Five years of treatment with anastrozole reduced the risk of breast cancer by 53% in postmenopausal women at high risk for developing the disease, according to an analysis of the International Breast Cancer Intervention Study (IBIS)-II trial. Anastrozole reduced the risk of estrogen receptor–positive invasive cancers by 58%. The study was published online in The Lancet1 to coincide with its presentation at the 2013 San Antonio Breast Cancer Symposium.2
“We believe these results provide strong support for prevention of breast cancer in high-risk [postmenopausal] women. We think anastrozole should be the first choice for this indication,” said lead author Jack Cuzick, PhD, of Wolfson Institute of Cancer Prevention at Queen Mary University of London. “The effect of tamoxifen is sustained for at least 10 years. We need longer-term follow-up to determine if the preventive effect of anastrozole is sustained after treatment.”
Session moderator Fabrice André, MD, PhD, Institut Gustave Roussy, Villejuif, France, said he felt that this was too strong a statement to make at this point and that additional evidence is needed before implementing this research finding. Dr. André noted that there are other good choices for prevention that are U.S. Food and Drug Administration–approved for this indication, including tamoxifen and raloxifene (Evista).
IBIS-II Details
The international, double-blind, placebo-controlled IBIS-II randomly assigned 3,864 postmenopausal women at high risk of breast cancer (due to family history, atypia, or lobular carcinoma in situ, or breast density) to treatment with anastrozole or placebo for 5 years. The study recruited women aged 40 to 70 years at 153 centers in 18 countries.
Median age was 59.5 years, and 695 women (18%) were older than age 65; one-third had body mass index > 29; and 47% previously used hormone replacement therapy. The vast majority of high-risk women had a family history of breast cancer; 50% had at least two family members with breast or ovarian cancer, 35% had one first-degree relative with breast cancer aged 50 years or younger, 9% had one first-degree relative with bilateral breast cancer, and 16% had lobular carcinoma in situ or estrogen receptor–positive ductal carcinoma in situ.
At a median follow-up of 5 years, breast cancer occurred in 40 women in the anastrozole group (2%) and 85 (4%) in the placebo group. The predicted cumulative incidence of primary breast cancers (including ductal carcinoma in situ) occurring at 7 years of follow-up was 5.6% of women in the placebo group vs 2.8% of the anastrozole group, representing a 53% decrease in risk (P < .0001).
Estrogen receptor–positive invasive breast cancers developed in 3.3% of the placebo group vs 1.4% of the anastrozole group, representing a 58% decrease in risk (P = .001). No effect of anastrozole was seen in estrogen receptor–negative tumors, Dr. Cuzick said.
Five years of treatment were completed by 72% of placebo patients and 68% of those taking anastozole, Dr. Cuzick noted. “An important finding was the high percentage of side effects that occurred in the placebo arm. In uncontrolled situations, they would likely be linked to the treatments,” Dr. Cuzick said.
Adverse Events
Bone fractures were increased from 7.7% with placebo to 8.5% with anastrozole. Dr. Cuzick noted that all participants had a dual x-ray absorptiometry scan upfront and osteoporotic women were given bisphosphonate treatment, which could account for a smaller-than-expected incidence of musculoskeletal/fracture side effects.
Musculoskeletal aches and pains were the most common adverse events in the anastrozole group and were reported in significantly more women given the aromatase inhibitor than in placebo recipients: (64% vs 58%, P = .0001). This difference between the two treatment arms was driven mostly by moderate arthralgia, noted Dr. Cuzick. Other joint symptoms were also increased in the anastrozole group, including joint stiffness and carpal tunnel syndrome.
Other side effects more frequently seen in the anastrozole group were dry eye and vasomotor symptoms.
Thirty-five deaths were recorded by data cutoff (May 2013). Only two were breast cancer–related, and these occurred in the anastrozole group.
Unexpectedly, the incidence of other cancers was reduced from 70 (4%) in the placebo group to 40 (2%) in the anastrozole group. These were primarily skin cancers and colorectal cancers.
“This was highly significant and merits further study,” Dr. Cuzick said. ■
Disclosure: The study was funded by Cancer Research UK, the National Health and Medical Research Council of Australia, AstraZeneca, and Sanofi-Aventis. Dr. Cuzick is on the speaker’s bureau for AstraZeneca. Dr. André has received research grants from Novartis.
References
2. Cuzick J, Sestak I, Forbes JF, et al: First results of the International Breast Cancer Intervention Study II (IBIS-II): A multicentre prevention trial of anastrozole versus placebo in postmenopausal women at increased risk of developing cancer. 2013 San Antonio Breast Cancer Symposium. Abstract S3-01. Presented December 12, 2013.
