Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics

J Natl Cancer Inst. 2008 Oct 1;100(19):1380-8. doi: 10.1093/jnci/djn309. Epub 2008 Sep 23.

Abstract

Background: Understanding how tumor response is related to relapse risk would help clinicians make decisions about additional treatment options for patients who have received neoadjuvant endocrine treatment for estrogen receptor-positive (ER+) breast cancer.

Methods: Tumors from 228 postmenopausal women with confirmed ER+ stage 2 and 3 breast cancers in the P024 neoadjuvant endocrine therapy trial, which compared letrozole and tamoxifen for 4 months before surgery, were analyzed for posttreatment ER status, Ki67 proliferation index, histological grade, pathological tumor size, node status, and treatment response. Cox proportional hazards were used to identify factors associated with relapse-free survival (RFS) and breast cancer-specific survival (BCSS) in 158 women. A preoperative endocrine prognostic index (PEPI) for RFS was developed from these data and validated in an independent study of 203 postmenopausal women in the IMPACT trial, which compared treatment with anastrozole, tamoxifen, or the combination 3 months before surgery. Statistical tests were two-sided.

Results: Median follow-up in P024 was 61.2 months. Patients with confirmed baseline ER+ clinical stage 2 and 3 tumors that were downstaged to stage 1 or 0 at surgery had 100% RFS (compared with higher stages, P < .001). Multivariable testing of posttreatment tumor characteristics revealed that pathological tumor size, node status, Ki67 level, and ER status were independently associated with both RFS and BCSS. The PEPI model based on these factors predicted RFS in the IMPACT trial (P = .002).

Conclusions: Breast cancer patients with pathological stage 1 or 0 disease after neoadjuvant endocrine therapy and a low-risk biomarker profile in the surgical specimen (PEPI score 0) have an extremely low risk of relapse and are therefore unlikely to benefit from adjuvant chemotherapy.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Analysis of Variance
  • Anastrozole
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Aromatase Inhibitors / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Chemotherapy, Adjuvant
  • Clinical Trials as Topic
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / analysis
  • Letrozole
  • Lymphatic Metastasis
  • Middle Aged
  • Neoadjuvant Therapy / methods*
  • Neoplasm Staging
  • Nitriles / therapeutic use
  • Postmenopause
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Receptors, Estrogen / analysis*
  • Reproducibility of Results
  • Risk Assessment
  • Risk Factors
  • Tamoxifen / therapeutic use
  • Treatment Outcome
  • Triazoles / therapeutic use

Substances

  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Nitriles
  • Receptors, Estrogen
  • Triazoles
  • Tamoxifen
  • Anastrozole
  • Letrozole