Impact of triple negative phenotype on breast cancer prognosis

Breast J. 2008 Sep-Oct;14(5):456-63. doi: 10.1111/j.1524-4741.2008.00622.x. Epub 2008 Jul 24.

Abstract

Triple negative (TN) [estrogen receptor (ER), progesterone receptor (PgR)] (ER-/PgR-/Her2/neu-) breast cancer (BC) is an aggressive disease without tumor-specific treatment options. Our objective is to evaluate the relative contribution of combined Her2/neu (Her2) and hormone receptor (HR) status to BC progression. A prospective primary BC cohort of 1550 patients at our institution, stage I-IV, from 1998 to 2003 were categorized by HR and Her2 status into ER+/PgR+/Her2- (HR+/Her2-) (n = 1134), ER+/PgR+/Her2+ [triple positive (TP)] (n = 138), ER-/PgR-/Her2- (TN) (n = 183), and ER-/PgR-/Her2+ (HR-/Her2+) (n = 95). Clinical variables were chart abstracted and vital and disease status updated annually. Log-rank tests and Cox regression analyses were used to assess associations with survival. Patient age ranged from 21 to 88 years and average length of follow-up was 4.24 years. Overall survival at 5 years was 94% (HR+/Her2-), 91% (TP), and 81% (TN and HR-/Her2+) (log rank test = 22.22, p < 0.001). Disease-specific survival at 5 years was 98% (HR+/Her2-), 93% (TP), 88% (TN), and 86% (HR-/Her2+) (log rank test = 25.85, p < 0.001) and 5-year relapse-free survival was 95% (HR+/Her2-), 89% (TP), 84% (TN), and 76% (HR-/Her2+) (log rank test = 20.29, p < 0.001). In a model adjusted for age, race, TNM stage, and treatment using HR+/Her2- patients as the reference group, recurrence risk was 1.98 for TP (95% CI = 1.02 to 3.84), 2.32 for TN (95% CI = 1.32 to 4.08), and 4.25 for HR-/Her2+ patients (95% CI = 2.33, 7.75). A hierarchy of BC phenotypes defined by HR and Her2 status exists with progressively worse disease outcomes by category.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Biopsy, Needle
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / therapy*
  • Cohort Studies
  • Combined Modality Therapy
  • Confidence Intervals
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Staging
  • Odds Ratio
  • Phenotype
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism*
  • Retrospective Studies
  • Risk Assessment
  • Sensitivity and Specificity
  • Survival Analysis
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2