A Phase III Trial of Accelerated Whole Breast Irradiation With Hypofractionation Plus Concurrent Boost Versus Standard Whole Breast Irradiation Plus Sequential Boost for Early-Stage Breast Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Pathologically proven diagnosis of breast cancer resected by lumpectomy and
whole-breast irradiation (WBI) with boost without regional nodal irradiation planned

- Must meet one of the following three criteria:

- pStage I or II breast cancer AND at least one of the following:

- Age < 50 years or

- Positive axillary nodes or

- Lymphovascular space invasion (LVI) or

- At least 2 close resection margins (> 0 mm to ≤ 2 mm) or

- One close resection margin and extensive in-situ component (EIC) or

- Focally positive resection margins or

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

- Grade III histology or

- Oncotype recurrence score > 25 or

- pStage 0 breast cancer with nuclear grade 3 ductal carcinoma in situ (DCIS) and
patient age < 50 years or

- 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:

- 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

- Two or more close resection margins

- A focally positive resection margin

- Allowable options for mandatory axillary staging include:

- Sentinel node biopsy alone (if sentinel node is negative, pN0, pN0[IHC-,+])

- Sentinel node biopsy alone, OR followed by axillary node dissection, for
clinically node-negative patients as described below:

- Microscopic sentinel node (SN) positive (pN1mic)

- One or two SNs positive (pN1) without extracapsular extension

- Negative SN biopsy after neoadjuvant chemotherapy

- Axillary node dissection is required following 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)

- CT-imaging of the ipsilateral breast within 28 days of study entry for the radiation
treatment planning.

- Must be able to delineate on CT scan the extent of the target lumpectomy cavity
for boost (placement of surgical clips to assist in treatment planning of the
boost is strongly recommended)

- 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

- Bilateral or right and left mammography within 90 days prior to neoadjuvant
chemotherapy, or diagnostic biopsy establishing diagnosis, or last surgery
(breast or axilla)

- No prior invasive or in-situ carcinoma of the breast (prior LCIS is eligible)

- No American Joint Committee on Cancer (AJCC) pathologic T4, N2 or N3, or M1 breast
cancer

- Must not have two or more breast cancers that are not resectable through a single
lumpectomy incision

- Must not be DCIS and ≥ 50 years old

- Must not be DCIS < 50 years old, and nuclear, grade 1-2

- No suspicious unresected microcalcification, densities, or palpable abnormalities (in
the ipsilateral or contralateral breast) unless biopsied and found to be benign

- No non-epithelial breast malignancies such as sarcoma or lymphoma

- No Paget disease of the nipple

- No male breast cancer

- Breast implants allowed

PATIENT CHARACTERISTICS:

- ANC ≥ 1,800/mm³

- Platelet count ≥ 75,000/mm³

- Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is
acceptable)

- Negative serum pregnancy test within 14 days of study entry

- Women of childbearing potential must not be pregnant or nursing and willing to use
medically acceptable form of contraception during radiotherapy

- No prior invasive non-breast malignancy (except non-melanomatous skin cancer or
carcinoma in situ of the cervix) unless disease free for a minimum of 5 years prior
to study entry

- No severely active co-morbidity, defined as follows:

- Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months

- Transmural myocardial infarction within the past 6 months

- Acute bacterial or fungal infection requiring intravenous antibiotics at the
time of registration

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days before
registration

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
note, however, that laboratory tests for liver function and coagulation
parameters are not required for entry into this protocol

- Acquired Immune-Deficiency Syndrome (AIDS) based upon current CDC definition

- HIV testing is not required for entry into this protocol

- No active systemic lupus, erythematosus, or any history of scleroderma or
dermatomyositis with active rash

- Medical, psychiatric, or other condition that would prevent the patient from
receiving the protocol therapy or providing informed consent

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Study entry must be within 50 days of last breast/axillary surgery and/or last
chemotherapy

- No treatment plan that includes regional-node radiotherapy

- No prior radiotherapy to the breast or prior radiation to the region of the
ipsilateral breast that would result in overlap of radiation therapy fields

- No intention to administer concurrent chemotherapy for current breast cancer