PIK3CA mutations are associated with decreased benefit to neoadjuvant human epidermal growth factor receptor 2-targeted therapies in breast cancer Journal Article
| Authors: | Majewski, I. J.; Nuciforo, P.; Mittempergher, L.; Bosma, A. J.; Eidtmann, H.; Holmes, E.; Sotiriou, C.; Fumagalli, D.; Jimenez, J.; Aura, C.; Prudkin, L.; Diaz Delgado, M. C.; de la Pena, L.; Loi, S.; Ellis, C.; Schultz, N.; de Azambuja, E.; Harbeck, N.; Piccart-Gebhart, M.; Bernards, R.; Baselga, J. |
| Article Title: | PIK3CA mutations are associated with decreased benefit to neoadjuvant human epidermal growth factor receptor 2-targeted therapies in breast cancer |
| Abstract: | Purpose We investigated whether mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) correlates with response to neoadjuvant human epidermal growth factor receptor 2 (HER2) -targeted therapies in patients with breast cancer. Patients and Methods Baseline tissue biopsies were available from patients with HER2-positive early breast cancer who were enrolled onto the Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial (NeoALTTO). Activating mutations in PIK3CA were identified using mass spectrometry-based genotyping. Results PIK3CA mutations were identified in 23% of HER2-positive breast tumors, and these mutations were associated with poorer outcome in all of the treatment arms. Patients treated with a combination of trastuzumab and lapatinib who had wild-type PIK3CA obtained a total pathologic complete response (pCR) rate of 53.1%, which decreased to 28.6% in patients with tumors that carried PIK3CA activating mutations (P = .012). Conclusion Activating mutations in PIK3CA predicted poor pCR in patients with HER2-positive breast cancer treated with neoadjuvant therapies that target HER2. Consequently, the combination of anti-HER2 agents and PI3K inhibitors is being investigated. (C) 2015 by American Society of Clinical Oncology |
| Keywords: | survival; adjuvant chemotherapy; lapatinib; colorectal-cancer; activation; plus; multicenter; trastuzumab resistance; open-label; phase-3 trial |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 33 |
| Issue: | 12 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2015-04-20 |
| Start Page: | 1334 |
| End Page: | 1339 |
| Language: | English |
| ACCESSION: | WOS:000356058800006 |
| DOI: | 10.1200/jco.2014.55.2158 |
| PROVIDER: | wos |
| PUBMED: | 25559818 |
| PMCID: | PMC5087318 |
| Notes: | Article -- Source: Wos |
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