A Randomized Phase III Trial Comparing a Neoadjuvant Regimen of FEC-75 Followed by Paclitaxel Plus Trastuzumab With a Neoadjuvant Regimen of Paclitaxel Plus Trastuzumab Followed by FEC-75 Plus Trastuzumab in Patients With HER-2 Positive Operable Breast Cancer

Inclusion Criteria:

- Diagnosis of invasive adenocarcinoma by core needle biopsy

- Fine needle aspiration allowed provided primary tumor size < 2 cm and lymph node
metastases are present

- Excisional biopsy of the primary tumor allowed provided biopsy-positive lymph
nodes are present

- Primary tumor ≥ 2 cm and/or ≥ 1 biopsy-positive lymph node

- HER2-positive disease

- Confirmation by fluorescent in situ hybridization (FISH) requires gene
amplification

- Confirmation by immunohistochemistry (IHC) requires a strongly positive (3+)
staining intensity score

- Ductal carcinoma in situ (DCIS) or synchronous DCIS of the contralateral breast
regardless of prior therapy allowed

- Synchronous invasive breast cancer not allowed

- Ipsilateral DCIS treated by local excision with or without hormonal therapy allowed

- Those treated with radiation therapy are not allowed

- No definitive clinical or radiologic evidence of metastatic disease

- No history of invasive breast cancer

- Hormone receptor status known

- Menopausal status not specified

- ECOG performance status of 0 -1

- Absolute neutrophil count ≥ 1,200/mm³

- Platelet count ≥ 100,000/mm³

- Total bilirubin normal unless the patient has a grade 1 bilirubin elevation (normal
to 1.5 times upper limit of normal [ULN]) resulting from Gilbert disease or similar
syndrome due to slow conjugation of bilirubin

- Alkaline phosphatase ≤ 2.5 times ULN

- AST ≤ 1.5 times ULN

- Creatinine normal

- Left ventricular ejection fraction (LVEF) ≥ 55 by multi gated acquisition scan (MUGA)
or echocardiogram (ECHO) within the past 3 months

- Patients with either skeletal pain or alkaline phosphatase that is > ULN but ≤ 2.5
times ULN allowed if bone scans fail to demonstrate metastatic disease

- Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI, or
biopsy

- Prior non-breast malignancies allowed if disease-free for 5 years since completion of
initial treatment regimen and deemed by their physician to be at low risk for
recurrence

- Patients who had the following cancers are eligible if diagnosed and treated
within the past 5 years:

- Carcinoma in situ of the cervix

- Colon carcinoma in situ

- Melanoma in situ

- Basal cell and squamous cell carcinoma of the skin

- No cardiac disease that would preclude the use of epirubicin hydrochloride or
trastuzumab (Herceptin®) including any of the following:

- Active cardiac disease

- Angina pectoris that requires the use of antianginal medication

- Cardiac arrhythmia requiring medication

- Severe conduction abnormality

- Clinically significant valvular disease

- Cardiomegaly on chest x-ray

- Ventricular hypertrophy on EKG

- Patient's with poorly controlled hypertension ( i.e., diastolic greater than 100
mm/Hg)

- Patients with hypertension that is well controlled on medication are
eligible

- History of cardiac disease

- Myocardial infarction documented as a clinical diagnosis or by EKG or any other
tests

- Documented congestive heart failure

- Documented cardiomyopathy

- No sensory or motor neuropathy ≥ grade 2, as defined by the NCI's CTCAE v3.0

- Women of reproductive potential must agree to use an effective non-hormonal method of
contraception during therapy

- Women of child bearing potential must have a negative urine or serum pregnancy test
within 2 weeks of registration

- Not pregnant or nursing

- 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 non-malignant systemic disease (e.g., cardiovascular, renal, hepatic) that would
preclude treatment with either of the treatment regimens

- No prior surgical axillary staging procedure

- Prior non-excisional biopsy of an axillary node allowed

- No prior treatment for this breast cancer

- Hormonal therapy allowed if had been given for up to a total of 28 days anytime
after diagnosis and before study entry

- Hormonal therapy must stop at or before study entry and be re-started, if
indicated, following surgery

- No prior therapy with anthracyclines or taxanes for any malignancy

- No other investigational agents within the past 30 days

- No concurrent sex hormonal therapy (e.g., birth control pills, ovarian hormonal
replacement therapy)

- No concurrent therapy with any hormonal agent such as raloxifene, tamoxifen, or other
selective estrogen receptor modulator (SERM), either for osteoporosis or breast
cancer prevention