Résumé
Background: In HER2-positive (HER2+) metastatic breast cancer (MBC), the clinical presentation at metastatic diagnosis (dg), de novo (dnMBC) or recurrent (rMBC), is an independent prognostic factor. In contemporary clinical trials, the proportion of patients (pts) with dnMBC is high, likely due to improvements in the efficacy of (neo)adjuvant therapy. ESME-MBC, a national cohort of real-world data, recruiting pts consecutively treated for MBC in all comprehensive cancer centers in France since 2008, allows capturing of this evolution over time. Methods: We selected pts with HER2+ (immunohistochemistry, IHC 3+ or ISH amplified) MBC diagnosed between 2008 and 2022, excluding pts whose hormone receptor (HR) and HER2 status were unknown and those who did not receive systemic treatment for MBC. We compared clinicopathologic characteristics based on presentation at metastatic dg (dnMBC i.e. metastasis found within 6 months from initial diagnosis, or rMBC). We evaluated the trends in presentation according to year of MBC dg (YOD) using a Cochran-Armitage test, and studied factors associated with first-line progression-free survival (PFS1) and overall survival (OS) using multivariable Cox models. Results: Among the 35,687 pts in the ESME MBC cohort, 5,573 pts were treated for HER2+ MBC, including 2,800 (50.2%) with rMBC and 2,773 (49.8%) with dnMBC. Most pts were women (99.4%) with a median age of 57 years (range, 19-97). Compared with rMBC pts, dnMBC pts had significantly more often a premenopausal status (41.6% vs 35.9%, p <0.0001), have a BMI ≥30 (23.5% vs 17.8%; p <0.0001) and have ductal tumors (86.8% vs 78.8%; p <0.0001). In dnMBC pts compared with rMBC pts, there were more visceral involvement in absence of central nervous system (CNS) disease (54.1% vs 42.6%; p <0.0001), and less CNS involvement (4.7% vs 16.9%; p <0.0001), respectively. HR-positive status was similar in both categories (dnMBC vs rMBC, 60.5% vs 59.7%, p= 0.54) while HER2 score 3+ on IHC was more frequent in dnMBC (86.8% vs 82.5%, p <0.0001). Types of therapy by dnMBC and rMBC differed: first-line anti-HER2 treatment + chemotherapy +/- endocrine therapy (ET), anti-HER2 treatment + ET, anti-HER2 treatment alone or no anti-HER2 treatment in 88.4% and 66.6%, 3.2% and 6.6%, 1.6% and 7.6%, and 6.8% and 19.1% of pts, respectively. The proportion of rMBC significantly decreased from 63.5% in 2008 to 32.9% in 2022 (Cochran–Armitage test; p < 0.0001), whereas the proportion of HR+ tumors significantly increased from 53.2% in 2008 to 68.3% in 2022 (Cochran–Armitage test; p < 0.0001) both in dnMBC (50.0% to 67.0%) and rMBC (55.0% to 70.9%) pts from 2008 to 2022 (Cochran–Armitage test; p=0.0197 and 0.0008, respectively). With a median follow-up of 82.8 months (mo) (95%CI: 79.7-84.6), the median OS of dnMBC vs rMBC pts were 72.5 mo (95%CI: 66.4-77.3) vs 43.8 mo (95%CI: 41.6-46.4) and the median PFS1 were 18.9 mo (95%CI: 17.7-20.3) vs 9.4 mo (95%CI: 8.9-9.9). In the multivariable analysis, dnMBC was associated with better OS (adjusted hazard ratio (aHR): 0.65 (95%CI: 0.61-0.70); p < 0.001) and PFS1 (aHR: 0.64 (95% CI: 0.60-0.68); p < 0.001). In both categories of pts, HR- status, older age at metastatic diagnosis, presence of CNS disease, and multiple metastases were independently associated with poorer OS and PFS1. HER2 3+ status was an independent favorable factor for PFS1 in both dnMBC and rMBC pts, and for OS in dnMBC pts only. Conclusion: Between 2008 and 2022, in a large national cohort of pts with HER2+ MBC, we observed an epidemiological shift from a majority of rMBC pts to a vast majority of dnMBC pts, along with an increase in the proportion of HR+ pts among those with HER2+ cancer. Patients with dnMBC experienced significantly longer PFS1 and OS than those with rMBC. Attention to dnMBC vs rMBC enrollment in studies of HER2+ MBC is needed in the design and contextualization of study results.
Citation Format: Thomas Grinda, Amélie Lusque, Stefania Morganti, David Pasquier, Aurélie Bertaut, Thierry Petit, Thomas Bachelot, Monica Arnedos, Fanny Le Du, Vincent Massard, Anthony Gonçalves, Caroline Bailleux, Jean-Sebastien Frenel, Paul Cottu, Christelle Levy, Aude-Marie Savoye, Nathalie Olympios, Marie-Ange Mouret-Reynier, Harold J. Burstein, Heather A. Pearsons, Lise Bosquet, Thomas Filleron, Suzette Delaloge, William Jacot, Nancy U. Lin. Trends in Presentation of HER2+ Breast Cancer: A Retrospective study of De Novo Versus Recurrent Metastatic Breast Cancer (MBC) in the Real-World French National ESME Cohort (2008-2022) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-08-03.