POSNOC—POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy: a randomised controlled trial of axillary treatment in women with early-stage breast cancer who have metastases in one or two sentinel nodes

IntroductionACOSOG-Z0011(Z11) trial showed that axillary node clearance (ANC) may be omitted in women with ≤2 positive nodes undergoing breast conserving surgery (BCS) and whole breast radiotherapy (RT). A confirmatory study is needed to clarify the role of axillary treatment in women with ≤2 macrometastases undergoing BCS and groups that were not included in Z11 for example, mastectomy and those with microscopic extranodal invasion. The primary objective of POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy (POSNOC) is to evaluate whether for women with breast cancer and 1 or 2 macrometastases, adjuvant therapy alone is non-inferior to adjuvant therapy plus axillary treatment, in terms of 5-year axillary recurrence.Methods and analysisPOSNOC is a pragmatic, multicentre, non-inferiority, international trial with participants randomised in a 1:1 ratio. Women are eligible if they have T1/T2, unifocal or multifocal invasive breast cancer, and 1 or 2 macrometastases at sentinel node biopsy, with or without extranodal extension. In the intervention group women receive adjuvant therapy alone, in the standard care group they receive ANC or axillary RT. In both groups women receive adjuvant therapy, according to local guidelines. This includes systemic therapy and, if indicated, RT to breast or chest wall. The UK Radiotherapy Trials Quality Assurance Group manages the in-built radiotherapy quality assurance programme. Primary endpoint is 5-year axillary recurrence. Secondary outcomes are arm morbidity assessed by Lymphoedema and Breast Cancer Questionnaire and QuickDASH questionnaires; quality of life and anxiety as assessed with FACT B+4 and State/Trait Anxiety Inventory questionnaires, respectively; other oncological outcomes; economic evaluation using EQ-5D-5L. Target sample size is 1900. Primary analysis is per protocol. Recruitment started on 1 August 2014 and as of 9 June 2021, 1866 participants have been randomised.Ethics and disseminationProtocol was approved by the National Research Ethics Service Committee East Midlands—Nottingham 2 (REC reference: 13/EM/0459). Results will be submitted for publication in peer-reviewed journals.Trial registration numberISRCTN54765244; NCT0240168Cite Now

Risk factors for lymphedema after breast surgery: A prospective cohort study in the era of sentinel lymph node biopsy

INTRODUCTION: The Objective was to investigate the incidence of lymphedema after breast cancer treatment and to analyze the risk factors involved in a tertiary level hospital. METHODS: Prospective longitudinal observational study over 3 years post-breast surgery. 232 patients undergoing surgery for breast cancer at our institution between September 2013 and February 2018. Sentinel lymph node biopsy (SLNB) or axillary lymphadenectomy (ALND) were mandatory in this cohort. In total, 201 patients met the inclusion criteria and had a median follow-up of 31 months (range, 1–54 months). Lymphedema was diagnosed by circumferential measurements and truncated cone calculations. Patients and tumor characteristics, shoulder range of motion limitation and local and systemic therapies were analyzed as possible risk factors for lymphedema. RESULTS: Most cases of lymphedema appeared in the first 2 years. 13.9% of patients developed lymphedema: 31% after ALND and 4.6% after SLNB (p < 0.01), and 46.7% after mastectomy and 11.3% after breast-conserving surgery (p < 0.01). The lymphedema rate increased when axillary radiotherapy (RT) was added to radical surgery: 4.3% for SLNB alone, 6.7% for SLNB + RT, 17.6% for ALND alone, and 35.2% for ALND + RT (p < 0.01). In the multivariate analysis, the only risk factors associated with the development of lymphedema were ALND and mastectomy, which had hazard ratios (95% confidence intervals) of 7.28 (2.92–18.16) and 3.9 (1.60–9.49) respectively. CONCLUSIONS: The main risk factors for lymphedema were the more radical surgeries (ALND and mastectomy). The risk associated with these procedures appeared to be worsened by the addition of axillary radiotherapy. A follow-up protocol in patients with ALND lasting at least two years, in which special attention is paid to these risk factors, is necessary to guarantee a comprehensive control of lymphedema that provides early detection and treatment.

Risk Factors for Lymphedema After Breast Surgery: a Prospective Cohort Study in the Era of Sentinel Lymph Node Biopsy

Introduction: We aimed to investigate the incidence of lymphedema after breast cancer treatment, to analyze the risk factors involved, and to improve existing protocols for the prevention of lymphedema. Patients and methods: This was a prospective cohort study of 232 patients undergoing surgery for breast cancer at our institution between September 2013 and February 2018. Sentinel lymph node biopsy (SLNB) or axillary lymphadenectomy (ALND) were mandatory in this cohort. Lymphedema was diagnosed by circumferential measurements and truncated cone calculations. Patients and tumor characteristics, as well as local and systemic therapies, were analyzed as possible risk factors for lymphedema. Results: In total, 201 patients met the inclusion criteria and had a median follow-up of 31 months (range, 1–54 months). Most cases of lymphedema cases appeared in the first 2 years. 13.9% developed lymphedema: 31% after ALND and 4.6% after SLNB (p < 0.01), and 46.7% after mastectomy and 11.3% after breast-conserving surgery (p < 0.01). The lymphedema rate increased when axillary radiotherapy (RT) was added to radical surgery: 4.3% for SLNB alone, 6.7% for SLNB + RT, 17.6% for ALND alone, and 35.2% for ALND + RT (p < 0.01). In the multivariate analysis, the only risk factors associated with the development of lymphedema were ALND and mastectomy, which had hazard ratios (95% confidence intervals) of 7.28 (2.92–18.16) and 3.9 (1.60–9.49), respectively. Conclusions: The main risk factors for lymphedema were the most radical surgeries (ALND and mastectomy), while the risk associated with these appeared to be worsened by the addition of axillary radiotherapy. A follow-up protocol in patients with ALND for at least two years, where these risk factors are recognized, is necessary to guarantee a comprehensive control of lymphedema that provides early detection and treatment.

Locoregional Management of Early-Stage Breast Cancer

Locoregional management of early-stage breast cancer has been trending toward less-extensive axillary resections, based on increasing evidence showing that patients with 1 or 2 positive sentinel nodes and/or micrometastases can safely be managed with sentinel node biopsy alone, thereby avoiding complete axillary lymph node dissection (cALND) in the significant majority of patients. Because of the 15% to 20% lymphedema risk associated with cALND, increasing efforts are being made to avoid the procedure when evidence suggests that more limited procedures are safe, as reflected by acceptable locoregional recurrence rates. Axillary radiotherapy (RT) has been shown to be an effective alternative to ALND for patients fitting criteria from the pivotal AMAROS trial: patients with T1/T2 disease and are clinically node-negative, who undergo either breast-conserving therapy or mastectomy. Considerations for RT begin with the question of nodal involvement, with treatment planned accordingly. With more neoadjuvant therapy being used, there are nuances in locoregional management that clinicians must now appreciate, both in terms of ALND and axillary RT.