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

A Randomized Clinical Trial of Bioimpedance Spectroscopy or Tape Measure Triggered Compression Intervention in Chronic Breast Cancer Lymphedema Prevention

Background: This study compared rates of progression to chronic breast cancer-related lymphedema (defined as a greater than or equal to 10% arm volume change from baseline requiring complex decongestive physiotherapy (CDP) ) following an intervention for subclinical lymphedema (S-BCRL) triggered by bioimpedance spectroscopy (BIS) or by tape measurement (TM). Methods and Results: This stratified, randomized, international trial enrolled new breast cancer patients undergoing: mastectomy/partial mastectomy, axillary treatment (dissection, sentinel lymph node biopsy >6 nodes or radiation), radiation therapy (chest wall/ breast, supraclavicular fossa), or taxane-based chemotherapy. Following post-surgery eligibility reassessment, centralized, 1:1 randomization to prospective surveillance by BIS or TM occurred. S-BCRL detection triggered a 4-week, 12-hour per day, compression sleeve and gauntlet intervention. The primary outcome (n=209), rates of post-intervention progression to CDP, were assessed over three years. Between June 24, 2014 and September 11, 2018, 1,200 patients were enrolled, 963 randomized (BIS n=482;TM n=481) and 879 analyzed (BIS n=442;TM n=437). Median follow-up was 32.9 months (IQR=22,35). BIS patients triggered an intervention at a lower rate than TM patients (20.1%, n=89 vs 27.5%, n=120, p = 0.011). Median months to trigger was longer with BIS than TM (9.7; 95%CI,8.2-12.6 vs 3.9; 95%CI,2.8-4.5, p = 0.001). Overall, 14.4%(n=30) progressed post-intervention, with reduced likelihood for BIS patients than TM patients (7.9%, n=7 vs 19.2%, n=23; RR=0.41; 95%CI,0.13-0.81; absolute reduction 11.3%; 95%CI,2.3%-20.3%; p = 0.016). Conclusions: As compared to TM, BIS provides a more precise identification of patients likely to benefit from an early compression intervention.

Management of the Axilla in Early-Stage Breast Cancer: Ontario Health (Cancer Care Ontario) and ASCO Guideline

PURPOSE To provide recommendations on the best strategies for the management and on the best timing and treatment (surgical and radiotherapeutic) of the axilla for patients with early-stage breast cancer. METHODS Ontario Health (Cancer Care Ontario) and ASCO convened a Working Group and Expert Panel to develop evidence-based recommendations informed by a systematic review of the literature. RESULTS This guideline endorsed two recommendations of the ASCO 2017 guideline for the use of sentinel lymph node biopsy in patients with early-stage breast cancer and expanded on that guideline with recommendations for radiotherapy interventions, timing of staging after neoadjuvant chemotherapy (NAC), and mapping modalities. Overall, the ASCO 2017 guideline, seven high-quality systematic reviews, 54 unique studies, and 65 corollary trials formed the evidentiary basis of this guideline. RECOMMENDATIONS Recommendations are issued for each of the objectives of this guideline: (1) To determine which patients with early-stage breast cancer require axillary staging, (2) to determine whether any further axillary treatment is indicated for women with early-stage breast cancer who did not receive NAC and are sentinel lymph node–negative at diagnosis, (3) to determine which axillary strategy is indicated for women with early-stage breast cancer who did not receive NAC and are pathologically sentinel lymph node–positive at diagnosis (after a clinically node-negative presentation), (4) to determine what axillary treatment is indicated and what the best timing of axillary treatment for women with early-stage breast cancer is when NAC is used, and (5) to determine which are the best methods for identifying sentinel nodes. Additional information is available at www.asco.org/breast-cancer-guidelines .

