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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 2/2014

01-06-2014 | Clinical trial

Characterization of breast cancers with PI3K mutations in an academic practice setting using SNaPshot profiling

Authors: Vandana G. Abramson, M. Cooper Lloyd, Tarah Ballinger, Melinda E. Sanders, Liping Du, Darson Lai, Zengliu Su, Ingrid Mayer, Mia Levy, Delecia R. LaFrance, Cindy L. Vnencak-Jones, Yu Shyr, Kimberly B. Dahlman, William Pao, Carlos L. Arteaga

Published in: Breast Cancer Research and Treatment | Issue 2/2014

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Abstract

Mutations in the PIK3CA gene are common in breast cancer and represent a clinically useful therapeutic target. Several larger, population-based studies have shown a positive prognostic significance associated with these mutations. This study aims to further identify characteristics of patients harboring PIK3CA mutations while evaluating the clinical impact of genomic testing for these mutations. Tumors from 312 patients at Vanderbilt-Ingram Cancer Center were analyzed for PIK3CA mutations using a multiplex screening assay (SNaPshot). Mutation rates, receptor status, histopathologic characteristics, and time to recurrence were assessed. The number of patients participating in clinical trials, specifically trials relating to the PIK3CA mutation, was examined. Statistically significant differences between wild-type and mutated tumors were determined using the Wilcoxon, Pearson, and Fischer exact tests. The PIK3CA mutation was found in 25 % of tumors tested. Patients with PIK3CA mutations were significantly more likely to express hormone receptors, be of lower combined histological grade, and have a reduced time to recurrence. Patients found to have a PIK3CA mutation were significantly more likely to enter a PIK3CA-specific clinical trial. In addition to confirming previously established positive prognostic characteristics of tumors harboring PIK3CA mutations, this study demonstrates the feasibility and utility of mutation profiling in a clinical setting. PIK3CA mutation testing impacted treatment and resulted in more patients entering mutation-specific clinical trials.
Literature
1.
Dillon RL, White DE, Muller WJ (2007) The phosphatidyl inositol 3-kinase signaling network: implications for human breast cancer. Oncogene 26(9):1338–1345PubMedCrossRef
2.
Campbell IG et al (2004) Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res 64(21):7678–7681PubMedCrossRef
3.
Li SY et al (2006) PIK3CA mutations in breast cancer are associated with poor outcome. Breast Cancer Res Treat 96(1):91–95PubMedCrossRef
4.
Kalinsky K et al (2009) PIK3CA mutation associates with improved outcome in breast cancer. Clin Cancer Res 15(16):5049–5059PubMedCrossRef
5.
Cizkova M et al (2012) PIK3CA mutation impact on survival in breast cancer patients and in ERalpha, PR and ERBB2-based subgroups. Breast Cancer Res 14(1):R28PubMedCentralPubMedCrossRef
6.
Miller TW et al (2011) Mutations in the phosphatidylinositol 3-kinase pathway: role in tumor progression and therapeutic implications in breast cancer. Breast Cancer Res 13(6):224PubMedCentralPubMedCrossRef
7.
Maruyama N et al (2007) Clinicopathologic analysis of breast cancers with PIK3CA mutations in Japanese women. Clin Cancer Res 13(2 Pt 1):408–414PubMedCrossRef
8.
Janku F et al (2012) PI3K/AKT/mTOR inhibitors in patients with breast and gynecologic malignancies harboring PIK3CA mutations. J Clin Oncol 30(8):777–782PubMedCentralPubMedCrossRef
9.
Jensen DJ et al (2011) PIK3CA mutations may be discordant between primary and corresponding metastatic disease in breast cancer. Clin Cancer Res 17(4):667–677CrossRef
10.
Isakoff SJ et al (2005) Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells. Cancer Res 65(23):10992–11000PubMedCrossRef
11.
12.
Gonzalez-Angulo AM et al (2013) Frequency of mesenchymal-epithelial transition factor gene (MET) and the catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevation and correlation with outcome in patients with early stage breast cancer. Cancer 119(1):7–15PubMedCentralPubMedCrossRef
13.
Perez-Tenorio G et al (2007) PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer. Clin Cancer Res 13(12):3577–3584PubMedCrossRef
14.
