RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and
paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the
cells or by stopping them from dividing. Giving more than one drug (combination
chemotherapy) may kill more tumor cells. Giving chemotherapy after surgery may kill any
tumor cells that remain after surgery.
PURPOSE: This phase II trial is studying how well doxorubicin, cyclophosphamide, and/or
paclitaxel work in treating women with nonmetastatic breast cancer.
- Determine the pharmacogenomics of adjuvant chemotherapy comprising doxorubicin and
cyclophosphamide and/or paclitaxel in women with nonmetastatic invasive breast cancer.
- Determine treatment-induced myelosuppression (e.g., neutropenia) in patients treated
with adjuvant doxorubicin and cyclophosphamide who have polymorphisms in drug
activation and metabolism genes.
- Correlate the incidence of peripheral neuropathy with pharmacogenomic analysis in
patients treated with paclitaxel.
- Determine response (i.e., relapse in the adjuvant setting) during a 10-year follow-up
period in patients treated with these regimens.
OUTLINE: This is a multicenter study. Patients receive treatment on The Cancer and Leukemia
Group B study(CALGB) CALGB-40101 OR are assigned to receive 1 of 2 treatment regimens on
- Regimen 1: Patients receive doxorubicin IV over 10 minutes and cyclophosphamide IV over
30 minutes on day 1. Treatment repeats every 21 days for 4 courses.
- Regimen 2: Patients receive doxorubicin and cyclophosphamide as in regimen 1. Patients
then receive paclitaxel IV over 1 hour once weekly for 12 weeks.
After completion of study treatment, patients are followed at 3, 6, and 12 months and then
annually for up to 10 years.
PROJECTED ACCRUAL: A total of 500 patients (300 treated with doxorubicin and
cyclophosphamide and 200 treated with paclitaxel) will be accrued for this study within 3-4
- Histologically confirmed invasive breast cancer
- node negative stage > T1c or T1b with poor prognostic features (high grade, Her2/neu
FISH positive, ER negative) or stage 2 (T2, N0) or
- enrolled on CALGB 40101, CALGB 49909, or the National Cancer Institute of Canada
study MA-21 or
- any node positive patient or locally advanced undergoing neoadjuvant chemotherapy
with either AC or paclitaxel
- Age greater than or equal to 18 years.
- >/=2 weeks from major surgery (wide excision / lumpectomy / mastectomy)
- No evidence of systemic metastasis
- Undergoing adjuvant treatment with standard dose AC or AC followed by weekly
Paclitaxel at 80mg/m2
- Adequate bone marrow, hepatic and renal functions (absolute neutrophil count >1,500/
μl, platelet count > 100,000/ μl, serum creatinine <2.0 mg/dl, total Bilirubin <2.0 x
the upper limit of normal (ULN)
- Ability to answer and understand study surveillance questionnaires
- No concurrent drug therapy (within 2 weeks) with agents that are known inducers or
inhibitors of Cytochrome P450 (CYP450).
- Other anticancer cytotoxic or endocrine therapy, immunotherapy, or biologic response
modifiers,Study Drugs or other concomitant medications known to cause
myelosuppression especially neutropenia and neuropathy
- Eastern Cooperative Oncology Group Performance Status(ECOG) functional status > 2.
- Serious co-morbidities including poorly controlled diabetes mellitus, ischaemic heart
disease,uncontrolled hypertension or active infection.
- Use of growth factor during cycle 1 of chemotherapy (AC) under pharmacokinetic
- Grade >/=2 peripheral neuropathy symptoms based on National Cancer Institute- Common
Terminology Criteria for Adverse Events (NCI-CTCAE) Scale. Exception: a chronic
neurologic disorder will be reviewed on a case by case basis by the study PI.
- Prior treatment with weekly paclitaxelDISEASE CHARACTERISTICS:
- Histologically confirmed invasive breast cancer, meeting 1 of the following
- Node negative disease AND meets 1 of the following stage criteria:
- Primary tumor > T1c
- Primary tumor > T1b AND poor prognostic features, defined as the
- High-grade disease
- Human Epidermal Growth Factor Receptor 2 (HER2)/neu-positive
disease by fluorescence in situ hybridization
- Estrogen receptor-negative disease
- Stage II disease (T2, N0)
- Node positive nonmetastatic disease
- Locally advanced disease AND receiving neoadjuvant chemotherapy comprising
doxorubicin and cyclophosphamide OR paclitaxel
- Enrolled in clinical trial CALGB-40101
- No evidence of systemic metastasis
- Hormone receptor status:
- Not specified