Stanniocalcin Expression as a Predictor of Late Breast Cancer Recurrence

• Type of Material: Article
• Authors: Kristen D Brantley, Emory University; Anders Kjaersgaard, Aarhus University Hospital; Deidre Cronin-Fenton, Aarhus University Hospital; Rami Yacoub, Emory University; Anja S Nielsen, Aarhus University Hospital; Kristina L Lauridsen, Aarhus University Hospital; Stephen Hamilton-Dutoit, Aarhus University Hospital; Timothy L Lash, Emory University
• Language: English
• Date: 2018-06-01
• Publisher: American Association for Cancer Research
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 American Association for Cancer Research.
• Final Published Version (URL): http://dx.doi.org/10.1158/1055-9965.EPI-17-0905
• Title of Journal or Parent Work: Cancer Epidemiology, Biomarkers and Prevention
• ISSN: 1055-9965
• Volume: 27
• Issue: 6
• Start Page: 653
• End Page: 659
• Grant/Funding Information: The results reported herein correspond to the Specific Aims of R21 CA185932, a grant from the National Cancer Institute awarded to Timothy L. Lash.; The study was additionally supported by funding from the National Cancer Institute (R01 CA118708 and R01 CA166825) awarded to Timothy L. Lash; the Danish Cancer Society (DP06117) awarded to Stephen Hamilton-Dutoit; the Lundbeck Foundation (R167-2013-15861) awarded to Deirdre Cronin-Fenton; the Danish Medical Research Council (DOK 1158869) awarded to Timothy L. Lash; the Karen Elise Jensen Foundation awarded to Henrik Toft Sørensen; the Program for Clinical Research Infrastructure established by the Lundbeck and the Novo Nordisk Foundations awarded to Henrik Toft Sørensen; and a pilot grant awarded from the Glenn Family Breast Center at the Winship Cancer Institute.
• Keywords: ESTROGEN-RECEPTOR ANALYSES; ELEVATED EXPRESSION; GENE; Life Sciences & Biomedicine; COLORECTAL-CANCER; Public, Environmental & Occupational Health; DISTANT RECURRENCE; Science & Technology; CELLS; METASTASIS; Oncology; COOPERATIVE-GROUP DBCG; RISK; STC2 PROMOTES
• Research Categories: Health Sciences, Pathology; Health Sciences, Oncology; Health Sciences, Epidemiology

Abstract

Background: Expression of human paracrine hormones stanniocalcin 1 (STC1) and stanniocalcin 2 (STC2) May potentiate late breast cancer recurrence. We tested the hypothesis that expression of STC1 and STC2 in primary breast tumors is more strongly associated with late versus early recurrences. Methods: A total of 541 estrogen receptor–positive, tamoxifen-treated (ER þ /TAM þ ) and 300 ER-negative, tamoxifen-untreated (ER/TAM) breast cancer patients who experienced recurrence within 10 years of primary diagnosis and matched recurrence-free controls were selected from a cohort of 11,251 Danish breast cancer patients diagnosed with stage I, II, or III breast cancer during 1985 to 2001. The association between IHC expression of STC1 and STC2 in primary breast tumor tissue microarrays and breast cancer recurrence was evaluated within median time to recurrence quintiles. Results: The association between STC1 expression, dichotomized as positive or negative, and recurrence was strongly positive for the final time quintile (6–10 years postdiagnosis) in the ER þ / TAM þ group [aOR ¼ 2.70; 95% confidence interval (CI): 1.22–5.98]. Regression of the log ORs relating dichotomous STC1 and STC2 expression to recurrence by median time to recurrence (year) resulted in a relatively large positive effect estimate for STC1 (b ¼ 0.16; 95% CI, 0.03–0.36) and a near-null positive effect estimate for STC2 (b ¼ 0.04; 95% CI, 0.14–0.21). Conclusions: Our results suggest a stronger association between primary tumor STC1 expression and late recurrence, as opposed to early recurrence, although no clear trend was apparent. Impact: STC1 expression in the primary tumor May potentiate late recurrences, suggesting dormancy pathways that merit further investigation.