MRI-Based Preoperative Accelerated Partial Breast Irradiation

This study will examine the feasibility, complication rates, cosmetic results and local
control rate of 3D-CRT confined to the region of the lumpectomy cavity for patients with
Stage I and IIa (less than or equal to 3 cm) carcinoma of the breast (non-lobular histology)
treated with APBI using 3D-CRT before lumpectomy. This study also will test the feasibility
of MRI-based treatment planning for preoperative accelerated partial breast irradiation and
compare dosimetric data from treatment planning with patients treated on a previous
institutional post-op APBI protocol. It will also look at overall survival rates. Correlative
studies include measuring the changes in tumor gene expression and immune response to
radiation therapy and correlate this with pathologic response.

Inclusion Criteria:

- Pathologically proven diagnosis of invasive breast cancer, clinically stage I-II.

- Female

- Age ≥50 years

- Estrogen receptor positive

- Patients with both her2 positive and her2 negative tumors are eligible

- Unifocal disease

- Invasive ductal carcinoma diagnosed by core needle biopsy

- Clinically node negative both by physical exam and by ultrasound. All enlarged or
abnormal appearing lymph nodes must be biopsied.

- Zubrod performance status 0-2

- Study entry must be within 120 days from initial diagnosis of breast cancer.

- CBC/differential obtained within 14 days prior to study entry, with adequate bone
marrow function defined as follows: Absolute neutrophil count ≥ 1,800 cells/mm3;
Platelets ≥ 75,000 cells/mm3; Hemoglobin ≥8.0g/dl.

- Not pregnant or lactating; willing to use acceptable forms of contraception during
radiation therapy.

- Prior breast augmentation, including breast implants, is allowed.

- Patients with a prior history of contralateral breast cancer will be considered
eligible if they completed all treatment (including anti-endocrine therapy) more than
five years prior to registration.

- Patients must not have a prior treatment of malignancy diagnosed or treated within the
past five years, with the exception of non-melanomatous skin cancer, carcinoma in situ
of the cervix and contralateral breast cancer.

- Interested patients must meet with a medical oncologist prior to study entry to
determine if Oncotype testing is recommended. If recommended and patient is amenable
to the possibility of receiving chemotherapy, there must be adequate biopsy tissue for
testing. If adequate tissue is not available for the Oncotype testing, patients who
are very interested in participation may undergo additional biopsies. If a patient
plans to refuse chemotherapy regardless of a high Oncotype results and elects to forgo
the test, they will still be eligible for enrollment.

- Patients must have had estrogen and progesterone receptor analysis performed on the
biopsy specimen prior to study entry according to current ASCO/CAP Guideline
Recommendations for hormone receptor testing. Testing for her2 neu expression must
also be performed and recorded prior to study entry.

- Appropriate stage and pre-treatment evaluation 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) with documentation of weight and Zubrod Performance Status of 0-2
within 28 days prior to study entry.

- Right and left mammography within 60 days of diagnostic biopsy establishing
diagnosis.

- Evaluation of the axilla by ultrasound and biopsy of all enlarged or abnormal
appearing lymph nodes within 28 days prior to study entry.

- Clip placed within the biopsy proven breast cancer, with verification of
placement by mammogram.

Exclusion Criteria:

- AJCC clinical T3, N1-3, M1, stage IIB, stage III or stage IV breast cancer

- Prior invasive non-breast malignancy (exceptions include non-melanomatous skin cancer,
carcinoma in situ of the cervix, or prior contralateral breast cancer as described in
3.1.11) unless disease free and off treatment for a minimum of five years prior to
study entry.

- Multifocal breast cancer

- Modified Bloom-Richardson Grade 3 disease

- Estrogen receptor negative disease

- Lymphovascular space invasion noted on biopsy

- Invasive lobular carcinoma

- Purely non-invasive breast cancer (i.e. ductal carcinoma in situ, lobular carcinoma in
situ)

- Non-epithelial breast malignancies such as sarcoma or lymphoma

- Paget's disease of the nipple

- Male breast cancer

- Prior history of radiation therapy to the chest in the region of the ipsilateral
breast that would result in overlap of radiation fields.

- Patients having received or having planned neoadjuvant chemotherapy or concurrent
chemotherapy. A recommendation for adjuvant chemotherapy will not preclude
eligibility. However, if a patient has an Oncotype score that would lead to a
recommendation for systemic chemotherapy (see section 3.1.13), and chemotherapy is
planned to be given in the neoadjuvant setting, the patient would then be ineligible
for enrollment.

- Patients who are unable to undergo MRI. This could include patients with a severe
allergy to gadolinium contrast or patients with renal function insufficient to receive
contrast (GFR less than 30). Patients who have a minor allergy (for example, skin rash
or hives) to gadolinium contrast may still be considered for enrollment. These
patients would have to receive prophylactic prednisone and diphenhydramine per MCW
department of radiology protocol. Such cases should be reviewed with the principal
investigator and radiology co-chair prior to enrollment.

- History of connective tissue disorder, including lupus, dermatomyositis and
scleroderma.

- Zubrod performance status of 3 or greater

- Known BRCA mutation

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

- Patients, who under the best estimates of the treating radiation oncologist, have a
life expectancy of 10 years or less.

- Patients who are pregnant.

- Severe, 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 last 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