Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Neoplasm Metastasis

Breast Diseases

Skin Diseases

Patients in this arm will not receive axillary treatment (axillary lymph node dissection or axillary radiotherapy). Supraclavicular fossa radiotherapy is not allowed when randomised to this arm.

Patients in this arm will receive axillary treatment. Axillary treatment can be axillary lymph node dissection or axillary radiotherapy.

Participants will undergo removal of at least level I and II axillary lymph nodes.

Axillary lymph node dissection

Axillary radiotherapy will be delivered as per the Radiotherapy Trials Quality Assurance (RTTQA) guidelines.

Axillary radiotherapy

Breast or chest wall radiotherapy will be delivered as per the Radiotherapy Trials Quality Assurance (RTTQA) guidelines.

Breast or chest wall radiotherapy

Amit Goyal, MS, MD, FRCS

Claire Murphy

Ludger Barthelmes

Kaiyumars Contractor

Hisham Osman

Eileen Anderson

Sue Down

Brendan Smith

Jalal Kokan

Laura Pettit

Beatrix Elsberger

Anneliese Lawn

Pardeep Arora

Graeme Lumsden

Gareth Irwin

Daniel Henderson

Fiona Hoar

Ricardo Pardo-Garcia

Richard Linforth

Rathinasabapathy Rathinaezhil

Sasirekha Govindarajulu

Inder Kumar

John Benson

Anita Hargreaves

Susan Hignett

Sanjana Masinghe

Emanuele Garreffa

Lynda Wyld

Velin Voynov

Aisling Hennessy

Marjory Maclennan

Tareq Abdullah

Carolyn Bedi

Douglas Ferguson

Sunil Amonkar

Biswajit Ray

Kaustuv Das

Nicholas Holford

Werbena Hamilton-Burke

Kartikae Grover

Hussein Tuffaha

Musa Barkeji

Rishi Parmeshwar

Subodh Seth

Emma MacInnes

Monika Kaushik

Saira Khawaja

Lai Cheng Yew

Debashis Ghosh

Neeraj Garg

Katherine Krupa

Daniel Leff

Ruth James

Anjana Satpathy

Brinda Sethugavalar

Amanda Taylor

Henry Cain

Pankaj Roy

Abdulla Alhasso

Saed Ramzi

Tamara Kiernan

Tahir Masudi

Lee Min Lai

Muhammed Baki

Matei Dordea

Sekhar Marla

Zoe Goldthorpe

Lubna Noor

Duncan Wheatley

Daniel Glassman

Abdul Syed

Konstantinos Zacharioudakis

Shaveta Mehta

Raman Vinayagam

Raghavan Vidya

Caroline Osborne

Bhavani Rengabashyam

The aim of this study is 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 cancer in the lymph nodes on sentinel node biopsy, is non-inferior to axillary treatment in terms of disease free survival (DFS) and results in reduced risk of lymphoedema at 5 years.

Background: The presence of cancer in the axillary lymph nodes on needle biopsy in patients with early stage breast cancer before neoadjuvant chemotherapy (NACT) has been the determinant of the need for axillary treatment (in the form of axillary lymph node dissection (ALND) or axillary radiotherapy (ART)) after completion of NACT. Treatment to the axilla damages lymphatic drainage from the arm and patients can subsequently develop lymphoedema, restricted shoulder movement, pain, numbness, and other sensory problems. As more effective chemotherapy is now available that results in complete eradication of cancer in the axilla in around 40 to 70% of patients, extensive axillary treatment might no longer be necessary in patients with no evidence of residual nodal disease.

Aim: 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 cancer in the lymph nodes on sentinel node biopsy, is non-inferior to axillary treatment in terms of disease free survival (DFS) and results in reduced risk of lymphoedema at 5 years.

Methods:

Study design: A pragmatic, phase 3, open, randomised, multicentre trial and embedded economic evaluation in which participants will be randomised in a 1:1 ratio.

