Current status of aromatase inhibitors in the management of breast cancer and critique of the NCIC MA-17 trial.
BACKGROUND
The third-generation aromatase inhibitors reduce circulating estrogen levels in postmenopausal women and are well tolerated orally for breast cancer. Their role in the management of advanced breast cancer has already been recognized. This article reviews the evidence for their role in the adjuvant treatment of early-stage disease.


METHODS
Three large multicenter trials are reviewed. The ATAC trial compared anastrozole and tamoxifen or a combination of the two, for 5 years from the point of diagnosis. The NCIC trial published the results of letrozole compared with placebo after the completion of 5 years of tamoxifen. Most recently, the Intergroup Exemestane Study reported a comparison of 5 years of tamoxifen vs 2 years of tamoxifen followed by 3 years of exemestane.


RESULTS
The aromatase inhibitor arm in each of these studies was associated with improved disease-free survival and good tolerability. Because of the three different settings, cross-trial comparisons of the different aromatase inhibitors are impossible, but in each case the novel therapy appears promising.


CONCLUSIONS
This review is critical of the early stopping of the NCIC study and recommends more mature follow-up in each case until distant disease-free or overall survival rates can be measured and then correlated with adverse events. The late onset of osteoporotic fractures is a concern that must be addressed before tamoxifen can be abandoned in favor of the aromatase inhibitor in each of the three clinical points: at diagnosis, at midway through a course of tamoxifen, and as an extension to the conventional 5-year period of endocrine therapy.
University College London, The Portland Hospital, London, UK. michael@mbaum.freeserve.co.uk
Michael
M
Baum
D000077384:Anastrozole; D000730:Androstadienes / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D016889:Endometrial Neoplasms / Q000139:chemically induced; D005260:Female; D019584:Hot Flashes / Q000139:chemically induced; D006801:Humans; D000077289:Letrozole; D015337:Multicenter Studies as Topic; D009570:Nitriles / Q000627:therapeutic use; D012107:Research Design; D020521:Stroke / Q000139:chemically induced; D013629:Tamoxifen / Q000627:therapeutic use; D013923:Thromboembolism / Q000139:chemically induced; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use; D014592:Uterine Hemorrhage / Q000139:chemically induced; D019522:Vaginal Discharge / Q000139:chemically induced
D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole; D000077289:Letrozole; C056516:exemestane