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, 105 (11), 1676-83

Androgen Receptor Genotypes Predict Response to Endocrine Treatment in Breast Cancer Patients

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Androgen Receptor Genotypes Predict Response to Endocrine Treatment in Breast Cancer Patients

K B Lundin et al. Br J Cancer.

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.

Figures

Figure 1
Figure 1
Frequencies of AR SNPs and diplotypes among 627 women diagnosed with breast cancer. Genotypes and frequencies are presented for each SNP. Diplotypes present in <1% of the patients were clustered together into a composite group of rare diplotypes. Seven patients were missing due to failed SNP analysis.
Figure 2
Figure 2
Flowchart displaying patient selection for the different analyses.
Figure 3
Figure 3
(A) Kaplan–Meier survival analysis of disease-free survival with respect to AR diplotypes. (B) Disease-free survival in group A and group B. Group A includes patients with AR diplotypes GGAAGC/AAGAGT, GGAAGC/GGAAAC, or rare diplotypes. Group B includes patients with AR diplotypes GGAAGC/GGAAGC, GGAAGC/GAGGGT, or GGAAGC/GGAAGT.
Figure 4
Figure 4
Disease-free survival in group B patients who had ER-positive tumours and who had not received chemotherapy. (A) Patients treated with TAM. (B) Patients treated with AI.

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