EarlyR signature predicts response to neoadjuvant chemotherapy in breast cancer

Steven A. Buechler, Yesim Polar, Sunil Badve

Research output: Contribution to journalArticle

Abstract

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
JournalBreast
Volume43
DOIs
StatePublished - Feb 1 2019

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Breast Neoplasms
Drug Therapy
Hormones
Adjuvant Chemotherapy
Survival
Recurrence
Therapeutics
Genes

Keywords

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

ASJC Scopus subject areas

  • Surgery

Cite this

EarlyR signature predicts response to neoadjuvant chemotherapy in breast cancer. / Buechler, Steven A.; Polar, Yesim; Badve, Sunil.

In: Breast, Vol. 43, 01.02.2019, p. 74-80.

Research output: Contribution to journalArticle

@article{195df77ec8364e818ad021f71450e30f,
title = "EarlyR signature predicts response to neoadjuvant chemotherapy in breast cancer",
abstract = "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.",
keywords = "Breast cancer, Gene signature, Neoadjuvant chemotherapy response, Outcomes",
author = "Buechler, {Steven A.} and Yesim Polar and Sunil Badve",
year = "2019",
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journal = "Breast",
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TY - JOUR

T1 - EarlyR signature predicts response to neoadjuvant chemotherapy in breast cancer

AU - Buechler, Steven A.

AU - Polar, Yesim

AU - Badve, Sunil

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Gene signature

KW - Neoadjuvant chemotherapy response

KW - Outcomes

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