Study population: T1-3N1M0 breast cancer patients aged 18 years or older, with needle biopsy proven nodal metastases, who after NACT have no residual cancer in the lymph nodes on dual tracer sentinel node biopsy and removal of at least 3 lymph nodes (sentinel nodes and marked involved node).

Intervention: All participants will receive human epidermal growth factor receptor 2 (HER2)-targeted treatment, endocrine therapy and radiotherapy to breast or chest wall, if indicated according to local guidelines. Patients in the intervention group will not receive further axillary treatment (ALND or ART), whereas those receiving standard care will receive axillary treatment (ALND or ART) as per local guidelines. Follow-up is annually for at least 5 years.

Outcomes: The co-primary outcomes are disease free survival(DFS) and self-reported lymphoedema defined as 'yes' to the two questions participants will be asked - 'arm heaviness during the past year' and 'arm swelling now' from the Lymphoedema and Breast Cancer Questionnaire at 5 years.

Secondary outcomes: arm function assessed by the QuickDASH (disabilities of the arm, shoulder and hand) questionnaire; health related quality of life assessed using euroqol EQ-5D-5L; axillary recurrence free interval (ARFI); local recurrence; regional (nodal) recurrence; distant metastasis; overall survival; contralateral breast cancer; non-breast malignancy; costs; quality adjusted life years (QALYs) and cost-effectiveness.

Sample size: A sample size of 1900 patients would have the ability to demonstrate a 3.5% non-inferiority margin with a 5% 1-sided significance level and 85% power, allowing for 7% non-collection of primary outcome data assuming a 90% 5-year disease free survival rate in the control arm. It would also be able to detect at least a 5% difference in proportion of patients with lymphoedema with 90% power, a 5% 2-sided significance level and allowing for 25% non-collection of primary outcome data over 5 years.

Analysis plan: All analyses will be carried out on an intention-to-treat basis to preserve randomisation, avoid bias from exclusions and preserve statistical power. Time to event outcomes, including disease free survival and axillary recurrence free interval, will be assessed using Kaplan-Meier curves and compared using Cox proportional hazards models. The proportion of patients experiencing lymphoedema at 5 years will be compared across trial arms using a chi-squared test and a logistic regression model used to adjust for stratification variables. Arm morbidity and health related quality of life will be scored using the appropriate manuals and assessed using a longitudinal mixed model regression analysis if model assumptions valid or a standardised area-under-the-curve analysis. For economic evaluation, incremental cost per QALY gained at 5 years will be estimated.

Timelines for delivery: Total project duration is 120 months based on 6 months for set up; 60 months recruitment period (including an 18 months internal pilot phase); and 54 months for follow up, analysis, writing up and dissemination.

Axillary Management in Breast Cancer Patients With Needle Biopsy Proven Nodal Metastases After Neoadjuvant Chemotherapy

ATNEC - Axillary Management in T1-3N1M0 Breast Cancer Patients With Needle Biopsy Proven Nodal Metastases at Presentation After Neoadjuvant Chemotherapy

DFS calculated as the time from randomisation until the date of first event of either a loco-regional invasive breast cancer relapse, distant relapse, ipsilateral or contralateral new invasive primary breast cancer or death by any cause or the censor date.

Lymphoedema is self-reported based on two items from the validated Lymphoedema and Breast Cancer Questionnaire (arm "swelling now" and arm "heaviness in the past year"). Lymphoedema is defined as 'yes' to both questions.

Arm function will be assessed using shortened version of the Disability of the Arm, Shoulder and Hand (DASH), the 11-item QuickDASH questionnaire. Physical disability is defined as a change from baseline in the QuickDASH score of at least 14 points.

Health related quality of life will be assessed with EQ-5D-5L

Axillary recurrence free interval, calculated from the date of randomisation to the date of axillary recurrence or the censor date.

Overall survival calculated as the time from randomisation until the date of death by any cause or the censor date.

Number of participants with local (breast or chest wall) recurrence

Number of participants with regional (nodal) recurrence

Number of participants with distant metastasis.

Number of participants with contralateral breast cancer.

