This randomized phase III trial studies radiation therapy to see how well it works with or without trastuzumab in treating women with ductal carcinoma in situ who have undergone lumpectomy. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether radiation therapy is more effective with or without trastuzumab in treating ductal carcinoma in situ.
PRIMARY OBJECTIVES: I. To determine the value of trastuzumab given during radiation therapy (RT) compared to RT alone in preventing subsequent occurrence of ipsilateral breast cancer recurrence, ipsilateral skin cancer recurrence, or ipsilateral ductal carcinoma in situ (IIBCR-SCR-DCIS) in women with human epidermal growth factor receptor 2 (HER2)-positive DCIS resected by lumpectomy. SECONDARY OBJECTIVES: I. Determine the value of trastuzumab given during RT compared to RT alone in prolonging invasive or DCIS disease-free survival (IDFS)-DCIS. II. Determine the value of trastuzumab given during RT compared to RT alone in increasing invasive or DCIS recurrence-free interval. III. Determine the value of trastuzumab given during RT compared to RT alone in improving regional or distant recurrence. IV. Determine the value of trastuzumab given during RT compared to RT alone in improving the incidence of contralateral invasive or DCIS breast cancer. V. Determine the value of trastuzumab given during RT compared to RT alone in improving survival. VI. To explore the effect of trastuzumab on ovarian function. TERTIARY OBJECTIVES: I. To determine if the benefit of trastuzumab added to RT will be significantly higher in v-myc avian myelocytomatosis viral oncogene homolog (cMYC)-amplified tumors than in the cMYC non-amplified subset. II. To determine if the benefit of trastuzumab added to RT will be less in tumors with mutations in the phosphatidylinositol 3 (PI3) kinase gene than in tumors without PI3 kinase gene mutations. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo standard whole breast irradiation (WBI) over 5-6 weeks. ARM II: Patients receive trastuzumab intravenously (IV) over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in Arm I. After completion of study treatment, patients are followed up every 6 months for 5 years and then every 12 months for 5 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2,014
Correlative studies
Given IV
Undergo standard whole breast irradiation
Northeast Alabama Regional Medical Center
Anniston, Alabama, United States
Providence Hospital
Mobile, Alabama, United States
University of South Alabama Mitchell Cancer Institute
Mobile, Alabama, United States
Alaska Breast Care and Surgery LLC
Anchorage, Alaska, United States
Alaska Women's Cancer Care
Anchorage, Alaska, United States
Ipsilateral Invasive Breast Cancer, Ipsilateral Skin Cancer Recurrence, or Ipsilateral DCIS-Free Survival
Patients who are free from Ipsilateral Invasive Breast Cancer, Ipsilateral Skin Cancer Recurrence or Ipsilateral DCIS as estimated by (1- cumulative incidence) x 100%.
Time frame: 5 years
Invasive or DCIS Disease-free Survival
Events for analysis of IDFS-DCIS include: local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, contralateral breast cancer, second primary cancer (other than squamous and basal cell carcinoma of the skin, melanoma in situ, and carcinoma in situ of the colon and cervix), or death from any cause prior to recurrence or second primary cancer. Invasive breast cancer, ipsilateral recurrence, and contralateral breast cancer will be compared across treatment arms using cumulative incidence functions. Percentage of patients by a Kaplan-Meier analysis who are free of invasive or DCIS disease
Time frame: 5 years
Invasive or DCIS Recurrence-free Interval
Cox proportional hazards models will be used to evaluate the effect of treatment on time to event. The distributions of time to event will be estimated by the Kaplan-Meier method for each treatment group and will be compared between treatments by simple and stratified log-rank tests. Compared across treatment arms using cumulative incidence functions.Percentage of patients who are invasive or DCIS recurrence free estimated by (1-cumulative incidence) x 100%.
Time frame: 5 years
Invasive Regional or Distant-Free Recurrence
Percentage of patients who are free of invasive regional or distant recurrence as estimated by (1 - cumulative incidence) x 100%.
Time frame: 5 years
Contralateral Breast Cancer (Invasive or DCIS) - Free Survival
Percentage of patients free of Contralateral Breast Cancer (Invasive or DCIS) as estimated by (1- cumulative incidence) x 100%.
Time frame: 5 years
Overall Survival
Percentage of patients surviving as estimated by a Kaplan-Meier
Time frame: 5 years
Incidence of Post-treatment Amenorrhea in Women Who Were Premenopausal at the Time of Study Entry Premenopausal at the Time of Study Entry
Proportion of patients who were pre-menopausal at randomization and who self-reported as not having menstrual periods afterwards
Time frame: 18 months
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