Letrozole to prevent breast cancer in postmenopausal women with BRCA1/2 mutations (LIBER study).
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| Názov: | Letrozole to prevent breast cancer in postmenopausal women with BRCA1/2 mutations (LIBER study). |
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| Autori: | Pujol P; University Hospital of Montpellier - Arnaud De Villeneuve, Montpellier, France. Electronic address: p-pujol@chu-montpellier.fr., Roca L; Unité de biométrie, Institut de Cancérologie de Montpellier, Montpellier, France., Lortholary A; Hôpital privé du confluent - Centre Catherine De Sienne, Nantes, France., Lasset C; Centre Léon Bérard, Lyon, France., Crivelli L; Centre Eugène Marquis, Rennes, France., Berthet P; Centre François Baclesse, Caen, France., Tennevet I; Centre Henri Becquerel, Rouen, France., Petit T; Centre Paul Strauss, Strasbourg, France., Chabbert-Buffet N; Hôpital Tenon-APHP Sorbonne Université, Paris, France., Gesta P; Centre Hospitalier De Niort, Niort, France., Saule C; Institut Curie, Paris, France., Chiesa J; Centre Hospitalier Universitaire De Nimes - Hopital Caremeau, Nimes, France., Nguyen TD; Institut Jean Godinot, Reims, France., Mailliez A; Centre Oscar Lambret, Lille, France., Callet NA; Institut Curie, Saint-Cloud, France., Noguès C; Institut Paoli-Calmettes, Marseille, France., Dreyfus H; Institut Sainte Catherine, Avignon, France., Delnatte C; Institut de Cancérologie de l'Ouest - Site René Gauducheau, Saint-Herblain, France., Prieur F; Centre Hospitalier Universitaire De Saint Etienne - Hôpital Nord, Saint-Priest, France., Gladieff L; Oncopole Claudius Regaud, IUCT-Oncopole, Toulouse, France., Ingster O; Institut de Cancérologie de l'Ouest - Site Paul Papin, Angers, France., Galibert V; University Hospital of Montpellier - Arnaud De Villeneuve, Montpellier, France., Lemonnier J; Unicancer, Paris, France., Delaloge S; Gustave Roussy, Villejuif, France. |
| Zdroj: | European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2025 Dec 09; Vol. 231, pp. 116101. Date of Electronic Publication: 2025 Nov 07. |
| Spôsob vydávania: | Journal Article; Randomized Controlled Trial; Clinical Trial, Phase III; Multicenter Study |
| Jazyk: | English |
| Informácie o časopise: | Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9005373 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0852 (Electronic) Linking ISSN: 09598049 NLM ISO Abbreviation: Eur J Cancer Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford : Elsevier Science Ltd Original Publication: Oxford ; New York : Pergamon Press, c1990- |
| Výrazy zo slovníka MeSH: | Breast Neoplasms*/genetics , Breast Neoplasms*/prevention & control , Letrozole*/therapeutic use , Aromatase Inhibitors*/therapeutic use , Aromatase Inhibitors*/adverse effects , BRCA2 Protein*/genetics , BRCA1 Protein*/genetics, Humans ; Female ; Postmenopause ; Middle Aged ; Double-Blind Method ; Aged ; Adult ; Germ-Line Mutation ; Quality of Life ; Genes, BRCA2 ; Genetic Predisposition to Disease ; Mutation ; Treatment Outcome |
| Abstrakt: | Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. PP has received honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, MSD, Novartis,Pfizer, Onco DNA, HEDERADx, Predilife, and Seqone; Consulting fees from Janssen, Astrazeneca, Exact Sciences; Research: Novartis (PI, Phase III), Pfizer (PI, Phase III and IV),Astrazeneca (research grant). SD has received research grants from Pfizer, Novartis, AstraZeneca, Roche Genentech, Lilly, Orion, Amgen, Sanofi, BMS, Pierre Fabre, Taiho; has received support for attending meetings from Novartis, Roche, Seagen and has served as a scientific advisor for Pfizer, Gilead, Sanofi, Elsan, Besins, Decibio, AstraZeneca. AL has received honoraria from AstraZeneca, Clovis Oncology, TESARO/GSK, ROCHE, MSD and Novartis. Other authors have nothing to declare Background: Women carrying a germline BRCA1 or BRCA2 mutation (gBRCAm) have a 70 % lifetime risk of breast cancer (BC). Aromatase inhibitors (AI) decrease BC incidence in high-risk populations but have not been specifically assessed in gBRCAm carriers. Methods: LIBER was a randomized, double-blind, placebo-controlled, phase III trial. Post-menopausal women aged between 40 and 70 years carrying a gBRCAm were randomly allocated either 5 years