Whole Breast Irradiation vs Twice Daily vs. Once Daily Accelerated Partial Breast Irradiation

Inclusion Criteria: Tumor characteristics * Histologically confirmed invasive adenocarcinoma of the breast * Tumors must be ≤ 3 cm. Gross disease must be unifocal. Negative lymph nodes * Hormone receptor status: Estrogen receptor (ER) status known Progesterone status known if ER analysis is negative Marginal or borderline results are considered positive Surgery * Tumor removed with conservative breast surgery with adequate margin * Re-excision of surgical margins allowed * No prior breast implants * Prior axillary staging required for patients including 1 of the following: * Sentinel node biopsy alone (if sentinel node is negative) * Sentinel node biopsy followed by axillary dissection if sentinel node is positive) * Axillary dissection alone with ≥ 6 axillary nodes * Target lumpectomy cavity clearly delineated AND target lumpectomy/whole breast reference volume ≤ 30% based on postoperative pre-randomization CT scan * Final surgery (i.e., lumpectomy, re-excision of margins, or axillary staging procedure) within the past 42 days * No prior biologic therapy for this malignancy Chemotherapy * No prior chemotherapy for this malignancy * No concurrent chemotherapy during study radiotherapy Endocrine therapy * No prior hormonal therapy for this malignancy * Concurrent hormonal therapy allowed provided it is not administered during chemotherapy * No concurrent raloxifene, tamoxifen, or other selective estrogen receptor modulating drugs * No concurrent hormone replacement therapy Radiotherapy * No prior radiotherapy for this malignancy * No prior breast or thoracic radiotherapy * No concurrent regional nodal irradiation Other * No other concurrent anticancer therapy Menopausal status * Premenopausal or postmenopausal Performance status * WHO 0-1 Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective non-hormonal contraception Exclusion Criteria: * Multicentric carcinoma in more than 1 quadrant or separated by ≥ 4 cm. * Non-epithelial breast malignancies (e.g., sarcoma or lymphoma). * Positive axillary nodes. * Palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes unless there is histologic confirmation that these nodes are negative for tumor. * Suspicious microcalcifications, densities, or palpable abnormalities in the ipsilateral or contralateral breast unless biopsied and found to be benign * Paget's disease of the nipple * Previous history of invasive breast cancer or DCIS. * Synchronous bilateral invasive or non-invasive breast cancer * Collagen vascular disease (e.g., systemic lupus erythematosus or scleroderma), specifically dermatomyositis with a CPK level above normal, or active skin rash * Psychiatric or addictive disorder that would preclude study therapy