Post-surgical highly sensitive C-reactive protein and prognosis in early-stage breast cancer
- 283 Downloads
Obesity, associated with inflammation, has been linked to poor prognosis in breast cancer. Research investigating the potential role of C-reactive protein (CRP), an obesity-associated systemic marker of inflammation, as a mediator of adverse prognostic effects of obesity has yielded inconsistent results. We examined the association of highly sensitive CRP (hsCRP) with obesity-related factors and breast cancer outcome. A cohort of 535 non-diabetic women diagnosed with T1-3, N0-1, M0 breast cancer, was assembled between 1989 and 1996 and followed prospectively. Circulating levels of hsCRP were analyzed on blood obtained postoperatively, prior to systemic therapy, in 501 women. Correlations and prognostic associations were analyzed using one-way analysis of variance, Spearman’s rank correlation coefficients (r) and Cox models. hsCRP was significantly correlated with body mass index (r = 0.60), insulin (r = 0.44), leptin (r = 0.54), and lipids, but not T or N stage, grade or estrogen receptor/progesterone receptor. At a median follow-up of 12 years, hsCRP was not associated with distant disease-free survival or overall survival in univariable [Q4 vs. Q1 hazard ratio (HR) 1.03, 95 % confidence interval (CI) 0.69–1.52, P = 0.9 and HR 1.27, 95 % CI 0.86–1.86, P = 0.24, respectively] or multivariable [Q4 vs Q1 HR 1.02, 95 % CI 0.66–1.59, P = 0.93 and HR 1.17, 95 % CI 0.76–1.81, P = 0.48 respectively] analyses. hsCRP was associated with age, comorbidities, and the insulin resistance syndrome but not with breast cancer outcome.
KeywordsBreast cancer hsCRP Inflammation Obesity Prognosis
This work was funded by The Breast Cancer Research Foundation and The Canadian Cancer Society Research Institute (formerly The Canadian Breast Cancer Research Initiative). Dr. Ariadna Tibau is a recipient of a Spanish Society of Medical Oncology (SEOM) Translational Research Grant.
Conflicts of interest
The authors declare that there are no conflicts of interest.
- 16.Gauldie J, Richards C, Harnish D, Lansdorp P, Baumann H (1987) Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci USA 84(20):7251–7255PubMedCrossRefGoogle Scholar
- 18.Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW (1999) C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 19(4):972–978PubMedCrossRefGoogle Scholar
- 22.Alfano CM, Imayama I, Neuhouser ML, Kiecolt-Glaser JK, Smith AW, Meeske K, McTiernan A, Bernstein L, Baumgartner KB, Ulrich CM, Ballard-Barbash R (2012) Fatigue, inflammation, and omega-3 and omega-6 fatty acid intake among breast cancer survivors. J Clin Oncol 30(12):1280–1287PubMedCrossRefGoogle Scholar
- 25.Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, Kaasa S, Klee M, Osaba D, Razavi D, Rofe PB, Schraub S, Sneeuw K, Sullivan M, Takeda F (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85(5):365–376PubMedCrossRefGoogle Scholar
- 26.Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, Monauni T, Muggeo M (2000) Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 23(1):57–63PubMedCrossRefGoogle Scholar
- 34.Pierce BL, Ballard-Barbash R, Bernstein L, Baumgartner RN, Neuhouser ML, Wener MH, Baumgartner KB, Gilliland FD, Sorensen BE, McTiernan A, Ulrich CM (2009) Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. J Clin Oncol 27(21):3437–3444PubMedCrossRefGoogle Scholar
- 37.Albuquerque KV, Price MR, Badley RA, Jonrup I, Pearson D, Blamey RW, Robertson JF (1995) Pre-treatment serum levels of tumour markers in metastatic breast cancer: a prospective assessment of their role in predicting response to therapy and survival. Eur J Surg Oncol 21(5):504–509PubMedCrossRefGoogle Scholar
- 42.Irwin ML, Duggan C, Wang CY, Smith AW, McTiernan A, Baumgartner RN, Baumgartner KB, Bernstein L, Ballard-Barbash R (2011) Fasting C-peptide levels and death resulting from all causes and breast cancer: the health, eating, activity, and lifestyle study. J Clin Oncol 29(1):47–53PubMedCrossRefGoogle Scholar
- 43.Pritchard KI, Shepherd LE, Chapman JA, Norris BD, Cantin J, Goss PE, Dent SF, Walde D, Vandenberg TA, Findlay B, O’Reilly SE, Wilson CF, Han L, Piura E, Whelan TJ, Pollak MN (2011) Randomized trial of tamoxifen versus combined tamoxifen and octreotide LAR Therapy in the adjuvant treatment of early-stage breast cancer in postmenopausal women: NCIC CTG MA.14. J Clin Oncol 29(29):3869–3876PubMedCrossRefGoogle Scholar