Combined pathologic-genomic algorithm for early-stage breast cancer improves cost-effective use of the 21-gene recurrence score assay

Ann Oncol. 2018 May 1;29(5):1280-1285. doi: 10.1093/annonc/mdy074.

Abstract

Background: The 21-gene recurrence score (RS) (Oncotype DX®; Genomic Health, Redwood City, CA) partitions hormone receptor positive, node negative breast cancers into three risk groups for recurrence. The Anne Arundel Medical Center (AAMC) model has previously been shown to accurately predict RS risk categories using standard pathology data. A pathologic-genomic (P-G) algorithm then is presented using the AAMC model and reserving the RS assay only for AAMC intermediate-risk patients.

Patients and methods: A survival analysis was done using a prospectively collected institutional database of newly diagnosed invasive breast cancers that underwent RS assay testing from February 2005 to May 2015. Patients were assigned to risk categories based on the AAMC model. Using Kaplan-Meier methods, 5-year distant recurrence rates (DRR) were evaluated within each risk group and compared between AAMC and RS-defined risk groups. Five-year DRR were calculated for the P-G algorithm and compared with DRR for RS risk groups and the AAMC model's risk groups.

Results: A total of 1268 cases were included. Five-year DRR were similar between the AAMC low-risk group (2.7%, n = 322) and the RS < 18 low-risk group (3.4%, n = 703), as well as between the AAMC high-risk group (22.8%, n = 230) and the RS > 30 high-risk group (23.0%, n = 141). Using the P-G algorithm, more patients were categorized as either low or high risk and the distant metastasis rate was 3.3% for the low-risk group (n = 739) and 24.2% for the high-risk group (n = 272). Using the P-G algorithm, 44% (552/1268) of patients would have avoided RS testing.

Conclusions: AAMC model is capable of predicting 5-year recurrences in high- and low-risk groups similar to RS. Further, using the P-G algorithm, reserving RS for AAMC intermediate cases, results in larger low- and high-risk groups with similar prognostic accuracy. Thus, the P-G algorithm reliably identifies a significant portion of patients unlikely to benefit from RS assay and with improved ability to categorize risk.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Biomarkers, Tumor / genetics*
  • Breast / pathology
  • Breast / surgery
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy
  • Chemotherapy, Adjuvant / methods
  • Cost-Benefit Analysis
  • Female
  • Follow-Up Studies
  • Genetic Testing / economics
  • Genetic Testing / methods*
  • Humans
  • Incidence
  • Mastectomy
  • Middle Aged
  • Models, Genetic*
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / prevention & control
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Risk Assessment / economics
  • Risk Assessment / methods
  • Time Factors
  • Treatment Outcome
  • Tumor Burden / genetics

Substances

  • Biomarkers, Tumor