PIK3CA mutations are associated with decreased benefit to neoadjuvant human epidermal growth factor receptor 2-targeted therapies in breast cancer

Ian J Majewski; Paolo Nuciforo; Lorenza Mittempergher; Astrid J Bosma; Holger Eidtmann; Eileen Holmes; Christos Sotiriou; Debora Fumagalli; Jose Jimenez; Claudia Aura; Ludmila Prudkin; Maria Carmen Díaz-Delgado; Lorena de la Peña; Sherene Loi; Catherine Ellis; Nikolaus Schultz; Evandro de Azambuja; Nadia Harbeck; Martine Piccart-Gebhart; René Bernards; José Baselga

doi:10.1200/JCO.2014.55.2158

PIK3CA mutations are associated with decreased benefit to neoadjuvant human epidermal growth factor receptor 2-targeted therapies in breast cancer

Ian J Majewski, Paolo Nuciforo, Lorenza Mittempergher, Astrid J Bosma, Holger Eidtmann, Eileen Holmes, Christos Sotiriou, Debora Fumagalli, Jose Jimenez, Claudia Aura, Ludmila Prudkin, Maria Carmen Díaz-Delgado, Lorena de la Peña, Sherene Loi, Catherine Ellis, Nikolaus Schultz, Evandro de Azambuja, Nadia Harbeck, Martine Piccart-Gebhart, René BernardsJosé Baselga

Molecular Cancer Research

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	1334-1339
Number of pages	6
Journal	Journal of Clinical Oncology
Volume	33
Issue number	12
DOIs	https://doi.org/10.1200/JCO.2014.55.2158
Publication status	Published - 20 Apr 2015

Keywords

Aged
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols
Breast Neoplasms
Chemotherapy, Adjuvant
Female
Humans
Middle Aged
Molecular Targeted Therapy
Mutation
Neoadjuvant Therapy
Neoplasm Staging
Phosphatidylinositol 3-Kinases
Quinazolines
Receptor, ErbB-2
Trastuzumab

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10.1200/JCO.2014.55.2158

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Majewski, I. J., Nuciforo, P., Mittempergher, L., Bosma, A. J., Eidtmann, H., Holmes, E., Sotiriou, C., Fumagalli, D., Jimenez, J., Aura, C., Prudkin, L., Díaz-Delgado, M. C., de la Peña, L., Loi, S., Ellis, C., Schultz, N., de Azambuja, E., Harbeck, N., Piccart-Gebhart, M., ... Baselga, J. (2015). PIK3CA mutations are associated with decreased benefit to neoadjuvant human epidermal growth factor receptor 2-targeted therapies in breast cancer. Journal of Clinical Oncology, 33(12), 1334-1339. https://doi.org/10.1200/JCO.2014.55.2158

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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.",

keywords = "Aged, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Chemotherapy, Adjuvant, Female, Humans, Middle Aged, Molecular Targeted Therapy, Mutation, Neoadjuvant Therapy, Neoplasm Staging, Phosphatidylinositol 3-Kinases, Quinazolines, Receptor, ErbB-2, Trastuzumab",

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note = "{\textcopyright} 2015 by American Society of Clinical Oncology.",

year = "2015",

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doi = "10.1200/JCO.2014.55.2158",

language = "English",

volume = "33",

pages = "1334--1339",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

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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 & Baselga, J 2015, 'PIK3CA mutations are associated with decreased benefit to neoadjuvant human epidermal growth factor receptor 2-targeted therapies in breast cancer', Journal of Clinical Oncology, vol. 33, no. 12, pp. 1334-1339. https://doi.org/10.1200/JCO.2014.55.2158

PIK3CA mutations are associated with decreased benefit to neoadjuvant human epidermal growth factor receptor 2-targeted therapies in breast cancer. / Majewski, Ian J; Nuciforo, Paolo; Mittempergher, Lorenza et al.
In: Journal of Clinical Oncology, Vol. 33, No. 12, 20.04.2015, p. 1334-1339.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - PIK3CA mutations are associated with decreased benefit to neoadjuvant human epidermal growth factor receptor 2-targeted therapies in breast cancer

AU - Majewski, Ian J

AU - Nuciforo, Paolo

AU - Mittempergher, Lorenza

AU - Bosma, Astrid J

AU - Eidtmann, Holger

AU - Holmes, Eileen

AU - Sotiriou, Christos

AU - Fumagalli, Debora

AU - Jimenez, Jose

AU - Aura, Claudia

AU - Prudkin, Ludmila

AU - Díaz-Delgado, Maria Carmen

AU - de la Peña, Lorena

AU - Loi, Sherene

AU - Ellis, Catherine

AU - Schultz, Nikolaus

AU - de Azambuja, Evandro

AU - Harbeck, Nadia

AU - Piccart-Gebhart, Martine

AU - Bernards, René

AU - Baselga, José

PY - 2015/4/20

Y1 - 2015/4/20

N2 - 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.

AB - 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.

KW - Aged

KW - Antibodies, Monoclonal, Humanized

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Breast Neoplasms

KW - Chemotherapy, Adjuvant

KW - Female

KW - Humans

KW - Middle Aged

KW - Molecular Targeted Therapy

KW - Mutation

KW - Neoadjuvant Therapy

KW - Neoplasm Staging

KW - Phosphatidylinositol 3-Kinases

KW - Quinazolines

KW - Receptor, ErbB-2

KW - Trastuzumab

UR - https://www.scopus.com/pages/publications/84927620697

U2 - 10.1200/JCO.2014.55.2158

DO - 10.1200/JCO.2014.55.2158

M3 - Article

C2 - 25559818

SN - 0732-183X

VL - 33

SP - 1334

EP - 1339

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 12

ER -

PIK3CA mutations are associated with decreased benefit to neoadjuvant human epidermal growth factor receptor 2-targeted therapies in breast cancer

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Keywords

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