Impact of PTEN protein expression on benefit from adjuvant trastuzumab in early-stage human epidermal growth factor receptor 2-positive breast cancer in the North Central Cancer Treatment Group N9831 trial
Open accessAbstract
PURPOSE: It has been suggested that PTEN, a negative regulator of PI3K/AKT signaling, is involved in tumor sensitivity to trastuzumab. We investigated the association between tumor PTEN protein expression and disease-free survival (DFS) of patients randomly assigned to receive chemotherapy alone (arm A) or chemotherapy with sequential (arm B) or concurrent trastuzumab (arm C) in the phase III early-stage human epidermal growth factor receptor 2 (HER2) -positive trial-North Central Cancer Treatment Group (NCCTG) N9831. PATIENTS AND METHODS: The intensity and percentage of invasive cells with cytoplasmic PTEN staining were determined in tissue microarray sections containing three cores per block (n = 1,286) or in whole tissue sections (WS; n = 516) by using standard immunohistochemistry (138G6 monoclonal antibody). Tumors were considered positive for PTEN (PTEN-positive) if any core or WS had any invasive cells with ≥ 1+ staining. Median follow-up was 6.0 years. RESULTS: Of 1,802 patients included in this analysis (of 3,505 patients registered to N9831), 1,342 (74%) had PTEN-positive tumors. PTEN positivity was associated with hormone receptor negativity (χ(2) P < .001) and nodal positivity (χ(2) P = .04). PTEN did not have an impact on DFS within the various arms. Comparing DFS of arm C to arm A, patients with PTEN-positive and PTEN-negative tumors had hazard ratios (HRs) of 0.65 (P = .003) and 0.47 (P = .005), respectively (interaction P = .16). For arm B versus arm A, patients with PTEN-positive and PTEN-negative tumors had HRs of 0.70 (P = .009) and 0.85 (P = .44), respectively (interaction P = .47). CONCLUSION: In contrast to selected preclinical and limited clinical studies suggesting a decrease in trastuzumab sensitivity in patients with PTEN-negative tumors, our data show benefit of adjuvant trastuzumab for patients with HER2-positive breast cancer, independent of tumor PTEN status.
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The correlation between PTEN loss and lower response to trastuzumab was not found in patients with early breast cancer treated with adjuvant trastuzumab.
“This correlation was not found in patients with early breast cancer treated with adjuvant trastuzumab (Perez et al., 2013).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Perez et al., 2013
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ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics
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- Authors
- Perez, E. A., Dueck, A. C., McCullough, A. E., Chen, B., Geiger, X. J., Jenkins, R. B., Lingle, W. L., Davidson, N. E., Martino, S., Kaufman, P. A., Kutteh, L. A., Sledge, G. W., Harris, L. N., Gralow, J. R., & Reinholz, M. M.
- Affiliations
- Dartmouth–Hitchcock Medical Center (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2013-06-10
- Volume
- 31
- Issue
- 17
- Pages
- 2115-2122
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC3731983
- OpenAlex
- W2140864342
- Cited by
- 106
- References
- 29
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 12 · 2018: 4 · 2017: 11 · 2016: 16 · 2015: 27 · 2014: 15 · 2013: 5
- FWCI
- 11.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Breast Cancer Research Foundation (CA25224)
- National Institutes of Health (CA-25224)
- National Cancer Institute (CA129949, CA25224-31, R01CA129949, U24CA114740, CA114740, U10CA025224)
- Topics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gastric Cancer Management and Outcomes
- Keywords
- PTEN protein expression, trastuzumab, HER2-positive breast cancer, adjuvant therapy, disease-free survival, PI3K/Akt signaling, hormone receptor status, lymph node status, biomarker predictive value, tumor suppressor, prognostic factors, predictive biomarkers
- MeSH terms
- Trastuzumab, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Cyclophosphamide, Doxorubicin, Female, Humans, Immunohistochemistry, Middle Aged, Chemotherapy, Adjuvant, Paclitaxel, Disease-Free Survival, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, PTEN Phosphohydrolase, Young Adult, Antibodies, Monoclonal, Humanized
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