Long-Term Follow-Up Supports Anastrozole Treatment to Prevent Breast Cancer Recurrence

Five years of treatment with anastrozole (Arimidex) safely and effectively prevented breast cancer recurrence in high-risk postmenopausal women at 10.9 years of follow-up, according to data from the International Breast Cancer Intervention Study II (IBIS-II) Prevention trial presented at the San Antonio Breast Cancer Symposium, held December 10-14, in San Antonio, Texas.¹

“These data provide further support for the use of anastrozole in breast cancer prevention in high-risk women. It has been recommended by NICE and the United Kingdom National Institute of Excellence, and the US Preventive Task Force in the United States,” Jack Cuzick, PhD, co-chairman of the International Breast Cancer Intervention Studies, said during a press briefing held at the conference. 

In total, 3,864 postmenopausal women at increased risk for developing breast cancer¾including those who had 2 or more blood relatives with breast cancer, a mother or sister who developed breast cancer before the age of 50, or a mother or sister who had breast cancer in both breasts¾were enrolled in the IBIS-II Prevention study from 2003 to 2012. 

The follow-up entailed clinic visits, questionnaires, and registry data.

Patients were randomized to receive either 1 mg/day of anastrozole for 5 years (n = 1,920) or placebo (n = 1,944). Five-year adherence to treatment was 74.6% for anastrozole and 77.0% for placebo, which was not significantly different. Cuzick attributed the slightly lower adherence to the adverse events (AEs) experienced by patients.

The updated results were also simultaneously published in the Lancet.²

After the 10.9-year follow-up, women’s chance of having their breast cancer recur was reduced by 50%, compared with those who received placebo. This is slightly less than the 53% reduction seen in results presented after the first 7 years following treatment.³ However, Cuzick explained, 1 way to still show this reduction is significant is its translation into an estimated 29 women needing to be treated with anastrozole for 5 years to prevent 1 breast cancer during treatment and in the next 5 years.

The reduction was larger in the first 5 years after treatment (HR, 0.39; 95% CI, 0.27–0.58; P < ·0001); however, a substantial reduction of 36% was seen in the post-treatment period (HR, 0.64; 95% CI, 0.45–0.91; P = 0.014), which is still larger than tamoxifen. “This is substantial information about the long-term data, which is particularly relevant because tamoxifen has been looked at and has been shown that the 30% reduction you get with tamoxifen for 5 years is maintained for at least 20 years, so that is a crucial question for the aromatase inhibitor,” said Cuzick, who is also director of the Wolfson Institute of Preventive Medicine, head of the Centre for Cancer Prevention, and the John Snow Professor of Epidemiology at Queen Mary University of London.

Moreover, invasive estrogen receptor (ER)-positive breast cancer was reduced by 54% (HR, 0.46; 95% CI, 0.33–0.65, P < .0001), with a continued significant effect in the period after treatment. In addition, a 59% reduction in ductal carcinoma in situ was observed (HR, 0.41; 95% CI, 0.22–0.79; P = 0.0081), especially in ER-positive patients (HR, 0.22; 95% CI, 0.78–0.65; P < 0.0001).

No significant difference in deaths was observed overall (HR, 0,96; 95% CI, 0.69–1.34; P = 0.82) or for breast cancer. In addition, a significant decrease in non-breast cancers was also observed with anastrozole treatment (OR, 0.72; 95% CI, 0.57–0.91; P = 0.0042), namely in non-melanoma skin cancer. 

Also of note, no new AEs were reported in the longer follow-up, as well as no excess of fractures or other serious AEs previously seen with the aromatase inhibitor. 

This highlights the need, particularly in prevention studies, for long-term follow-up. We’ve learned a lot going on to 12 years, another 10 years of follow-up will tell us a lot more about the impact on mortality,” Cusick said.

Reference:

1. Cuzick J, Sestak I, Forbes JF, et al. Ten year results of the international breast cancer intervention study II. Presented at: the San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, Texas. Abstract GS4-04.

2. Cuzick J, Sestak I, Forbes JF, et al. Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial. Lancet. doi:10.1016/S0140-6736(19)32955-1.

3. Cuzick J, Sestak I, Forbes JF, et al. Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial. Lancet. doi:10.1016/S0140-6736(19)32955-1.