Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants

Matteo Lambertini,Marie Daphne T’Kint De Roodenbeke,Octavi Córdoba,Luis Teixeira,Marco Bruzzone,Maria Del Pilar Estevez-Diz,Fedro Alessandro Peccatori ,Albert Grinshpun,Estela Carrasco,Claire Sénéchal ,Cynthia Villarreal‐Garza ,Ann H Partridge,Riccardo Ponzone,Christine Jablonski ,Maria Vittoria Dieci,Lieveke Ameye,Angela Toss,François P Duhoux ,Amir Sonnenblick,Marcello Ceppi,Katarzyna Pogoda,Fabio Puglisi,Kevin Punie,Antonio Di Meglio,Philip D Poorvu,José Alejandro Pérez Fidalgo ,Shani Paluch‐Shimon ,Olivier Caron,Alberta Ferrari,Claire Saule,Anne-Sophie Hamy,Florian Clatot,Arlindo R Ferreira,Luca Livraghi,Rossella Graffeo,Lucia Del Mastro,Laura De Marchis,Judith Balmañà ,Hatem A Azim

doi:10.1038/s41523-021-00224-w

Abstract

Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR−]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I–III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60–0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94–2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients’ counseling on treatment, prevention, and surveillance strategies.

Highlights

In women aged ≤40 years, breast cancer is the most common malignancy and the first cause of cancer-related mortality[1]
1234567890():,; Other age-related issues should be considered in the manage- BRCA1 and BRCA2 cohorts according to hormone receptor status, ment of breast cancer in young women[4]
Results were consistent with those reported in the main analyses (Supplementary Tables 11–14 and Supplementary Figs. 2–5). This large unique dataset allowed an in-depth investigation of the impact of the type of mutated gene (BRCA1 vs BRCA2) and hormone receptor status on clinical behavior and outcomes of BRCA-mutated breast cancer in young women

Summary

Introduction

In women aged ≤40 years, breast cancer is the most common malignancy and the first cause of cancer-related mortality[1]. Despite the higher risk of developing triple-negative and HER2-positive breast cancer, the majority of breast malignancies arising in young patients are hormone receptor-positive tumors[2]. The prognosis for hormone receptor-positive breast cancers is worse when compared to their older counterparts[3]. Other age-related issues should be considered in the manage- BRCA1 and BRCA2 cohorts according to hormone receptor status, ment of breast cancer in young women[4]. 12% of cases arising in women aged ≤40 years are related to germline pathogenic variants in BRCA1 or BRCA25,6. Young age at diagnosis is a primary malignancies (5.2% vs 1.4%, P = 0.005) in the BRCA1 cohort with hormone receptor-positive disease, being mostly ovarian cancer (Supplementary Table 4)

Methods

Results

Conclusion