Postmenopausal women at increased risk of breast cancer are half as likely to develop the cancer after a five-year treatment with Arimidex (anastrozole), compared to a placebo, and this reduced likelihood holds for up to seven years after stopping the therapy, a long-term follow-up study has found.
The findings suggest that Arimidex is a better preventive treatment for postmenopausal women than tamoxifen — which reduces cancer rates by 29% — and could replace it as the standard approach for this indication.
The study, “Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial,” was published in The Lancet and simultaneously presented at the 2019 San Antonio Breast Cancer Symposium, in Texas.
Because exposure to estrogen in postmenopausal women increases the risk of breast cancer, those at high risk are often offered preventive treatments that delay or prevent cancer from developing.
Preventive therapies such as tamoxifen — a hormone therapy that blocks the action of estrogen by binding to the estrogen receptor — have been shown to reduce about one-third of breast cancers in long-term studies.
Arimidex, by AstraZeneca, is also a hormonal therapy, but prevents the effects of estrogen in a different way. It is an aromatase inhibitor that blocks the production of estrogen by inhibiting aromatase, an enzyme necessary for this process.
In 2013, researchers in the U.K. showed that five-year treatment with Arimidex reduced the incidence of all breast cancers by 53% compared to a placebo.
The Phase 3 clinical trial — called International Breast Cancer Intervention Study II (IBIS-II) (NCT00078832) — included 3,864 postmenopausal women from 40 to 70 years old. After five years, 40 women taking Arimidex (2%) developed breast cancer compared to 85 women (4%) in the placebo group.
Despite these results, the long-term impact of Arimidex therapy had not been assessed, and due to this uncertainty, this therapy is not offered to all women who could benefit.
Thus, the team continued to follow the trial participants for an additional seven years after treatment was stopped, and collected information every year on breast cancer incidence, death, other cancers, and major adverse events, such as bone fractures or cardiovascular problems.
After a 12-year follow-up, a total of 250 breast cancers were reported. Of these, 165 women in the placebo group developed breast cancer (8.5%) compared to 85 women taking Arimidex (4.4%) — representing a significant 49% reduction in all breast cancers.
Specifically, this reduction was seen in women with estrogen receptor-positive cancers, where a 54% reduction in breast cancer was found. Arimidex therapy also led to a significant 59% reduction in ductal carcinoma in situ (cancer of the milk ducts) regardless of their estrogen receptor status.
These results were independent of whether cancers were positive for human epidermal growth factor receptor 2 (HER-2) or not, with Arimidex preventing both types.
“Previous research has confirmed that [Arimidex] is very effective while women are still taking the drug but this is the only trial looking at whether it offers long term protection for women at high risk of developing breast cancer,” lead author of the study, Jack Cuzick, PhD, of Queen Mary University of London, and co-chairman of IBIS, said in a press release. “After a detailed analysis of the IBIS-II data, we have concluded that it is highly effective in reducing breast cancer occurrence for at least 12 years.”
In addition, during the first five years of treatment, nearly 80% of women continued to take Arimidex which indicated that the therapy was well-tolerated. While there was a small non-significant increase in the number of adverse events during the treatment period, a small reduction was reported after treatment.
Overall, no major adverse events were reported, with no increased risk of fracture or cardiovascular problems from Arimidex therapy.
During the study, 139 women died: 69 on Arimidex therapy and 70 in the placebo group. Of these, three women taking Arimidex died of breast cancer compared to two women in the placebo group.
While this may suggest that Arimidex did not prevent breast cancer deaths, the numbers are small and according to the researchers, “it is too early to expect an effect on this outcome, which is a limitation of this analysis.”
“The findings mean that for every 29 women taking anastrozole for five years, one case of breast cancer will be prevented during a 12-year period,” said study co-author Ivana Sestak, PhD, reader in medical statistics at Queen Mary. “Around 49 women would need to take tamoxifen for five years to prevent one breast cancer case during the same period.”
Cuzick added: “This is an exciting finding which makes a strong case for anastrozole being the drug of choice for post-menopausal women at high risk of developing breast cancer. Tamoxifen could be offered to the relatively few women who experience serious side-effects from anastrozole.”
The study was funded by Cancer Research UK, the National Health and Medical Research Council Australia, Sanofi-Aventis, and AstraZeneca.