Abstract B87: Acute-phase proteins (C-reactive protein and Serum Amyloid A) and post-diagnosis mammographic density in breast cancer survivors
Authors: Dee Anne , McKean-Cowdin Roberta , McTiernan Anne , Baumgartner Richard N. , Baumgartner Kathy B. , Ballard-Barbash Rachel , Bernstein Leslie 
Published: January 2014

Mammographic density (MD) is positively associated with breast cancer risk and with breast cancer recurrence. Factors that influence MD include age, circulating endogenous hormone levels, hormone therapy, menopausal status, parity, adiposity, and genetic variation. The association between MD and estrogen levels may be regulated to an extent by the immune system. Cytokines such as IL-6 influence aromatase activity and therefore estrogen synthesis. Experiments on breast cancer cell lines have shown that IL-6, in combination with estrone sulfate enhances cellular proliferation through their action on aromatase. Acute phase proteins C-Reactive Protein (CRP) and Serum Amyloid A (SAA) are nonspecific inflammatory markers that increase with systemic inflammation in response to elevated levels of IL-6. The purpose of this study is to evaluate whether CRP or SAA are associated with MD among postmenopausal women who are breast cancer survivors. Circulating levels of CRP, SAA, and percent MD approximately 30 months after diagnosis were obtained from 479 women participating in the Health, Eating, Activity, and Lifestyle Study (HEAL). HEAL is a prospective cohort study of 1,183 breast cancer survivors identified through Surveillance, Epidemiology, and End Results registries in Los Angeles County, New Mexico, and Western Washington. For this analysis, regression models were used to estimate associations between CRP/SAA and MD after adjustments for age, race, body mass index (BMI), post-menopausal hormone use, tamoxifen use, and study center. Potential effect modification by factors that could influence inflammation or estrogen levels was evaluated by stratification and with formal tests of interaction. After adjusting for covariates, we found a negative association between CRP and MD (β=-0.13, p=0.03) and no association between SAA and MD (β=-0.09, p=0.31). These associations were not modified by race, use of non-steroidal anti-inflammatory drug, smoking, or physical activity. Further, we found that women with CRP levels that were lower than the median (&lt;2.4 CRP mg/L) had higher geometric mean percent MD than women at or above the median; this association was consistent across 5-year age groups. The largest association between CRP and MD was found among women &lt;50 years of age (β=-0.33, p=.01) although there was no statistically significant interaction between CRP and age. Our results suggest CRP is inversely associated with MD after adjusting for BMI and other covariates. These findings should be confirmed in independent disease free population that includes direct measures of cytokine activity such as IL-6. Additional exploration of biological mechanism is needed.

Citation Format: Anne Dee, Roberta McKean-Cowdin, Anne McTiernan, Richard N. Baumgartner, Kathy B. Baumgartner, Rachel Ballard-Barbash, Leslie Bernstein. Acute-phase proteins (C-reactive protein and Serum Amyloid A) and post-diagnosis mammographic density in breast cancer survivors. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B87.