title: Prognostic utility of the breast cancer index and comparison to Adjuvant! Online in a clinical case series of early breast cancer.
abstract: BACKGROUND
  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.
authors: Department of Medicine, Division of Hematology/Oncology, UPMC, University of Pittsburgh Cancer Institute, 300 Halket Street, Suite 4628, Pittsburgh, PA 15213, USA. jankowitzr@upmc.edu
authors: Rachel C
authors: RC
authors: Jankowitz
authors: Kristine
authors: K
authors: Cooper
authors: Mark G
authors: MG
authors: Erlander
authors: Xiao-Jun
authors: XJ
authors: Ma
authors: Nicole C
authors: NC
authors: Kesty
authors: Hongying
authors: H
authors: Li
authors: Mamatha
authors: M
authors: Chivukula
authors: Adam
authors: A
authors: Brufsky
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020690:GTPase-Activating Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D000072379:NIMA-Related Kinases; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009862:Online Systems; D011379:Prognosis; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D053722:Receptors, Interleukin-17; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D020690:GTPase-Activating Proteins; C484414:HOXB13 protein, human; D018398:Homeodomain Proteins; C408922:IL17RB protein, human; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; C115995:mgcRacGAP; D013629:Tamoxifen; C090464:Bub1 spindle checkpoint protein; C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases