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

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 (Ptrend=0.020), and higher histological grade (Ptrend=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.

Given breast cancer, does breast size matter? Data from a prospective breast cancer cohort

“…A recent report from a subset of the current patient cohort, showed that certain androgen receptor (AR) genotypes were associated with significantly larger breast size, but not with increased WHR. These AR genotypes were also significantly associated with shorter disease-free survival (47 (9). In Enger's study, only 73% of the tumors were ER-positive compared to over 85% in Lund.…”

Age at first childbirth and oral contraceptive use are associated with risk of androgen receptor-negative breast cancer: the Malmö Diet and Cancer Cohort

“…Other preclinical data showed that AR blocks ERstimulated growth in breast cancer cells (6) and that overexpression of AR decreased ER transcriptional activity (48). Whether different AR genotypes are reflected in AR expression in breast tumors is unknown, but we have recently reported on AR genotypes predicting response to TAM treatment (49). The treatment predictive value of tumor-specific AR expression has been addressed in endocrine-treated cohorts, demonstrating high AR expression to be a predictive factor for response to endocrine treatment (10).…”

Combined Androgen and Estrogen Receptor Status in Breast Cancer: Treatment Prediction and Prognosis in a Population-Based Prospective Cohort

“…In a previous study, we reported a treatment predictive value of AR genotyping for adjuvant TAM, but not for AIs (9). In this study, we hypothesized that the prognostic value of tumor AR expression may depend on ER status and have predictive value for endocrine treatment response.…”

“…Information on breast cancer events and date of death was obtained from patient charts, the regional tumor registry, and the population registry. Genotyping of the six haplotypes tagging single nucleotide polymorphisms in the AR (rs1337080, rs17302090, rs6152, rs7061037, rs5031002, and rs5964607) was done as previously described (9).…”