Analysis of Axillary Management Following Mastectomy With a Positive Sentinel Lymph Node Biopsy

BACKGROUND: Axillary lymph node dissection (ALND) with or without postmastectomy radiation therapy (PMRT) was traditionally the standard of care for patients with a positive sentinel node following mastectomy. However, recent clinical trial data has led to an interest in de-escalating therapy and a debate over optimal axillary management. We sought to assess current practice patterns and the impact of different approaches to managing positive sentinel nodes following mastectomy. METHODS: Using the National Cancer Database (NCDB), patients with clinical T1-2 N0 M0 breast cancer from 2012-2015 treated with a mastectomy who were found to have a single positive sentinel node were analyzed. A logistic regression model stratified by patients’ characteristics in association to the type of axillary treatment received was performed.RESULTS: We identified 12,137 women with a positive sentinel lymph node biopsy (SLNB) at the time of mastectomy. Of these, 4,221 had an ALND; 1,609 received PMRT; 1,565 underwent combination therapy, and 4,742 had no further treatment following SLNB (NFT). Factors associated with an increased likelihood of further axillary treatment included younger age (<40), Midwest location, larger primary tumor size (T2), and high grade. There was no difference in short-term overall survival among these approaches. CONCLUSION: Our study indicates significant practice variation in the axillary management of patients with metastasis limited to a single sentinel node undergoing mastectomy. The clinical variation observed raises the possibility of unnecessary or overtreatment of the axilla. These findings suggest a need to expand the adoption of evidenced-based clinical protocols to improve quality of care.

Axillary management in T1-3N1M0 breast cancer patients with needle biopsy proven nodal metastases at presentation after neoadjuvant chemotherapy (ATNEC).

TPS600 Background: Neoadjuvant chemotherapy (NACT) results in eradication of cancer in the axillary nodes in 40% to 70% of patients. This raises questions about the benefit of further axillary treatment in those patients with no evidence of residual nodal disease (ypN0) after NACT. Methods: Design: ATNEC is a phase 3, randomised (1:1), multi-centre trial, with embedded economic evaluation, comparing standard axillary treatment (axillary lymph node dissection [ALND] or axillary radiotherapy [ART]) with no further axillary treatment in T1-3N1M0 breast cancer patients with needle biopsy proven axillary nodal metastases, who after NACT have no residual nodal disease (ypN0) on dual tracer sentinel node biopsy (SNB) and removal of at least 3 nodes (sentinel nodes and marked involved node). Stratification: Institution, type of surgery (breast conserving surgery vs mastectomy), receptor status (triple negative vs HER2 positive vs ER positive and/or PR positive and HER2 negative). Inclusion criteria are: Age ≥ 18, Male or female, T1-3N1M0 breast cancer at diagnosis (pre-NACT), FNA or core biopsy confirmed axillary nodal metastases at presentation, ER and HER2 status evaluated on primary tumour, received standard NACT as per local guidelines, ultrasound of the axilla at completion of NACT, dual tracer SNB after NACT and at least 3 nodes removed (sentinel nodes and marked node), no evidence of nodal metastases post NACT (ypN0). Exclusion criteria are: bilateral invasive breast cancer, SNB prior to NACT, marked node not removed except where at least one node removed shows evidence of down-staging with complete pathological response e.g. fibrosis/scarring and at least 3 nodes removed, previous ipsilateral axillary surgery, previous cancer within last 5 years or concomitant malignancy except basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, in situ or stage 1 melanoma, contra- or ipsilateral in situ breast cancer. Aims: To assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy - who after NACT have no residual nodal disease on SNB (ypN0) - is non-inferior to axillary treatment in terms of disease free survival, and reduces the risk of lymphoedema at 5 years. Statistical methods: All analyses will be carried out on an intention-to-treat basis to preserve randomisation, avoid bias from exclusions and preserve statistical power. Radiotherapy quality assurance: Study has in-built radiotherapy QA programme that will be co-ordinated by National Radiotherapy Trials QA (RTTQA) group. Target accrual: 1900. Trial status: Recruiting. Number of sites: 100. Clinical trial information: NCT04109079.

Postoperative Survival of Breast Cancer Patients Aged 85 Years or Older: A Retrospective Study

Background: Data on the postoperative outcomes of extremely elderly patients with breast cancer are lacking. Methods: We evaluated a series of 46 breast cancer patients aged 85 years or older (mean age: 87.4 years) who underwent surgical treatment, accumulated over the past 10 years. Results: The most common comorbidity was hypertension. Sixteen patients (34.8%) did not receive axillary treatment. The mean hospital stay was 12.8 days, and no in-hospital deaths were recorded. The 5-year overall survival rate was 78.2% (95% confidence interval: 63.5–96.3) over a median follow-up of 41 months.Conclusions: Surgical treatment of breast cancer patients aged 85 years or older is warranted.