Chemotherapy Before Surgery and Tissue Sample Collection in Patients With Stage IIA-IIIC Breast Cancer

PRIMARY OBJECTIVES:

I. To evaluate the effects of preoperative neoadjuvant paclitaxel and doxorubicin
(doxorubicin hydrochloride)/cyclophosphamide (AC) on: senescence; invasion/motility (tumor
microenvironment of metastasis [TMEM] and 67 kDa laminin receptor [67LR]).

II. To create a biospecimen repository for future studies derived from patients with breast
cancer receiving standard neoadjuvant chemotherapy.

OUTLINE: Patients with human epidermal growth factor receptor 2 (HER2)-positive disease are
assigned to Stratum A, and patients with HER2-negative disease are randomized to Stratum B or
C.

STRATUM A: Patients receive paclitaxel intravenously (IV) over 1 hour and trastuzumab IV over
30-90 minutes weekly for 12 weeks. Beginning 2-3 weeks later, patients receive doxorubicin
hydrochloride IV over 5-10 minutes and cyclophosphamide IV over 30-60 minutes every 2 weeks
for 8 weeks

STRATUM B: Patients receive paclitaxel, doxorubicin hydrochloride, and cyclophosphamide as in
Stratum A.

STRATUM C: Patients receive doxorubicin hydrochloride IV over 5-10 minutes and
cyclophosphamide IV over 30-60 minutes every 2 weeks for 8 weeks. Patients then receive
paclitaxel IV over 1 hour weekly for 12 weeks.

Patients undergo surgery 2-6 weeks after the last chemotherapy dose.

In all arms, treatment continues in the absence of unacceptable toxicity.

Inclusion Criteria:

- Patients must have histologically confirmed adenocarcinoma of the breast associated
with the following clinical stage: IIA, IIB, IIIA, IIIB, or IIIC; patients with stage
IV disease are also eligible if there is an intention to perform breast surgery after
neoadjuvant therapy is completed, or in patients participating in clinical trials
where surgery after neoadjuvant therapy may be an option (eg. E2108)

- Estrogen receptor (ER), progesterone receptor (PR), and HER2/neu status documented by
core needle biopsy of the primary tumor and/or regional lymph node must be known prior
to beginning systemic therapy

- Patients must have had a bilateral diagnostic mammogram within 6 months of
registration, and may also have a targeted sonography of the breast and/or ipsilateral
axilla and magnetic resonance imaging (MRI) if clinically indicated

- Patients with clinically suspicious axillary lymph node involvement must have either
aspiration cytology or biopsy prior to beginning therapy

- It is strongly encouraged that all patients have metallic clips placed in the tumor
prior to neoadjuvant therapy in order to facilitate evaluation for microscopic disease
at the time of surgery; placement of clips is particularly encouraged for patients
being considered for breast conserving surgery

- No prior chemotherapy, irradiation, or definitive therapeutic surgery (eg, mastectomy
or lumpectomy or axillary dissection) for this malignancy; patients who have had a
prior sentinel lymph node biopsy for this malignancy are eligible

- Patients who received tamoxifen or another selective estrogen receptor modulator
(SERM) for prevention or for other indications (e.g., osteoporosis, prior ductal
carcinoma in situ [DCIS]) are eligible; tamoxifen therapy or other SERMs should be
discontinued at least 1 week before the patient is enrolled on this study

- The patient is medically suitable candidate for preoperative chemotherapy and surgery
in the judgment of the treating physicians

- Ability to understand and the willingness to sign a written informed consent document,
and willing to provide blood samples before and during preoperative therapy; patients
are also asked but not required to have research biopsies performed before and after
therapy