Number of participants with non-breast cancer

University Hospitals of Derby and Burton NHS Foundation Trust

Consultant Oncoplastic Breast Surgeon & Associate Professor

All Drugs and Chemicals

Mitogens

Women in this arm will have adjuvant therapy but no treatment to their armpit after surgery. Axillary and supraclavicular fossa radiotherapy is not allowed when randomised to this arm.

Women in this arm will have adjuvant therapy plus treatment to their armpit after surgery. Axillary treatment can be axillary node clearance or axillary radiotherapy as per local guidelines.

Adjuvant therapy will include chemotherapy and/or endocrine therapy for all women, and radiotherapy to breast or chest wall if indicated. Human epidermal growth factor receptor 2 (HER2) targeted treatment may also be administered when indicated.

Adjuvant therapy

Axillary treatment can be axillary node clearance or axillary radiotherapy as per local guidelines.

Axillary treatment

Amit Goyal

POSNOC is a pragmatic, randomised, multicentre, non-inferiority trial.

Aim For women with early stage breast cancer and one or two sentinel node macrometastases, to assess whether adjuvant therapy alone is no worse than adjuvant therapy plus axillary treatment, in terms of axillary recurrence within 5 years.

Stratification: Institution, Age (\<50, ≥50), Breast-conserving surgery (BCS) or mastectomy, Estrogen receptor (ER) status (positive, negative), Number of positive nodes (1, 2), Intra-operative sentinel assessment using OSNA (yes, no).

Interventions The study will compare adjuvant therapy alone with adjuvant therapy plus axillary treatment (axillary node clearance (ANC) or axillary radiotherapy (ART)).

Sample Size: 1900 participants

Follow-up: Participants will be followed up for 5 years.

Adjuvant Therapy: All participants will receive adjuvant systemic therapy (chemotherapy and/or endocrine therapy). All participants may receive breast/chest wall radiotherapy. Axillary and supraclavicular fossa radiotherapy is not allowed when randomised to adjuvant therapy alone.

POSNOC - A Trial Looking at Axillary Treatment in Early Breast Cancer

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

Axillary recurrence is defined as pathologically (cytology or biopsy) confirmed recurrence in lymph nodes draining the primary tumour site.

Arm morbidity will be assessed by the Lymphoedema and Breast Cancer and QuickDASH (disabilities of the arm, shoulder and hand) questionnaires.

Quality of life will be assessed using the Functional Assessment of Cancer Therapy-Breast+4 questionnaire.

Anxiety will be assessed with the Spielberger State/Trait Anxiety Inventory.

Health-related quality of life will be evaluated using the EQ-5D-5L (EuroQoL) instrument.

Number of participants with local (breast or chest wall) recurrence.

Number of participants with regional (nodal) recurrence.

Number of participants with non-breast malignancy.

University of Nottingham

Sussex Health Outcomes Research & Education in Cancer (SHORE-C)

NCRI Radiotherapy Trials QA Group (RTTQA)

Breast Cancer Trials, Australia and New Zealand

clinically node-negative T1-2 invasive breast cancer patients treated with upfront mastectomy

Mastectomy

ALBERTO BOUZÓN

BENIGNO ACEA

EULALIA VIVES

MANUEL DÍAZ

MARÍA EFIGENIA ARIAS

GONZALO DE CASTRO

GEORGINA FREIRÍA

MARÍA ALEJANDRA GARCÍA

LAURA MUÍÑOS

PATRICIA VÁZQUEZ

MANUEL GARCÍA

MARÍA TERESA FERNÁNDEZ

Sentinel lymph node biopsy (SLNB) is the standard procedure to stage the axilla in clinically node-negative invasive breast cancer (IBC) patients undergoing upfront surgery.

The ACOSOG-Z0011 and the AMAROS trial demonstrated that SLNB with or without radiotherapy provided equivalent local control and survival to axillary lymph node dissection (ALND) in early-stage breast cancer patients with 1 or 2 positive SLNs. However, the ACOSOG-Z0011 trial did not included patients treated with mastectomy, and the AMAROS trial only included 17% of mastectomy patients.

