Microarray-based comparative genomic hybridisation of breast cancer patients receiving neoadjuvant chemotherapy

Pierga, J-Y., Reis-Filho, J. S., Cleator, S. J., Dexter, T., MacKay, A., Simpson, P., Fenwick, K., Iravani, M., Salter, J., Hills, M., Jones, C., Ashworth, A., Smith, I. E., Powles, T. and Dowsett, M. (2007) Microarray-based comparative genomic hybridisation of breast cancer patients receiving neoadjuvant chemotherapy. British Journal of Cancer, 96 2: 341-351. doi:10.1038/sj.bjc.6603483


Author Pierga, J-Y.
Reis-Filho, J. S.
Cleator, S. J.
Dexter, T.
MacKay, A.
Simpson, P.
Fenwick, K.
Iravani, M.
Salter, J.
Hills, M.
Jones, C.
Ashworth, A.
Smith, I. E.
Powles, T.
Dowsett, M.
Title Microarray-based comparative genomic hybridisation of breast cancer patients receiving neoadjuvant chemotherapy
Journal name British Journal of Cancer   Check publisher's open access policy
ISSN 0007-0920
1532-1827
Publication date 2007
Sub-type Article (original research)
DOI 10.1038/sj.bjc.6603483
Open Access Status DOI
Volume 96
Issue 2
Start page 341
End page 351
Total pages 11
Editor A. Harris
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2006
Language eng
Abstract We analysed the molecular genetic profiles of breast cancer samples before and after neoadjuvant chemotherapy with combination doxorubicin and cyclophosphamide (AC). DNA was obtained from microdissected frozen breast core biopsies from 44 patients before chemotherapy. Additional samples were obtained before the second course of chemotherapy (D21) and after the completion of the treatment (surgical specimens) in 17 and 21 patients, respectively. Microarray-based comparative genome hybridisation was performed using a platform containing approx5800 bacterial artificial chromosome clones (genome-wide resolution: 0.9 Mb). Analysis of the 44 pretreatment biopsies revealed that losses of 4p, 4q, 5q, 12q13.11–12q13.12, 17p11.2 and 17q11.2; and gains of 1p, 2p, 7q, 9p, 11q, 19p and 19q were significantly associated with oestrogen receptor negativity. 16q21–q22.1 losses were associated with lobular and 8q24 gains with ductal types. Losses of 5q33.3–q4 and 18p11.31 and gains of 6p25.1–p25.2 and Xp11.4 were associated with HER2 amplification. No correlations between DNA copy number changes and clinical response to AC were found. Microarray-based comparative genome hybridisation analysis of matched pretreatment and D21 biopsies failed to identify statistically significant differences, whereas a comparison between matched pretreatment and surgical samples revealed a statistically significant acquired copy number gain on 11p15.2–11p15.5. The modest chemotherapy-driven genomic changes, despite profound loss of cell numbers, suggest that there is little therapeutic selection of resistant non-modal cell lineages.
Keyword Breast cancer
Comparative genomic hybridisation
Microarrays
Neoadjuvant chemotherapy
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2007 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 09:59:49 EST