Benefield HC, et al. - Researchers investigated if established immunohistochemical subtypes are the sole or definitive means of etiologically subdividing breast cancers. Using a population-based study of incident breast cancers, the Carolina Breast Cancer Study, they analyzed cases and controls for clinical biomarkers and tumor suppressor p53 with risk factor data. To differentiate the etiologic heterogeneity of various classification schema, an aggregate measure was calculated for each individual marker and combinations of markers. The greatest variability in risk factor profiles was individually explained by estrogen receptor [ER]. However, the degree of etiologic heterogeneity was significantly increased by further subdivision by p53. The heterogeneous association of age at diagnosis, nulliparity, and race, with ER/p53 subtypes, was evident. Overall, the established value of clinical marker-based intrinsic subtypes was supported, yet significant etiologic insights may be gained via other schema.