Overall Survival for HER2-Positive Breast Cancer Patients in the HER2-Targeted Era: Evidence From a Population-Based Study

  • Vicente Rodrigues Marczyk
    Thyroid Unit, Endocrine division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Medical School, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
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  • Daniela Dornelles Rosa
    Hospital Moinhos de Vento, Porto Alegre, RS, Brazil

    Brazilian Breast Cancer Study Group (GBECAM), Brazil
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  • Ana Luiza Maia
    Thyroid Unit, Endocrine division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Medical School, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
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  • Iuri Martin Goemann
    Address for correspondence: Iuri Martin Goemann, MD, PhD, Thyroid Section, Endocrine Division, Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90035-903, Porto Alegre, RS, Brazil.
    Thyroid Unit, Endocrine division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Medical School, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Medical School, Universidade do Vale do Rio dos Sinos, São Leopoldo, RS, Brazil
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Published:March 22, 2022DOI:



      HER2-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.


      We 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).


      A 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.


      HER2-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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