ABSTRACT
BACKGROUND: Obesity is associated with an increased breast cancer risk in postmenopausal women and may contribute to worse outcomes. Black women experience higher obesity and breast cancer mortality rates than non-Black women. We examined associations between race, obesity, and clinical tumor stage with breast cancer prognosis. METHODS: We conducted a prospective cohort study in 1,110 breast cancer patients, using univariable and multivariable Cox regression analyses to evaluate the effects of obesity, race/ethnicity, and clinical tumor stage on progression-free and overall survival (PFS and OS). RESULTS: 22% of participants were Black, 64% were Hispanic White, and 14% were non-Hispanic White or another race. 39% of participants were obese (body mass index [BMI] ≥ 30 kg/m2). In univariable analyses, tumor stage III-IV was associated with worse PFS and OS compared to tumor stage 0-II (hazard ratio [HR] = 4.68, 95% confidence interval [CI] = 3.52-6.22 for PFS and HR = 5.92, 95% CI = 4.00-8.77 for OS). Multivariable analysis revealed an association between Black race and worse PFS in obese (HR = 2.19, 95% CI = 1.06-4.51) and non-obese (HR = 2.11, 95% CI = 1.05-4.21) women with tumors staged 0-II. Obesity alone was not associated with worse PFS or OS. CONCLUSIONS: Results suggest a complex interrelationship between obesity and race in breast cancer prognosis. The association between the Black race and worse PFS in tumor stages 0-II underscores the importance of early intervention in this group. Future studies are warranted to evaluate whether alternative measures of body composition and biomarkers are better prognostic indicators than BMI among Black breast cancer survivors.
Subject(s)
Breast Neoplasms , Obesity , Humans , Female , Breast Neoplasms/mortality , Breast Neoplasms/ethnology , Obesity/complications , Prospective Studies , Middle Aged , Prognosis , Neoplasm Staging , Hispanic or Latino/statistics & numerical data , Aged , Black or African American/statistics & numerical data , Body Mass Index , Adult , White People/statistics & numerical data , Cohort Studies , Proportional Hazards Models , Racial Groups/statistics & numerical dataABSTRACT
BACKGROUND: Post-surgery adjuvant radiotherapy (RT) significantly improves clinical outcomes in breast cancer patients; however, some patients develop cancer or treatment-related pain that negatively impacts quality of life. This study examined an inflammatory biomarker, C-reactive protein (CRP), in RT-related pain in breast cancer. METHODS: During 2008 and 2014, breast cancer patients who underwent RT were prospectively evaluated for pre- and post-RT pain. Pre- and post-RT plasma CRP levels were measured using a highly sensitive CRP ELISA kit. Pain score was assessed as the mean of four pain severity items (i.e., pain at its worst, least, average, and now) from the Brief Pain Inventory. Pain scores of 4-10 were classified as clinically relevant pain. Multivariable logistic regression analyses were applied to ascertain the associations between CRP and RT-related pain. RESULTS: In 366 breast cancer patients (235 Hispanic whites, 73 black/African Americans, and 58 non-Hispanic whites), 17% and 30% of patients reported pre- and post-RT pain, while 23% of patients had RT-related pain. Both pre- and post-RT pain scores differed significantly by race/ethnicity. In multivariable logistic regression analysis, RT-related pain was significantly associated with elevated pre-RT CRP (≥ 10 mg/L) alone (odds ratio (OR) = 2.44; 95% confidence interval (CI) = 1.02, 5.85); or combined with obesity (OR = 4.73; 95% CI = 1.41, 15.81) after adjustment for age and race/ethnicity. CONCLUSIONS: This is the first pilot study of CRP in RT-related pain, particularly in obese breast cancer patients. Future larger studies are warranted to validate our findings and help guide RT decision-making processes and targeted interventions.
Subject(s)
Breast Neoplasms/complications , Breast Neoplasms/metabolism , C-Reactive Protein/metabolism , Pain/epidemiology , Pain/etiology , Radiotherapy, Adjuvant/adverse effects , Adult , Aged , Biomarkers , Breast Neoplasms/epidemiology , Breast Neoplasms/radiotherapy , Comorbidity , Female , Florida/epidemiology , Humans , Middle Aged , Pilot Projects , Prospective Studies , Quality of Life , Radiotherapy, Adjuvant/methods , Risk FactorsABSTRACT
Purpose: Obesity is associated with an increased breast cancer risk in postmenopausal women and may contribute to worse outcomes. Black women experience higher obesity and breast cancer mortality rates than non-Black women. We examined associations between race, obesity, and clinical tumor stage with breast cancer prognosis. Methods: We conducted a prospective cohort study in 1,110 breast cancer patients, using univariable and multivariable Cox regression analyses to evaluate the effects of obesity, race/ethnicity, and clinical tumor stage on progression-free and overall survival (PFS and OS). Results: 22% of participants were Black, 64% were Hispanic White, and 14% were non-Hispanic White or another race. 39% of participants were obese (body mass index [BMI] ≥ 30 kg/m2). In univariable analyses, tumor stage III-IV was associated with worse PFS and OS compared to tumor stage 0-II (hazard ratio [HR] = 4.68, 95% confidence interval [CI] = 3.52-6.22 for PFS and HR = 5.92, 95% CI = 4.00-8.77 for OS). Multivariable analysis revealed an association between Black race and worse PFS in obese (HR = 2.19, 95% CI = 1.06-4.51) and non-obese (HR = 2.11, 95% CI = 1.05-4.21) women with tumors staged 0-II. Obesity alone was not associated with worse PFS or OS. Conclusion: Results suggest a complex interrelationship between obesity and race in breast cancer prognosis. The association between Black race and worse PFS in tumor stages 0-II underscores the importance of early intervention in this group. Future studies are warranted to evaluate whether alternative measures of body composition and biomarkers are better prognostic indicators than BMI among Black breast cancer survivors.
ABSTRACT
Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27(kip1) and E-cadherin and an upregulation of ß-catenin signaling [Bi,X. et al. (2008) Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis, 29, 1435-1440]. However, the regulation of E-cadherin by decorin and its implication in cancer formation and metastasis is largely unknown. Using a decorin knockout mouse model (Dcn(-/-) mice) and manipulated expression of decorin in human colorectal cancer cells, we found that E-cadherin, a protein that regulates cell-cell adhesion, epithelial-mesenchymal transition and metastasis, was almost completely lost in Dcn(-/-) mouse intestine, and loss of decorin and E-cadherin accelerated colon cancer cell growth and invasion in Dcn(-/-) mice. However, increasing decorin expression in colorectal cancer cells attenuated cancer cell malignancy, including inhibition of cancer cell proliferation, promotion of apoptosis and importantly, attenuation of cancer cell migration. All these changes were linked to the regulation of E-cadherin by decorin. Moreover, overexpression of decorin upregulated E-cadherin through increasing of E-cadherin protein stability as E-cadherin messenger RNA and promoter activity were not affected. Co-immunoprecipitation assay showed a physical binding between decorin and E-cadherin proteins. Taken together, our results provide direct evidence that decorin-mediated inhibition of colorectal cancer growth and migration are through the interaction with and stabilization of E-cadherin.