Trial Information

Contrast-Enhanced Breast MRI, MRS, And Correlative Science Studies To Characterize Tumor Response In Patients Undergoing Neoadjuvant Treatment For Locally Advanced Breast Cancer

OBJECTIVES:

Primary

- Support accrual to the ACRIN-6657/CALGB-150012 magnetic resonance imaging (MRI)
correlative science study.

- Determine whether molecular markers, alone or in combination with MRI, at the time of
diagnosis or early in the course of therapy, predict 3-year disease-free survival (DFS)
in women with locally advanced breast cancer who are receiving neoadjuvant
chemotherapy.

- Identify two groups of participants who have statistically different 3-year DFS, based
on 1 or more biomarkers, including MRI.

- Determine whether biomarkers, in combination with MRI, early in the course of
chemotherapy, improve the prediction of 3-year DFS and are at least as good of a
predictor of DFS as residual disease at the time of surgery in these patients.

- Determine whether molecular markers are associated with specific imaging patterns seen
on MRI of these patients.

- Predict response with MRI results and marker data from cell cycle check points,
proliferation, angiogenesis, hormone receptors, and molecular profiles in these
patients.

Secondary

- Determine the molecular predictors of lack of radiologic complete response (CR) in
HER-2/neu negative patients (immunohistochemistry [IHC] score of 0, 1+, 2 and
fluorescence in situ hybridization [FISH] not amplified) after a neoadjuvant
anthracycline-based regimen.

- Determine the molecular predictors of lack of radiologic CR in HER-2/neu positive
patients (IHC 3+ or FISH amplified > 2.0) after a neoadjuvant anthracycline-based
regime followed by a taxane alone regimen or in combination with trastuzumab.

- Determine the molecular predictors of complete magnetic resonance imaging radiologic
response to a neoadjuvant anthracycline-based regimen when gene expression profiling is
performed in a sequential, real-time fashion.

OUTLINE: This is a diagnostic, multicenter study conducted concurrently with
CALGB-150012/ACRIN-6657 imaging protocol and concurrently with neoadjuvant
anthracycline-based chemotherapy.

Patients receive an injection of gadopentetate dimeglumine and undergo magnetic resonance
imaging (MRI) of the breast before initiation, 1-3 days after initiation, and then after
completion of neoadjuvant anthracycline-based chemotherapy and prior to surgery. Patients
who previously received a taxane also undergo an additional contrast-enhanced MRI scan.

Patients undergo biopsies before initiation and at the time of surgery. Patients also
undergo blood draws at the time of the first biopsy and prior to surgery. Serum and tissue
samples are used to assess biomarkers of genetic instability, cell cycle progression and
cellular proliferation as predictors for anthracycline responsiveness, markers of apoptotic
potential as predictors for taxane responsiveness in vivo, angiogenesis, hormone receptors,
and molecular profiles using immunohistochemical methods.

Mammograms and possibly ultrasounds are performed prior to and after chemotherapy (before
surgery).

Patients are followed every 6 months for 5 years and then annually for up to 10 years.

PROJECTED ACCRUAL: A total of 384 patients will be accrued for this study within 3 years.