Breast Cancer
Conditions
Brief summary
In clinically node-positive (cN+) breast cancer, preoperative systemic therapy (PST) is common. With increasing rates of complete tumour eradication, there is a need for de-escalation of locoregional treatment in the interest of decreased morbidity. In order to individually adapt postoperative therapies, axillary staging is crucial. Axillary lymph node dissection (ALND) comes at a high risk of arm morbidity. There is extreme divergence in the use of less extensive staging methods, i.e. targeted lymph node biopsy (TLNB), sentinel node biopsy (SNB) or both (TAD), and in the use of subsequent locoregional treatment, since prospective data are largely lacking. The main purpose of the European INDAX trial is to implement de-escalated staging and evaluate which regional treatment, individually adapted to the response after PST, is oncologically safe but least harmful. Population: cN+ breast cancer patients receiving PST, recruited 2021-2025. Staging by TLNB, TAD or SNB. Intervention: Negative staging (ypN0, Randomisation A, N=1433): no regional treatment. Positive staging (ypN+, Randomisation B, N=1513): no ALND but regional radiotherapy (rRT). Control: Randomisation A: rRT only. Randomisation B: ALND plus rRT. Outcome: Invasive disease-free survival (non-inferiority), arm morbidity and quality of life. Drug tests in whole-tumour organoid cultures, algorithm-based digital image analysis and gene expression analysis are performed to improve response prediction, facilitate tailoring of PST and increase eradication rates.
Interventions
PROCEDUREOmission of axillary lymph node dissection
Axillary lymph node dissection will be replaced by axillary radiotherapy in Randomisation B
RADIATIONOmission of regional irradiation
Regional irradiation will be omitted in the interventional arm of Randomisation A.
Sponsors
Karolinska Institutet
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with primary invasive breast cancer cT1-cT3 * cN1 status prior to PST * Cytological or histological proof of axillary metastasis before PST * Full tumour biology available before initiation of PST * Oral and written consent * Age ≥ 18 years
Exclusion criteria
* Biopsy-confirmed regional nodal metastases outside of the ipsilateral axilla * Distant metastases at diagnosis * Inflammatory breast cancer * Previous axillary surgery * Previous radiotherapy to ipsilateral breast, chest or axilla * History of prior invasive breast cancer * Ongoing pregnancy or breast-feeding * Bilateral invasive breast cancer * Medical contraindication for radiotherapy or inability to receive recommended radiotherapy * Medical contraindication for adjuvant endocrine treatment, if indicated * Inability to absorb or understand the meaning of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| iDFS | 5 years | Invasive disease-free survival |
Outcome results
None listed