Biomarker investigations from the ATAC trial: the role of TA01.
cDNA arrays and proteomic analyses have allowed the rapid identification of specific genes and proteins implicated in multiple tumor types. These molecules must then be validated as clinically relevant prognostic and predictive markers, and this translational research is best conducted in the context of clinical trials. Outcomes data and clinical specimens collected in the 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) study, for example, can now be used to compare the expression of biomarkers with clinical outcomes. In this study, adjuvant tamoxifen and anastrozole ('Arimidex') were compared alone and in combination in more than 9000 women with breast cancer. Anastrozole was found to be superior to tamoxifen in terms of disease-free survival, time to recurrence, and reduction in the incidence of contralateral tumors. Importantly, tissue specimens from surgical excision, local relapse, and contralateral breast cancer were collected and paraffin-embedded for storage. In the TA01 (TransATAC) program, these specimens will be studied (after obtaining patient consent) using tissue microarrays; tissue biopsy cores 0.6 mm in diameter will be removed from donor blocks and placed on recipient blocks, which will be sectioned to allow the simultaneous analysis of the same samples for multiple biomarkers. These analyses can help determine differential benefits of treatment with anastrozole or tamoxifen, depending on the expression of particular biomarkers in tumor cells. This research also should clarify de novo and acquired resistance mechanisms, and the validation of relevant molecular pathways could guide the development of new drugs. Ultimately, the TA01 program has the potential to favorably impact treatment choices for breast cancer.
Dowsett
Mitch
M
Academic Biochemistry, The Royal Marsden Hospital, Fulham Road, SW3 6JJ, London, UK. mitch.dowsett@icr.ac.uk
D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009364:Neoplasm Recurrence, Local; D009570:Nitriles / Q000627:therapeutic use*; D020411:Oligonucleotide Array Sequence Analysis; D010347:Patient Care Planning; D011379:Prognosis; D013629:Tamoxifen / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole