PEARL: Lasofoxifene reduced incidence of total breast cancer by 79%

LaCroix AZ. J Natl Cancer Inst. 2010;DOI: 10.1093/jnci/djq415.

The risk for total breast cancer declined by 79% and risk for ER-positive invasive disease declined by 83% in post-menopausal women assigned to 0.5 mg lasofoxifene, according to results from the PEARL trial.

In PEARL, 8,556 post-menopausal women aged 59 to 80 years with low bone density and normal mammograms were randomly assigned to 0.25 mg lasofoxifene (n=2,852), 0.5 mg lasofoxifene (n=2,852) or placebo (n=2,852). Roughly 96% of women in each group had at least one follow-up mammogram, and 77% of the cohort completed a closeout visit at 5 years.

At 5 years, 62% of women in the lasofoxifene groups were still taking the medication compared with 64% in the placebo group.

There were five cases diagnosed in the 0.5 mg group compared with 24 in the placebo group. Researchers said 0.5 mg lasofoxifene reduced incidence of all breast cancers by 79% (HR=0.21; 95% CI, 0.08-0.55). Incidence rates were also reduced for ER-positive disease (HR=0.17; 95% CI, 0.05 to 0.57).

Baseline age, body mass index and Gail score did not have any impact on treatment effect.

In contrast, hazard ratios for the 0.25 mg group were less than 1.0 for all categories of disease and the dose produced no reductions in incidence that were significantly different than placebo.

Neither dose of lasofoxifene reduced incidence of ER-negative disease.

The higher dose of lasofoxifene seemed to have more efficacy for women with higher levels of estradiol (OR=0.11; 95% CI, 0.02-0.51) compared with women with lower estradiol levels (OR=0.78; 95% CI, 0.16-3.79). Researchers said the interaction between estradiol level and lasofoxifene was statistically significant (P=.04) for total breast cancer but not for invasive ER-positive disease (P=.16).

Writing in an accompanying editorial, Victor G. Vogel, MD, MHS, director of the Geisinger Health System Cancer Institute, said lasofoxifene might represent a tipping point in breast cancer chemoprevention.

“Lasofoxifene appears to represent an advance in the progression of pharmacological agents at our disposal, which can reduce both the risk of fractures in women with osteoporosis and the risk of breast cancer in postmenopausal women,” he wrote. “We need more complete information about the long-term effects of lasofoxifene on both beneficial and unfavorable outcomes, but the early data regarding its risks and benefits are encouraging.”

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