My long-term goal is to prevent cancer recurrence and improve survival using nutritional/dietary approaches. Breast cancer is my primary focus. Breast cancer is the most commonly diagnosed female malignancy in the US, leaving approximately 2.4 million cancer survivors facing increased risk of disease recurrence and early death. It is increasingly important to identify modifiable lifestyle factors to improve the disease prognosis. Our hypothesis is that higher cruciferous vegetable intake may reduce risk of recurrence and increase survival among breast cancer patients, depending upon their genetic background. The rationale includes: (1) Cruciferous vegetables are rich sources of isothiocyanates (ITCs), a group of promising anti-cancer agents;(2) Polymorphic genes of key enzymes in the pathway of ITC metabolism may affect the bioavailability of ITCs;(3) ITCs potently inhibit the growth of breast cancer cells in vitro and in vivo;(4) ITCs effectively target both estrogen receptor (ER) positive and negative breast cancer cells;(5) ITCs modulate immune function, and inhibit cancer angiogenesis and metastasis;and (6) ITCs potently induce NAD(P)H:quinone oxidoreductase 1 (NQO1), while polymorphisms of NQO1 resulting in low activity strongly predict poor prognosis in breast cancer patients.
Two specific aims are proposed:
Aim 1 is to examine the effect of cruciferous vegetable intake on breast cancer recurrence and survival. The interactions with functional polymorphisms of key ITC-metabolizing and -inducible genes will be examined. We will use data and specimens from The Pathways Study, a funded prospective cohort study of breast cancer patients.
Aim 2 is to evaluate the effect of ITC- rich broccoli sprout extract (ITC-BSE) on breast tumor cells in early stage breast cancer patients in a neoadjuvant study. Biomarkers including Ki-67, cleaved caspase-3, ER, and NQO1 will be examined and the pre-post changes will be compared between treatment and control group. This pilot intervention trial is the mechanistic investigation for the Aim 1 study;it also helps to identify potential biomarkers for monitoring efficacy of dietary ITCs. The proposed study will be the first to address the interactions between cruciferous vegetable intake and individual genetic background in relation to breast cancer prognosis. Due to the wide availability of cruciferous vegetables and the high diet-change motivation of breast cancer patients, the findings from the study may have a significant impact on the lifestyle of breast cancer survivors.

Public Health Relevance

In the US, the growing population of breast cancer survivors is facing increased risk of disease recurrence and early death, and is highly motivated to change the diet and/or take supplements to modify the risk. The proposed study will be the first to address whether intake of cruciferous vegetables can reduce the risk of breast cancer recurrence and improve breast cancer survival as well as help to identify the most beneficial patient population based on individual genetic background. Due to the wide availability of cruciferous vegetables and the high diet-change motivation of breast cancer patients, the findings from the study may have a significant impact on the lifestyle of breast cancer survivors.

Agency
National Institute of Health (NIH)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07CA148888-04
Application #
8722460
Study Section
Subcommittee B - Comprehensiveness (NCI)
Program Officer
Perkins, Susan N
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
City
Buffalo
State
NY
Country
United States
Zip Code
14263