Lifestyle Factors & Breast Ca Prognosis in Asian-Americans

Institution: University of Southern California
Investigator(s): Anna Wu, Ph.D. -
Award Cycle: 2003 (Cycle IX) Grant #: 9PB-0089 Award: $1,050,107
Award Type: Request for Applications
Research Priorities
Community Impact of Breast Cancer>Disparities: eliminating the unequal burden of breast cancer

Initial Award Abstract (2003)
Should women with breast cancer include green tea and soy foods in their diet? Does intake of soy foods negate the beneficial effects of tamoxifen therapy among women with breast cancer? The primary objective of this application is to determine if pre-and post-diagnostic dietary and other lifestyle factors (e.g., physical activity, body size) are associated with breast cancer outcome. Demographic factors, tumor characteristics, and treatment information will be considered in our investigation of the role of pre- and post-diagnostic lifestyle factors.

This proposed study will consist of 1,200 Asian Americans diagnosed with an incident breast cancer between 1995-2000 and have been interviewed as part of a case-control study of breast cancer in Los Angeles County. We propose to recontact this group of women (or their next of kin) to obtain information on current disease status and recurrences, initial and subsequent treatment, and selected lifestyle factors after cancer diagnosis. Overall survival will be determined using the Los Angeles County Cancer Surveillance Program, the population-based tumor registry of the study area.

This study population is particularly well-suited to investigate the role of green tea and soy, two dietary factors that are common in the Asian diet and are found to be inversely associated with risk of breast cancer in our parent case-control study. If these dietary factors can be shown to also have beneficial effects on breast cancer outcome, there is enormous potential for these foods since they are non-toxic, inexpensive, and can be incorporated easily into the diet of women of all racial/ethnic background.

Final Report (2008)
The influence of lifestyle factors on the prognosis of breast cancer was poorly understood. The primary objective of this study was to determine if pre-diagnostic dietary and non-dietary lifestyle factors are associated with breast cancer prognosis in Asian-American women. A secondary objective was to explore if prognosis is associated with post-diagnostic lifestyle factors such as intake of soy and green tea, physical activity and body size. Demographic factors obtained in the parent case-control study and tumor characteristics and treatment information obtained post-diagnostically will be considered in each of the above specific aims.

Through the funding support of the California Breast Cancer Research Program since 1995 (1RB-0287, 3PB-0102, 5PB-0018), we conducted a large case-control study of breast cancer among Asian-American women in Los Angeles County that included in-person interviews with 1,463 women (488 Chinese, 384 Japanese, 503 Filipino, 88 other Asians) who provided detailed information regarding their lifestyle habits prior to diagnosis. From our December 2007 linkage to the database of the Los Angeles County Cancer Surveillance Program (CSP), 194 women of these women (55 Chinese, 46 Japanese, 77 Filipino, 16 other Asians) were identified as deceased; only 24 of these women were re-interviewed and therefore we do not have re-interview information on 170 of the 194 deceased women.. In preliminary analyses using Cox proportional hazard regression, the risk of mortality was not associated with intake of green tea or black tea but risk was increased in association with high pre-diagnostic body weight and low pre-diagnostic soy intake. These findings associated with high body weight and low soy intake became stronger and statistically significant in analyses restricted to in situ/localized breast cancer.

Additional information was collected from a follow-up telephone interview that asked about treatment, recurrence, second cancers, and post-diagnostic health status (e.g., hospitalization, specific medical conditions), menopausal status, use of exogenous hormones, and lifestyle factors including physical activity patterns, body weight, dietary habits and use of vitamin supplements. We completed re-interviews with 780 breast cancer patients; 88 of these women were diagnosed of a second primary/or had recurrence and 20 were later identified by the CSP as deceased. We conducted preliminary analyses to examine the role of post-diagnostic dietary habits in relation to the risk of recurrence/second cancers. To date, risk of recurrence/second cancer was not associated with post-diagnostic body weight, intake of green tea or black tea. However, risk was inversely associated with high intake of soy and seafood post-diagnostically and positively associated with high intake of red meat. Analyses are ongoing to thoroughly examine the effect of soy pre-diagnostically and post-diagnostically in relation to risk of mortality and risk of recurrence/new cancer after adjustment for relevant covariates. Additional analyses will be conducted to examine the separate and combined effects of soy intake and use of tamoxifen on risk.

