The most common cancer in women

Breast cancer is the most common cancer in women in the United States, with incidence increasing about 0.5% per year. In the year 2004, an estimated 215,900 new cases of invasive breast cancer (stages I-IV) will be diagnosed, and about 40,100 women and 470 men will die of the disease.' New strategies to decrease the risk of breast cancer are being studied and implemented. Although breast cancer is a leading cause of death in women (second only to lung cancer), mortality rates have declined recently. This reduction in mortality, despite the increase in incidence, is attributed to improvements in screening, diagnosis, and treatment.

Aromatase Inhibitors (AIs) are a new class of hormonal therapies for breast cancer treatment. They work by blocking the conversion of the enzyme aromatase, found in fatty tissue, which is the main source of oestrogen in the post-menopausal woman, whose ovaries have stopped functioning. With less oestrogen available, the growth of oestrogen-sensitive cancer cells are slowed down or stopped, and tumour size may reduce. AIs have been shown to be effective in reducing the risk of a recurrence in postmenopausal women with hormone sensitive early breast cancer (ATAC Trialists' Group, 2005). These agents, anastrozole, exemestane, and letrozole, have been shown in several robust clinical studies to be more efficacious and better tolerated than tamoxifen (Houghton, 2005).

AIs may be used in several settings:

• Preoperatively to shrink tumours and render them amenable to surgery

• Postoperatively (adjuvant treatment), either alone or following 2-3 years of tamoxifen therapy

• As 'extended adjuvant' treatment (5 years of AI following 5 years of tamoxifen therapy). Letrozole has a licence for use in the neoadjuvant setting, and anastrozole and letrozole have both been shown in trials (Thurlimann, 2005) to be effective as first-Hne endocrine agents when used in the adjuvant setting. Anastrozole and exemestane have also been shown to be effective after 2-3 years of tamoxifen therapy (Boccardo, 2003). Anastrozole is currently the only AI licensed for first-line use in the adjuvant treatment of postmenopausal women with hormone receptor-positive early-invasive breast cancer. However, letrozole is awaiting a licence in this setting, following the 2.6% disease-free survival rate found at 5 years from the Breast International Group 1-98 trial — a head-tohead comparison of letrozole and tamoxifen, either alone or in sequence, as initial therapy (Thurhmann, 2005).

The 5-year results of the ATAC study show that, when compared with tamoxifen, anastrozole offers an additional 26% reduction in the risk of breast cancer recurrence anywhere in the body. A new analysis from the ATAC trial, presented at the American Society of Clinical Oncology in June, demonstrated that the risk of breast cancer recurrence reaches its peak in the first 2 years after a patient undergoes surgery — a risk reduced significantly among those women treated with anastrozole immediately after surgery. Exemestane is currently awaiting a licence for use specifically after 2—3 years tamoxifen therapy. This is based on data from the Intergroup Exemestane Study (IES) trial, in which women who were recurrence-free after 2-3 years of tamoxifen were randomized to receive a further 2-3 years of exemestane or tamoxifen to complete 5 years of treatment. Switching to exemestane led to a 32% reduction in the risk of recurrence at 3 years when compared with continued tamoxifen (Coombes et al, 2004). Letrozole is licensed for postadjuvant (extended adjuvant) use following standard tamoxifen therapy as a result of the A4A17 trial (Goss, 2004), (92 recurrences in the letrozole arm compared with 155 in the placebo arm).

Last updated Jan 4/07