Persistent reduction of breast cancer risk after anastrozole cessation

Roshini Claire Anthony
09 Jan 2020
Persistent reduction of breast cancer risk after anastrozole cessation

The reduced incidence of breast cancer with 5-year prophylaxis with the aromatase inhibitor anastrozole among women at high risk of the disease persists even after anastrozole cessation, suggests long-term results of the IBIS-II* trial presented at SABCS 2019.

“In 2013, we reported that in the first 7 years of follow-up, anastrozole significantly reduced breast cancer incidence compared with placebo and that it did so with very few side effects,” said study lead author Professor Jack Cuzick from the Wolfson Institute of Preventive Medicine, Queen Mary University London, UK.

“Our new data show that after a median of 10.9 years of follow-up there continues to be a significant reduction in breast cancer incidence,” he added.

Study participants were 3,864 postmenopausal women (age 40–70 years; median 59.4 years at study entry) at high risk of developing breast cancer. They were randomized to receive daily doses of oral anastrozole (1 mg/day; n=1,920) or placebo (n=1,944) for 5 years.

After a median follow-up of 131 months, the incidence of breast cancer (invasive or ductal carcinoma in situ) was almost halved in women who had received anastrozole compared with placebo (hazard ratio [HR], 0.51, 95 percent confidence interval [CI], 0.39–0.66; p<0.0001), with 85 and 165 cases reported in the anastrozole and placebo groups, respectively. [SABCS 2019, abstract GS4-04; Lancet 2019;doi:10.1016/S0140-6736(19)32955-1]

The reduction in incidence appeared to be greater in the first 5 years (HR, 0.39, 95 percent CI, 0.27–0.58; p<0.0001), though the incidence remained low after that period (HR, 0.64, 95 percent CI, 0.45–0.91; p=0.014).

The incidence of invasive oestrogen receptor-positive breast cancer was more than halved with anastrozole (HR, 0.46, 95 percent CI, 0.33–0.65; p<0.0001), as was the risk of ductal carcinoma in situ (HR, 0.41, 95 percent CI, 0.22–0.79; p=0.0081), particularly for oestrogen receptor-positive cases (HR, 0.22, 95 percent CI, 0.07–0.65; p=0.0062). The reduced incidence of invasive oestrogen receptor-negative breast cancer with anastrozole was not significant (HR, 0.77; p=0.41).

There was also a reduced incidence of non-breast cancers with anastrozole vs placebo (odds ratio [OR], 0.72, 95 percent CI, 0.57–0.91; p=0.0042), primarily due to a reduction in non-melanoma skin cancer (OR, 0.59; p=0.0058). There was no apparent reduction in endometrial cancer with anastrozole.

There was no between-group difference pertaining to all-cause mortality (HR, 0.96, 95 percent CI, 0.69–1.34; p=0.82) or deaths due to breast cancer (n=2 vs 3 [anastrozole vs placebo]), though follow-up is ongoing to assess this outcome. There was no increase in fracture incidence (OR, 1.04), while myocardial infarction post-treatment occurred at a comparable rate between anastrozole and placebo recipients (n=8 in each group).

“No other side effects have been identified with longer follow-up, and the small 11 percent excess of fractures during the active treatment period has not continued after 5 years of follow-up,” the researchers pointed out.

Although the reduced breast cancer incidence was lower than that in the previous analysis, the effect remained significant and was greater than that exerted by tamoxifen, noted Cuzick.

“[T]he data … translates into an estimated 29 women needing to be treated with anastrozole for 5 years to prevent one breast cancer during treatment and in the next 5 years. This is far fewer women than the estimated 49 women that need to be treated with tamoxifen for 5 years to prevent one breast cancer in the same time period,” he said.

“[O]ur new results strongly suggest that anastrozole should be the preferred therapy for breast cancer prevention in postmenopausal women at increased risk for the disease, with tamoxifen used for women who experience severe side effects from anastrozole,” he added.



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