The investigators conduct an observational cohort study of early stage breast cancer patients receiving upfront mastectomy with 1 or 2 macrometastases after SLNB. The study aim to demonstrate a 5-year disease-free survival of not less than 80% when ALND is omitted and replaced by axillary radiotherapy, and determine the axillary recurrence rate.

This is a multi-center, prospective study with an estimated sample size of 60 early-stage IBC patients.

Clinically node-negative T1-2 IBC patients undergoing mastectomy with up to 2 macrometases after SLNB will be informed about this study.

Patients will be checked with annual mammography and clinical examination. The axilla will be checked with ultrasound at 3 and 5 years of the surgery.

After surgery, patients will receive axillary radiotherapy, but no ALND, and adjuvant systemic treatment based on international guidelines.

Locoregional Control With Radiotherapy of Breast Cancer Patients With MACrometastases Treated With MAstectomy (MACMA)

Locoregional Control With Radiotherapy of cT1-2N0 Invasive Breast Cancer Patients With MACrometastases in the Sentinel Node Treated With MAstectomy: a Multi-center Observational Study

Results will be published by the investigators in academic journals

recurrence in the ipsilateral breast/thoracic wall, regional recurrence, distant recurrence or death

recurrence rate in the ipsilateral axillary lymph nodes

Complejo Hospitalario Universitario de Pontevedra

Complejo Hospitalario Universitario de Vigo

Complejo Hospitalario Universitario de Santiago

Hospital Universitario Lucus Augusti

Complexo Hospitalario de Ourense

University Hospital A Coruña

Principal Investigator, M.D., Ph.D.

Completion axillary treatment according to the Dutch breast cancer guideline

Completion axillary treatment

Marjolein L Smidt, MD, PhD

Hans JW de Wilt, MD, PhD

STUDY AIM To decrease the number of breast cancer patients receiving overtreatment of the axilla, in order to positively influence the axillary morbidity rate and quality of life.

PRIMARY OBJECTIVE To determine whether omitting completion axillary treatment is not inferior to the current axillary treatment regimen in sentinel node positive breast cancer patients undergoing a mastectomy, in terms of regional recurrence rate.

HYPOTHESIS Completion axillary treatment can be safely omitted in sentinel node positive breast cancer patients undergoing a mastectomy. This will lead to a decreased axillary morbidity rate and to an increased quality of life, with non-inferior regional control, distant-disease free- and overall survival rates.

Omitting Completion Axillary Treatment in Sentinel Node Positive Breast Cancer Patients Undergoing a Mastectomy

The Value of Completion Axillary Treatment in Sentinel Node Positive Breast Cancer Patients Undergoing a Mastectomy. A Dutch Randomized Controlled Multicentre Trial.

Regional recurrence is defined as tumour recurrence and as residual tumour that became clinically apparent in ipsilateral axillary, infraclavicular and supraclavicular lymph nodes (pathologically proven).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Axillary Management in Breast Cancer Patients With Needle Biopsy Proven Nodal Metastases After Neoadjuvant Chemotherapy	NCT04109079	Breast Cancer Sentinel Lymph ... Neoplasm, Breas...	Axillary lymph ... Axillary radiot... Breast or chest...	18 Years -	University Hospitals of Derby and Burton NHS Foundation Trust
POSNOC - A Trial Looking at Axillary Treatment in Early Breast Cancer	NCT02401685	Breast Cancer	Adjuvant therap... Axillary treatm...	18 Years -	University Hospitals of Derby and Burton NHS Foundation Trust
Locoregional Control With Radiotherapy of Breast Cancer Patients With MACrometastases Treated With MAstectomy (MACMA)	NCT06378294	Breast Cancer	Mastectomy	18 Years - 85 Years	University Hospital A Coruña
Omitting Completion Axillary Treatment in Sentinel Node Positive Breast Cancer Patients Undergoing a Mastectomy	NCT02112682	Breast Neoplasm...	Completion axil...	18 Years -	Maastricht University Medical Center

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