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Supplementary Table 3. Risk of death from breast cancer between diagnostic periods, for each molecular subtype 5 and 15 years after diagnosis (Cox regression analysis).

Supplementary Figure 2. Subtype-specific incidence rates according to age and year of birth. Blue lines: Women born before 1929. Red lines: Women born in 1929 or later. Dotted lines (red and blue) represent incidence rates of subtyped cases. Solid lines (red and blue) represent average incidence rates from 50 imputed datasets with corresponding 95% confidence intervals (CIs).

Supplementary Figure 3. Cumulative incidence of death from breast cancer according to breast cancer subtypes. A: Women diagnosed before 1995 (Gray's test: p=0.0002). B: Women diagnosed in 1995 or later (Gray's test: p

Supplementary Table 1. Characteristics of the study population used in estimations of breast cancer incidence.

Supplementary Table 2. Incidence rates and incidence rate ratios of breast cancer according to hormone and HER2 receptor status, age at diagnosis and year of birth. Observed and imputed estimates.

Supplementary Figure legends.

Supplementary Table 5. Risk of death from breast cancer between diagnostic periods, for each breast cancer subtype 5 and 15 years after diagnosis (Cox regression analysis).

Background: Secular trends in incidence and prognosis of molecular breast cancer subtypes are poorly described. We studied long-term trends in a population of Norwegian women born 1886–1977.Methods: A total of 52,949 women were followed for breast cancer incidence, and 1,423 tumors were reclassified into molecular subtypes using IHC and in situ hybridization. We compared incidence rates among women born 1886–1928 and 1929–1977, estimated age-specific incidence rate ratios (IRR), and performed multiple imputations to account for unknown subtype. Prognosis was compared for women diagnosed before 1995 and in 1995 or later, estimating cumulative risk of death and HRs.Results: Between 50 and 69 years of age, incidence rates of Luminal A and Luminal B (HER2−) were higher among women born in 1929 or later, compared with before 1929 [IRRs 50–54 years; after imputations: 3.5; 95% confidence interval (CI), 1.8–6.9 and 2.5; 95% CI, 1.2–5.2, respectively], with no clear differences for other subtypes. Rates of death were lower in women diagnosed in 1995 or later, compared to before 1995, for Luminal A (HR 0.4; 95% CI, 0.3–0.5), Luminal B (HER2−; HR 0.5; 95% CI, 0.3–0.7), and Basal phenotype (HR 0.4; 95% CI, 0.2–0.9).Conclusions: We found a strong secular incidence increase restricted to Luminal A and Luminal B (HER2−) subtypes, combined with a markedly improved prognosis for these subtypes and for the Basal phenotype.Impact: This study documents a clear secular increase in incidence and a concomitant improved prognosis for specific molecular breast cancer subtypes. Cancer Epidemiol Biomarkers Prev; 25(12); 1625–34. ©2016 AACR.

BackgroundLong-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.MethodsAmong 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.ResultsAmong 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.ConclusionsThere has been a temporal increase in both low- and high-proliferative breast cancers.

The long non-coding RNA NEAT1 locus is transcribed into two overlapping isoforms, NEAT1_1 and NEAT1_2, of which the latter is essential for the assembly of nuclear paraspeckles. NEAT1 is abnormally expressed in a wide variety of human cancers. Emerging evidence suggests that the two isoforms have distinct functions in gene expression regulation, and recently it was shown that NEAT1_2, but not NEAT1_1, expression predicts poor clinical outcome in cancer. Here, we report that NEAT1_2 expression correlates with HER2-positive breast cancers and high-grade disease. We provide evidence that NEAT1_1 and NEAT1_2 have distinct expression pattern among different intrinsic breast cancer subtypes. Finally, we show that NEAT1_2 expression and paraspeckle formation increase upon lactation in humans, confirming what has previously been demonstrated in mice. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.