Abstract 3281: TGFβ pathway alteration, body mass index, physical activity and breast cancer outcomes: The Shanghai Breast Cancer Survival Study (2014)

Abstract Background: Cumulative evidence suggests that the transforming growth factor-beta (TGF-β) pathway may have prognostic significance in human breast cancer. It also has been shown that the TGF-β pathway may play a role in glucose regulation and energy homeostasis. However, no previous study has examined the potential modifying effects of obesity and physical activity on associations between TGF-β pathway biomarkers, such as TGFβRII and pSmad2, and breast cancer outcomes. Methods: Breast cancer patients aged 20 to 75 years were recruited 6 months after diagnosis between 2002 and 2005 and participated in in-person baseline and follow-up surveys that collected information on cancer diagnosis, treatment, lifestyle exposures, anthropometrics, and physical activity. The expression of TGFβRII and nuclear pSmad2 in breast cancer cells and breast stromal tissue cells was evaluated immunohistochemically. Five-year disease-free survival (DFS) and overall survival (OS) rates were estimated by Kaplan Meier method. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for other prognostic variables and further stratified by body mass index (BMI) or physical activity. Results: Breast cancer cells exhibited either a membranous or a cytoplasmic expression pattern of TGFβRII. Compared with the membranous pattern, the cytoplasmic pattern was more prevalent among patients with low BMI (P&amp;lt;0.01) and was associated with lower five-year DFS (91% vs. 83%, P=0.04; adjusted HR=1.66, 95% CI: 1.03-2.68). Compared with lower nuclear pSmad2 expression intensity, higher expression intensity of nuclear pSmad2 in breast cancer cells was associated with lower five-year DFS (87% vs. 82%, P=0.02; adjusted HR=1.31, 95%CI: 0.96-1.79). This association was predominantly seen among participants with moderate physical activity levels (&amp;lt;9.4 MET-hr/wk; adjusted HR=2.05, 95% CI: 1.11-3.79 for five-year DFS) and lower BMI (&amp;lt;25; adjusted HR=1.80, 95% CI: 1.17-2.77 for five-year DFS), although the test for multiplicative interaction was only significant for BMI (Pinteraction=0.02). Analyses of OS showed similar patterns of association with a significant interaction between BMI and pSmad2 (adjusted HR=2.09, 95% CI: 1.38-3.15 for patients with low BMI, Pinteraction&amp;lt;0.001). The expression of TGFβRII and nuclear pSmad2 in stromal cells was unrelated to breast cancer outcomes. Conclusion: Expression levels of TGFβRII and nuclear pSmad2 in cancer cells were associated with breast cancer outcomes. These associations may be modified by BMI. Citation Format: Yinghao Su, Wei Zheng, Hui Cai, Ying Zheng, Qingchao Qiu, Wei Lu, Xiao-Ou Shu, Qiuyin Cai. TGFβ pathway alteration, body mass index, physical activity and breast cancer outcomes: The Shanghai Breast Cancer Survival Study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3281. doi:10.1158/1538-7445.AM2014-3281