Open Access Study protocol

SUBMIT: Systemic therapy with or without up front surgery of the primary tumor in breast cancer patients with distant metastases at initial presentation

Jetske Ruiterkamp1, Adri C Voogd2, Vivianne CG Tjan-Heijnen3, Koop Bosscha4, Yvette M van der Linden5, Emiel JTh Rutgers6, Epie Boven7, Maurice JC van der Sangen8, Miranda F Ernst39* and In collaboration with Dutch Breast Cancer Trialists' Group (BOOG)

Author affiliations

1 Department of Surgery, Máxima Medical Center, Veldhoven, The Netherlands

2 Department of Epidemiology, GROW--School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands

3 Division of Medical Oncology, Department Internal Medicine, GROW--School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands

4 Department of Surgery, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands

5 Radiotherapeutic Institute Friesland, Leeuwarden, The Netherlands

6 Department of Surgical oncology, Dutch Cancer Institute--Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

7 Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands

8 Department of Radiotherapy, Catharina Hospital, Eindhoven, The Netherlands

9 Department of Surgery, Jeroen Bosch Hospital, Postbus 90153, 5200 ME 's-Hertogenbosch, The Netherlands

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Citation and License

BMC Surgery 2012, 12:5  doi:10.1186/1471-2482-12-5

Published: 2 April 2012

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.

Design

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.

Discussion

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.

Trial registration

NCT01392586.

Keywords:
Primary metastatic breast cancer; surgery; randomised controlled trial