Systemic Therapy With or Without Upfront Surgery in Metastatic Breast Cancer (SUBMIT)

• Survival [ Time Frame: participants will be followed until death (expected median survival 31 months for surgery group) ] [ Designated as safety issue: No ]
  Survival is defined in months from the time of randomization until death. Overall survival will be expressed as the median survival in months.
  
  

• Quality of Life [ Time Frame: 5 years after randomisation ] [ Designated as safety issue: No ]
  The EORTC QLQ - C30 and BR23 questionnaires will be used for the measurement of the quality of life. The quality of life will be assessed at 3, 6, 12, 18 months and 2,3,4,5 years after randomisation
  
  
• Two year survival [ Time Frame: 2 yrs after randomisation ] [ Designated as safety issue: No ]
  The percentage of patients who survive two years after randomization will be determined.
  
  
• Number of unplanned local therapies [ Time Frame: 5-6 months after randomisation ] [ Designated as safety issue: No ]
  The number of patients who will receive local treatment at another point than scheduled
  
  
• Difference in systemic therapy given [ Time Frame: 6 months after randomisation ] [ Designated as safety issue: No ]
  register which patients receive what treatments
  
  
• Determination of pathological resection margin [ Time Frame: Pathological report approximately 1 day after surgery ] [ Designated as safety issue: No ]
  The definition of a complete resection in this trial means free resection margins for the invasive component.
  
  
• Number of treatments of the axillary lymph nodes [ Time Frame: 6 months after randomisation ] [ Designated as safety issue: No ]
  register which patients receive these treatments
  
  

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.