1. PIK3CA mutations are associated with decreased benefit to neoadjuvant human epidermal growth factor receptor 2-targeted therapies in breast cancer.
- Author
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Majewski IJ, Nuciforo P, Mittempergher L, Bosma AJ, Eidtmann H, Holmes E, Sotiriou C, Fumagalli D, Jimenez J, Aura C, Prudkin L, Díaz-Delgado MC, de la Peña L, Loi S, Ellis C, Schultz N, de Azambuja E, Harbeck N, Piccart-Gebhart M, Bernards R, and Baselga J
- Subjects
- Aged, Antibodies, Monoclonal, Humanized administration & dosage, Breast Neoplasms enzymology, Breast Neoplasms genetics, Breast Neoplasms pathology, Chemotherapy, Adjuvant, Class I Phosphatidylinositol 3-Kinases, Female, Humans, Lapatinib, Middle Aged, Molecular Targeted Therapy, Neoadjuvant Therapy, Neoplasm Staging, Quinazolines administration & dosage, Receptor, ErbB-2 antagonists & inhibitors, Trastuzumab, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Mutation, Phosphatidylinositol 3-Kinases genetics, Receptor, ErbB-2 metabolism
- 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., Competing Interests: Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article., (© 2015 by American Society of Clinical Oncology.)
- Published
- 2015
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