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

  • STATUS
    Recruiting
  • End date
    Feb 28, 2030
  • participants needed
    1900
  • sponsor
    University Hospitals of Derby and Burton NHS Foundation Trust
Updated on 27 January 2021
cancer
estrogen
breast cancer
progesterone
metastasis
HER2
progesterone receptor
erbb2
estrogen receptor
axillary lymph node dissection
sentinel node
breast cancer staging
core needle biopsy
sentinel lymph node biopsy

Summary

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.

Description

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.

Details
Condition Breast Cancer, Sentinel Lymph Node, Breast Cancer Diagnosis, Sentinel Node, breast carcinoma, cancer, breast, breast tumors, tumor of the breast, breast tumor
Treatment Axillary Lymph Node Dissection, axillary radiotherapy, Breast or chest wall radiotherapy
Clinical Study IdentifierNCT04109079
SponsorUniversity Hospitals of Derby and Burton NHS Foundation Trust
Last Modified on27 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Breast Cancer or Sentinel Lymph Node?
Do you have any of these conditions: breast tumor or breast carcinoma or Breast Cancer Diagnosis or Sentinel Node or breast tumors or cancer, breast or Breast Cancer or Sentinel Lymph Nod...?
Do you have any of these conditions: cancer, breast or tumor of the breast or breast carcinoma or Breast Cancer Diagnosis or Sentinel Lymph Node or Breast Cancer or breast tumor or breast...?
Do you have any of these conditions: cancer, breast or tumor of the breast or breast tumors or Sentinel Lymph Node or breast tumor or Sentinel Node or Breast Cancer Diagnosis or Breast Ca...?
Do you have any of these conditions: Breast Cancer or Breast Cancer Diagnosis or breast tumor or Sentinel Lymph Node or cancer, breast or Sentinel Node or tumor of the breast or breast ca...?
Do you have any of these conditions: breast tumors or breast tumor or Breast Cancer or tumor of the breast or Sentinel Node or cancer, breast or Breast Cancer Diagnosis or Sentinel Lymph ...?
T1-3N1M0 breast cancer at diagnosis (prior to NACT) by American Joint Committee on Cancer (AJCC) staging 7th edition
Fine-needle aspiration (FNA) or core biopsy confirmed axillary nodal metastases at presentation
Oestrogen receptor, progesterone receptor and HER2 status evaluated on primary tumour
Received standard NACT as per local guidelines
Ultrasound of the axilla at completion of NACT
Undergo dual tracer sentinel node biopsy after NACT and at least 3 nodes removed (sentinel nodes and marked node). If axillary node sampling is performed following failed localisation of sentinel nodes, patient will be eligible if at least 3 nodes removed (including the marked node)
No nodal metastases post NACT (isolated tumour cells, micro or macrometastasis)

Exclusion Criteria

Bilateral invasive breast cancer
Sentinel node biopsy prior to NACT
Marked node not removed except where the node/s removed show
evidence of downstaging with complete pathological response e.g. fibrosis or scarring
Previous axillary surgery on the same body side as the scheduled targeted sampling
Radiation therapy for the currently diagnosed breast cancer prior to randomisation
Previous cancer within 5 years or concomitant malignancy except
basal or squamous cell carcinoma of the skin
in situ carcinoma of the cervix
in situ melanoma
contra- or ipsilateral in situ breast cancer
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