Representation of CYP3A4, CYP3A5 and UGT1A4 Polymorphisms within Croatian Breast Cancer Patients’ Population

Single nucleotide polymorphism (SNP) in genes encoding drug-metabolizing enzymes (DME) could have a critical role in individual responses to anastrozole. Frequency of CYP3A4*1B, CYP3A5*3 and UGT1A4*2 SNPs in 126 Croatian breast cancer (BC) patients and possible association with anastrozole-induced undesirable side effects were analyzed. Eighty-two postmenopausal patients with estrogen receptor (ER)-positive BC treated with anastrozole and 44 postmenopausal ER-positive BC patients before hormonal adjuvant therapy were included in the study. Genomic DNA was genotyped by TaqMan Real-Time PCR. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. The homozygotes for the variant G allele of CYP3A5*3 were predominant (88%), and the homozygotes for the reference A allele were not detected. While homozygotes for the variant G allele of CYP3A4*1B were not detected, predominantly wild type homozygotes for A allele (94%) were present. CYP3A4*1B and CYP3A5*3 SNPs were in 84.3% linkage disequilibrium (D’ = 0.843) and 95.1% (D’ = 0.951) in group treated with anastrozole and w/o treatment, respectively. Homozygotes for the A allele of UGT1A4*2 were not detected in our study groups. Although the variant CYP3A5*3 allele, which might result in poor metabolizer phenotype and more pronounced side effects, was predominant, significant association with BMD changes induced by anastrozole were not confirmed.

Adjuvant Hormone Therapy after Radical Prostatectomy: Indications and Results

Despite recent advances in staging modalities, nearly 30–40% of patients undergoing radical prostatectomy for clinically localized prostate cancer have residual disease. In these cases, one or more of the following conditions may be present: extracapsular disease, positive margins, invasion of the seminal vesicles, lymph node metastases or the postoperative persistence of PSA values above the biological threshold. The optimal management for residual prostate cancer remains controversial and in this setting adjuvant therapy could be appropriate. In the present review we examine the conditions in which hormonal adjuvant therapy can be indicated and the results available from retrospective or non-randomized studies. From the data in the literature and in the absence of randomized prospective studies, prudent conclusions could be drawn on the efficacy of adjuvant hormonal therapy. In cases of small volume, low grade (Gleason score «7) prostate cancer in stage C or D1, radical surgery coupled with adjuvant hormonal therapy leads to survival rates in stage C similar to those in the intraprostatic stage, and in stage D1 with minimal lymph involvement, seems to delay clinical development of metastases. Finally, the quality of life associated with adjuvant therapy and the drug regimens available for this therapy are reviewed.