Phase II Multicenter Clinical Trial of Prophylactic Irradiation to the Contralateral Breast for BRCA Mutation Carriers Undergoing Treatment for Breast Cancer
Trial design and statistics:
This is a multi center- phase II open comparative trial. "Patients" - Those who choose
prophylactic contralateral breast irradiation. "Controls" - Those that do not opt for
prophylactic irradiation or mastectomy. Objective - to compare the rate of contralateral
breast cancer in "patients" versus "controls".
Assuming that 2/3 of the eligible carrier breast cancer patients refuse the procedure: To
detect a difference of 10% vs. 25% in the incidence of contralateral breast cancer with
power = 80%, alpha = 0.05, 80 patients and 160 controls need to be enrolled.
Chemotherapy, Hormonal therapy and XRT to the affected breast as per treating institution.
Patients will undergo a pre-treatment planning CT with 5mm cuts in the treatment position,
on a breast board, with both arms extended above their head. The organs at risk (heart,
lungs) will be contoured on the CT scan.
The affected breast (with the index lesion) and associated lymphatic drainage will be
treated according to the treating physician decision. The contralateral breast will be
treated with 2 tangent fields, using 1.8-2 Gy/fx to a total dose of 50-50.4 Gy. The whole
breast will be treated according to traditional guidelines and as described in the
RTOG/NSABP B39 study. The heart should be completely blocked for left sided breasts,
included lung tissue should be reduced to minimum. No overlapping field is allowed on the
skin between the two breast fields in the midline. Maximal dose should not exceed 110%.
The treating physician will follow the patient every 2 weeks during the radiation treatment.
Side effects will be scored and recorded in the patients chart according to the Common
Terminology Criteria for Adverse Events v3.0.
Subsequent follow-up schedule according to the treating institution and ASCO guidelines.
Patients will undergo annual mammogram and breasts US. Annual breasts MRI and bilateral
salpingo-oophorectomy will be recommended.
Ipsilateral and contralateral breast cancer will be recorded and reported. Any subsequent
malignancy other than breast cancer will be reported. Long-term radiation side effects will
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Rate of contralateral breast cancer in carrier patients that received prophylactic radiation to the contralateral breast compared with carrier patients that did not receive that treatment.
To compare the rate of contralateral breast cancer in carrier patients that received prophylactic radiation to the contralateral breast to the rate in carrier patients that did not receive that treatment
Ella Evron, MD
Assaf-Harofeh Medical Center
Israel: Israeli Health Ministry Pharmaceutical Administration