Anastrozole Reduces Primary Breast Cancer Incidence by More Than 50% in High-Risk Postmenopausal Women


Key Points

  • Five years of anastrozole reduced the risk of primary breast cancer by more than 50% in postmenopausal women at high risk.
  • Anastrozole reduced the risk of estrogen receptor–positive invasive breast cancer by 58%.

Five years of treatment with anastrozole reduced the risk of primary breast cancer by 53% in postmenopausal women at high risk for developing the disease, according to an analysis of the IBIS II trial. Anastrozole reduced the risk of estrogen receptor–positive invasive cancers by 58%. The study was published online in The Lancet to coincide with its presentation at the 2013 San Antonio Breast Cancer Symposium (Abstract S3-01).

“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, MD, of Wolfson Institute of Cancer Prevention at Queen Mary University of London. “We need longer-term follow-up to determine if the preventive effect is sustained after treatment,” he added.

Session moderator Fabrice Andre, MD, Institut Gustave Roussy, Villejuif, France, said he felt that this was too strong a statement to make at this point. Dr. Andre noted that there are other good options for breast cancer prevention that are FDA-approved for this indication, including tamoxifen and raloxifene (Evista).


IBIS-II randomly assigned 3,864 postmenopausal women at high risk of breast cancer (either due to family history, atypia, lobular carcinoma in situ, or breast density) to treatment with anastrozole or placebo for 5 years.

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 anastrozole. Dropouts in the anastrozole group were mostly due to drug-related side effects, Dr. Cuzick noted.

Adverse Events

Bone fractures occurred in 7.7% of those on placebo compared to 8.5% of women receiving 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 10% higher than in the placebo patients. Dr. Cuzick said that at baseline many women in both groups reported joint pains.

“Most of these complaints were not treatment-related. We think it’s clear that 90% of these complaints have nothing to do with the drug,” he stated. Other joint symptoms were also increased in the anastrozole group, including joint stiffness and carpal tunnel syndrome.

A lower incidence of cancers other than breast cancer was noted in the anastrozole group compared to the placebo group (40 cases of other cancers in the anastrozole group vs 70 cases in the placebo group). These were primarily skin cancers and colorectal cancers. Dr. Cuzick noted that the reasons for this effect are unclear but “this was highly significant and merits further study," Dr. Cuzick said, adding that "We also saw this in the exemestane trials.”

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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.