This randomized phase III trial studies standard or comprehensive radiation therapy in treating patients with early-stage breast cancer who have undergone surgery. Radiation therapy uses high-energy x rays to kill tumor cells. It is not yet known whether comprehensive radiation therapy is more effective than standard radiation therapy in treating patients with breast cancer
PRIMARY OBJECTIVES: To evaluate whether the addition of chest wall + regional nodal radiation therapy (XRT) after mastectomy or breast + regional nodal XRT after breast conserving surgery will significantly reduce the rate of events for invasive breast cancer recurrence-free interval (IBC-RFI) in patients who present with histologically positive axillary nodes but convert to histologically negative axillary nodes following neoadjuvant chemotherapy. SECONDARY OBJECTIVES: I. To evaluate whether the addition of chest wall + regional nodal XRT after mastectomy or breast + regional nodal XRT after breast conserving surgery will significantly prolong overall survival (OS) in patients who present with histologically positive axillary nodes but convert to histologically negative axillary nodes following neoadjuvant chemotherapy. II. To evaluate whether the addition of chest wall + regional nodal XRT after mastectomy or breast + regional nodal XRT after breast conserving surgery will significantly reduce the rates of events for local-regional recurrence-free interval (LRRFI) in patients who present with histologically positive axillary nodes but convert to histologically negative axillary nodes following neoadjuvant chemotherapy. III. To evaluate whether the addition of chest wall + regional nodal XRT after mastectomy or breast + regional nodal XRT after breast conserving surgery will significantly reduce the rate of events for distant recurrence-free interval (DRFI) in patients who present with histologically positive axillary nodes but convert to histologically negative axillary nodes following neoadjuvant chemotherapy. IV. To compare the rates of disease-free survival (DFS)-ductal carcinoma in situ (DCIS) by treatment arm. V. To compare the rates of second primary cancer (SPC) by treatment arm. VI. To compare the effect of adding XRT on the cosmetic outcomes in mastectomy patients who have had reconstruction. VII. To compare the effect of adding XRT on quality of life including arm problems, lymphedema, pain, and fatigue. VIII. To evaluate the toxicity associated with each of the radiation therapy regimens. IX. To determine whether computed tomography (CT)-based conformal methods (intensity-modulated radiation therapy \[IMRT\] and 3-dimensional conformal radiation therapy \[3DCRT\]) for chestwall + regional nodal XRT post mastectomy and regional nodal XRT with breast XRT following breast conserving surgery are feasible in a multi-institutional setting and whether dose-volume analyses can be established to assess treatment adequacy and to develop normal tissue complication probabilities (NTCP) for the likelihood of toxicity. X. To compare the effect of XRT in patients receiving mastectomy and in patients receiving lumpectomy. XI. To examine the role of proliferation measures as a prognosticator for patients with residual disease after neoadjuvant chemotherapy. XII. To develop predictors of the degree of reduction in local regional recurrence (LRR). OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM 1: Patients are assigned to 1 of 2 treatment groups. GROUP 1A: Lumpectomy patients undergo whole breast radiation therapy using IMRT or 3DCRT once daily 5 days a week for 5 weeks followed by a radiation therapy boost to the lumpectomy cavity once daily 5 days a week for 1-1/2 weeks. GROUP 1B: Mastectomy patients do not undergo radiation therapy. ARM 2: Patients are assigned to 1 of 2 treatment groups. GROUP 2A: Lumpectomy patients undergo regional nodal radiation therapy with whole breast radiation therapy using IMRT or 3DCRT once daily 5 days a week for 5 weeks followed by a radiation therapy boost to the lumpectomy cavity once daily 5 days a week for 1-1/2 weeks. GROUP 2B: Mastectomy patients undergo regional nodal radiation therapy and chestwall XRT using IMRT or 3DCRT once daily 5 days a week for 5 weeks. All patients also receive systemic therapy as planned (hormonal therapy for patients with hormone-receptor positive breast cancer and trastuzumab or other anti-human epidermal growth factor receptor 2 \[HER2\] therapy for patients with breast cancer that is HER2-positive). After completion of study treatment, patients are followed up at 6, 12, 18, and 24 months and then yearly for 8 years.
IBC-RFI
Time frame: Time from randomization until invasive local, regional, or distant recurrence, or death from breast cancer, assessed up to 10 years
OS
Time frame: Time from randomization to death from any cause, assessed up to 10 years
LRRFI
Time frame: Time from randomization to recurrence of primary cancer w/in breast or lymph nodes in ipsilateral axilla, infraclavicular fossa, or ipsilateral internal mammary chain w/out evidence distant disease, or death due to breast cancer, assessed up to 10 years
DRFI
Time frame: Time from randomization to the development of tumor in all areas beyond local or regional limits, or death due to breast cancer, assessed up to 10 years
DFS-DCIS
Time frame: Time from randomization to local recurrence post-mastectomy/in ipsilateral breast post-lumpectomy, regional/distant recurrence, contralateral disease, second primary cancer, or death from any cause prior to recurrence or SPC, assessed up to 10 years
Time to SPC
Time frame: Time from randomization to the development of a second primary invasive cancer of any site excluding squamous and basal cell carcinoma of the skin, assessed up to 10 years
Effect of radiation therapy on cosmetic outcome in mastectomy and lumpectomy patients as assessed by quality of life questionnaire
Time frame: Assessed prior to randomization, 3 months or at end of RT, and 6, 12, and 24 months from randomization
Frequencies of adverse events graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
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Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,636
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
University of South Alabama Mitchell Cancer Institute
Mobile, Alabama, United States
Providence Alaska Medical Center
Anchorage, Alaska, United States
Arizona Breast Cancer Specialists-Gilbert
Gilbert, Arizona, United States
Arizona Center for Cancer Care-Peoria
Peoria, Arizona, United States
Arizona Breast Cancer Specialists-Phoenix
Phoenix, Arizona, United States
Arizona Breast Cancer Specialists-Scottsdale
Scottsdale, Arizona, United States
Arizona Center for Cancer Care-Surprise
Surprise, Arizona, United States
Arizona Oncology Associates-West Orange Grove
Tucson, Arizona, United States
The University of Arizona Medical Center-University Campus
Tucson, Arizona, United States
...and 504 more locations
Time frame: Up to 30 days after completion of study treatment
Molecular predictors of recurrence
To test the prognostic role of gene expression profiles in residual tumor tissue and to develop predictors of the degree of reduction of loco-regional recurrence.
Time frame: Tissue samples collected within 90 days after randomization