Abstract
BackgroundConsiderably little is known about the biological role and clinical significance of androgen receptor expression in breast cancer. The objectives of this study were to characterize AR-CAG repeat genotypes in a cohort of women with breast cancer and to determine the influence of AR on response to neoadjuvant chemotherapy and clinical outcome.Materials and methodsGenotyping of the AR CAG repeat region was done on 70 patients and 80 healthy aged- matched female controls. To assess response to NACT, tissue samples from 30 LABC cases were evaluated quantitatively by real time for AR mRNA expression. The clinical response was correlated with both the pre and post chemotherapy AR expression. The CAG alleles did not show differences between cases and controls when the mean of short, long and average length of both CAG alleles was considered. However, analysis when done defining short allele as CAGn < 20 (AR1) and the long as CAGn ≥ 20 (AR2), risk was found associated with AR2 allele with marginal significance (P = 0.09). Stratification by age of onset, FH, stage, grade ER and AR status failed to reveal any association with breast cancer risk. Genotype carriers with ≥20 CAGn showed decrease of AR mRNA expression although significance could not be established (P = 0.47). Tumours in responders had the higher AR mRNA expression levels in pre neo-adjuvant chemotherapy condition (p < 0.02) which got reduced after neoadjuvant chemotherapy and the difference was found to be significant (P = 0.014).ConclusionsAlthough, expansion of the CAGn in the AR gene doesn't show any major effect on breast cancer risk, patients with positive AR expression, pre neoadjuvant chemotherapy, were found to be good responders and a decrease in mRNA level of AR gene related to the chemotherapy-induced apoptosis could serve as an important independent predictor of response to NACT.
Highlights
Breast cancer is one of the most frequent malignancies amongst women across the world, as well as in India [1]
Conclusions: expansion of the CAGn in the AR gene doesn’t show any major effect on breast cancer risk, patients with positive AR expression, pre neoadjuvant chemotherapy, were found to be good responders and a decrease in mRNA level of AR gene related to the chemotherapy-induced apoptosis could serve as an important independent predictor of response to NACT
For the study subject the size of the Correlation between AR mRNA Expression and (CAGn) Length Polymorphism To investigate the influence of CAG repeat length polymorphism on AR mRNA level in breast cancer, total RNA from breast tumour samples were reversed transcribed to cDNAs and nAR values were estimated, simultaneously from the same samples which were used for the genotyping of CAG repeat length
Summary
Breast cancer is one of the most frequent malignancies amongst women across the world, as well as in India [1]. Results from recent clinical trials with aromatase inhibitors, agents that suppress estrogen synthesis through peripheral aromatization, in postmenopausal women with ER- or progesterone-receptor-positive breast cancer reinforce the importance of estrogen in breast-cancer growth. Several large, randomized trials have compared aromatase inhibitors with tamoxifen in postmenopausal women with early or advanced steroid-receptor-positive breast cancer (Yager and Davidson 2006). Polymorphisms in AR-CAG repeat have been intensively studied as determinant of susceptibility to prostate cancer in Indian population [8,9] ; its association with breast carcinoma in Indian population is not yet explored. The objectives of this study were to characterize AR-CAG repeat genotypes in a cohort of women with breast cancer and to determine the influence of AR on response to neoadjuvant chemotherapy and clinical outcome
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