Abstract
Background
Efficacy of endocrine therapy in HR+/HER2− metastatic breast cancer could differ depending on the presence of BRCA1/2 germline mutation.
Methods
The ESME metastatic breast cancer platform (NCT03275311) is a French real world database. Multivariable models including a time-varying approach and landmark analyses assessed the association between time-dependent gBRCA status (categorised as gBRCAm, gBRCAwt (wild type), and untested), overall survival (OS), and first-line progression-free survival (PFS1).
Results
A total of 170 patients were gBRCAm carriers, 676 gBRCAwt, and 12,930 were untested at baseline. In the multivariable analysis, gBRCAm carriers overall had a lower OS compared to gBRCAwt (adjusted HR [95% CI] 1.26 [1.03–1.55]). gBRCAm patients treated with front-line endocrine therapy had lower adjusted OS (adjusted HR [95% CI] = 1.54 [1.03–2.32]) and PFS1 (adjusted HR [95% CI] 1.58 [1.17–2.12]) compared to gBRCAwt patients. However, for patients who received frontline chemotherapy, neither OS nor PFS1 differed between gBRCAm carriers and the other groups (HR versus gBRCAwt for OS: 1.12 [0.88–1.41], p = 0.350; PFS1: 1.09 [0.90–1.31], p = 0.379).
Conclusion
In this large cohort of HR+/HER2− MBC patients treated in a pre-CDK4/6 inhibitors era, gBRCAm status was associated with a lower OS and lower PFS following first-line endocrine therapy, but not following first-line chemotherapy.
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Data availability
All data are contained in the ESME database, which is managed by Unicancer (http://www.unicancer.fr/). However, the ESME database is not publicly available for the following reason: in the ESME Research programme, public data sharing is not automatic in order to ensure that only trained users can analyse the ESME datasets. The analysis datasets will be made available only under data transfer and use agreements executed between Unicancer and the potential licensee. Interested parties should contact the corresponding author. Amélie Lusque had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Data supporting the findings of this study are available from UNICANCER but restrictions apply to the availability of these data, which was used under licence for this study and is therefore not publicly available. However, the data are available from the authors upon reasonable request and with permission from UNICANCER.
Code availability
Codes used to generate the data are available upon reasonable request.
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Acknowledgements
We thank the 18 French Comprehensive Cancer Centres for providing the data and each ESME local coordinator for managing the project at the local level. 18 Participating French Comprehensive Cancer Centres (FCCC):; I. Curie, Paris/ Saint-Cloud, G. Roussy, Villejuif, I. Cancérologie de l’Ouest, Angers/Nantes, C. F. Baclesse, Caen, ICM Montpellier, C. L. Bérard, Lyon, C. G-F Leclerc, Dijon, C. H. Becquerel, Rouen; I. C. Regaud, Toulouse; C. A. Lacassagne, Nice; Institut de Cancérologie de Lorraine, Nancy; C. E. Marquis, Rennes; I. Paoli-Calmettes, Marseille; C. J. Perrin, Clermont Ferrand; I. Bergonié, Bordeaux; C. P. Strauss, Strasbourg; I. J. Godinot, Reims; C. O. Lambret, Lille. Moreover, we thank the ESME Scientific Group, the Strategic Committee, and the ESME coordination team for their ongoing support. Prior presentations This work has been presented at the ESMO meeting as a poster in 2021.
Funding
The ESME MBC database receives financial support from an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai, and Daiichi Sankyo). Data collection, analysis, and publication are managed entirely by UNICANCER independently of the industrial consortium.
