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This Article Accepted manuscript (PDF) All Versions of this Article: ERC-08-0078v1 15/3/755    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yamashita, H. Articles by Iwase, H. Search for Related Content PubMed PubMed Citation Articles by Yamashita, H. Articles by Iwase, H.

H Yamashita, Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan
M Nishio, Nagoya, Japan
T Toyama, Nagoya, Japan
H Sugiura, Nagoya, Japan
N Kondo, Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
S Kobayashi, Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
Y Fujii, Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
H Iwase, Breast and Endocrine Surgery, Kumamoto University, Kumamoto, Japan

Correspondence: Hiroko Yamashita, Email: hirokoy{at}med.nagoya-cu.ac.jp

Abstract

Endocrine therapy has become the most important treatment option for women with estrogen receptor (ER)-positive breast cancer. Urgently needed are prognostic assays that can identify those who need additional adjuvant therapy, such as signal transduction inhibitors or chemotherapy, for ER-positive early breast cancer. We examined phosphorylation of ER serine (Ser) 118, ER Ser167, p44/42 MAPK and Akt, and expression of progesterone receptor (PR), AIB1, HER2, p53 and Ki67 in ER-positive breast cancers by immunohistochemistry, and analyzed their significance for prognosis. Phosphorylation levels of ER Ser118, ER Ser167, MAPK and Akt were positively correlated. AIB1 expression was significantly associated with phosphorylation of ER Ser118, MAPK and Akt, and HER2 expression. Low phosphorylation of ER Ser118 and high phosphorylation of ER Ser167 were associated with significantly improved disease-free (P = 0.0003 and P = 0.0002, respectively) and overall survival (P = 0.0007 and P = 0.0016, respectively) in multivariate analyses. Our data suggest that phosphorylation of ER Ser118 and ER Ser167 affects survival in ER-positive breast cancer and could be helpful in distinguishing patients who are likely to benefit from endocrine therapy alone from those who are not.