BRCA1 protein levels and PIK3CA mutations as predictive biomarkers for response to neoadjuvant chemotherapy in locally advanced breast cancer: An exploratory analysis

Hilton,J.; Weberpals,J.; Lorimer, i.; Amin,S.; Islam,S.; Pelletier,L.; Daneshmand,M.; Hanson,J.; Nabavi,M.; Parolin,D.; Mallick,R.; Verma,S.

doi:10.3892/ol.2012.697

July 2012 Volume 4 Issue 1

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July 2012 Volume 4 Issue 1

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Article

BRCA1 protein levels and PIK3CA mutations as predictive biomarkers for response to neoadjuvant chemotherapy in locally advanced breast cancer: An exploratory analysis

Authors:
- J. Hilton
- J. Weberpals
- i. Lorimer
- S. Amin
- S. Islam
- L. Pelletier
- M. Daneshmand
- J. Hanson
- M. Nabavi
- D. Parolin
- R. Mallick
- S. Verma
View Affiliations / Copyright

Affiliations: Department of Medical Oncology, Ottawa Hospital, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada, Ottawa Hospital Research Institute, Ottawa Hospital, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada, Department of Pathology, Ottawa Hospital, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada, Department of Biostatistics, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada
Pages: 141-145
|
Published online on: April 26, 2012

https://doi.org/10.3892/ol.2012.697
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Abstract

BRCA1 overexpression and phosphoinositide 3-kinase (PIK3CA) pathway activation are involved in the resistance to DNA damaging agents. Thus, we hypothesized that BRCA1 protein expression and activating PIK3CA mutations are potential tumor biomarkers for the chemotherapeutic response to doxorubicin/cyclophosphamide plus docetaxel in locally advanced breast cancer. Informed consent was obtained and clinical, pathological and response data were collected. BRCA1 protein expression levels were assessed by immunohistochemistry of the archived tissue by two independent pathologists. The PIK3CA mutation status was assessed by nested PCR amplification and DNA sequencing. BRCA1 protein levels and the PIK3CA mutation status were correlated with pathological complete response and a partial response or better using the Chi‑square test, Fisher's exact test and logistic regression. Of the 136 eligible participants, 59 samples could be analyzed. There was a trend of relatively low levels of BRCA1 protein achieving a pathological complete response (pCR), although this was not statistically significant [odds ratio (OR)=1.74; p=0.437]. Twenty-eight percent of patients had PIK3CA mutations, but no statistically significant association with pCR (OR=0.977; p=0.971) was noted. Neither BRCA1 protein levels (OR=1.18; p=0.818) nor PIK3CA mutations (OR=1.03; p=0.971) appeared to be associated with the likelihood of achieving a partial response or better from neoadjuvant chemotherapy. PIK3CA wild-type mutation status showed a trend towards an increased likelihood of not presenting with inflammatory disease (OR=5.34; p=0.101). In this exploratory study, neither BRCA1 protein expression levels nor the presence of PIK3CA mutations were significantly associated with chemotherapy response in locally advanced breast cancer. However, the relatively small sample size limits the overall interpretation.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

BRCA1 protein levels and PIK3CA mutations as predictive biomarkers for response to neoadjuvant chemotherapy in locally advanced breast cancer: An exploratory analysis

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