Divergent estrogen receptor-positive and -negative breast cancer trends and etiologic heterogeneity in Denmark

Long-term breast cancer trends in incidence in the United States (US) show rising estrogen receptor (ER)-positive rates and falling ER-negative rates. We hypothesized that these divergent trends reflect etiologic heterogeneity and that comparable trends should be observed in other countries with similar risk factor profiles. Therefore, we analyzed invasive female breast cancers in Denmark, a country with similar risk factors as the US. We summarized the overall trend in age-standardized rates with the estimated annual percentage change (EAPC) statistic (1993-2010) and used age-period-cohort models to estimate age-specific EAPCs, cohort rate ratios and projections for future time periods (2011-2018). In Denmark, the overall rate of ER-positive cancers rose between 1993 and 2010 by 3.0% per year (95% CI: 2.8-3.3% per year), whereas the overall rate of ER-negative cancers fell by 2.1% per year (95% CI: -2.5 to -1.6% per year). The ER-positive rate increased fastest among postmenopausal women and the ER-negative rate decreased fastest among premenopausal women, reflecting that cohorts born after 1944 were at relatively higher risk of ER-positive tumors and lower risk of ER-negative tumors. If current trends continue, ER-positive cancers will increase at least 13% by 2018 in Denmark, ER-negative cancers will fall 15% by 2018, and breast cancer overall will increase at least 7% by 2018. Divergent ER-specific trends are consistent with distinct etiologic pathways. If trends in known risk factors are responsible, the Danish and US experience may foreshadow a common pattern worldwide. What's new? Estrogen receptor- (ER-)negative breast cancer incidence rates are declining nationwide in Denmark and the United States, whereas rates for ER-positive breast cancers are rising. This report suggests that the divergent trends in ER breast cancers in both countries can be explained by parallel trends in environmental and lifestyle factors that are known to either increase or decrease risk for ER-positive or ER-negative malignancies. The patterns observed in Denmark and the United States may foreshadow a common pattern for many countries worldwide.