Genesis and Outcome of a Breast Cancer Trial to Develop the Aromatase Inhibitor Anastrozole

Featured Article: Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, ATAC Trialists' Group. Lancet 2005;365:60–2.2Aromatase inhibitors block the enzyme aromatase, which is responsible for conversion of the adrenal derived precursor, androstenedione, to estrogen in tissues such as fat, muscle, and in the breast in postmenopausal women. Estrogens drive the proliferation and metastasis of estrogen receptor positive breast cancer (about 70% of the total). In the mid 20th century bilateral adrenalectomy was used to reduce postmenopausal estrogens but this major operation was replaced by use of the adrenal steroid hormone synthesis inhibitor, aminoglutethimide, although corticosteroid replacement had to be used. Aromatase inhibitors were the real advance, and the introduction of a simple once per day pill in the 1990s (1) lead the way to evaluation of their value, first in advanced breast cancer against standard therapy of tamoxifen …