• Pathologically proven diagnosis of breast cancer resected by lumpectomy and whole breast irradiation with boost without regional nodal irradiation planned

• The patient must be female

• The patient must meet at least one of the three following criteria:

‣ A. Pathological stage I, II Breast Cancer AND at least one of the following:

• Age \< 50 years or

∙ Positive axillary nodes or

∙ Lymphovascular space invasion or

∙ 2 or more close resection margins (\> 0 mm to ≤ 2 mm) or

∙ 1 close resection margin and extensive intraductal component (EIC) \[Per College of American Pathologist (CAP) Recommendation\] or

∙ Focally positive resection margins or

∙ Non-hormone sensitive breast cancer (estrogen receptor (ER)- and progesterone receptor(PR)-negative) or

∙ Grade III histology or

∙ Oncotype recurrence score \> 25 or

⁃ B. Pathological stage 0 breast cancer with nuclear grade 3 ductal carcinoma in situ (DCIS) and patient age \<50 years or

⁃ C. Post-neoadjuvant pathological 0, I, II breast cancer resected by lumpectomy after neoadjuvant systemic therapy

• Study entry must be within 50 days from whichever comes later: last surgery (breast or axilla) or last chemotherapy. The day of surgery is Day 0.

• If multifocal breast cancer, then it must have been resected through a single lumpectomy incision with negative margins

• Breast-conserving surgery with margins defined as follows: (also see 3.1.3 for eligibility)

‣ Negative margins defined as no tumor at the resected specimen edge.

⁃ Close resection margins \> 0 mm to ≤ 2 mm. as follows:

• One close resection margin and EIC (per College of American Pathologist (CAP) Recommendation)

∙ 2 or more close resection margins.

⁃ A focally positive resection margin

• For invasive breast cancer the axilla must be staged by one of the following:

‣ Sentinel node biopsy alone, if sentinel node is negative, i.e. any of the following:

• pN0: no regional lymph node metastasis identified histologically,

∙ pN0(i-): pN0 and immunohistochemical (IHC) negative, or

∙ pN0(i+): pN0 and IHc positive;

⁃ Sentinel node biopsy alone, OR followed by axillary node dissection per investigator discretion, for clinically node negative patients as described below:

• microscopic sentinel node positive (pN1mic)

∙ one or two sentinel nodes positive (pN1) without extracapsular extension

∙ negative sentinel node biopsy after neoadjuvant chemotherapy

⁃ Axillary node dissection is required following sentinel node (SN) biopsy with a minimum total of 6 axillary nodes if any of the following exist:

• for \> 2 positive SN

∙ any positive SN biopsy after neoadjuvant chemotherapy

∙ for clinically (by either imaging or examination) T3 disease

∙ for extracapsular extension

⁃ Axillary dissection alone (with a minimum of 6 axillary nodes)

• Age ≥ 18

• CT-imaging of the ipsilateral breast within 28 days prior to study entry for the radiation treatment planning. Must be able to delineate on CT scan the extent of the target lumpectomy cavity for boost

⁃ Appropriate stage for protocol entry, including no clinical evidence for distant metastases, based upon the following minimum diagnostic workup:

∙ History/physical examination, including breast exam (inspection and palpation of the breasts) and documentation of weight and Zubrod Performance Status of 0-2 within 28 days prior to study entry;

‣ Right and left mammography within 90 days of diagnostic biopsy establishing diagnosis

⁃ Patients must have had ER analysis performed on the primary breast tumor prior to study entry according to current American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) Guideline Recommendations for hormone receptor testing. If negative for ER, assessment of PR must also be performed according to current ASCO/CAP Guideline Recommendations for hormone receptor testing (http://www.asco.org)

⁃ Complete blood count (CBC)/differential obtained within 14 days prior to study entry, with adequate bone marrow function defined as follows:

∙ Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3

‣ Platelets ≥ 75,000 cells/mm3

‣ Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)

⁃ Women of childbearing potential must have a negative urine or serum pregnancy test within 14 days of study entry

⁃ Women of childbearing potential must be non-pregnant and non-lactating and willing to use medically acceptable form of contraception during radiation therapy

⁃ Patient must provide study specific informed consent prior to study entry

⁃ Breast implants allowed