Résumé
Introduction. Evidence suggests that human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) patients have different clinical characteristics and outcomes according to the hormone receptor (HR) status. We aimed to evaluate the impact of HR status in this population extracted from a large real-world database. Methods. We performed a retrospective analysis of HER2+ MBC patients (pts) included in the real world ESME MBC database (NCT03275311) between 2008 and 2017. Descriptive statistics, the Kaplan-Meier method and Cox proportional hazards models were used to report characteristics, outcomes and prognostic factors. Results. Of 4,145 HER2+ MBC pts eligible for our analysis, 1,449 (35%) had HR-negative (HR-), while 2,696 (65%) had HR-positive (HR+) tumors. Pts with HR- tumors had metastases earlier (median 9.3 vs 28.0 mo from primary cancer), had more often de novo MBC (47.6% vs 38.1%), grade III tumors (50.9% vs 33.6%), visceral metastases (70.9% vs 60.8%) and less often bone only disease (8.4% vs 21.1%) compared to those with HR+ tumors, all p<0.001. Pts with HR+ MBC received less frequently an anti-HER2+ targeted therapy during first line of treatment than pts with HR- tumors (74.9% vs 90.8%, p<0.001). Pts with HR- MBC had significantly worse outcomes than those with HER2+/HR+ MBC, with median overall survival (OS) 42.0 mo [95% CI 38.8-45.2] vs 55.9 mo [95% CI 53.7-59.4], p<0.001, and median progression-free survival (PFS) 9.8 mo [95%CI 9.2-11] vs 12.2 mo [95%CI 11.5-12.9], p=0.012, respectively. The independent prognostic value of HR status was confirmed in a multivariable analysis for OS (HR- versus HR+, hazard ratio=1.25 [1.13-1.39], p<0.001) but not for PFS (hazard ratio=1.03 [95%CI 0.95-1.13], p=0.8) (Table 1 for OS). The multivariable analysis also included tumor grade, age at and time to MBC diagnosis, presence of visceral metastases, number of metastatic sites and performance status as prognostic factors. In the HR+ population, ER and PR statuses were not prognostic. Conclusions. These data confirm the remaining strong and independent adverse prognostic effect of negative hormone receptors among pts with HER2+ MBC treated in the past 12 years. Cox multivariable model for overall survival in patients with HER2-positive MBCCategoriesNHazard ratio95% CIp valueTumor gradeGrade I/II17711<0.001Grade III15741.13[1.03-1.25]NA5811.15[1.01-1.31]ER/PR statusER+/PR+14571<0.001ER+/PR-9711.03[0.92-1.16]ER-/PR+1021.03[0.77-1.36]ER-/PR-13961.25[1.13-1.39]Age at MBC diagnosis<55 years17561<0.001≥55 years21701.26[1.16-1.38]Time to MBC diagnosis<6 months16351<0.0016-24 months5082.53[2.22-2.89]24-60 months8721.75[1.56-1.96]≥60 months9111.19[1.06-1.35]Visceral metastasesNo14061<0.001Yes25201.54[1.38-1.71]No of metastatic sites<330911<0.001≥38351.65[1.48-1.84]ECOG PSPS 010101<0.001PS 18021.62[1.4-1.87]PS 2-43923.34[2.83-3.95]NA17222.34[2.07-2.64] Citation Format: Luc Cabel, Matthieu Carton, Veronique Dieras, Thierry Petit, Severine Guiu, Corinne Veyret, Anthony Goncalves, Lionel Uwer, Paule Augereau, Jean-Marc Ferrero, Christelle Levy, Florence Dalenc, Isabelle Desmoulins, Marie Ange Mouret-Reynier, Marc Debled, Thomas Bachelot, Jean-Christophe Eymard, Barbara Pistilli, Jean Sebastien Frenel, Michael Chevrot, Audrey Mailliez, Marcela Carausu. Impact of hormone receptor status on clinicopathological characteristics and outcomes among HER2-positive metastatic breast cancer patients in the ESME database [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-05-02.