Abstract ES05-2: Divergent trends in breast cancer subtypes, a manifestation of cancer heterogeneity

Abstract

Abstract Recent studies in the United States show an unexpected divergence of ER positive and ER negative breast cancer incidence rates (JNCI 103: 1397-1402, 2011). ER positive cancers have risen while ER negative cancers have declined over the long-term. Divergent ER-specific trends might reflect statistical anomalies, lower assay thresholds for classifying breast cancers as ER positive, and/or the implementation of widespread screening mammography with increased sensitivity for ER positive cancers. However, the analysis of secular trends in Denmark, where there was better control of these potentially confounding factors, showed similar trends as in the United States (IJC 133: 2201-2206, 2013). ER positive cancers had increased among middle-aged and older Danish women in earlier birth-cohorts (or generations), implying a confluence of risk factor exposures during the peri- and the post-menopausal time periods of a woman's lifetime. In contrast, ER negative cancers had decreased among younger women in more recent birth-cohorts during the premenopausal time periods. Divergent ER-specific trends among different birth-cohorts in younger and older generations is consistent with breast cancer heterogeneity due to distinct etiologic pathways for ER positive and ER negative breast cancers, which could be due to trends in environmental and lifestyle risk factors with dual effects by ER expression. Two such possible risk factors are pregnancy (or parity) and obesity, which are decreasing and increasing, respectively, in both the United States and Denmark. For example, parity tends to reduce breast cancer risk for ER positive cancer and to increase risk for ER negative cancers. In fact, new breast cancer cases appear to be rising worldwide due to the consequences of changing reproductive, hormonal, and dietary risk factors. For this reason, it is plausible that the same risk factors or at the least risk factors acting through common mechanisms in the United States and Denmark may foreshadow a common pattern worldwide. This is good news since ER negative breast cancers are the most difficult to treat subtypes of breast cancer, especially the so-called triple negative cancers. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr ES05-2.