Breast cancer outcome and predictors of outcome: are there age differentials?

Several questions were addressed regarding breast cancer outcome, predictors of outcome, and young age at diagnosis. Is there evidence that outcome is worse in younger women compared with other age groups? Do younger patients have a greater frequency of adverse prognostic factors? If younger age is associated with a poor outcome, is it an intrinsic independent adverse predictor, or is the outcome worse due to poor prognostic factor profiles? Several methods were used to answer these questions and applied to those reports in which age categories were carefully defined: 1) detailed review of population-based breast cancer outcome literature, 2) synthesis of published cooperative group and single institution univariate and multivariate analyses, and 3) a new analysis of the 8738-patient San Antonio database. Overall, epidemiologic studies suggested that younger women have the worst survival outcome, when matched with similarly staged older cohorts. Univariate trends analyses confirmed that younger women more often had more positive lymph nodes, larger tumors, and negative steroid hormone receptors. Significantly more cancers in women less than 35 years of age had high S-phase fractions and abnormal expression of p53. Multivariate modeling confirmed that young age was an independent adverse predictor when a few standard factors were considered in the model, but other descriptors such as tumor grade or high S-phase fraction were more important when available. These data support the conclusion that "young age" serves as a surrogate for a greater frequency of adverse prognostic factor profiles and suggest important questions for future study.