ER+/HER2+ Breast Cancer Has Different Metastatic Patterns and Better Survival Than ER-/HER2+ Breast Cancer

Clin Breast Cancer. 2019 Aug;19(4):236-245. doi: 10.1016/j.clbc.2019.02.001. Epub 2019 Feb 14.


Background: Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is generally treated with HER2-targeted therapy combined with chemotherapy. Patients with HER2+ and estrogen receptor-positive (ER+) cancer are additionally treated with long-term hormone therapy. This study examined the metastatic pattern and prognosis of both ER+/HER2+ and ER-/HER2+ breast cancer.

Patients and methods: A total of 54,147 patients with HER2+ breast cancer from the National Cancer Data Base (NCDB, 2010-2013) and 31,946 patients with HER2+ breast cancer from the Surveillance, Epidemiology, and End Results Program (SEER, 2010-2014) were examined. Sites of metastasis and overall survival (OS) were examined in the NCDB, while OS and breast cancer-specific survival were examined in the SEER database.

Results: Compared to ER-/HER2+ breast cancer, ER+/HER2+ breast cancer was more likely to metastasize to bone but less likely to brain, liver, and lung and less likely to result in multiple metastases. In univariate analysis based on the NCDB, patients with ER-/HER2+ breast cancer had worse OS in all metastasis subsets, including patients who received HER2-targeted therapy. This poor survival for ER-/HER2+ persisted in patients with metastasis to bone and lung, and multiple metastases. In multivariate analysis adjusting for age, tumor grade, surgery, chemotherapy, HER2-targeted therapy, and hormone therapy, ER-/HER2+ patients with bone metastasis still had worse OS. In the SEER, ER-/HER2+ patients had both worse OS and breast cancer-specific survival in univariate analysis.

Conclusion: This large study showed patients with ER+/HER2+ and ER-/HER2+ breast cancers had different metastatic patterns. Patients with ER-/HER2+ breast cancer may require more aggressive treatment.

Keywords: Bone metastasis; Breast cancer subtype; Liver metastasis; Lung metastasis; Metastasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Neoplasm Metastasis
  • Prognosis
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*
  • SEER Program
  • Survival Rate


  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2