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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/22803

Title: PTEN Loss Is Associated with Worse Outcome in HER2-Amplified Breast Cancer Patients but Is Not Associated with Trastuzumab Resistance
Authors: Stern, Howard M.
Gardner, Humphrey
Burzykowski, Tomasz
Elatre, Wafaa
O'Brien, Carol
Lackner, Mark R.
Pestano, Gary A.
Santiago, Angela
Villalobos, Ivonne
Eiermann, Wolfgang
Pienkowski, Tadeusz
Martin, Miguel
Robert, Nicholas
Crown, John
Nuciforo, Paolo
Bee, Valerie
Mackey, John
Slamon, Dennis J.
Press, Michael F.
Issue Date: 2015
Citation: CLINICAL CANCER RESEARCH, 21(9), p. 2065-2074
Abstract: PURPOSE: To investigate the clinical relevance of PTEN in HER2-amplified and HER2-nonamplified disease. EXPERIMENTAL DESIGN: We assessed PTEN status in two large adjuvant breast cancer trials (BCIRG-006 and BCIRG-005) using a PTEN immunohistochemical (IHC) assay that was previously validated in a panel of 33 breast cancer cell lines and prostate cancer tissues with known PTEN gene deletion. RESULTS: In the HER2-positive patient population, absence of tumor cell PTEN staining occurred at a rate of 5.4% and was independent of ER/PR status. In contrast, 15.9% of HER2-negative patients exhibited absence of PTEN staining with the highest frequency seen in triple-negative breast cancer (TNBC) subgroup versus ER/PR-positive patients (35.1% vs. 10.9%). Complete absence of PTEN staining in tumor cells was associated with poor clinical outcome in HER2-positive disease. Those patients whose cancers demonstrated absent PTEN staining had a significant decrease in disease-free survival (DFS) and overall survival (OS) compared with patients with tumors exhibiting any PTEN staining patterns (low, moderate, or high). Trastuzumab appeared to provide clinical benefit even for patients lacking PTEN staining. In the HER2-negative population, there were no statistically significant differences in clinical outcome based on PTEN status. CONCLUSIONS: This study is the largest to date examining PTEN status in breast cancer and the data suggest that the rate and significance of PTEN status differ between HER2-positive and HER2-negative disease. Furthermore, the data clearly suggest that HER2-positive patients with PTEN loss still benefit from trastuzumab.
Notes: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).
URI: http://hdl.handle.net/1942/22803
DOI: 10.1158/1078-0432.CCR-14-2993
ISI #: 000353708200014
ISSN: 1078-0432
Category: A1
Type: Journal Contribution
Validation: ecoom, 2017
Appears in Collections: Research publications

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