EarlyR signature predicts response to neoadjuvant chemotherapy in breast cancer

Steven A. Buechler, Yesim Polar, Sunil Badve

Research output: Contribution to journalArticle

1 Scopus citations


Background: EarlyR gene signature uses ESPL1, SPAG5, MKI67, PLK1 and PGR to classify ER+ breast cancer (ER+ BC) into EarlyR-Low, EarlyR-Int, and EarlyR-High risk strata and is prognostic in patients treated with adjuvant chemotherapy. The ability of EarlyR to predict pathological complete response (pCR) and long-term survival following neoadjuvant chemotherapy (NACT) is evaluated herein. Materials: The ability of EarlyR gene signature to predict pCR was assessed in publicly available Affymetrix microarray datasets (Cohort A; n = 659; 74 pCR events) derived from NACT-treated ER+ BC patients. Distant relapse-free survival (DRFS) results were analyzed in patients treated with NACT and adjuvant hormone therapy (AHT) (n = 281) and compared with patients treated with AHT alone (n = 455) (Cohort B; n = 736; 142 events). Results: In cohort A, EarlyR was a significant predictor of pCR (p = 5.8 × 10−11) (EarlyR-Low, n = 400, pCR = 40, 5%; EarlyR-Int, n = 69, pCR = 7, 15% and EarlyR-High, n = 190, pCR = 47, 24%). In EarlyR-Low of Cohort B, the 5-year DRFS was not significantly (p = 0.55) different between NACT + AHT [0.81 (95%CI 0.73–0.90)] and AHT-only [0.85 (95%CI 0.81–0.90)]. In contrast, in EarlyR-High, the 5-year DRFS was higher (p = 0.019) in NACT + AHT [0.81 (95%CI 0.70–0.93)] as compared to AHT-only [0.60 (95%CI 0.51–0.71)]. Conclusions: High EarlyR is strongly associated with pCR in patients treated with neoadjuvant chemotherapy. EarlyR also predicts poor DRFS outcomes for patients in EarlyR-High not receiving NACT, and improved survival in NACT-treated EarlyR-High patients. EarlyR is not only a prognostic assay but also a predictive assay that identifies patients, who are also likely to respond to chemotherapy.

Original languageEnglish (US)
Pages (from-to)74-80
Number of pages7
StatePublished - Feb 1 2019


  • Breast cancer
  • Gene signature
  • Neoadjuvant chemotherapy response
  • Outcomes

ASJC Scopus subject areas

  • Surgery

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