Predicting response and resistance to endocrine therapy: profiling patients on aromatase inhibitors.
Selection for endocrine therapy requires the identification of markers that accurately predict response/resistance. In this report, the authors review their published work and abstract results from an unpublished study to illustrate the potential of RNA microarrays from sequential tumor biopsies from patients who were offered neoadjuvant endocrine therapy treatment to identify the molecular signatures associated with tumor sensitivity/resistance. Clinical response was assessed by serial ultrasound measurements in postmenopausal women with large, primary, estrogen receptor-rich breast cancers who received neoadjuvant treatment with letrozole for 3 months. Tumor RNA from biopsies that were taken before and after 14 days of treatment was hybridized on Affymetrix U133A chips to determine expression profiles. Classic estrogen-dependent genes and markers of proliferation were changed with treatment in most tumors but were poorly associated with clinical response (they frequently were changed in letrozole-resistant tumors). Differential expression patterns could be used to identify heterogeneity in clinically resistant tumors. The results indicated that molecular profiling of early changes with letrozole treatment offers the opportunity to distinguish between clinically responsive and nonresponsive tumors and provides important information about the heterogeneity of endocrine resistance.
Miller
William R
WR
Breast Research Group, University of Edinburgh, Edinburgh, United Kingdom.
Larionov
Alexey
A
Breast Research Group, University of Edinburgh, Edinburgh, United Kingdom.
Anderson
Thomas J
TJ
Breast Research Group, University of Edinburgh, Edinburgh, United Kingdom.
Walker
John R
JR
Genomics Institute of the Novartis Research Foundation, San Diego, California.
Krause
Andreas
A
Novartis Pharma AG, Basel, Switzerland.
Evans
Dean B
DB
Novartis Pharma AG, Basel, Switzerland.
Dixon
J Michael
JM
Breast Research Group, University of Edinburgh, Edinburgh, United Kingdom.
D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000627:therapeutic use*; D020411:Oligonucleotide Array Sequence Analysis; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000378:metabolism*; D014230:Triazoles / Q000627:therapeutic use*
D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; D000077289:Letrozole