Omission of Axillary Lymph Node Dissection in Case of Tumor Spread to Lymph Nodes in the Armpit in Breast Cancer (SENOMAC-ULTRA)

SENOMAC-ULTRA: A Prospective Randomised Trial on the Omission of Axillary Lymph Node Dissection in Ultrasound-detectable Axillary Metastases in Primary Breast Cancer Treated by Upfront Surgery

SENOMAC-ULTRA enrols patients who are planned for upfront surgery for a breast cancer that has spread to lymph nodes in the armpit, and that have been detected already prior to surgery by imaging, e.g. ultrasonography. In this situation, a full axillary lymph node dissection, removing more than 10 lymph nodes from the arm pit, is unnecessarily extensive in about half of the patients. More extensive surgery leads to a risk for arm lymphedema and functional problems with the arm and shoulder region, which should be avoided if not beneficial for diagnosis or prognosis. This trial seeks to ascertain that less extensive surgery, performed by only removing the first lymph node/s in the armpit (the sentinel lymph node/s) and the known metastatic lymph nodes (targeted axillary dissection, TAD), offers non-inferior survival outcomes to a full axillary lymph node dissection.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Surgery; Breast Cancer; Breast Carcinoma
• Intervention / Treatment: Procedure: Targeted axillary dissection; Procedure: Axillary lymph node dissection

• Study Type: Interventional
• Enrollment (Estimated): 1380
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jana de Boniface, Professor; Phone Number: +46702472305; Email: jana.de-boniface@ki.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with primary invasive breast cancer clinical stage II-III
• Palpable or non-palpable axillary metastases visible by ultrasound (other imaging accepted if confirmatory ultrasound is performed) and confirmed by fine needle aspiration or core biopsy
• Written informed consent
• Age ≥ 18 years

Exclusion Criteria:

• Distant metastases
• Ipsilateral metastases in internal mammary, infra- or supraclavicular lymph nodes without confirmed axillary nodal involvement
• Preoperative suspicion of extensive nodal involvement, i.e. locally advanced disease
• Nodes fixed to each other or to neighbouring structures on palpation or imaging
• History of contralateral invasive breast cancer within 5 years
• Bilateral invasive breast cancer if (i) one side meets any exclusion criteria or (ii) both sides meet all inclusion criteria
• Pregnancy
• Neoadjuvant systemic treatment (short course of neoadjuvant endocrine therapy <three months is allowed)
• Medical contraindications for or expressed preoperative wish to abstain from radiotherapy or the recommended adjuvant systemic treatment which complies with standard of care, taking age and comorbidity into consideration
• Inability to absorb or understand the meaning of the study information; for example, through disability, inadequate language skills or dementia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Axillary lymph node dissection	Procedure: Axillary lymph node dissection; Routine axillary clearance removing about 10+ lymph nodes from axillary levels I and II
Experimental: Targeted axillary dissection; Removal of the marked metastasis/-es and a sentinel lymph node biopsy	Procedure: Targeted axillary dissection; Known metastases are marked before surgery and removed together with a sentinel lymph node biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free survival	Time to event where an event is death if any cause or a recurrence of breast cancer	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arm morbidity	Arm function as reported by patients via the Lymphedema Functioning, Disability and Health questionnaire (Lymph-ICF), which consists of 29 questions about impairments in function, activity limitations, and participation restrictions of patients with breast cancer and arm lymphedema. The questionnaire is divided into 5 domains: physical function, mental function, household activities, mobility activities, and life and social activities. Each item is scored on a visual analogue scale (0-100 mm) resulting in domain scores ranging from 0 to 100. Higher scores indicate more severe arm dysfunction. Lymph-ICF scores also categorize into "no problem", "a small problem", "a moderate problem", "a severe problem", and "a very severe problem".	1, 3, 5 years
Health-related quality of life	Health-related quality of life measured by EORTC C30. The EORTC QLQ-C30 questionnaire measures HRQoL among cancer patients in general and consists of 30 items divided into multi-item scales and single items. The multi-item scales include one global health and quality of life (QoL) scale, five function subscales (physical, role, emotional, cognitive, social) and three symptom subscales (fatigue, nausea and vomiting, pain). The single items are dyspnoea, insomnia, appetite loss, constipation, diarrhoea, financial difficulties. Each scale produces a total score from 0 to 100. High scores on functional subscales indicate better function, and high scores on symptom subscales indicate more severe problems.	1, 3, 5 years
Overall survival	Time to event where an event is death of any cause	5 years
Health-related quality of life - breast cancer	The EORTC QLQ-BR23 questionnaire measures functions and symptoms related to breast cancer treatment and consists of 23 items divided into two functional subscales (body image and sexuality) and three symptom subscales (systemic therapy side effects, arm symptoms, breast symptoms) and three single items (sexual enjoyment, upset by hair loss, future perspective). The functional and symptom subscales as well as the single items correspond to a response scale 1-4 (not at all, a little, quite a bit, very much). Each scale produces a total score from 0 to 100. High scores on functional subscales indicate better function, and high scores on symptom subscales indicate more severe problems.	1, 3, 5 years

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Investigators: Principal Investigator: Jana de Boniface, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2040

Study Registration Dates

• First Submitted: March 4, 2025
• First Submitted That Met QC Criteria: March 10, 2025
• First Posted (Actual): March 11, 2025

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: November 27, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: axillary lymph node dissection; sentinel lymph node biopsy; targeted axillary dissection; axillary metastases; axillary ultrasonography
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: SENOMAC-ULTRA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD may be shared upon reasonable request and with all relevnt legal and ethical requirements fulfilled. No request will be accepted before the publication of the primary endpoint.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No