The optimal goal of neoadjuvant chemotherapy (NAC) for breast cancer is to achieve pathologic complete response (pCR) with the least toxicity. As more effective therapies become available, one challenge is how to evaluate the response of tumor in a timely manner, so an optimal regimen can be given to the patient. Reliable imaging methods that can monitor and predict NAC response are critically needed. In addition to therapy response monitoring, imaging parameters are associated with phenotype of cancer and may be used as prognostic markers. We have been performing NAC studies for close to 10 years, and in this renewal we will continue to develop and validate imaging markers for evaluating and predicting therapeutic response, as well as for predicting prognosis.
Three aims are proposed.
Aim -1 will follow all previously enrolled NAC patients since 2003 (more than 180 patients) to obtain their prognostic information. Other than previously analyzed imaging parameters, two novel imaging markers that are shown to have prognostic value, i.e. the change of breast density (fibroglandular tissue volume) and the stromal tissue contrast enhancement, will be analyzed using a comprehensive quantitative method developed by us. The primary analysis is to use imaging parameters to predict local recurrence, but the disease-free and overall survival will be collected and used in exploratory analyses.
Aim -2 and -3 will be performed using the prospectively collected data from a new clinical trial to enroll 75 NAC patients into an imaging monitoring study by using a combined MRI and scinti-mammography (MR-SMM) system. Despite of the research interest in investigating the role of complex multi- parametric imaging methods, there is always a need of an easy method that can measure the tumor size accurately;and SMM has a great potential.
Aim -2 will compare the diagnostic performance of SMM and MRI at different times before, during, and after NAC. Also, the diagnostic accuracy of the post-NAC residual disease measured by SMM and MRI will be determined by comparing to pathological examination results as the goldstandard.
Aim -3 will evaluate the respective and combined ability of MRI and SMM, based on pre-treatment and early changes in the first follow-up imaging, for predicting pathologic complete response (pCR). The diagnostic results obtained using MRI and SMM from tumors of varying stages at different times during NAC will provide important information for establishing the role of a standalone SMM system, as well as the combined MR-SMM system, for management of breast cancer patients.

Public Health Relevance

Neoadjuvant chemotherapy (NAC) has become an important treatment option for breast cancer patients. Imaging can provide very useful information for monitoring and predicting response, as well as prognosis. With many years of research, MRI has become a very important clinical breast imaging tool. Molecular imaging has gradually evolved as a complementary modality. In this study the NAC response of the same cancer evaluated by MRI and molecular imaging will be directly compared by using a novel MR-compatible scintimammography system. The success of this project will continue to advance the clinical role of breast imaging, not only for NAC monitoring but also for general screening and diagnosis, to aid in improved, personalized, management and care that can be provided to each individual breast cancer patient.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA127927-07
Application #
8642609
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Henderson, Lori A
Project Start
2007-04-01
Project End
2018-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
7
Fiscal Year
2014
Total Cost
$484,812
Indirect Cost
$170,764
Name
University of California Irvine
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
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Chen, J H; Chen, W P; Chan, S et al. (2013) Correlation of endogenous hormonal levels, fibroglandular tissue volume and percent density measured using 3D MRI during one menstrual cycle. Ann Oncol 24:2329-35
Chen, Jeon-Hor; Su, Min-Ying (2013) Clinical application of magnetic resonance imaging in management of breast cancer patients receiving neoadjuvant chemotherapy. Biomed Res Int 2013:348167
Chen, Jeon-Hor; Chan, Siwa; Yeh, Dah-Cherng et al. (2013) Response of bilateral breasts to the endogenous hormonal fluctuation in a menstrual cycle evaluated using 3D MRI. Magn Reson Imaging 31:538-44
Chen, Jeon-Hor; Pan, Wei-Fan; Kao, Julian et al. (2013) Effect of taxane-based neoadjuvant chemotherapy on fibroglandular tissue volume and percent breast density in the contralateral normal breast evaluated by 3T MR. NMR Biomed 26:1705-13
Kuzucan, Aida; Chen, Jeon-Hor; Bahri, Shadfar et al. (2012) Diagnostic performance of magnetic resonance imaging for assessing tumor response in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy is associated with molecular biomarker profile. Clin Breast Cancer 12:110-8
Lin, Muqing; Chan, Siwa; Chen, Jeon-Hor et al. (2011) A new bias field correction method combining N3 and FCM for improved segmentation of breast density on MRI. Med Phys 38:5-14
Chen, J-H; Mehta, R S; Baek, H-M et al. (2011) Clinical characteristics and biomarkers of breast cancer associated with choline concentration measured by 1H MRS. NMR Biomed 24:316-24

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