Utilization of the 21-Gene Recurrence Score in a Diverse Breast Cancer Patient Population: Development of a Clinicopathologic Model to Predict High-Risk Scores and Response to Neoadjuvant Chemotherapy

Ann Surg Oncol. 2018 Jul;25(7):1921-1927. doi: 10.1245/s10434-018-6440-7. Epub 2018 Apr 20.

Abstract

Introduction: The 21-gene expression profile [Oncotype DX Recurrence Score (RS)] stratifies benefit from adjuvant chemotherapy in hormone receptor (HR)-positive, HER2/neu-negative, node-negative breast cancer. It is not routinely applied to predict neoadjuvant chemotherapy (NACT) response; data in diverse patient populations also are limited. We developed a statistical model based on standard clinicopathologic features to identify high-risk cases (RS > 30) and then evaluated ability of predicted high RS to predict for NACT downstaging.

Methods: Primary surgery patients with Oncotype DX RS testing 2012-2016 were identified from a prospectively-maintained database. A RS predictive model was created and applied to a dataset of comparable NACT patients. Response was defined as tumor size decrease ≥ 1 cm.

Results: Of 394 primary surgery patients-60.4% white American; 31.0% African American-RS distribution was similar for both groups. No single feature reliably identified high RS patients; however, a model accounting for age, HR expression, proliferative index (MIB1/Ki67), histology, and tumor size was generated, with receiver operator area under the curve 0.909. Fifty-six NACT patients were identified (25 African American). Of 21 cases with all relevant clinicopathology, 14 responded to NACT and the model generated high-risk RS in 14 (100%); conversely, of 16 cases generating high-risk RS, only 2 did not respond.

Conclusions: Predictive modelling can identify high RS patients; this model also can identify patients likely to experience primary tumor downstaging with NACT. Until this model is validated in other datasets, we recommend that Oncotype-eligible patients undergo primary surgery with decisions regarding chemotherapy made in the adjuvant setting.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / drug therapy
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / pathology*
  • Carcinoma, Lobular / drug therapy
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / pathology*
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling*
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology*
  • Prognosis
  • Survival Rate

Substances

  • Biomarkers, Tumor