Takayuki Iwamoto    Department   Kawasaki Medical School  Kawasaki Medical School, Department of Breast and Thyroid Surgery,    Position   Assistant Professor
Article types	原著
Language	English
Peer review	Peer reviewed
Title	Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers.
Journal	Formal name：Breast cancer research : BCR Abbreviation：Breast Cancer Res ISSN code：1465542X/14655411
Domestic / Foregin	Foregin
Volume, Issue, Page	15(5),pp.R86
International coauthorship	International coauthorship
Author and coauthor	Giampaolo Bianchini, Lajos Pusztai, Thomas Karn, Takayuki Iwamoto, Achim Rody, Catherine Kelly, Volkmar Müller, Schmidt Schmidt, Yuan Qi, Uwe Holtrich, Sven Becker, Libero Santarpia, Angelica Fasolo, Gianluca Del Conte, Milvia Zambetti, Christos Sotiriou, Benjamin Haibe-Kains, W Fraser Symmans, Luca Gianni
Publication date	2013
Summary	INTRODUCTION:We examined if a combination of proliferation markers and estrogen receptor (ER) activity could predict early versus late relapses in ER-positive breast cancer and inform the choice and length of adjuvant endocrine therapy.METHODS:Baseline affymetrix gene-expression profiles from ER-positive patients who received no systemic therapy (n = 559), adjuvant tamoxifen for 5 years (cohort-1: n = 683, cohort-2: n = 282) and from 58 patients treated with neoadjuvant letrozole for 3 months (gene-expression available at baseline, 14 and 90 days) were analyzed. A proliferation score based on the expression of mitotic kinases (MKS) and an ER-related score (ERS) adopted from Oncotype DX® were calculated. The same analysis was performed using the Genomic Grade Index as proliferation marker and the luminal gene score from the PAM50 classifier as measure of estrogen-related genes. Median values were used to define low and high marker groups and four combinations were created. Relapses were grouped into time cohorts of 0-2.5, 0-5, 5-10 years.RESULTS:In the overall 10 years period, the proportional hazards assumption was violated for several biomarker groups indicating time-dependent effects. In tamoxifen-treated patients Low-MKS/Low-ERS cancers had continuously increasing risk of relapse that was higher after 5 years than Low-MKS/High-ERS cancers [0 to 10 year, HR 3.36; p = 0.013]. High-MKS/High-ERS cancers had low risk of early relapse [0-2.5 years HR 0.13; p = 0.0006], but high risk of late relapse which was higher than in the High-MKS/Low-ERS group [after 5 years HR 3.86; p = 0.007]. The High-MKS/Low-ERS subset had most of the early relapses [0 to 2.5 years, HR 6.53; p < 0.0001] especially in node negative tumors and showed minimal response to neoadjuvant letrozole. These findings were qualitatively confirmed in a smaller independent cohort of tamoxifen-treated patients. Using different biomarkers provided similar results.CONCLUSIONS:Early relapses are highest in high
DOI	10.1186/bcr3481
PMID	24060333