NSABP Biospecimen Discovery Project

This study will be conducted at select NSABP sites where investigators are willing to give
paclitaxel plus trastuzumab or a trastuzumab/pertuzumab-based combination as the initial
component of neoadjuvant therapy as a pilot for a comprehensive 'omics approach using next
generation sequencing and protein expression and post-translational modification analysis
using mass spectrometry (MS) based and Reverse Phase Protein Array-based proteomics. Tumor
samples will be obtained at baseline and 48 to 72 hours after initial drug treatment to
study variation in the biological responses to these agents. The study of tumors both before
and early after the first treatment probes the biological responses to treatment and is rich
source of predictive biomarkers.

Inclusion Criteria:

- The diagnosis of invasive adenocarcinoma of the breast must have been made by core
needle biopsy or limited incisional biopsy.

- The breast cancer must be HER2-positive based on current ASCO/CAP (American Society
of Clinical Oncology/College of American Pathologists) Guideline Recommendations for
Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer.

- The patient must have a mass in the breast measuring greater than or equal to 2.0 cm
by physical exam and/or ultrasound that is accessible and safe for repeat biopsy.
Patients with a diagnosis of inflammatory breast cancer are eligible if there is a
palpable or detectable breast mass that is accessible and safe for repeat biopsy.

- Planned initial treatment with a combination of paclitaxel and trastuzumab or a
trastuzumab/pertuzumab-based combination. Schedule for paclitaxel/trastuzumab or
trastuzumab/pertuzumab administration is per the investigator.

Exclusion Criteria:

- Excisional biopsy or lumpectomy performed prior to registration.

- Previous therapy with chemotherapy or targeted therapy for any malignancy.

- Treatment, including radiation therapy (RT), chemotherapy, and/or targeted therapy,
administered for the currently diagnosed breast cancer prior to registration.

- Other nonmalignant systemic disease that would preclude the patient from receiving
chemotherapy and targeted therapy.