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Publications

Journal Article Epublish

PubMed: 42747633 DOI: 10.1007/s10549-026-08067-4

Metastatic phenotype and post-metastatic survival across HER2-0, HER2-low, and HER2-positive breast cancer.

Breast Cancer Res Treat 219(3)

Authors: Ali Sanjari Moghaddam, Zhirui Deng, Susan M Sereika, Maryam Habib, Anna Homeniuk, Adam M Brufsky, Margaret Q Rosenzweig

Affiliations

  • Department of Medicine, University of Pittsburgh Medical Center, Harrisburg, PA, USA.
  • University of Pittsburgh School of Nursing, Pittsburgh, PA, USA.
  • Department of Medicine, Division of Hematology/Oncology, Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  • University of Pittsburgh School of Nursing, Pittsburgh, PA, USA.

Abstract

PURPOSE

HER2-low breast cancer is treatment-relevant, but whether it is clinically distinct from HER2-0 disease remains unclear. We evaluate metastasis-free interval (MFI), first metastatic site, and survival after metastasis among HER2 classes in metastatic breast cancer.

METHODS

We retrospectively examined patients with metastatic breast cancer classified as HER2-0, HER2-low, or HER2-positive. Analyses included the chi-square test of independence, Welch one-way ANOVA, Kaplan-Meier estimation, and binary and ordinal logistic and Cox regression models.

RESULTS

Among 1,599 patients, 647 (40.5%) had HER2-0 tumors, 672 (42%) had HER2-low tumors, and 280 (17.5%) had HER2-positive tumors. HER2-positive tumors had the shortest MFI compared with HER2-low and HER2-0 tumors (median 2.7 vs. 3.3 vs. 3.7 years, respectively; p = 0.002) and lower odds of late recurrence (≥ 5 years) compared with HER2-0 tumors (OR 0.39, 95% CI 0.22-0.68). HER2-low and HER2-0 tumors had similar metastatic timing. First metastatic site differed across HER2 groups in unadjusted analyses, although HER2 status was not independently associated with bone-only or CNS-only presentation in adjusted binary models. In adjusted Cox regression, HER2-low disease (HR 0.85, 95% CI 0.74-0.97) and HER2-positive disease (HR 0.73, 95% CI 0.60-0.88) were associated with lower hazard of death compared with HER2-0 disease.

CONCLUSION

HER2-positive disease was associated with earlier metastatic recurrence but more favorable post-metastatic survival. HER2-low disease had modestly improved post-metastatic survival but otherwise resembled HER2-0 disease in metastatic timing and adjusted metastatic presentation. These findings support HER2-low status for outcome stratification but suggest it may not independently define a distinct metastatic pattern.

CLINICAL TRIAL NUMBER

Not applicable.

MeSH

Breast Neoplasms, Neoplasms, Phenotype, Neoplasm Metastasis, Breast