Androgen receptor status predicts response to chemotherapy, not risk of breast cancer in Indian women

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.

Complexities of androgen receptor signalling in breast cancer

“…In cohorts not selected on the basis of estrogen receptor-a (ERa (ESR1)) status, AR positivity has been associated with longer relapse-free, metastasis-free and overall survival, smaller tumour size and lower histological grade (Bryan et al 1984, Langer et al 1990, Kuenen-Boumeester et al 1992, Soreide et al 1992, Schippinger et al 2006, Agrawal et al 2008, Gonzalez et al 2008, Hanley et al 2008, Ogawa et al 2008, Soiland et al 2008, Park et al 2010, Yu et al 2011, Peters et al 2012, Honma et al 2013. High AR levels have also been associated with a favourable response to chemotherapy and hormonal therapy, including antioestrogens, aromatase inhibitors and progestins (Teulings et al 1980, Bryan et al 1984, Birrell et al 1995, Agrawal et al 2008, Chintamani et al 2010, Chanplakorn et al 2011, Loibl et al 2011. Importantly, AR has also been shown to be an independent predictor of relapse-free, metastasis-free and/or overall survival in some studies (Soreide et al 1992, Gonzalez et al 2008, Soiland et al 2008, Yu et al 2011.…”

The CAG repeat polymorphism of the androgen receptor gene and breast cancer

“…Many authors [15][16][17][18][19][20][21][22][23][24][25][26] have found no relationship between the number of CAG repeats in the androgen Table 4. Association of CAG repeat genotypes and alleles in the AR gene with the clinical-pathological parameters of breast cancer.…”

Evaluation and Validation of Neo-Adjuvant Response Index (NRI) and It’s Correlation with Various Predictive Biomarkers and RECIST in Locally Advanced Breast Cancer

“…Decrease in mRNA levels of Androgen Recepator (AR) gene related to the chemotherapyinduced apoptosis could serve as an important independent predictor of response to NACT. The AR may thus serve as an important independent predictor of response to NACT and may help in tailoring of the regime for a particular patient.AR appears as a promising predictive biomarker for assessing response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer [25] Immunohistochemical AR expression was evaluated on a tissue microarray of 673 core biopsies from primary breast cancer patients treated with neoadjuvant docetaxel/ doxorubicin/cyclophosphamide (TAC) chemotherapy in the prospective GeparTrio phase-III trial. AR was detected in 53.2 % of tumors while it was detected in 13.33 % tumors in the present study.…”