Phase II Multicenter Clinical Trial of Prophylactic Irradiation to the Contralateral Breast for BRCA Mutation Carriers Undergoing Treatment for Breast Cancer
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- Assaf-Harofeh Medical Center
- Enrollment
- 240
- Locations
- 1
- Primary Endpoint
- 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.
Study Overview
Brief Summary
Women with BRCA germline mutations face a very high risk of developing breast cancer during their lives. It was shown that for carrier patients, breast conservation, comprising of lumpectomy followed by whole breast radiation, was not associated with increased risk of ipsilateral breast cancer recurrence as compared with non carriers (10-15% over 10 years), especially if they also underwent prophylactic oophorectomy. Yet their risk of subsequent contralateral breast cancer was significantly increased, reported as high as 25-30% over 10 years and 40% over 15 years, as compared to 3% and 7% respectively in non carriers. The reduction in ipsilateral disease was attributed to radiation of the affected breast. We propose that for breast cancer patients with BRCA germline mutation that choose to have breast-conserving therapy and refuse prophylactic contralateral mastectomy, prophylactic radiation to the contralateral breast may reduce the rate of subsequent contralateral breast cancer and offer an option for risk reduction.
Detailed Description
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.
Treatment:
Chemotherapy, Hormonal therapy and XRT to the affected breast as per treating institution.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 30 Years to 90 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Female patient diagnosed with stage I-III breast cancer (AJCC 6), undergoing breast irradiation as part of her adjuvant therapy.
- •The patient must be a carrier of a deleterious mutation in BRCA 1/
- •Age above 30 years.
- •The patient may receive any regimen of adjuvant chemotherapy, according to the treating physician. All cycles of chemotherapy must be completed at least 3 weeks prior to the start of radiation therapy.
- •The patient may be treated with hormonal therapy before, during or after study entry, according to the guidelines of her treating center.
- •The patient must have negative gadolinium based MRI of the contralateral breast, no more than 6 months prior to study entry.
- •The patient refused prophylactic contralateral mastectomy.
- •The patient is aware that subsequent breast cancer in the irradiated breast will probably mandate mastectomy.
- •The patient consent for contralateral prophylactic irradiation. -
Exclusion Criteria
- •Metastatic breast cancer.
- •Previous irradiation of the breast or chest wall.
- •No concurrent chemotherapy is allowed
- •Patients with active connective tissue diseases are excluded due to the potential risk of significant radiotherapy toxicity.
- •Patients who are unable to lie on their back and raise their arms above their heads in the treatment planning position for radiotherapy are excluded -
Arms & Interventions
prophylactic irradiation
prophylactic contralateral breast irradiation
Intervention: Prophylactic radiation to the contralateral breast (Radiation)
controls
Those that do not opt for prophylactic irradiation or mastectomy
Outcomes
Primary Outcomes
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.
Time Frame: 15 years
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
Secondary Outcomes
- factors that influence patient's choice of treatment(15 years)
- Short and long term adverse effects of prophylactic contralateral breast irradiation.(15 years)