Loi S et al (2013) Somatic mutation profiling and associations with prognosis and trastuzumab benefit in early breast cancer. J Natl Cancer Inst 105(13):960–967PubMedCrossRef
15.
Saal LH et al (2005) PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res 65(7):2554–2559PubMedCrossRef
16.
Dumont AG, Dumont SN, Trent JC (2012) The favorable impact of PIK3CA mutations on survival: an analysis of 2587 patients with breast cancer. Chin J Cancer 31(7):327–334PubMedCentralPubMedCrossRef
17.
18.
Campbell RA et al (2001) Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance. J Biol Chem 276(13):9817–9824PubMedCrossRef
19.
Berns K et al (2007) A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 12(4):395–402PubMedCrossRef
20.
Eichhorn PJ et al (2008) Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Cancer Res 68(22):9221–9230PubMedCentralPubMedCrossRef
21.
Cizkova M et al (2013) Outcome impact of PIK3CA mutations in HER2-positive breast cancer patients treated with trastuzumab. Br J Cancer 108(9):1807–1809PubMedCentralPubMedCrossRef
22.
Jensen JD et al (2012) PIK3CA mutations, PTEN, and pHER2 expression and impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab. Ann Oncol 23(8):2034–2042PubMedCrossRef
23.
Baselga, J., et al.,: Biomarker analyses in CLEOPATRA: a phase III, placebo-controlled study of pertuzumab in HER2-positive, first-line metastatic breast cancer (MBC). In: Thirty-fifth annual CTRC-AACR San Antonio Breast Cancer Symposium, San Antonio, TX, 4–8 Dec 2012; Cancer. Res. 72(24 Supplement), S5–1 (2012)
24.
Baselga J, M.I., Nuciforo PG et al. (2013) PI3KCA mutations and correlation with pCR in the NeoALTTO trial (BIG 01-06). Presented at European Cancer Congress 2013; Sep 27–Oct 1,2013 ; Amsterdam. Abstract 1859, 2013
25.
Janku F et al (2013) PIK3CA mutation H1047R is associated with response to PI3K/AKT/mTOR signaling pathway inhibitors in early-phase clinical trials. Cancer Res 73(1):276–284PubMedCentralPubMedCrossRef
26.
Bendell JC et al (2012) Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. J Clin Oncol 30(3):282–290PubMedCrossRef
27.
Hurst CD et al (2009) A SNaPshot assay for the rapid and simple detection of four common hotspot codon mutations in the PIK3CA gene. BMC Res Notes 2:66PubMedCentralPubMedCrossRef
28.
Su Z et al (2011) A platform for rapid detection of multiple oncogenic mutations with relevance to targeted therapy in non-small-cell lung cancer. J Mol Diagn 13(1):74–84PubMedCentralPubMedCrossRef
29.
Lovly CM et al (2012) Routine multiplex mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials. PLoS One 7(4):e35309PubMedCentralPubMedCrossRef
30.
Hammond ME et al (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med 134(7):e48–e72PubMed
31.
Wolff AC et al (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 131(1):18–43PubMed
32.
Zhao L, Vogt PK (2008) Helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms. Proc Natl Acad Sci U S A 105(7):2652–2657PubMedCentralPubMedCrossRef
33.
Board RE et al (2008) Multiplexed assays for detection of mutations in PIK3CA. Clin Chem 54(4):757–760PubMedCrossRef
34.
Lurkin I et al (2010) Two multiplex assays that simultaneously identify 22 possible mutation sites in the KRAS, BRAF, NRAS and PIK3CA genes. PLoS One 5(1):e8802PubMedCentralPubMedCrossRef
35.
Ramirez-Ardila DE et al (2013) Hotspot mutations in PIK3CA associate with first-line treatment outcome for aromatase inhibitors but not for tamoxifen. Breast Cancer Res Treat 139(1):39–49PubMedCrossRef
36.
Knight WA et al (1977) Estrogen receptor as an independent prognostic factor for early recurrence in breast cancer. Cancer Res 37(12):4669–4671PubMed
37.
Kinne DW et al (1981) Estrogen receptor protein in breast cancer as a predictor of recurrence. Cancer 47(10):2364–2367PubMedCrossRef
Metadata
Title
Characterization of breast cancers with PI3K mutations in an academic practice setting using SNaPshot profiling
Authors
Vandana G. Abramson
M. Cooper Lloyd
Tarah Ballinger
Melinda E. Sanders
Liping Du
Darson Lai
Zengliu Su
Ingrid Mayer
Mia Levy
Delecia R. LaFrance
Cindy L. Vnencak-Jones
Yu Shyr
Kimberly B. Dahlman
William Pao
Carlos L. Arteaga
Publication date
01-06-2014
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2014
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-014-2945-3

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