Poster LIBER san antonio 2011 [Mode de compatibilité]

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.
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