The aromatase inhibitor anastrozole reduced the risk for breast cancer by 53% among postmenopausal women at high-risk for the disease, according to trial results presented at SABCS.
SAN ANTONIO-The aromatase inhibitor anastrozole reduced the risk for breast cancer by 53% among postmenopausal women at high-risk for the disease, according to first results of the International Breast Cancer Intervention Study II (IBIS-II) presented at the 2013 San Antonio Breast Cancer Symposium and published simultaneously online in the Lancet.
At 7 years, breast cancer incidence was 5.6% among women assigned to placebo compared with 2.8% for women assigned anastrozole (HR = 0.47; 95% CI, 0.32-0.68; P < .0001). Among women with estrogen-receptor-positive tumors, there was a 58% reduction in incidence from 3.3% for placebo to 1.4% for anastrozole (HR = 0.42; 95% CI, 0.25-0.71; P = .001).
Based on these results, Jack Cuzick, PhD, chairman of the IBIS-II Steering Committee and head of the Cancer Research UK Centre for Cancer Prevention, said that anastrozole should be the treatment of first choice for these patients compared with other preventive therapies such as selective estrogen-receptor modulators or tamoxifen.
“Aromatase inhibitors show better effectiveness than SERMs and they show better effectiveness than tamoxifen or raloxifene, and overall serious side effects are substantially less,” Cuzick said. “For that reason we think they are the appropriate first choice.”
However, Cuzick also added that long-term follow-up would be essential in painting the full picture of the risks and benefits of anastrozole.
The IBIS II trial enrolled 3,864 postmenopausal women considered to be at high risk for breast cancer. High-risk criteria included having two or more blood relatives with breast cancer, having a mother or sister who developed breast cancer before age 50 years, and having a mother or sister who had breast cancer in both breasts. Women were randomly assigned to treatment with anastrozole (n = 1,920) for 5 years or placebo (n = 1,944).
Only a four percentage point difference in compliance was found between treatment arms, with 72% compliance in the placebo arm compared with 68% in the anastrozole arm. In addition to the overall risk reductions, the researchers found risk reductions for women with ductal carcinoma in situ (HR = 0.30) and all invasive cancers (HR = 0.50).
Although researchers were concerned that anastrozole would increase bone fracture rates, safety analyses showed only a small, nonsignificant increase in total number of fractures (8.5% vs 7.7%). Researchers also found a significant 10% increase in musculoskeletal aches and pains (63.9% vs 57.6%), a common reason for drug discontinuation.
“The striking finding is that there were extremely high rates of musculoskeletal pain in the placebo arm,” Cuzick said. “About 90% of aches and pains had nothing to do with the drug.”
Interestingly, patients in the anastrozole arm also had significantly lower rates of other cancers, specifically, lower rates of gastrointestinal cancers (P = .05) and skin cancers (P = .07).
In an editorial comment published with the trial in the Lancet, David A. Cameron, MD, of Edinburgh Cancer Centre, United Kingdom, questioned the strength of the study’s findings. One question always surrounding prevention trials is whether the intervention is preventing “clinically significant, life-threatening breast cancers,” or “early treatment of tumors overdiagnosed by intrinsic screening programs,” he wrote.
“The consistent finding of an increased effect of prevention therapy on hormone receptor–positive tumors supports the prediction made by modeling data that pharmacological prevention of breast cancer is actually early treatment of subclinical tumors,” Cameron wrote. “With two-thirds of the anastrozole benefit in screen-detected cancers … the likelihood of an eventual breast cancer mortality benefit seems small.”
Therefore, it may be difficult to convince women to take anti-estrogen therapy for 5 years knowing that there may be little benefit to their overall survival, especially given the toxicity, Cameron wrote.
However, Cuzick supported the drive to educate women that this is an effective way to reduce risk for breast cancer by more than 50%, and added that if toxicities, which are limited, are too much, patients can simply stop treatment.
Cuzick is on the speaker’s bureau for AstraZeneca and his institute has received grant support from AstraZeneca, Sanofi-Aventis, and Cancer Research UK.