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
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical Breast CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.Science (80-). 1987; 235https://doi.org/10.1126/science.3798106
- HER2-positive breast cancer.Lancet. 2017; 389https://doi.org/10.1016/S0140-6736(16)32417-5
- Molecular portraits of human breast tumours.Nature. 2000; 406: 747-752https://doi.org/10.1038/35021093
- Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications.Proc Natl Acad Sci U S A. 2001; 98https://doi.org/10.1073/pnas.191367098
- Repeated observation of breast tumor subtypes in independent gene expression data sets.Proc Natl Acad Sci U S A. 2003; 100https://doi.org/10.1073/pnas.0932692100
- The molecular portraits of breast tumors are conserved across microarray platforms.BMC Genom. 2006; 7https://doi.org/10.1186/1471-2164-7-96
- Supervised risk predictor of breast cancer based on intrinsic subtypes.J Clin Oncol. 2009; 27: 1160-1167https://doi.org/10.1200/JCO.2008.18.1370
- The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups.Nature. 2012; (Published online)https://doi.org/10.1038/nature10983
- The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes.Nat Commun. 2016; 7https://doi.org/10.1038/ncomms11479
- The mutational landscape of the SCAN -B real-world primary breast cancer transcriptome.EMBO Mol Med. 2020; 12https://doi.org/10.15252/emmm.202012118
- Clinical value of RNA sequencing–based classifiers for prediction of the five conventional breast cancer biomarkers: a report from the population-based multicenter sweden cancerome analysis network—breast initiative.JCO Precis Oncol. 2018; (Published online)https://doi.org/10.1200/po.17.00135
- The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data.Cancer Discov. 2012; (Published online)https://doi.org/10.1158/2159-8290.CD-12-0095
- Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.Sci Signal. 2013; (Published online)https://doi.org/10.1126/scisignal.2004088
- Missing covariate data within cancer prognostic studies: a review of current reporting and proposed guidelines.Br J Cancer. 2004; 91https://doi.org/10.1038/sj.bjc.6601907
- Comprehensive molecular portraits of human breast tumours.Nature. 2012; (Published online)https://doi.org/10.1038/nature11412
- The Sweden Cancerome Analysis Network - Breast (SCAN-B) Initiative: a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine.Genome Med. 2015; 7https://doi.org/10.1186/s13073-015-0131-9
- Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib.J Clin Oncol. 2016; 34https://doi.org/10.1200/JCO.2015.62.1268
- Meta-analysis of HER2-enriched subtype predicting the pathological complete response within HER2-positive breast cancer in patients who received neoadjuvant treatment.Front Oncol. 2021; 11https://doi.org/10.3389/fonc.2021.632357
- Incidence trends of breast cancer molecular subtypes by age and race/ethnicity in the US from 2010 to 2016.JAMA Netw Open. 2020; 3https://doi.org/10.1001/jamanetworkopen.2020.13226
- Trends in advanced breast cancer incidence rates after implementation of a mammography screening program in a German population.Cancer Epidemiol. 2016; 44https://doi.org/10.1016/j.canep.2016.07.006
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.