Abstract
Background
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.
Methods
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).
Results
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.
Conclusions
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.
Keywords
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Article info
Publication history
Published online: March 22, 2022
Accepted:
March 20,
2022
Received in revised form:
March 9,
2022
Received:
December 7,
2021
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
