Trial Information

Neoadjuvant Chemotherapy in Palpable Breast Cancer: Evaluation of Physiologic, Radiologic, and Molecular Markers in Predicting Response

OBJECTIVES:

Primary

- Determine whether tumors in women with palpable invasive breast cancer with wild type
p53 are more sensitive to doxorubicin than to paclitaxel when given as sequential
single-agent neoadjuvant chemotherapy.

- Determine whether tumors with inactivated p53 are more sensitive to paclitaxel than to
doxorubicin when given as sequential single-agent neoadjuvant chemotherapy in these
patients.

Secondary

- Correlate other biological markers (physiological and molecular) with tumor response in
patients treated with these regimens.

- Determine changes in these biological markers during and after neoadjuvant chemotherapy
in these patients.

- Compare breast MRI, in terms of assessing tumor response, with physical exam,
mammogram, and ultrasound in patients treated with these regimens.

- Determine whether there are MRI indicators (e.g., tumor morphology or lesion
enhancement) that are predictive of response in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor
size (> 5 cm vs ≤ 3-5 cm) and presence of palpable regional lymph nodes (yes vs no).
Patients are randomized to 1 of 2 treatment arms.

All patients undergo biopsy, bilateral mammogram, MRI, ultrasound, blood marker, molecular
(gene microarrays and functional p53 status), and physiologic studies before initiation of
neoadjuvant chemotherapy. Some of these studies are repeated after completion of treatment
with the first chemotherapeutic agent and after completion of treatment with the second
chemotherapeutic agent as outlined below.

- Arm I: Patients receive doxorubicin IV on days 1, 15, 29, and 43. Patients with no
residual tumor (indicated by clinical evaluation and radiologic studies) after
completion of doxorubicin undergo definitive surgery. After surgery, patients receive
paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, and 57.

Patients with residual tumor > 2 cm after completion of doxorubicin undergo 8-12 core needle
biopsies. Patients with residual tumor < 2 cm after completion of doxorubicin undergo 4-6
core needle biopsies. After core needle biopsies, patients receive paclitaxel as above.

- Arm II: Patients receive paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43,
50, and 57. Patients with no residual tumor (indicated by clinical evaluation and
radiologic studies) after completion of paclitaxel undergo definitive surgery. After
surgery, patients receive doxorubicin IV on days 1, 15, 29, and 43.

Patients with residual tumor > 2 cm after completion of paclitaxel undergo 8-12 core needle
biopsies. Patients with residual tumor < 2 cm after completion of paclitaxel undergo 4-6
core needle biopsies. After core needle biopsies, patients receive doxorubicin as above.

In both arms, treatment continues in the absence of disease progression or unacceptable
toxicity.

Samples from core needle biopsies are analyzed by microarray analysis for gene expression
profiles.

Patients are followed every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this
study within 4-5 years.