Genetic Testing in Predicting Response to Paclitaxel in Women With Breast Cancer

OBJECTIVES:

Primary

- Determine the feasibility of accruing women with unresected infiltrating carcinoma of
the breast to a clinical trial involving serial breast biopsies and administration of
neoadjuvant paclitaxel before formal assessment of axillary lymph node status.

- Determine a standard protocol template for gene microarray analysis, in terms of the
timing and method of collecting tissue samples, before and after administration of
neoadjuvant paclitaxel in these patients.

- Determine the safety and efficacy of tissue sampling in these patients.

Secondary

- Identify gene(s) or gene clusters that exhibit significant differences between
responding and non-responding tumors before treatment with neoadjuvant paclitaxel in
these patients.

- Identify gene(s) or gene clusters that exhibit changes in gene expression before and
after the administration of neoadjuvant paclitaxel in these patients.

- Compare significant differences in gene expression between responding and non-responding
tumors in patients treated with this drug.

- Develop, preliminarily, a statistical model utilizing individual genes and/or gene
clusters that can best predict response to paclitaxel in these patients.

OUTLINE: This is a pilot, multicenter study.

Patients undergo core needle breast biopsy within 14 days before starting neoadjuvant
paclitaxel treatment. Patients receive neoadjuvant paclitaxel IV over 3 hours on day 1.
Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or
unacceptable toxicity.

Patients undergo core needle breast biopsy 48 hours after the first administration of
paclitaxel, upon completion of course 1, and either upon completion of the last course (in
patients with clinical or radiographic evidence of residual disease) or during definitive
breast surgery. Biopsy samples are analyzed for gene expression by gene microarray analysis.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 2 years.

Inclusion:

- Histologically confirmed infiltrating carcinoma of the breast

- Unresected disease

- High-risk (> 50% risk of relapse) disease, including any of the following
high-risk markers:

- Estrogen receptor- and progesterone receptor- negative

- Palpable axillary lymph nodes

- Grade 3 histology

- S phase fraction > 10%

- Ki67 > 30%

- Disease that warrants combination therapy with doxorubicin, cyclophosphamide, and
paclitaxel

- HER2/neu negative or positive

- Hormone receptor status:

- Not specified

Menopausal status

- Known

Performance status

- ECOG 0-2

- Absolute neutrophil count > 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Bilirubin ≤ 1. 5 times normal (except for patients with known Gilbert's disease)

- Creatinine ≤ 1.5 times normal

Exclusion:

- uncontrolled congestive heart failure

- myocardial infarction within the past 6 months

- unstable angina

- uncontrolled hypertension

- pregnant or nursing

- serious bacterial, viral, or fungal infection requiring ongoing treatment

- severe peripheral neuropathy

- poor psychiatric risk

- history of any other known serious co-morbid medical or psychiatric condition

- prior cytotoxic therapy for breast cancer