Safety and Efficacy Comparison of Docetaxel and Ixabepilone in Non Metastatic Poor Prognosis Breast Cancer

DISEASE CHARACTERISTICS:

Inclusion criteria:

* Histologically proven invasive unilateral breast cancer (regardless of the type)

  * Initial clinical condition compatible with complete initial resection
  * No residual macro or microscopic tumor after surgical excision
* Node-positive disease (i.e., positive sentinel node or positive axillary clearance) (N+) or node-negative disease (-) meeting the following criteria :

  * Stage II or III disease
  * pT \>20 mm (T1-4)
* Patients must meet 1 of the following hormone-receptor criteria:

  * Node-positive patients: triple-negative\* tumor (HER2 negative, estrogen-receptor \[ER\] negative, and progesterone receptor \[PR\] negative) OR double-negative (HER2 negative, PR negative, and ER+)
  * Node-negative patients: triple-negative\* tumor only
* NOTE: \*Hormone-receptor negativity is defined as ER \<10% and PR \<10% by IHC and HER2 negativity is defined as IHC 0-1+ OR IHC 2+ and FISH or CISH negative
* Must be able to begin chemotherapy no later than day 49 after the initial surgery

Exclusion criteria:

* Clinically or radiologically detectable metastases (M0)
* Bilateral breast cancer or contralateral ductal carcinoma in situ
* Any metastatic impairment, including homolateral subclavicular node involvement, regardless of its type
* Any tumor ≥T4a (cutaneous invasion, deep adherence, inflammatory breast cancer)
* HER 2 overexpression defined as IHC 3+ OR IHC 2+ and FISH or CISH positive
* Any clinically or radiologically suspect and non-explored damage to the contralateral breast

PATIENT CHARACTERISTICS:

Inclusion criteria:

* Female
* Pre- or postmenopausal
* ECOG performance status 0-1
* Peripheral neuropathy ≤grade 1
* Neutrophil count ≥2,000/mm³
* Platelet count ≥100,000/mm³
* Hemoglobin \>9 g/dL
* AST and ALT ≤1.5 times upper limit of normal (ULN)
* Alkaline phosphatase ≤2.5 times ULN
* Total bilirubin ≤1.0 times ULN
* Serum creatinine ≤1.5 times ULN
* LVEF ≥50% by MUGA scan or echocardiography
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for up to 8 weeks after completion of study treatment

Exclusion criteria:

* Previous cancer (except cutaneous baso-cellular epithelioma or uterine peripheral epithelioma) in the preceding 5 years, including invasive contralateral breast cancer
* Patients with any other concurrent severe and/or uncontrolled medical disease or infection that could compromise participation in the study
* Clinically significant cardiovascular disease within the past 6 months including any of the following:

  * Unstable angina
  * Congestive heart failure
  * Uncontrolled hypertension (i.e., blood pressure \>150/90 mm Hg)
  * Myocardial infarction
  * Cerebral vascular accidents
* Known prior severe hypersensitivity reactions to agents containing Cremophor EL
* Patients with any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
* Patients deprived of liberty or placed under the authority of a tutor

PRIOR CONCURRENT THERAPY:

* At least 2 weeks since prior minor surgery (excluding breast biopsy) and adequately recovered
* At least 3 weeks since prior major surgery and adequately recovered
* No prior chemotherapy, hormonal therapy, or radiotherapy
* More than 72 hours since prior and no concurrent treatment with any of the following strong inhibitors of CYP3A4:

  * Amiodarone
  * Clarithromycin
  * Amprenavir
  * Delavirdine
  * Voriconazole
  * Erythromycin
  * Fluconazole
  * Itraconazole
  * Ketoconazole
  * Indinavir
  * Nelfinavir
  * Ritonavir
  * Saquinavir
* No concurrent participation in another therapeutic trial involving an experimental drug