Uptake of a randomized breast cancer prevention trial comparing letrozole to placebo in BRCA1/2 mutations carriers: the LIBER trial Pascal Pujol1,2, Christine Lasset3, Pascaline Berthet4, Catherine Dugast5, Suzette Delaloge6, Jerome Lemonnier7, Lise Roca2, Sylvie Mijonnet7, Karen Baudry1, Catherine Nogues8, Anne Laure Martin7, on behalf the French Federation of Cancer Centres (Unicancer). 1Unité d'oncogénétique University hospital CHU Arnaud de Villeneuve, 371, av G. Giraud, 34295 Montpellier Cedex 5, France, Phone : 33 467 33 58 75 , e-mail: [email protected] 2 INSERM 896 CRCM Val d'Aurelle 34295 Montpellier. 3 Centre Léon Bérard, Lyon. 4 Centre Francois Baclesse, Caen. 5 Centre Eugene Marquis Rennes. 6 Institut Gustave Roussy, Villejuif. 7 Unicancer, 101 rue de Tolbiac, Paris. 8 Institut Curie, Paris, France Abstract Conclusion Results Background: Women with germline BRCA1 or BRCA2 (BRCA1/2) mutations have a 56-80% life-time risk of developing breast cancer. Prophylactic mastectomy provides a valid option to reduce it, but impacts the quality of life [1-3]. •According to the characteristics of the women included in the GENEPSO cohort and the survey, approximately one third of BRCA1/2 mutation carriers were eligible for the trial. Medical prevention by aromatase inhibitors (AI) has recently been shown to have preventive effect [4]. It may thus be considered as an alternative. LIBER is an ongoing double-blind, randomized phase III trial evaluating the efficacy of 5years letrozole vs placebo to decrease breast cancer incidence in postmenopausal BRCA1/2 mutation carriers (trial registration NCT00673335). •Uptake of drug prevention trial was 32 % of orally informed women and 15 % of overall eligible women. Methods: We compared characteristics of women in the LIBER trial (n=113) to those of women enrolled in the prospective ongoing national GENEPSO cohort of BRCA1/2 mutation carriers (n=1505). Uptake was evaluated through a survey sent to all active centres, with responses obtained from 17 of the 20 (85%) centres [5]. Study design Cumulative number of enrollments Post-menopausal women with a BRCA1/2 deleterious mutation •Out of the 534 women eligible from chart review informed by mail about the trial, 44% came to a dedicated medical visit. •The main reasons of refusal were: potential side effects, probability to receive the placebo and lack of support from their physicians. •Previous unilateral breast cancer and prophylactic oophorectomy were more frequently observed in women enrolled in the trial than in the French cohort (93% vs 60% and 50 % vs 39 %, respectively). Acceptability Eligibility Eligible women N= 798 (BRCA1/2, 40<age<70, no bilateral mastectomy, no previous BC) 534 women informed by mail Informed consent •The overall uptake of the study is 15%, a rate similar to the uptake of other preventive trials [6,7]. •Women with previous unilateral breast cancer or prophylactic oophorectomy are more likely to enter a medical prevention trial. •A greater and wider information of the trial should be offered to women with BRCA1/2 mutation for better recruitment. •Breast cancer prevention by AIs deserves to be evaluated since it could provide a precious alternative to bilateral mastectomy in postmenopausal patients. •The study has been proposed to other countries (Spain, Canada). Women with BRCA1/2 mutation N= 336 Women deceased N= 29 (9%) Alive at time of screening N = 307 (91%) Randomization Arm 1 40 > age >70 N= 73 (22%) Women with positive answer and informed during a visit at investigational site N= 237 (44%) Arm 2 letrozole placebo 1 tablet (2.5 mg/day) 1 tablet/day Treatment: 5 years Follow-up: 5years Enrollment Criteria • Women who carry a characterized germline BRCA1 or 2 deleterious mutation • Women who have not undergone and do not wish to undergo prophylactic mastectomy • Unaffected women or women who have suffered from unilateral invasive breast cancer diagnosed more than 5 years before enrollment with no previous aromatase inhibitor and no evidence of recurrence • 40 < age < 70 • ECOG performance status <2 • Post-menopausal women (spontaneous menopause or following bilateral oophorectomy) • No cancer detected by mammography and MRI during the current year • No osteoporosis, measured by bone densitometry during the last 2 years (T score > -2.5 DS) • Normal hematological, liver, kidney and cardiovascular functions • No hormone replacement therapy during the 3 months before enrollment Women refusal after solicitation or no answer 40 ≤ age <70 N= 234 (70%) N = 292 (55 %) Women with bilateral mastectomy N= 58 (17%) Patients' characteristics LIBER trial Patients' characteristics Type of mutation BRCA1 BRCA2 BRCA1+BRCA2 Oophorectomy (>40) Yes No Prior breast cancer Yes No Age > 40 and < 50 > 50 and < 70 n=113 % Without bilateral mastectomy N= 176 (52%) GENEPSO Cohort N=1505 % 63 49 1 56 43 1 949 556 0 63 37 0 103 10 91 9 527 337 61 39 56 57 49 51 580 925 39 61 41 72 36 64 418 446 28 30 Women with Criteria not validated (Tscore >-2,5 , no menopause) N= 29 (12% of informed women) Without previous invasive cancer< 5 years or concomitant HT N= 128 (38%) Women who signed the participation consent N= 75 (32% of orally informed women, 15% of mail informed women) Main Inclusion criteria validated N= 124 (37%) 1. Meijers-Heijboer, H., et al. N Engl J Med, 2001. 345(3): 159-64. 2. Gahm, J., et al., Breast, 2010 Dec;19(6):462-9. 3. Brandberg, Y., et al., J Clin Oncol, 2008. 26(24): p. 3943-9. Other inclusion criteria N= 4 (1 %) Women refusal after information visit N=134 (56% of orally informed women) References Women with invasive cancer history < 5 years or concomitant HT N= 48 (14%) 4. Goss PE, et al.; N Engl J Med. 2011 Jun 23;364(25):2381-91 5. Pujol P. et al., Fam Cancer (in press). 6. Evans, D., et al., Lancet, 2001. 358(9285): 889-90. 7. Evans D, et al., J Med Genet. 2010 ;47(12):853-5. Printed by