Therapy With Abraxane and 5-Fluorouracil, Epirubicin, Cyclophosphamide (FEC) for Patients With Breast Cancer
Therapy With Abraxane and 5-Fluorouracil, Epirubicin, Cyclophosphamide (FEC) for Patients With Breast Cancer
The purpose of this study is to learn how breast cancer tumors respond to a drug called
 Abraxane followed by a combination of 3 chemotherapy drugs commonly used for breast cancer.
This is a Phase 2, non-randomized study of neoadjuvant treatment with nanoparticle albumin
 bound paclitaxel (Abraxane) every week for 12 weeks followed by 5-FU, epirubicin, and
 cyclophosphamide (FEC) every 3 weeks for 4 cycles in women with locally advanced breast
 cancer. Patients with HER-2 overexpressing breast cancer may receive trastuzumab concurrently
 with the chemotherapy at the discretion of the investigator. The primary aim of this study is
 to determine the pathologic complete response rate (pCR) of this sequential regimen.

 Patients who achieve clinical complete response (cCR), clinical partial response (cPR), or
 have resectable stable disease (SD) will undergo surgery. Surgery will consist of modified
 radical mastectomy or excision of the primary tumor site with clear surgical margins
 accompanied by axillary staging. Tumor samples taken prior to initiation of treatment will be
 analyzed for molecular and genetic changes which will be correlated with tumor response.

 Patients must have a histologically confirmed diagnosis of breast cancer without documented
 evidence of distant metastatic disease. Patients with clinical Stage IIB (T3N0 only), IIIA,
 or IIIB breast cancer will be potential candidates for this trial.
Inclusion Criteria:

 -  Signed consent

 -  Diagnosis made by core biopsy or incisional biopsy

 -  Histologic confirmation of invasive breast cancer

 -  Clinical staging as IIB (cT3N0 only), IIIA (cT3N1 or cT0-3N2), or IIIB (cT4N0-2)

 -  ECOG performance 0 or 1

 -  At the time of entry: *Absolute neutrophil count (ANC) must be greater than or equal
 to 1200/mm3; *platelet count must be greater than or equal to 100,000/mm3; *hemoglobin
 must be greater than or equal to 10 g/dl; *serum creatinine must be less than or equal
 to ULN for the lab.

 -  The following criteria for evidence of adequate hepatic function must be met: *Total
 bilirubin must be less than or equal to ULN for the lab unless the patient has a grade
 1 bilirubin elevation (> ULN to 1.5 x ULN) due to Gilbert's disease or similar
 syndrome involving slow conjugation of bilirubin; and *alkaline phosphatase must be <
 2.5 x ULN for the lab; and

 *AST must be less than or equal to 1.5 x ULN for the lab.

 -  MUGA scan or echocardiogram within 3 months prior to entry if: *age greater than or
 equal to 60, or *history of hypertension, or *plan to receive trastuzumab. For any
 patient who has a MUGA scan or echocardiogram performed for any reason, the baseline
 LVEF must be greater than or equal to LLN for the facility performing the procedure
 and there must be no regional wall abnormalities

 Exclusion Criteria:

 -  Clinical stage IIB disease that is cT2N1.

 -  Definitive evidence of metastatic disease (M1 by AJCC criteria)

 -  Prior history of invasive breast cancer in either breast or ductal carcinoma in situ
 (DCIS) in the ipsilateral breast treated with radiation therapy (patients with a
 history of lobular carcinoma in situ [LCIS] are eligible).

 -  Any treatment for the currently diagnosed breast cancer prior to study entry including
 radiation therapy, chemotherapy, and/or hormonal therapy.

 -  Pregnancy or lactation at the time of study entry.

 -  Prior anthracycline or taxane-containing chemotherapy for any malignancy.

 -  Nonmalignant systemic disease (cardiovascular, renal, hepatic, diabetes, etc.) that
 would preclude the patient from receiving study treatment or would prevent required
 follow-up.

 -  Grade 2 or greater peripheral polyneuropathy at the time of entry.

 -  Cardiac disease that would preclude the use of anthracyclines or trastuzumab. This
 includes:

 *myocardial infarction documented by elevated cardiac enzymes or persistent regional
 wall abnormalities on assessment of LV function; *angina pectoris that requires the
 use of anti-anginal medication; *any history of documented congestive heart failure;
 *serious cardiac arrhythmia requiring medication; *severe conduction abnormality;
 *valvular disease with documented cardiac function compromise; or *uncontrolled
 hypertension defined as blood pressure > 160/100 mm/Hg.

 -  Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement
 therapy, etc. (These patients are eligible if this therapy is discontinued prior to
 randomization.) Women of reproductive potential must agree to use an effective
 non-hormonal method of contraception during therapy.

 -  Therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective
 estrogen receptor modulator (SERM), either for osteoporosis or breast cancer
 prevention. Patients are eligible only if these medications are discontinued prior to
 randomization.

 -  Use of any investigational agent within the month before enrollment in the study.