Breast tumor tissue inflammation but not lobular involution is associated with survival among breast cancer patients in the Multiethnic Cohort

Background: This study investigated the association of breast lobular involution status and three inflammatory markers as predictors of survival among breast cancer patients in the Multiethnic Cohort. Methods: Lobular involution was evaluated in tissue sections of normal breast tissue and COX-2, TNF-alpha, and TGF-beta proteins were assessed by immunohistochemistry in tumor microarrays. A summary score added the expression levels of the three markers. Cox regression was applied to estimate hazard ratios (HRs) and 95 % confidence intervals (CI) with age as the time metric and adjustment for factors known to affect mortality. Results: Among 254 women (mean age = 61.7 +/- 8.7 years) with pathologic blocks and follow-up information, 54 all-cause and 10 breast cancer-specific deaths were identified after a mean follow-up time of 16.0 +/- 3.1 years. For 214 participants, an inflammatory score was available and 157 women had information on lobular involution. Lobular involution was not significantly associated with survival. Expression of both COX-2 and TNF-alpha were significant predictors of lower survival (p = 0.02 and 0.04), while the association for TGF-beta was weaker (p = 0.09). When combined into one overall inflammation score, both intermediate (HR = 2.72; 95 % CI 0.90-8.28) and high (HR = 4.21; 95 % CI 1.51-11.8) scores were associated with higher mortality but only the latter was statistically significant. No significant association with breast cancer-specific mortality was detected. Conclusions: These results suggest that strong expression of inflammatory markers in breast tissue predicts a poorer prognosis possibly due to a system-wide state of chronic inflammation.