In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 27, No. 15_suppl ( 2009-05-20), p. 536-536
Abstract:
536 Background: The optimal duration of endocrine therapy ranges between 5 and 7 years. Recent data suggest that a subset of patients could benefit from extended adjuvant TAM. The goal of this biomarker study was to identify potential candidates for extended TAM. Methods: After 2–3 yrs of adjuvant TAM, 3793 patients (pts) were randomized to continue TAM up to 10 yrs, or to stop treatment (Delozier, J Clin Oncol. 2000). The tumor blocks of 587/988 pts included at the Institut Gustave-Roussy, were used to construct a tissue micro-array (TMA). Immunohistochemical stainings were performed for ER, PR, bcl2, p53 (+: 〉 10% of stained cells), HER-2 (+: score 3+), EGFR1 (+: any positivity), PAK1, IGFR1 (+: intensity = 2 or 3). Median follow-up was 12 years. The prognostic values of biomarkers were assessed by a Cox model adjusted for clinical prognostic parameters and predictive values by interaction tests. Only statistical tests with P 〈 0.01 were considered significant because of multi-hypothesis testing. Time-to-relapse (TTR), excluding contralateral cancer, was the main study endpoint. Results: Median age of the cohort included in the TMA was 63. Tumor characteristics : 54% node-positive, 85% ER+, 64% PR+, 7% HER-2+, 68% bcl2+, 14% p53+, 8% EGFR1+, 46% PAK1, 45% IGFR1. None of the biomarkers were prognostically significant. However, PR expression was strongly predictive for the efficacy of extended TAM on TTR (interaction test, p = 0.003). Long-term TAM was associated with a hazard ratio of 0.56, (95% CI: 0.30–1.03) and 1.94 (95%CI = 0.80–4.70) for PR+ and PR- pts respectively. A trend towards interaction between ER (p = 0.04), HER-2 (p = 0.05) and Bcl2 (p = 0.03) expression and a benefit from TAM was also observed, with a trend towards greater efficacy of prolonged TAM in ER+/HER-2-/ bcl2+ tumors. P53, EGFR1, PAK1, IGFR1 expression had no predictive value. Conclusions: PR expression, probably reflective of ER activation and functionality, strongly predicts benefit from continuation of TAM after 2–3 yrs. These data could provide a rationale for evaluating the efficacy of TAM after 5 years of anti-aromatase therapy in post-menopausal women with ER+/PR+/bcl2+/Her2-tumors. No significant financial relationships to disclose.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2009.27.15_suppl.536
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2009
detail.hit.zdb_id:
2005181-5
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