Systemic Therapy With or Without Up Front Surgery of the Primary Tumor in Breast Cancer Patients With Distant Metastases at Initial presenTation
In the Netherlands approximately one out of eight women will be diagnosed with breast
cancer; 5% have metastatic disease at presentation. Because metastatic breast cancer is
considered to be an incurable disease, it is only treated with a palliative intent. Recent
retrospective studies have demonstrated that (complete) resection of the primary tumor
significantly improves the outcome of patients with primary metastatic breast cancer.
However, other studies showed that the survival benefit in patients who underwent surgery is
caused by selection bias.
SUBMIT is a clinical trial that intends to answer the question whether up front breast
surgery in patients with primary distant metastatic breast cancer will result in an
improvement of the 2-year survival compared to the survival achieved with systemic therapy
and delayed local treatment or systemic therapy alone.
Patients to submit in this study are patients with primary distant metastatic breast cancer,
with no prior treatment of the breast cancer, who are 18 years or older and fit enough to
undergo surgery and systemic therapy. Exclusion criteria are: history of breast cancer,
other malignancy within the last 10 years, surgical treatment or radiotherapy of this breast
tumor before randomization, irresectable T4 tumor or synchronous bilateral breastcancer.
Randomization will take place immediately after the diagnosis of primary distant metastatic
breast cancer. Patients either randomize for up front surgery of the breast tumor (UFS)
followed by systemic therapy or for systemic therapy (ST) potentially followed by delayed
local treatment of the breast tumor.
The primary endpoint of this trial is the 2-years survival. Quality of life is one of the
most important secondary endpoints.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Survival is defined in months from the time of randomization until death. Overall survival will be expressed as the median survival in months.
participants will be followed until death (expected median survival 31 months for surgery group)
M.F. Ernst, dr
Jeroen Bosch Ziekenhuis
Netherlands: Medical Ethics Review Committee (METC)