Symposium Abstract (2007)
The role of diabetes in the etiology of breast cancer in Asian-Americans is not known. We investigated the relation between diabetes and breast cancer risk in a population-based case-control study in Los Angeles County that included 1,248 Asian American women with incident, histologically confirmed breast cancer and 1,148 control women, who were frequency matched to cases on age, Asian ethnicity and neighborhood of residence. The relation between history of diabetes and serum concentrations of estrogens, androgens and sex hormone-binding globulin (SHBG) was investigated in 212 postmenopausal control women. A history of diabetes was statistically significantly associated with breast cancer risk (odds ratio (OR)=1.68, 95% confidence interval (CI)=1.15-2.47) after adjusting for reproductive and other factors. This increased risk was unchanged after further adjustment for body mass index (BMI) and waist-hip ratio (WHR). We found a stronger diabetes-breast cancer association in women with lower BMI (<=22.7) (adjusted OR= 3.50, P=0.011) than those with higher BMI (>22.7) (adjusted OR=1.39, P=0.23) but this difference in ORs was not statistically significant. Our results also show that the diabetes-breast cancer association was observed only in low/intermediate soy consumers (OR=2.48, P=0.0008) but not among high soy consumers (OR=0.75, P=0.41) (P interaction =0.014). Controls who were diabetic showed significantly lower SHBG (20%) (P=0.02) but higher free testosterone levels (26%) (P=0.08) than women without such a history after adjusting for BMI and WHR. Our results support the hypothesis that diabetes may have a role in the development of breast cancer, influencing risk via both sex hormone and insulin pathways.

Symposium Abstract (2007)
Background: Soyfoods have been a staple in Asia for centuries but the consumption of this food in the west is recent. Intake of soy among women at high risk for or with breast cancer has become a public health concern because genistein, a major component of soy, has weak estrogenic effects on breast epithelium, and has been found to negate the benefit of tamoxifen in some animal and in vitro studies.

Methods: We conducted a cross-sectional study in Asian-Americans with breast cancer who were tamoxifen users (n=380) to investigate the association between soy intake and circulating levels of tamoxifen and its metabolites (N-desmethyl tamoxifen (N-DMT), 4-hydroxytamoxifen (4-OHT), and 4-hydroxy-N-desmethyl-tamoxifen (endoxifen)). Results: Serum levels of tamoxifen or its metabolites were unrelated to self reported intake of soy or serum levels of isoflavones. Blood levels of tamoxifen were 81% higher in postmenopausal women aged 65 or older compared to premenopaual women aged 45 or younger (P=0.005); similar patterns of results were observed for the tamoxifen metabolites. Levels of N-DMT were 27% (P=0.03) lower among women in the highest tertile of body mass index (BMI) (kg/m2) (>24.4 ) compared to those in the lowest category (BMI <=21.5). Women who used hypertensive medications had higher levels of tamoxifen (P=0.02) and of N-DMT (P=0.04) compared to non-users.

Conclusion: We found no evidence that soy intake adversely affected levels of tamoxifen or its metabolites. However, age, menopausal status, BMI and use of hypertensive medications significantly influenced circulating levels of tamoxifen and its metabolites in this population.

Tamoxifen, soy, and lifestyle factors in Asian American women with breast cancer.
Periodical:Journal of Clinical Oncology
Index Medicus: J Clin Oncol
Authors: Wu AH, Pike MC, Williams LD, Spicer D, Tseng CC, Churchwell MI, Doerge DR
Yr: 2007 Vol: 25 Nbr: 21 Abs: Pg:3024-30

Epidemiology of soy exposures and breast cancer risk.
Periodical:British Journal of Cancer
Index Medicus: Br J Cancer
Authors: Wu AH, Yu MC, Tseng CC, Pike MC.
Yr: 2008 Vol: 98 Nbr: 1 Abs: Pg:9-14