title: Associations of the Transforming Growth Factor β/Smad Pathway, Body Mass Index, and Physical Activity With Breast Cancer Outcomes: Results From the Shanghai Breast Cancer Study.
abstract: The transforming growth factor β (TGF-β) pathway plays an important role in breast cancer progression and in metabolic regulation and energy homeostasis. The prognostic significance of TGF-β interaction with obesity and physical activity in breast cancer patients remains unclear. We evaluated the expression of TGF-β type II receptor and pSmad2 immunohistochemically in breast cancer tissue from 1,045 patients in the Shanghai Breast Cancer Study (2002-2005). We found that the presence of nuclear pSmad2 in breast cancer cells was inversely associated with overall and disease-free survival, predominantly among participants with lower body mass index (BMI; weight (kg)/height (m)2) and a moderate level of physical activity. However, the test for multiplicative interaction produced a significant result only for BMI (for disease-free survival and overall survival, adjusted hazard ratios were 1.79 and 2.05, respectively). In 535 earlier-stage (T1-2, N0) invasive cancers, nuclear pSmad2 was associated with improved survival among persons with higher BMI (overall survival: adjusted hazard ratio = 0.27, 95% confidence interval: 0.09, 0.86). The cytoplasmic pattern of TGF-β type II receptor expression in cancer cells was significantly associated with a lower survival rate but was not modified by BMI or physical activity. Our study suggests that the TGF-β pathway in tumor cells is involved in breast cancer prognosis and may be modified by BMI through pSmad2.
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Su
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.forename: Qingchao
authors.initials: Q
authors.lastname: Qiu
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Xiao Ou
authors.initials: XO
authors.lastname: Shu
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D002467:Cell Nucleus / Q000378:metabolism; D002681:China; D018450:Disease Progression; D018572:Disease-Free Survival; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051899:Smad2 Protein / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: TGF-β pathway; TGF-β type II receptor; body mass index; breast cancer; pSmad2; physical activity; survival; transforming growth factor β