nodes to either undergo completion ALND (arm A) or not to have any further axillary surgery (arm B), and is conducted according to Good Clinical Practice (GCP) guidelines. Sample size The goal of the study is to establish that the intervention (no further axillary surgery) is statistically non-inferior to standard of care (completion ALND) for the primary endpoint breast cancer-specific survival (BCSS) at 5 years. Data monitoring committee An independent data monitoring committee will review the data and carry out one closed interim analysis 3 years after the date on which the first study patient was randomized, or when 2000 patients have been included in the study, whichever comes first The purpose of this interim analysis is to assess the recruitment to the study, the rate of overall breast-cancer related events and to make sure that patients in the intervention group do not appear to fare significantly worse than patients in the standard of care group. All analyses will be performed using StataCorp 2015 (College Station, TX: StataCorp LP)

Discussion

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