Prognostic implications of HER2NEU-low in metastatic breast cancer

Zachary Neubauer, Shaakir Hasan, Robert H. Press, Arpit M. Chhabra, Jana Fox, Richard Bakst, Charles B. Simone, J. Isabelle Choi

Research output: Contribution to journalArticlepeer-review


Introduction: We explored characteristics and clinical outcomes of HER2-negative and HER2-low metastatic breast cancers using real-world data. Methods: We queried the National Cancer Database to identify MBC patients that were HER2-low or HER2-negative per immunohistochemical staining. A binomial regression analysis identified demographic and clinical correlates of each subtype. A Cox multivariable regression analysis (MVA) and propensity-match analysis were performed to identify correlates of survival. Results: Excluding missing data, 24,636 MBC patients diagnosed between 2008 and 2015 were identified; 27.9% were HER2-negative and 72.1% were HER2-low. There were no relevant demographic differences between the groups. HER2-low tumors were half as likely to have concomitant hormone receptor-positive status (p < 0.01). The 3-year survival rate among hormone receptor-negative patients was 33.8% for HER2-low and 32.2% for HER2-negative (p < 0.05), and 60.9% and 55.6% in HER2-low and HER2-negative cases among hormone receptor-positive patients (p < 0.05), respectively. HER2-low cases were associated with better survival on MVA (HR =0.95, 95% CI 0.91–0.99) and remained superior with propensity-matching (HR = 0.92, 95% CI 0.89–0.96). In a subset analysis isolated to hormone receptor-positive cases, HER2-low remained correlated with improved survival (HR = 0.93, 95% CI 0.89–0.98) with propensity-matched MVA. Correlates of worse survival include older age as a continuous variable (HR = 1.02, 95% CI 1.02–1.02) and Black race (HR = 1.26, 95% CI 1.20–1.32) [all p < 0.01]. Conclusions: In the largest such analysis performed to date, our study demonstrates a small but statistically significant association with improved survival for HER2-low tumors compared to HER2-negative tumors in MBC.

Original languageEnglish
Article numbere6979
JournalCancer Medicine
Issue number2
StatePublished - Jan 2024


  • HER2 expression
  • National Cancer Database
  • hormone receptor status
  • metastatic breast cancer
  • overall survival


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