Long term trends of breast cancer incidence according to proliferation status

Background:Long-term breast cancer incidence trends according to proliferation status are poorly described. We studied time-trends in breast cancer incidence, using mitotic count and Ki-67 as markers of proliferation. Methods:Among 83,298 Norwegian women followed for breast cancer occurrence 1961-2012, 2995 incident breast cancers were diagnosed. Ki-67 was assessed using immunohistochemistry on tissue microarrays and mitoses were counted on whole sections. We compared incidence rates according to proliferation status among women born 1886-1928 and 1929-1977, estimating age-specific incidence rate ratios. We performed multiple imputations to account for unknown proliferation status. Mean values of Ki-67 and mitotic counts were calculated, according to age and birth year. We performed separate incidence analyses for HER2(+) and triple negative breast cancers. Results:Among women aged 40-69 years, incidence rates of tumours with low-proliferative activity were higher among those born in 1929 or later, compared to before 1929, according to Ki-67 and mitotic count. Incidence rates of tumours with high-proliferative activity were also higher in women born in 1929 or later compared to before 1929 according to Ki-67, but not according to mitotic count. Mean values of Ki-67 and mitotic count varied according to age and birth year. In subtype-specific analyses we found an increase of high-proliferative HER2(+) tumours according to Ki-67 in women born in 1929 or later, compared to before 1929. Conclusions:There has been a temporal increase in both low- and high-proliferative breast cancers.