of letrozole (2.5 mg/day) or placebo. Women with prior BC in remission for more than 5 years ago were eligible to assess the risk of second BC. Randomization was stratified by type of gBRCAm (BRCA1 versus BRCA2), previous bilateral oophorectomy, and prior BC. The primary endpoint was the 5-year incidence of invasive BC. Safety and quality of life were analyzed. Results: Between 2008 and 2013, 170 women were randomized: 86 to placebo and 84 to letrozole. At 5 years, treatment adherence was 73.5 % with placebo and 76.7 % with letrozole. After a median follow-up of 72.7 months (95 % CI 71.5-78.5), the 5-year incidence of invasive BC was 13.1 % with placebo and 7.8 % with letrozole: hazard ratio, 0.70 (95 % CI 0.29-1.66), p = 0.416. Safety events and quality of life did not statistically differ in the arm. Conclusion: Due to the underpowered nature of the trial and the observed trend, it cannot be ruled out that using AI to prevent invasive breast cancer could be effective for BRCA1/2 carriers overall, or for specific subgroups within a larger sample size. Further randomised controlled trials are needed to determine the potential benefits of AI for gBRCA1/2m carriers. (Copyright © 2025. Published by Elsevier Ltd.) |
| Contributed Indexing: | Keywords: Aromatase inhibitors; BRCA mutation; Breast cancer; Chemoprevention; Letrozole |
| Substance Nomenclature: | 7LKK855W8I (Letrozole) 0 (Aromatase Inhibitors) 0 (BRCA2 Protein) 0 (BRCA1 protein, human) 0 (BRCA2 protein, human) 0 (BRCA1 Protein) |
| Entry Date(s): | Date Created: 20251115 Date Completed: 20251126 Latest Revision: 20251201 |
| Update Code: | 20251202 |
| DOI: | 10.1016/j.ejca.2025.116101 |
| PMID: | 41240533 |
| Databáza: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. PP has received honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, MSD, Novartis,Pfizer, Onco DNA, HEDERADx, Predilife, and Seqone; Consulting fees from Janssen, Astrazeneca, Exact Sciences; Research: Novartis (PI, Phase III), Pfizer (PI, Phase III and IV),Astrazeneca (research grant). SD has received research grants from Pfizer, Novartis, AstraZeneca, Roche Genentech, Lilly, Orion, Amgen, Sanofi, BMS, Pierre Fabre, Taiho; has received support for attending meetings from Novartis, Roche, Seagen and has served as a scientific advisor for Pfizer, Gilead, Sanofi, Elsan, Besins, Decibio, AstraZeneca. AL has received honoraria from AstraZeneca, Clovis Oncology, TESARO/GSK, ROCHE, MSD and Novartis. Other authors have nothing to declare<br />Background: Women carrying a germline BRCA1 or BRCA2 mutation (gBRCAm) have a 70 % lifetime risk of breast cancer (BC). Aromatase inhibitors (AI) decrease BC incidence in high-risk populations but have not been specifically assessed in gBRCAm carriers.<br />Methods: LIBER was a randomized, double-blind, placebo-controlled, phase III trial. Post-menopausal women aged between 40 and 70 years carrying a gBRCAm were randomly allocated either 5 years of letrozole (2.5 mg/day) or placebo. Women with prior BC in remission for more than 5 years ago were eligible to assess the risk of second BC. Randomization was stratified by type of gBRCAm (BRCA1 versus BRCA2), previous bilateral oophorectomy, and prior BC. The primary endpoint was the 5-year incidence of invasive BC. Safety and quality of life were analyzed.<br />Results: Between 2008 and 2013, 170 women were randomized: 86 to placebo and 84 to letrozole. At 5 years, treatment adherence was 73.5 % with placebo and 76.7 % with letrozole. After a median follow-up of 72.7 months (95 % CI 71.5-78.5), the 5-year incidence of invasive BC was 13.1 % with placebo and 7.8 % with letrozole: hazard ratio, 0.70 (95 % CI 0.29-1.66), p = 0.416. Safety events and quality of life did not statistically differ in the arm.<br />Conclusion: Due to the underpowered nature of the trial and the observed trend, it cannot be ruled out that using AI to prevent invasive breast cancer could be effective for BRCA1/2 carriers overall, or for specific subgroups within a larger sample size. Further randomised controlled trials are needed to determine the potential benefits of AI for gBRCA1/2m carriers.<br /> (Copyright © 2025. Published by Elsevier Ltd.) |
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| ISSN: | 1879-0852 |
| DOI: | 10.1016/j.ejca.2025.116101 |