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


METHODS
Genotyping 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).


CONCLUSIONS
Although, 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.
Chintamani
Department of Surgery, Indian Council Of Medical Research, New Delhi, India. chintamani7@rediffmail.com
Kulshreshtha
Pranjal
P
Chakraborty
Anurupa
A
Singh
Lc
L
Mishra
Ashwani K
AK
Bhatnagar
Dinesh
D
Saxena
Sunita
S
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D007194:India / Q000453:epidemiology; D020360:Neoadjuvant Therapy; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies
C410798:AR protein, human; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm; D011944:Receptors, Androgen