Anderson, H., Hills, M., Zabaglo, L., A'Hern, R., Leary, A. F., Haynes, B. P., Smith, I. E., Dowsett, M. (2011) Relationship between estrogen receptor, progesterone receptor, HER-2 and Ki67 expression and efficacy of aromatase inhibitors in advanced breast cancer. ANNALS OF ONCOLOGY, 22 (8). pp. 1770-1776. ISSN 0923-7534

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Abstract

Background: Surprisingly few data are published on the relevance of even commonly used biomarkers of response to aromatase inhibitors (AIs) in advanced breast cancer. Here, we aim to determine the effectiveness of AIs in that setting according to quantitative levels of estrogen receptor (ER), progesterone receptor (PgR) and Ki67 or human epithelial growth factor receptor-2 (HER-2) status. Patients and methods: ER, PgR, HER-2 and Ki67 protein expressions were centrally assessed in 177 archival formalin-fixed paraffin-embedded primary or locally recurrent breast tumours from women who subsequently received AI treatment of advanced disease. Results: Among ER-positive patients (n = 146), higher PgR, but not ER, levels were associated with increased time to AI treatment failure (TTF). Higher Ki67 staining was associated with decreased TTF. ER-positive/HER-2-positive patients showed a non-significant trend for decreased TTF compared with ER-positive/HER-2-negative patients. PgR level, but not Ki67, remained a significant predictor of TTF in multivariate analysis of ER-positive patients. Conclusions: Higher PgR and Ki67 levels are significantly associated with increased and decreased TTF, respectively, in ER-positive patients receiving AI treatment of advanced disease. The higher proliferation seen in PgR-negative tumours does not explain the poorer clinical responsiveness of this subgroup.

Item Type:	Article
Authors (ICR Faculty only):	Ahern, Roger and Smith, Ian and Dowsett, Mitch
All Authors:	Anderson, H., Hills, M., Zabaglo, L., A'Hern, R., Leary, A. F., Haynes, B. P., Smith, I. E., Dowsett, M.
Additional Information:	ISI Document Delivery No.: 799QH Times Cited: 1 Cited Reference Count: 32 Anderson, H. Hills, M. Zabaglo, L. A'Hern, R. Leary, A. F. Haynes, B. P. Smith, I. E. Dowsett, M. NHS; Breakthrough Breast Cancer; The Mary-Jean Mitchell Green Foundation; National Health Service; AstraZeneca; Novartis We thank Janine Salter for help during the early stages of this project. We also acknowledge NHS funding to the National Institute for Health Research Biomedical Research Centre.Breakthrough Breast Cancer; The Mary-Jean Mitchell Green Foundation; National Health Service to the National Institute for Health Research Biomedical Research Centre.MD has acted as a paid advisor to AstraZeneca, Novartis and Pfizer and received research funding and honoraria in association with lectures from AstraZeneca and Novartis Oxford univ press Oxford
Uncontrolled Keywords:	aromatase inhibitor breast cancer estrogen receptor HER-2 Ki67 progesterone receptor southwest-oncology-group endocrine therapy randomized-trial neoadjuvant anastrozole tamoxifen letrozole combination er chemotherapy recurrence
Research teams:	Clinical Units > Breast Unit ICR divisions > Clinical Studies > Clinical Trials & Statistics Unit ICR divisions > Breast Cancer Research > Endocrinology ICR divisions > Molecular Pathology > Endocrinology
Depositing User:	Users 11 not found.
Date Deposited:	01 Sep 2011 11:06
Last Modified:	21 Jan 2014 16:44
URI:	http://publications.icr.ac.uk/id/eprint/10984

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