The role of human epidermal growth factor receptor 2 in the survival of women with estrogen and progesterone receptor-negative, invasive breast cancer: the California Cancer Registry, 1999-2004

Cancer. 2008 Feb 15;112(4):737-47. doi: 10.1002/cncr.23243.


Background: Breast cancers that are negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) (triple negative [TN]) have been associated with high-grade histology, aggressive clinical behavior, and poor survival. It has been determined that breast cancers that are negative for ER and PR but positive for HER2 (double negative [DN]) share features with TN breast cancers. In this report, the authors quantified the contribution of HER2 as well as demographic and tumor characteristics to the survival of women with TN tumors, DN tumors, and other breast cancers (OBC).

Methods: In total, 61,309 women who were diagnosed with invasive breast cancer between 1999-2004 were identified in the California Cancer Registry. Demographic and tumor characteristics of women with TN tumors were compared with those from women with DN tumors and women with OBC. A compound proportional hazards regression analysis (PHPH) (a generalization of the Cox proportional hazards model) was used to model these characteristics.

Results: Women with TN tumors were younger, African American, Hispanic, and of lower socioeconomic status (SES), whereas women with DN tumors were slightly older; African American, and Asian/Pacific Islander. Women with TN and DN tumors presented with larger, higher grade, and higher stage than women with OBC. Survival among women with TN tumors was poorer compared with that among women with OBC but was nearly the same as that of women with DN tumors. Results of the regression analysis indicated that disease stage, tumor grade, SES, and race/ethnicity were significant risk factors for survival. Negative ER and PR status was associated with an increased risk of death. There was a small but significant difference in both long-term and short-term survival patients who had TN tumors compared with patients who had DN tumors.

Conclusions: Patients with TN tumors shared many clinical, demographic, and tumor features and had survival that was very similar survival to that of patients with DN tumors, and survival for both groups contrasted greatly with survival for patients with OBC. Disease stage, tumor grade, SES, race/ethnicity, negative ER and PR status, rather than negative HER2 status, were risk factors for survival.

Publication types

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

MeSH terms

  • African Americans / statistics & numerical data
  • Algorithms
  • Asian Americans / statistics & numerical data
  • Breast Neoplasms / ethnology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • California / epidemiology
  • Female
  • Hispanic Americans / statistics & numerical data
  • Humans
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Receptor, ErbB-2 / analysis*
  • Receptor, ErbB-2 / physiology
  • Receptors, Estrogen / analysis*
  • Receptors, Progesterone / analysis*
  • Registries / statistics & numerical data
  • Regression Analysis
  • Social Class
  • Survival Analysis


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