PIK3CA-activating mutations and chemotherapy sensitivity in stage II-III breast cancer

Cornelia Liedtke, Luca Cardone, A. Tordai, Kai Yan, Henry L. Gomez, Luis J B Figureoa, Rebekah E. Hubbard, Vicente Valero, Eduardo A. Souchon, W. Fraser Symmans, Gabriel N. Hortobagyi, Alberto Bardelli, Lajos Pusztai

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Abstract

Introduction: In vitro evidence suggests that PIK3CA (phosphatidylinositol 3-kinase, catalytic, alpha polypeptide) activation may be associated with altered chemotherapy sensitivity in cancer.Methods: Tumor DNA from 140 patients with stage II-III breast cancer undergoing neoadjuvant chemotherapy was sequenced for PIK3CA mutations on exons 1, 9, and 20. Mutation status was correlated with clinical/pathological parameters and chemotherapy response as (a) pathological complete response (pCR) versus residual cancer or (b) quantitative residual cancer burden (RCB) scores, including stratification for estrogen receptor (ER) expression status, type of chemotherapy, and by exons.Results: Twenty-three patients (16.4%) harbored a PIK3CA mutation, with 12, 11, and 0 mutations located in exons 9, 20, and 1, respectively. PIK3CA exon 9 mutations were more frequent among node-negative (52% versus 25%; P = 0.012) than node-positive tumors, particularly among ER-positive tumors. pCR rates and RCB scores were similar among patients with the wild-type and mutant PIK3CA genes, even after stratification by ER status, chemotherapy regimen (anthracycline versus anthracycline plus paclitaxel), or exon.Conclusion: PIK3CA mutations are not associated with altered sensitivity to preoperative anthracycline-based or taxane-based chemotherapies in ER-positive and ER-negative breast tumors. In this study, PIK3CA mutation was associated with a decreased rate of node-positive disease, particularly among ER-positive tumors.

Original languageEnglish
Article numberR27
JournalBreast Cancer Research
Volume10
Issue number2
DOIs
Publication statusPublished - Mar 27 2008

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Estrogen Receptors
Breast Neoplasms
Drug Therapy
Mutation
Exons
Anthracyclines
Residual Neoplasm
Neoplasms
Phosphatidylinositol 3-Kinase
Paclitaxel
Peptides
DNA
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Liedtke, C., Cardone, L., Tordai, A., Yan, K., Gomez, H. L., Figureoa, L. J. B., ... Pusztai, L. (2008). PIK3CA-activating mutations and chemotherapy sensitivity in stage II-III breast cancer. Breast Cancer Research, 10(2), [R27]. https://doi.org/10.1186/bcr1984

PIK3CA-activating mutations and chemotherapy sensitivity in stage II-III breast cancer. / Liedtke, Cornelia; Cardone, Luca; Tordai, A.; Yan, Kai; Gomez, Henry L.; Figureoa, Luis J B; Hubbard, Rebekah E.; Valero, Vicente; Souchon, Eduardo A.; Symmans, W. Fraser; Hortobagyi, Gabriel N.; Bardelli, Alberto; Pusztai, Lajos.

In: Breast Cancer Research, Vol. 10, No. 2, R27, 27.03.2008.

Research output: Contribution to journalArticle

Liedtke, C, Cardone, L, Tordai, A, Yan, K, Gomez, HL, Figureoa, LJB, Hubbard, RE, Valero, V, Souchon, EA, Symmans, WF, Hortobagyi, GN, Bardelli, A & Pusztai, L 2008, 'PIK3CA-activating mutations and chemotherapy sensitivity in stage II-III breast cancer', Breast Cancer Research, vol. 10, no. 2, R27. https://doi.org/10.1186/bcr1984
Liedtke, Cornelia ; Cardone, Luca ; Tordai, A. ; Yan, Kai ; Gomez, Henry L. ; Figureoa, Luis J B ; Hubbard, Rebekah E. ; Valero, Vicente ; Souchon, Eduardo A. ; Symmans, W. Fraser ; Hortobagyi, Gabriel N. ; Bardelli, Alberto ; Pusztai, Lajos. / PIK3CA-activating mutations and chemotherapy sensitivity in stage II-III breast cancer. In: Breast Cancer Research. 2008 ; Vol. 10, No. 2.
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AU - Gomez, Henry L.

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AU - Hubbard, Rebekah E.

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AU - Souchon, Eduardo A.

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N2 - Introduction: In vitro evidence suggests that PIK3CA (phosphatidylinositol 3-kinase, catalytic, alpha polypeptide) activation may be associated with altered chemotherapy sensitivity in cancer.Methods: Tumor DNA from 140 patients with stage II-III breast cancer undergoing neoadjuvant chemotherapy was sequenced for PIK3CA mutations on exons 1, 9, and 20. Mutation status was correlated with clinical/pathological parameters and chemotherapy response as (a) pathological complete response (pCR) versus residual cancer or (b) quantitative residual cancer burden (RCB) scores, including stratification for estrogen receptor (ER) expression status, type of chemotherapy, and by exons.Results: Twenty-three patients (16.4%) harbored a PIK3CA mutation, with 12, 11, and 0 mutations located in exons 9, 20, and 1, respectively. PIK3CA exon 9 mutations were more frequent among node-negative (52% versus 25%; P = 0.012) than node-positive tumors, particularly among ER-positive tumors. pCR rates and RCB scores were similar among patients with the wild-type and mutant PIK3CA genes, even after stratification by ER status, chemotherapy regimen (anthracycline versus anthracycline plus paclitaxel), or exon.Conclusion: PIK3CA mutations are not associated with altered sensitivity to preoperative anthracycline-based or taxane-based chemotherapies in ER-positive and ER-negative breast tumors. In this study, PIK3CA mutation was associated with a decreased rate of node-positive disease, particularly among ER-positive tumors.

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