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Conceptualisation JSF, AL, SD, AMa, WJ, TDLM. Formal analysis JSF, AL, SD, AMa, WJ, TDLM. Project administration MC. Investigation JSF, AL, SD, JMF, TB, ID, CL, JCE, AG, AP, MAM, JCT, TP, LC, LU, MD, MC, WJ, TDLM. Writing original draught JSF, AL, SD, AMa, WJ, TDLM. Writing review and editing JSF, AL, SD, JMF, TB, ID, CL, JCE, AG, AP, MAM, JCT, TP, LC, LU, MD, MC, WJ, TDLM
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JSF reports personal fees from Roche Genentech, personal fees and non-financial support from SeattleGenetics, personal fees and non-financial support from Novartis, personal fees and non-financial support from Pfizer, personal fees and non-financial support from Lilly, personal fees and non-financial support from Novartis, personal fees and non-financial support from GSK, personal fees and non-financial support from Clovis oncoloy, personal fees and non-financial support from Astra Zeneca, personal fees and non-financial support from Daiichi Sankyo, personal fees and non-financial support from Gilead, personal fees and non-financial support from MSD, personal fees and non-financial support from Pierre Fabre, personal fees and non-financial support from Amgen, outside the submitted work. AL has declared no conflict of interest. SD reports grants and non-financial support from Pfizer, grants from Novartis, grants and non-financial support from Astra Zeneca, grants and non-financial support from Roche Genentech, grants from Lilly, grants from Puma, grants from Myriad, grants from Orion, grants from Amgen, grants from Sanofi, grants from Genomic Health, grants from GE, grants from Servier, grants from MSD, grants from BMS, grants from Pierre Fabre, grants from Seagen, grants from Exact Sciences, grants from Rappta, grants from Besins, grants from European Commission, grants from French government grants, grants from Fondation ARC, outside the submitted work. JMF reports personal fees from Pfizer, Novartis, Pierre Fabre, Lilly. TB reports personal fees and non-financial support from Roche, grants, personal fees and non-financial support from Astra Zeneca, grants, personal fees and non-financial support from Pfizer, grants and personal fees from SeaGen, grants, personal fees and non-financial support from Novartis, outside the submitted work; ID has declared no conflict of interest. CL has received reports personal fees from Daiichi, Astra Zeneca, Lilly, MSD. JCE has declared no conflict of interest. AG has declared no conflict of interest. AP reports from Lilly, other from Daiichi-Sankyo, other from Pfizer, other from Pierre Fabre, outside the submitted work; MAM has declared no conflict of interest. JCT has received reports personal fees from PFIZER, personal fees from MSD, personal fees from ASTRAZENECA, non-financial support from NOVARTIS, outside the submitted work. TP eports personal fees and non-financial support from Pfizer, personal fees from Lilly, personal fees and non-financial support from Novartis, personal fees and non-financial support from Astra-Zeneca, personal fees from Seagen, personal fees and non-financial support from Daiichi Sankyo, personal fees from Pierre Fabre, outside the submitted work. LC has declared no conflict of interest. LU has declared no conflict of interest. MD has declared no conflict of interest. MC has declared no conflict of interest. AM has declared no conflict of interest. WJ reports personal fees and non-financial support from Novartis, grants, personal fees and non-financial support from Astra Zeneca, personal fees and non-financial support from Roche Genentech, personal fees and non-financial support from Lilly, non-financial support from Sanofi, personal fees from Daiichi Sankyo, personal fees from MSD, personal fees from Rain Pharmaceuticals, non-financial support from Pierre Fabre, personal fees from Seagen, personal fees from BMS, personal fees and non-financial support from Eisai, personal fees and non-financial support from Pfizer, non-financial support from Glaxo Smithkline, non-financial support from Chugai Pharma, outside the submitted work. TDLM reports grants from Novartis, grants, personal fees and non-financial support from Astra Zeneca, personal fees and non-financial support from Roche Genentech, grants and personal fees from MSD, grants from Seagen, personal fees from Eisai, grants, personal fees and non-financial support from Pfizer, personal fees and non-financial support from Glaxo Smithkline, personal fees and non-financial support from CLOVIS ONCOLOGY, outside the submitted work.
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ESME MBC database was authorised by the French data protection authority (Registration ID 1704113 and authorisation N°DE-2013.-117).
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Frenel, JS., Lusque, A., Delaloge, S. et al. Efficacy of front-line treatment for hormone receptor-positive HER2-negative metastatic breast cancer with germline BRCA1/2 mutation. Br J Cancer 128, 2072–2080 (2023). https://doi.org/10.1038/s41416-023-02248-4
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DOI: https://doi.org/10.1038/s41416-023-02248-4