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


CONCLUSIONS
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.
Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, Lund, Sweden.
K B
KB
Lundin
M
M
Henningson
M
M
Hietala
C
C
Ingvar
C
C
Rose
H
H
Jernström
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005820:Genetic Testing; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000601:surgery; D020641:Polymorphism, Single Nucleotide; D011944:Receptors, Androgen / Q000235:genetics*; D013629:Tamoxifen / Q000627:therapeutic use
C410798:AR protein, human; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; D013629:Tamoxifen