Uptake of a randomized breast cancer prevention trial comparing letrozole to placebo in BRCA1/2 mutations carriers: the LIBER trial

Abstract

Women with germline BRCA1 or BRCA2 (BRCA1/2) mutations are considered as an extreme risk population for developing breast cancer. Prophylactic mastectomy provides a valid option to reduce such risk, impacting however, the quality of life. Medical prevention by aromatase inhibitor that has also recently shown to have preventive effect may thus be considered as an alternative. LIBER is an ongoing double-blind, randomized phase III trial to evaluate the efficacy of 5-year letrozole versus placebo to decrease breast cancer incidence in post-menopausal BRCA1/2 mutation carriers (NCT00673335). We present data on the uptake of this trial. We compared characteristics of women in the LIBER trial (n = 113) to those of women enrolled in the prospective ongoing national GENEPSO cohort (n = 1,505). Uptake was evaluated through a survey sent to all active centres, with responses obtained from 17 to the 20 (85%) centres. According to the characteristics of the women enrolled in the GENEPSO cohort and the survey, approximately one-third of BRCA1/2 mutation carriers were eligible for the trial. Five hundred and thirty-four women eligible from chart review have been informed by mail about the prevention trial and were invited to an oral information by participating centres. Forty-four percentage of them came to the dedicated medical visit. Uptake of drug prevention trial was 32% among women informed orally and 15% of all the eligible women. The main reasons of refusal were: potential side effects, probability to receive the placebo and lack of support from their physicians. Additionally, we noticed that prior prophylactic oophorectomy and previous unilateral breast cancer were more frequent in women enrolled in the LIBER trial than in the French cohort (93% vs. 60% and 50% vs. 39%, respectively). Based on an overall 15% uptake among all eligible subjects, greater and wider information of the trial should be offered to women with BRCA1/2 mutation to improve recruitment. Women with previous unilateral breast cancer or prior prophylactic oophorectomy are more likely to enter a medical prevention trial.

Challenging and Complex Decisions in the Management of the BRCA Mutation Carrier

“…Studies are underway evaluating AIs for chemoprevention in BRCA mutation carriers. 59 Raloxifene has not been studied in this population.…”

Decision making for breast cancer prevention among women at elevated risk

“…Only 15% of BRCA mutation carriers approached for a chemoprevention trial enrolled [2], and only 8.5% of BRCA mutation carriers offered chemoprevention started such a regimen within 4 years of receiving genetic test results [77]. These usage rates fall far short of the proportion of women interested in chemoprevention, which one study found to be upwards of 40% [93] of those with familial risk.…”

“…Most of these are significantly underused by women who may benefit in terms of reduced cancer risk and cancer-related worry. Only about half of BRCA mutation carriers undergo the recommended prophylactic oophorectomy [1] and fewer than 5% of the high-risk women likely to benefit from chemoprevention use it [2, 3]. Underuse may be driven by multiple factors: lack of physician or patient information or understanding; lack of clinician confidence discussing preventive interventions or identifying women who could benefit from them; psychological or social dynamics that shape women’s preferences, deliberations, or ability to act on their decisions; and fully informed choice.…”

Breast and ovarian cancer risk management in a French cohort of 158 women carrying a BRCA1 or BRCA2 germline mutation: patient choices and outcome

“…In our cohort, among the 35 women eligible to the LIBER trial, only 5 (14.30 %) were actually included. Recently the overall uptake in LIBER trial among all eligible women has been estimated to 15 % [16]. The acceptability of chemoprevention remains limited, probably due to the fear of adverse drug effects.…”

“…In France, since March 2008, the LIBER trial has been comparing the preventive efficacy of letrozole 2.5 mg daily for 5 years vs placebo in women with BRCA1/2 mutations [16].…”