XXXX as heterogeneous disease: contributing factors and @entity105 mechanisms.

@entity172 @entity1137 @entity9962 @entity0 @entity1420 @entity5 @entity105
The observed bimodal patterns of @entity0 incidence in the U.S. suggested that @entity0 may be viewed as more than one biological entity. We studied the factors potentially contributing to this phenomenon, specifically focusing on how disease heterogeneity could be linked to breast @entity105 mechanisms. Using empirical analyses and population-based biologically motivated modeling, age-specific patterns of incidence of @entity9962 from the SEER registry (1990-2003) were analyzed for heterogeneity and characteristics of @entity105 , stratified by race, stage, grade, and @entity172 (ER)/ @entity1420 (PR) receptor status. The heterogeneity of @entity0 age patterns decreased after stratification by grade, especially for @entity5 . Stratification by ER/PR status further reduced the heterogeneity, especially for ER(+)/PR(-) and ER(-)/(-) @entity5 ; however, the residual heterogeneity was still observed. The number of rate-limiting events of @entity105 and the latency of @entity1137 differed, decreasing from grade I to III, with poorly differentiated @entity5 associated with the least number of @entity105 stages and the shortest latency. @entity5 grades play important role in bimodal incidence of @entity0 and have distinct mechanisms of @entity105 . Race and @entity5 subtype could play modifying role. ER/PR status contributes to the observed heterogeneity, but is subdominant to @entity5 grade. Further studies on sources of "remaining" heterogeneity of population with @entity0 (such as genetic/epigenetic characteristics) are necessary. The results of this study could suggest stratification rather than unification of @entity0 prevention strategies, risk assessment, and treatment.
