Prognostic utility of the breast cancer index and comparison to Adjuvant! Online in a clinical case series of early breast cancer

Breast Cancer Res. 2011 Oct 14;13(5):R98. doi: 10.1186/bcr3038.

Abstract

Introduction: Breast Cancer Index (BCI) combines two independent biomarkers, HOXB13:IL17BR (H:I) and the 5-gene molecular grade index (MGI), that assess estrogen-mediated signalling and tumor grade, respectively. BCI stratifies early-stage estrogen-receptor positive (ER+), lymph-node negative (LN-) breast cancer patients into three risk groups and provides a continuous assessment of individual risk of distant recurrence. Objectives of the current study were to validate BCI in a clinical case series and to compare the prognostic utility of BCI and Adjuvant!Online (AO).

Methods: Tumor samples from 265 ER+LN- tamoxifen-treated patients were identified from a single academic institution's cancer research registry. The BCI assay was performed and scores were assigned based on a pre-determined risk model. Risk was assessed by BCI and AO and correlated to clinical outcomes in the patient cohort.

Results: BCI was a significant predictor of outcome in a cohort of 265 ER+LN- patients (median age: 56-y; median follow-up: 10.3-y), treated with adjuvant tamoxifen alone or tamoxifen with chemotherapy (32%). BCI categorized 55%, 21%, and 24% of patients as low, intermediate and high-risk, respectively. The 10-year rates of distant recurrence were 6.6%, 12.1% and 31.9% and of breast cancer-specific mortality were 3.8%, 3.6% and 22.1% in low, intermediate, and high-risk groups, respectively. In a multivariate analysis including clinicopathological factors, BCI was a significant predictor of distant recurrence (HR for 5-unit increase = 5.32 [CI 2.18-13.01; P = 0.0002]) and breast cancer-specific mortality (HR for a 5-unit increase = 9.60 [CI 3.20-28.80; P < 0.0001]). AO was significantly associated with risk of recurrence. In a separate multivariate analysis, both BCI and AO were significantly predictive of outcome. In a time-dependent (10-y) ROC curve accuracy analysis of recurrence risk, the addition of BCI+AO increased predictive accuracy in all patients from 66% (AO only) to 76% (AO+BCI) and in tamoxifen-only treated patients from 65% to 81%.

Conclusions: This study validates the prognostic performance of BCI in ER+LN- patients. In this characteristically low-risk cohort, BCI classified high versus low-risk groups with ~5-fold difference in 10-year risk of distant recurrence and breast cancer-specific death. BCI and AO are independent predictors with BCI having additive utility beyond standard of care parameters that are encompassed in AO.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • GTPase-Activating Proteins / genetics
  • Homeodomain Proteins / genetics
  • Humans
  • Middle Aged
  • NIMA-Related Kinases
  • Neoplasm Recurrence, Local / drug therapy
  • Online Systems*
  • Prognosis
  • Proportional Hazards Models
  • Protein-Serine-Threonine Kinases / genetics
  • Receptors, Interleukin / genetics
  • Survival Rate
  • Tamoxifen / therapeutic use

Substances

  • GTPase-Activating Proteins
  • HOXB13 protein, human
  • Homeodomain Proteins
  • IL17RB protein, human
  • Receptors, Interleukin
  • mgcRacGAP
  • Tamoxifen
  • Bub1 spindle checkpoint protein
  • NEK2 protein, human
  • NIMA-Related Kinases
  • Protein-Serine-Threonine Kinases