Genetic Testing in Predicting Tumor Response in Patients With Stage I-III HER2 Negative Invasive Breast Cancer

PRIMARY OBJECTIVES:

I. To determine the feasibility of implementation of molecular (genomic) predictive testing
for patients with localized (stage I-III) invasive carcinoma of the breast who are candidates
for either adjuvant or neoadjuvant treatment of their breast cancer.

SECONDARY OBJECTIVES:

I. Estimate the frequency of tumors in each of the four molecularly defined cohorts, overall
and within subsets defined by nodal status and estrogen receptor (ER) status.

II. Estimate the concordance of genomic analysis of gene expression levels for ER and HER2
from the microarray (published previously), compared with standard testing with
immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) to determine ER and
HER2 status in these tumors.

III. Estimate the rates of indeterminate results and other variables of feasibility for
tissue obtained by different procurement methods.

IV. Estimate the impact of adjuvant therapy as measured by disease free survival (DFS) at 3
and 5 years for the patients within each cohort who received a neoadjuvant or adjuvant
treatment that is concordant with the application of the prediction result.

V. Estimate the impact of neoadjuvant therapy for patients within each cohort, as measured by
pathologic response in the breast and regional lymph nodes (pathologic complete response rate
[pCR] and residual cancer burden [RCB]).

VI. Estimate the predictive performance of other pre-validated and published genomic
predictors of chemotherapy or endocrine therapy sensitivity by calculating those predictions
from the microarray data that are produced or by using available results if the test was
performed separately for clinical use.

VII. Determine molecular characteristics of residual disease by analyzing resected surgical
specimens of residual disease in patients who have received neoadjuvant chemotherapy.

VIII. Determine molecular characteristics of recurrent or metastatic disease by analyzing
tumor tissue obtained from diagnostic biopsies of a recurrent or metastatic tumor and
comparing these samples to the primary tumor.

OUTLINE:

Patients undergo biopsy or surgery to obtain tumor sample for genetic testing. Patients are
then assigned to 4 treatment cohorts as determined by genetic test results.

After completion of study, patients are followed up for 5 years.

Inclusion Criteria:

- The patient can undergo biopsy or surgery of a primary tumor site for suspected or
proven invasive breast cancer of clinical stage I to III; stage IV patients will be
allowed and included in the feasibility assessment, but will not be included in
outcomes analysis for secondary objectives

- The clinical or radiologic primary tumor size is at least 1 cm diameter

Exclusion Criteria:

- The patient has proven HER2-positive breast cancer, defined as a pathology report of
amplification of the gene or 3+ score for immunohistochemical staining

- The patient has received prior systemic therapy or radiation therapy for breast cancer

- The patient has a prior history of invasive or metastatic cancer within 5 years of
diagnosis of breast cancer, excluding squamous cell or basal cell carcinoma of the
skin

- The patient had prior excisional biopsy of the primary invasive breast cancer

- There is hematoma or biopsy site changes that obscure the primary tumor

- Patients deemed medically ineligible for any adjuvant or neoadjuvant therapy. Patients
with ER-positive (+) tumors deemed medically eligible for hormonal therapy, but not
chemotherapy will be considered eligible for this protocol. Patients with ER-negative
(-) tumors who are not candidates for adjuvant anthracycline based chemotherapy will
be considered ineligible for this protocol. Patients who undergo biopsy and are later
found to be ineligible for adjuvant therapy will be assessed for the primary
objective, but will be excluded from the secondary objectives