Abstract
In the IBIS II Prevention Study, postmenopausal women at high risk of breast cancer given the aromatase inhibitor anastrozole were 53% less likely to develop the disease after 10 years than women who took placebo.
Taking the aromatase inhibitor anastrozole (Arimidex; AstraZeneca) may significantly cut the risk of breast cancer in postmenopausal women at high risk of the disease, according to results from the IBIS II Prevention Study presented at the San Antonio Breast Cancer Symposium in San Antonio, TX, on December 12.
The study randomly assigned 3,864 women with a family history of breast cancer or genetic risk factors, including BRCA1/2 mutations, to receive either anastrozole or a placebo for 5 years. After an additional 5 years, women who took anastrozole were 53% less likely to develop breast cancer than women who took a placebo.
Although not everyone at the symposium agreed, “Anastrozole should be the first treatment of choice for breast cancer prevention in the postmenopausal setting,” said the study's principal investigator, Jack Cuzick, PhD, head of the Centre for Cancer Prevention at Queen Mary University of London, UK. “It's the most effective drug with the fewest side effects.”
IBIS II was launched in 2003 after results from the international Arimidex, Tamoxifen, Alone or in Combination (ATAC) study showed that anastrozole treatment for estrogen receptor–positive breast cancer is more effective than tamoxifen at preventing not just tumor recurrence, but also the future development of tumors in the second breast. The prevention of contralateral tumors serves as a surrogate for primary prevention of breast cancer.
Both tamoxifen and anastrozole block estrogen, but in different ways. Tamoxifen blocks the estrogen receptor in cancer cells, while anastrozole and other aromatase inhibitors block estrogen synthesis. Along with raloxifene, an osteoporosis treatment, tamoxifen is one of only two drugs approved in the United States to reduce the risk of breast cancer.
Tamoxifen can't block estrogen binding completely, but anastrozole significantly reduces local production of the hormone, said Cuzick. Importantly, anastrozole blocks the synthesis of only non-ovarian estrogen, explaining why it's most effective in postmenopausal women.
The ATAC trial also showed that anastrozole decreases bone density, increasing fracture risk. Therefore, all participants in the IBIS II study underwent bone-density scans at enrollment; those with very low bone density received a bisphosphonate, and those whose bone density wasn't low enough to warrant osteoporosis treatment were monitored and given a bisphosphonate as needed. With these precautionary measures, fracture risk was virtually eliminated, Cuzick said.
Moreover, the musculoskeletal aches typically associated with aromatase inhibitors were nearly equivalent—64% in the anastrozole arm compared with 58% in the placebo arm. According to Cuzick, this suggests that age—which was a median of 59 years at the time of enrollment—more than anastrozole, is the likely cause of these symptoms.
Per Hall, PhD, a professor in biostatistics and epidemiology at the Karolinska Institute in Stockholm, Sweden, who was not associated with the study, agreed that anastrozole can safely reduce breast cancer risk in postmenopausal women.
Still, Hall emphasized that chemoprevention, a strategy pursued by only 10% to 15% of eligible women in the United States and Europe, faces widespread ambivalence. “Doctors aren't used to the concept of reducing cancer risk with medications, even though they have no problem treating patients with statins and calcium channel blockers for hypercholesterolemia and hypertension,” he said.
