title: SUBMIT: Systemic therapy with or without up front surgery of the primary tumor in breast cancer patients with distant metastases at initial presentation.
abstract: BACKGROUND
  Five percent of all patients with breast cancer have distant metastatic disease at initial presentation. Because metastatic breast cancer is considered to be an incurable disease, it is generally treated with a palliative intent. Recent non-randomized studies have demonstrated that (complete) resection of the primary tumor is associated with a significant improvement of the survival of patients with primary metastatic breast cancer. However, other studies have suggested that the claimed survival benefit by surgery may be caused by selection bias. Therefore, a randomized controlled trial will be performed to assess whether breast surgery in patients with primary distant metastatic breast cancer will improve the prognosis.
  
  
  METHODS
  Randomization will take place after the diagnosis of primary distant metastatic breast cancer. Patients will either be randomized to up front surgery of the breast tumor followed by systemic therapy or to systemic therapy, followed by delayed local treatment of the breast tumor if clinically indicated.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 are eligible. Important exclusion criteria are: prior invasive breast cancer, surgical treatment or radiotherapy of this breast tumor before randomization, irresectable T4 tumor and synchronous bilateral breast cancer. The primary endpoint is 2-year survival. Quality of life and local tumor control are among the secondary endpoints.Based on the results of prior research it was calculated that 258 patients are needed in each treatment arm, assuming a power of 80%. Total accrual time is expected to take 60 months. An interim analysis will be performed to assess any clinically significant safety concerns and to determine whether there is evidence that up front surgery is clinically or statistically inferior to systemic therapy with respect to the primary endpoint.
  
  
  CONCLUSIONS
  The SUBMIT study is a randomized controlled trial that will provide evidence on whether or not surgery of the primary tumor in breast cancer patients with metastatic disease at initial presentation results in an improved survival.
  
  
  BACKGROUND
  NCT01392586.
authors.affiliation: Department of Surgery, Máxima Medical Center, Veldhoven, The Netherlands.
authors.forename: Jetske
authors.initials: J
authors.lastname: Ruiterkamp
authors.forename: Adri C
authors.initials: AC
authors.lastname: Voogd
authors.forename: Vivianne C G
authors.initials: VC
authors.lastname: Tjan-Heijnen
authors.forename: Koop
authors.initials: K
authors.lastname: Bosscha
authors.forename: Yvette M
authors.initials: YM
authors.lastname: van der Linden
authors.forename: Emiel J Th
authors.initials: EJ
authors.lastname: Rutgers
authors.forename: Epie
authors.initials: E
authors.lastname: Boven
authors.forename: Maurice J C
authors.initials: MJ
authors.lastname: van der Sangen
authors.forename: Miranda F
authors.initials: MF
authors.lastname: Ernst
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D002985:Clinical Protocols; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011788:Quality of Life; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents