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Androgen receptor genotypes predict response to endocrine treatment in breast cancer patients.

Lundin, Kristina LU ; Henningson, Maria LU ; Hietala, Maria LU ; Ingvar, Christian LU ; Rose, Carsten LU and Jernström, Helena LU (2011) In British Journal of Cancer 105(11). p.1676-1683
Abstract
Background:The androgen receptor (AR) is frequently expressed in breast cancers. The AR genotype may affect disease-free survival and response to endocrine therapy.Methods:In all, 634 women undergoing breast cancer surgery between 2002 and 2008 were followed until 30 June 2010. Six haplotype-tagging single-nucleotide polymorphisms in the AR, and the resulting AR diplotypes, were examined in relation to breast cancer patient characteristics, tumour characteristics, disease-free survival, and response to endocrine treatment.Results:Five common AR diplotypes were found. Seventeen rare variants were combined into a composite group. The resulting six AR diplotype groups were clustered into two subgroups, groups A (n=128) and B (n=499), with... (More)
Background:The androgen receptor (AR) is frequently expressed in breast cancers. The AR genotype may affect disease-free survival and response to endocrine therapy.Methods:In all, 634 women undergoing breast cancer surgery between 2002 and 2008 were followed until 30 June 2010. Six haplotype-tagging single-nucleotide polymorphisms in the AR, and the resulting AR diplotypes, were examined in relation to breast cancer patient characteristics, tumour characteristics, disease-free survival, and response to endocrine treatment.Results:Five common AR diplotypes were found. Seventeen rare variants were combined into a composite group. The resulting six AR diplotype groups were clustered into two subgroups, groups A (n=128) and B (n=499), with three diplotypes in each. Patients in group B had larger total breast volume (P=0.024), higher body mass index (BMI) (P=0.050), more axillary lymph node involvement (P(trend)=0.020), and higher histological grade (P(trend)=0.031). There were 59 breast cancer events in the 569 patients with invasive cancers and no preoperative treatment. Patients in group B also had shorter disease-free survival (P=0.037) than patients in group A. Among patients in group B with oestrogen receptor α positive tumours, tamoxifen (TAM) treatment was associated with longer disease-free survival (P=0.008), while treatment with aromatase inhibitors (AIs) was not (P=0.94). Response to endocrine treatment could not be predicted based on BMI, suggesting that the effect of AR diplotypes went beyond that of a higher BMI.Conclusion:A marker for a group of patients who responded to TAM, but not to AIs, was identified. If this finding is confirmed, AR genotyping may provide useful information for selection of endocrine treatment of breast cancer patients.British Journal of Cancer advance online publication, 27 October 2011; doi:10.1038/bjc.2011.441 www.bjcancer.com. (Less)
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Contribution to journal
publication status
published
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in
British Journal of Cancer
volume
105
issue
11
pages
1676 - 1683
publisher
Nature Publishing Group
external identifiers
  • wos:000297687600010
  • pmid:22033271
  • scopus:81955167440
ISSN
1532-1827
DOI
10.1038/bjc.2011.441
language
English
LU publication?
yes
id
6dc1681a-73a3-42b2-94f2-e8ce54ae8e1b (old id 2200097)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22033271?dopt=Abstract
date added to LUP
2011-11-02 21:39:32
date last changed
2017-04-02 03:01:15
@article{6dc1681a-73a3-42b2-94f2-e8ce54ae8e1b,
  abstract     = {Background:The androgen receptor (AR) is frequently expressed in breast cancers. The AR genotype may affect disease-free survival and response to endocrine therapy.Methods:In all, 634 women undergoing breast cancer surgery between 2002 and 2008 were followed until 30 June 2010. Six haplotype-tagging single-nucleotide polymorphisms in the AR, and the resulting AR diplotypes, were examined in relation to breast cancer patient characteristics, tumour characteristics, disease-free survival, and response to endocrine treatment.Results:Five common AR diplotypes were found. Seventeen rare variants were combined into a composite group. The resulting six AR diplotype groups were clustered into two subgroups, groups A (n=128) and B (n=499), with three diplotypes in each. Patients in group B had larger total breast volume (P=0.024), higher body mass index (BMI) (P=0.050), more axillary lymph node involvement (P(trend)=0.020), and higher histological grade (P(trend)=0.031). There were 59 breast cancer events in the 569 patients with invasive cancers and no preoperative treatment. Patients in group B also had shorter disease-free survival (P=0.037) than patients in group A. Among patients in group B with oestrogen receptor α positive tumours, tamoxifen (TAM) treatment was associated with longer disease-free survival (P=0.008), while treatment with aromatase inhibitors (AIs) was not (P=0.94). Response to endocrine treatment could not be predicted based on BMI, suggesting that the effect of AR diplotypes went beyond that of a higher BMI.Conclusion:A marker for a group of patients who responded to TAM, but not to AIs, was identified. If this finding is confirmed, AR genotyping may provide useful information for selection of endocrine treatment of breast cancer patients.British Journal of Cancer advance online publication, 27 October 2011; doi:10.1038/bjc.2011.441 www.bjcancer.com.},
  author       = {Lundin, Kristina and Henningson, Maria and Hietala, Maria and Ingvar, Christian and Rose, Carsten and Jernström, Helena},
  issn         = {1532-1827},
  language     = {eng},
  number       = {11},
  pages        = {1676--1683},
  publisher    = {Nature Publishing Group},
  series       = {British Journal of Cancer},
  title        = {Androgen receptor genotypes predict response to endocrine treatment in breast cancer patients.},
  url          = {http://dx.doi.org/10.1038/bjc.2011.441},
  volume       = {105},
  year         = {2011},
}