Prophylactic external radiotherapy versus screening strategy in women with BRCA 1/2 mutation: a multicenter, randomized, open-labelled clinical trial

Abstract

BRACKGROUND Breast cancer is the most prevalent cancer worldwide. It is the cancer that causes the most disability-adjusted life year globally, and the leading cause of death from cancer in women. Of all breast cancers, 5-10% correspond to hereditary cancer, in which BRCA is the main mutation with a 70% lifetime risk of developing breast cancer. In patients with BRCA 1/2 mutation, prophylactic mastectomy may be offered to reduce the risk of breast cancer. However, only 35.7% of women accept this measure, and it is an irreversible surgery with numerous complications and disadvantages. In order to offer new prophylactic options to these women, the use of contralateral prophylactic external radiation therapy has been studied in women with early breast cancer. This treatment demonstrated an 80% reduction of contralateral breast cancer and a delay in its onset. OBJECTIVE The aim of this study is to prove that prophylactic external radiotherapy of the breast can reduce the risk of subsequent breast cancers, compared to screening strategy. DESIGN AND SETTING The study will be based on a randomised, parallel-group, multicentre, and open-labelled clinical trial. It will be designed as a comparison between prophylactic external radiotherapy plus screening strategy vs. only screening strategy. It will be carried out in 3 hospitals of Institut Català d’Oncologia (ICO), with the ICO Girona being the coordinator center. PARTICIPANTS Women diagnosed with a deleterious mutation in BRCA 1/2 gene, without the presence of breast cancer, who declined undergoing bilateral prophylactic mastectomy. METHODS 216 patients will be enrolled with a consecutive non-probabilistic sampling. Recruitment will last 2 years and 6 months. Patients will be randomized in two groups: Group 1: Prophylactic external radiotherapy plus screening strategy (n= 108). Group 2: Only screening strategy (n=108). After the intervention there will be a subsequent follow-up of 5 years