histologies in the large National Institutes of Health (NIH)-AARP Diet and Health Cohort Study, where we showed that risk factors for invasive breast cancer may also influence the development of early breast lesions (Mullooly et al., American Journal of Epidemiology; 2017). To explore aetiological heterogeneity at the population level, in collaboration with the National Cancer Registry of Ireland (NCRI) and using the Irish population-based cancer registry, I evaluated secular trends in incidence of estrogen receptor (ER)-positive and ER-negative breast cancer. Previous studies have shown rising ER-positive and falling ER-negative breast cancer incidence rates in the US and Denmark, likely due to changing risk factor patterns with opposite effects on ER-positive and ER-negative breast cancer, which may have important implications for the burden of breast cancer subtypes, especially if validated in other populations. To this end, we examined breast cancer trends in the NCRI by ER status and for the first time by joint expression of ER and HER2 status. Our findings confirmed diverging ER-specific breast cancer trends, which were not substantially altered by HER2 expression (Mullooly et al., submitted to the European Journal of Cancer). These findings possibly foretell a common western and potentially worldwide pattern that highlights the need to adopt ER subtype-specific breast cancer analytical studies and prevention strategies. Through these analytical and descriptive epidemiologic studies, I have addressed important research questions of breast cancer heterogeneity which suggest aetiologic clues, and I will expand on these findings during the reintegration year as outlined in more detail below.