A Phase III Clinical Trial Comparing Trastuzumab Given Concurrently With Radiation Therapy and Radiation Therapy Alone for Women With HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy

Inclusion Criteria:

- Histologically confirmed ductal carcinoma in situ (DCIS)

- Mixed DCIS and lobular carcinoma in situ (LCIS) allowed

- HER2 receptor-positive as determined by central testing

- Must have undergone resection by lumpectomy and meets the following criteria:

- Margins of the resected specimen must be histologically free of DCIS
(re-excision to obtain clear margins allowed)

- No more than 120 days since the last surgery for excision of DCIS (lumpectomy or
re-excision of lumpectomy margins)

- None of the following allowed:

- Patients who require mastectomy

- Invasive (including microinvasion staged as T1mic) breast cancer (DCIS
"suspicious" for microinvasion, but not confirmed, allowed)

- Nodal staging of pN1 (including pN1mi) (axillary staging not required)

- DCIS present in more than one quadrant (multicentric)

- Masses or clusters of calcification that are clinically or mammographically
suspicious unless biopsied and proven to be benign

- Contralateral breast cancer (including DCIS)

- History of breast cancer, including DCIS (history of LCIS allowed)

- Hormone receptor status:

- Estrogen receptor and/or progesterone receptor-positive or -negative

- Must submit tumor block for correlative studies

- Pre- or postmenopausal

- ECOG performance status 0-1

- Life expectancy ≥ 10 years (excluding diagnosis of DCIS)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective non-hormonal contraception during and for 6
months after completion of treatment with trastuzumab (Herceptin®)

- No psychiatric or addictive disorders or other conditions that, in the opinion of the
investigator, would preclude the patient from meeting the study requirements

- No cardiac disease that would preclude the use of study treatment drugs, including,
but not limited to, any of the following:

- Active cardiac disease

- Angina pectoris that requires the use of anti-anginal medication

- Ventricular arrhythmias except for benign premature ventricular
contractions controlled by medication

- Conduction abnormality requiring a pacemaker

- Supraventricular and nodal arrhythmias requiring a pacemaker or not
controlled with medication

- Clinically significant valvular disease

- History of cardiac disease

- Myocardial infarction documented by elevated cardiac enzymes or persistent
regional wall abnormalities on assessment of left ventricular function

- Documented congestive heart failure

- Documented cardiomyopathy

- No uncontrolled hypertension (i.e., systolic BP > 180 mm Hg and/or diastolic BP > 100
mm Hg) (hypertension that is well controlled on medication allowed)

- No other nonmalignant systemic disease that would preclude a patient from receiving
trastuzumab or radiotherapy or would prevent prolonged follow-up

- No other malignancies unless patient has been disease-free ≥ 5 years and at low risk
for recurrence, except for treated carcinoma in situ of the cervix, carcinoma in situ
of the colon, melanoma in situ, or basal cell or squamous cell carcinoma of the skin

- No other cancer therapy until the time of first cancer recurrence or second primary
cancer

- No prior whole or partial breast irradiation

- No prior anthracycline chemotherapy for any malignancy

- No investigational agents within the past 30 days