Overall Survival for HER2-Positive Breast Cancer Patients in the HER2-Targeted Era: Evidence From a Population-Based Study |
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| Institution: | 1. Thyroid Unit, Endocrine division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil;2. Medical School, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil;3. Hospital Moinhos de Vento, Porto Alegre, RS, Brazil;4. Brazilian Breast Cancer Study Group (GBECAM), Brazil;5. Medical School, Universidade do Vale do Rio dos Sinos, São Leopoldo, RS, Brazil;1. Department of Plastic and Reconstructive Surgery, IFO – “Regina Elena” National Cancer Institute, Rome, Italy;2. Medicinaplasticaroma Center, Plastic Surgery, Rome, Italy;1. Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA;2. Division of Radiology, Massachusetts General Hospital, Boston, MA;1. Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Davie, FL;2. Division of Surgical Oncology, Department of Surgery, Miller School of Medicine, University of Miami, FL;1. Department of Radiology, Obafemi Awolowo University/Obafemi Awolowo University Teaching Hospitals Complex, Ile Ife, Nigeria;3. Department of Surgery, Obafemi Awolowo University/Obafemi Awolowo University Teaching Hospitals Complex, Ile Ife, Nigeria;5. Department of Community Health, Obafemi Awolowo University/Obafemi Awolowo University Teaching Hospitals Complex, Ile Ife, Nigeria;6. Department of Radiology, Lagos State University/Lagos State University Teaching Hospital, Lagos, Nigeria;1. Health data and assessment department, Survey Data Science and Assessment Division, National cancer institute, Boulogne-Billancourt, France;2. Loire-Atlantique/Vendée Cancer Registry, Nantes, France;3. CERPOP, Université de Toulouse, Toulouse, France;4. Santé Publique France, French National Public Health Agency, Saint-Maurice, France;5. Public health division, National cancer institute, Boulogne-Billancourt, France;6. National cancer Institute, Boulogne-Billancourt, France;7. Survey Data Science and Assessment Division, National cancer institute, Boulogne-Billancourt, France;8. Aix Marseille Univ, INSERM, IRD, Economics and Social Sciences Applied to Health & Analysis of Medical Information (SESSTIM), Marseille, France |
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| Abstract: | BackgroundHER2-positive breast cancer is an aggressive tumor subtype and it is usually associated with worse clinical outcomes. Given the advances in HER2-targeted therapies, we hypothesized that HER2 amplification is no longer a marker of poor prognosis.MethodsWe conducted a population-based observational study employing two independent cohorts of patients with breast cancer. Samples from the METABRIC cohort were collected before clinical availability of HER2-targeted therapies, whereas samples from the SCAN-B cohort were collected afterward. The primary endpoint was overall survival (OS).ResultsA total of 5121 patients were included in the analyses. In both cohorts, HER2-positive tumors were more likely to be node-positive (P < .05) and high grade (P < .001). Before HER2-targeted agents, HER2 patients had a significantly worse 5-year OS than hormone receptor-positive (HR+) patients (63.4% vs. 83.0%, HR = 2.49, P < .001). In contrast, after HER2-targeted agents entered clinical practice, 5-year OS no longer differed (88.3% vs. 90.4%, HR = 1.24, P = .17). Additionally, in an exploratory analysis using PAM50 subtypes, we identified that, after HER2-targeted therapies were implemented, patients clinically HER2-negative but PAM50-HER2-enriched have a lower OS (HR = 1.99, P = .009) than those who are both HER2-positive and PAM50-HER2-enriched, since they have not benefitted from HER2-targeted therapies.ConclusionsHER2-targeted therapies dramatically altered the natural history of HER2-positive breast cancer, with overall survival approaching those of luminal subtype. HER2 positivity is no longer a marker of poor prognosis if access to HER2-targeted therapies is granted. Future trials should assess whether HER2-negative PAM50-HER2-enriched patients may also benefit from such therapies. |
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