title: 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.
authors.affiliation: Genetics and Cancer, University Hospital CHU Arnaud de Villeneuve, 371, Av G. Giraud, 34295, Montpellier Cedex 5, France. p-pujol@chu-montpellier.fr
authors.forename: Pascal
authors.initials: P
authors.lastname: Pujol
authors.forename: Christine
authors.initials: C
authors.lastname: Lasset
authors.forename: Pascaline
authors.initials: P
authors.lastname: Berthet
authors.forename: Catherine
authors.initials: C
authors.lastname: Dugast
authors.forename: Suzette
authors.initials: S
authors.lastname: Delaloge
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fricker
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tennevet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chabbert-Buffet
authors.forename: Pascale
authors.initials: P
authors.lastname: This
authors.forename: Karen
authors.initials: K
authors.lastname: Baudry
authors.forename: Jerome
authors.initials: J
authors.lastname: Lemonnier
authors.forename: Lise
authors.initials: L
authors.lastname: Roca
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mijonnet
authors.forename: Paul
authors.initials: P
authors.lastname: Gesta
authors.forename: Jean
authors.initials: J
authors.lastname: Chiesa
authors.forename: Helene
authors.initials: H
authors.lastname: Dreyfus
authors.forename: Philippe
authors.initials: P
authors.lastname: Vennin
authors.forename: Capucine
authors.initials: C
authors.lastname: Delnatte
authors.forename: Yves Jean
authors.initials: YJ
authors.lastname: Bignon
authors.forename: Alain
authors.initials: A
authors.lastname: Lortholary
authors.forename: Fabienne
authors.initials: F
authors.lastname: Prieur
authors.forename: Laurence
authors.initials: L
authors.lastname: Gladieff
authors.forename: Anne
authors.initials: A
authors.lastname: Lesur
authors.forename: Krishna B
authors.initials: KB
authors.lastname: Clough
authors.forename: Catherine
authors.initials: C
authors.lastname: Nogues
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Martin
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009570:Nitriles / Q000627:therapeutic use*; D010052:Ovariectomy; D017698:Postmenopause / Q000187:drug effects / Q000235:genetics; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole
references.citation: Cancer. 2009 Dec 1;115(23):5404-12
references.pmid: 19787635
references.citation: Curr Oncol Rep. 2010 Jan;12(1):16-21
references.pmid: 20425603
references.citation: Lancet. 2001 Sep 15;358(9285):889-90
references.pmid: 11567707
references.citation: N Engl J Med. 2001 Jul 19;345(3):159-64
references.pmid: 11463009
references.citation: N Engl J Med. 2011 Jun 23;364(25):2381-91
references.pmid: 21639806
references.citation: J Natl Cancer Inst. 2007 Feb 21;99(4):283-90
references.pmid: 17312305
references.citation: J Clin Oncol. 2004 Mar 15;22(6):1055-62
references.pmid: 14981104
references.citation: Cancer. 2005 Oct 15;104(8):1567-74
references.pmid: 16155942
references.citation: Nat Rev Cancer. 2007 Jan;7(1):46-53
references.pmid: 17186017
references.citation: JAMA. 2001 Nov 14;286(18):2251-6
references.pmid: 11710890
references.citation: J Natl Cancer Inst. 2007 May 2;99(9):727-37
references.pmid: 17470740
references.citation: Int J Cancer. 2008 May 1;122(9):2017-22
references.pmid: 18196574
references.citation: N Engl J Med. 2007 Jul 12;357(2):154-62
references.pmid: 17625127
references.citation: Breast. 2010 Dec;19(6):462-9
references.pmid: 20605453
references.citation: J Clin Oncol. 2010 Jan 20;28(3):509-18
references.pmid: 19949017
references.citation: Womens Health (Lond). 2009 Jan;5(1):63-8
references.pmid: 19102642
references.citation: Cancer Prev Res (Phila). 2010 Jun;3(6):696-706
references.pmid: 20404000
references.citation: J Clin Oncol. 2007 Jul 10;25(20):2921-7
references.pmid: 17617523
references.citation: Breast Cancer Res Treat. 2011 Dec;130(3):927-38
references.pmid: 21761160
references.citation: J Natl Cancer Inst. 2005 Nov 16;97(22):1652-62
references.pmid: 16288118
references.citation: J Clin Oncol. 2010 Jul 20;28(21):3437-41
references.pmid: 20548000
references.citation: Breast. 2009 Oct;18 Suppl 3:S93-5
references.pmid: 19914552
references.citation: J Natl Cancer Inst. 2009 Jan 21;101(2):80-7
references.pmid: 19141781
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Feb;19(2):443-6
references.pmid: 20142242
references.citation: Lancet Oncol. 2005 Jun;6(6):431-4
references.pmid: 15925821
references.citation: J Clin Oncol. 2010 Jun 20;28(18):3090-5
references.pmid: 20458026
references.citation: J Med Genet. 2010 Dec;47(12):853-5
references.pmid: 20972247
references.citation: Oncogene. 2008 Jan 31;27(6):794-802
references.pmid: 17653086
references.citation: JAMA. 1999 Jun 16;281(23):2189-97
references.pmid: 10376571
references.citation: J Steroid Biochem Mol Biol. 2010 Feb 28;118(4-5):294-9
references.pmid: 19833206
references.citation: Curr Opin Obstet Gynecol. 2007 Feb;19(1):27-30
references.pmid: 17218848
references.citation: J Clin Oncol. 2009 Dec 10;27(35):5887-92
references.pmid: 19858402
references.citation: J Natl Cancer Inst. 2007 Feb 21;99(4):272-82
references.pmid: 17312304
references.citation: Clin Breast Cancer. 2007 Dec;7(11):895-900
references.pmid: 18269782
references.citation: Curr Opin Obstet Gynecol. 2010 Feb;22(1):56-60
references.pmid: 20019610
references.citation: Science. 2003 Oct 24;302(5645):643-6
references.pmid: 14576434
references.citation: Am J Hum Genet. 2003 May;72(5):1117-30
references.pmid: 12677558
references.citation: Expert Rev Anticancer Ther. 2008 Sep;8(9):1377-85
references.pmid: 18759690
references.citation: Lancet. 2003 Jan 25;361(9354):296-300
references.pmid: 12559863
references.citation: J Clin Oncol. 2008 Aug 20;26(24):3943-9
references.pmid: 18711183