Abstract PD10-08: Outcomes of germline BRCA carriers versus non-carriers in the french national metastatic breast cancer ESME cohort 2008-2016
Authors: Mailliez Audrey , D'Hondt Veronique , Lusque Amelie , Caron Olivier , Cabel Luc , Goncalves Antony , Debled Marc , Gladieff Laurence , Ferrero Jean-Marc , Petit Thierry , Mouret-Reynier Marie-Ange , Eymard Jean-Christophe , Frenel Jean-Sébastien , De La Motte Rouge Thibault , Simon Gaëtane , Delaloge Suzette 
Published: February 2021

BACKGROUND: Approximately 5% of breast cancer (BC) patients (pts) carry a deleterious germline BRCA mutation (gBRCAm). Retrospective studies suggest that overall survival (OS) is equivalent between gBRCAm carriers and non-carriers with metastatic BC (MBC). We aimed to use the large ESME multicentre national MBC database to compare outcomes of gBRCAm carriers, gBRCA wild-type (WT) and not tested (NT) pts. METHODS: We used the large ESME MBC database (NCT03275311), a unique national cohort of all consecutive pts who initiated a first-line treatment for MBC between 2008 and 2016 in one of the 18 French Comprehensive Cancer Centers. All pts with data available regarding gBRCA testing were selected for the present analysis. 26 pts with non-BRCA germline mutations were classified in the WT group. The primary endpoint was OS from date of treatment initiation in the 3 groups of patients: gBRCAm, gBRCA WT and gBRCA NT.Secondary endpoints were progression-free survival under first line treatment (PFS1), clinical and biological characteristics of the 3 groups and prognostic factors for OS. Multivariable analyses included the main known prognostic factors (age at MBC, MBC subtype, disease-free interval, presence of visceral disease, number of metastatic sites). They were conducted using Cox proportional analyses. RESULTS: 20624 pts were included in this analysis (414 gBRCAm, 1710 WT, 18500 gBRCA NT). Pts and disease characteristics are summarized in table 1. As expected, patients with gBRCAm were younger and had a higher rate of TNBC and G3 tumors.

Median follow-up was 50.5 months (95%CI 49.7-51.5). Non-adjusted median OS was 30.6 months [21.9-34.3] in the gBRCAm group, 35.8 [32.2-37.8] in the WT and 39.3 [38.3-40.3] in NT groups. Median PFS1 was 7.9 months [6.6-9.3] in the gBRCAm group, 7.8 [7.3-8.5] in the WT and 9.7 months [ 9.5-10.0] in the NT groups. In multivariable analyses, OS and PFS were not significantly different between MBC patients with gBRCA and others (respective HRs 1.01 [0.88;1.17], p=0.87 and 0.94 [0.84;1.06], p=0.31). CONCLUSION: In this large scale real-life ESME MBC database analysis, outcomes of gBRCAm carriers with MBC do not differ from non carriers or not tested subgroups, when adjusted for other prognostic factors.

Table 1: characteristics of patients and diseasegBRCAm. gBRCA WT. gBRCA NT Pvalue (chi-2)N = 414 N = 1710 N = 18500 Age (years) median [range]45 [23-82]48 [20- 88]61 [22-103]p&lt;0.0001Grade 3 N (%) Missing data202 (57.7) 64598 (41.1) 2545337 (34.5)3036p&lt;0.0001Triple negative breast cancer N (%)158 (38.2)370 (21.6)2331 (12.6)p&lt;0.0001De novo MBC N (%)74 (17.9)359 (21)5914 (32)p&lt;0.0001Disease-free interval (months) median [range]39.0 [-1.5- 425.7]36.3 [-2.1- 549.6]31.8 [-2.9- 657.8]p&lt;0.0001Metastatic sites ≥3 N (%)113 (27.3)349 (20.4)3943 (21.3)p=0.008Visceral metastases N (%)279 (67.4)964 (56.4)10659(57.6)p=0.0002Central Nervous System Metastases N (%)66 (15.9)132 (7.7)1145 (6.2)p&lt;0.0001

Citation Format: Audrey Mailliez, Veronique D'Hondt, Amelie Lusque, Olivier Caron, Luc Cabel, Antony Goncalves, Marc Debled, Laurence Gladieff, Jean-Marc Ferrero, Thierry Petit, Marie-Ange Mouret-Reynier, Jean-Christophe Eymard, Jean-Sébastien Frenel, Thibault De La Motte Rouge, Gaëtane Simon, Suzette Delaloge. Outcomes of germline BRCA carriers versus non-carriers in the french national metastatic breast cancer ESME cohort 2008-2016 [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD10-08.