Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer

J Clin Oncol. 2006 Aug 10;24(23):3726-34. doi: 10.1200/JCO.2005.04.7985. Epub 2006 May 23.

Abstract

Purpose: The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive, lymph node-negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known.

Methods: The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS.

Results: A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (> or = 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, -1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit.

Conclusion: The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / prevention & control
  • Cisplatin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Linear Models
  • Lymphatic Metastasis
  • Methotrexate / administration & dosage
  • Middle Aged
  • Mitomycins / administration & dosage
  • Neoplasm Proteins / metabolism*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / prevention & control
  • Odds Ratio
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Receptors, Estrogen / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Assessment
  • Risk Factors
  • Secondary Prevention
  • Tamoxifen / administration & dosage

Substances

  • Biomarkers, Tumor
  • Mitomycins
  • Neoplasm Proteins
  • Receptors, Estrogen
  • Tamoxifen
  • Cisplatin
  • Fluorouracil
  • Methotrexate

Supplementary concepts

  • CMF protocol
  • FuMi protocol