Epidermal growth factor receptor gene copy number may predict lapatinib sensitivity in HER2-positive metastatic breast cancer

Alessandra Fabi, Roberta Merola, Gianluigi Ferretti, Anna Di Benedetto, Barbara Antoniani, Cristiana Ercolani, Cecilia Nisticò, Paola Papaldo, Mariangela Ciccarese, Isabella Sperduti, Patrizia Vici, Mirella Marino, Stefania Gori, Claudio Botti, Paola Malaguti, Francesco Cognetti, Marcella Mottolese

Research output: Contribution to journalArticle

Abstract

Objective: Lapatinib, a dual HER2/EGFR tyrosine kinase inhibitor (TKI), associated to capecitabine represents the treatment of choice in HER2-positive metastatic breast cancer (BC) patients in progression after trastuzumab-based therapy. Though lapatinib-based therapy prolongs the time to progression, its efficacy is often limited by the development of drug resistance. It is aimed to evaluate novel biomarkers predictive of lapatinib response, we analyzed EGFR protein and gene status in a series of 50 metastatic HER2-positive BC patients. Methods: Lapatinib was given at 1250 mg/day continuously and capecitabine at 2000 mg/m2/day every 3 weeks. EGFR protein expression and gene copy number (GCN) were assessed by immunohistochemistry and FISH, respectively. Receiver operating curve (ROC) analysis identified the value of > 3.36 EGFR copies/nucleus as the cut-off point able to discriminate responders versus non-responders. Results: A statistical significant correlation between EGFR GCN value > 3.36 and response to lapatinib (p = 0.01) was found. Cox regression analysis further supported these findings evidencing that HER2 score 3+ and EGFR GCN increase are positive predictor factors of lapatinib response. Conclusions: Though further investigations are needed to confirm these findings, EGFR GCN could be a suitable screening to identify the subset of BC patients particularly responsive to the dual TKI lapatinib.

Original languageEnglish
Pages (from-to)699-706
Number of pages8
JournalExpert Opinion on Pharmacotherapy
Volume14
Issue number6
DOIs
Publication statusPublished - Apr 2013

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erbB-1 Genes
Gene Dosage
Breast Neoplasms
Protein-Tyrosine Kinases
lapatinib
Drug Resistance
Proteins
Therapeutics
Biomarkers
Immunohistochemistry
Regression Analysis

Keywords

  • EGFR amplification
  • HER2
  • HER3
  • Lapatinib
  • Metastatic breast cancer

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Epidermal growth factor receptor gene copy number may predict lapatinib sensitivity in HER2-positive metastatic breast cancer. / Fabi, Alessandra; Merola, Roberta; Ferretti, Gianluigi; Di Benedetto, Anna; Antoniani, Barbara; Ercolani, Cristiana; Nisticò, Cecilia; Papaldo, Paola; Ciccarese, Mariangela; Sperduti, Isabella; Vici, Patrizia; Marino, Mirella; Gori, Stefania; Botti, Claudio; Malaguti, Paola; Cognetti, Francesco; Mottolese, Marcella.

In: Expert Opinion on Pharmacotherapy, Vol. 14, No. 6, 04.2013, p. 699-706.

Research output: Contribution to journalArticle

Fabi, A, Merola, R, Ferretti, G, Di Benedetto, A, Antoniani, B, Ercolani, C, Nisticò, C, Papaldo, P, Ciccarese, M, Sperduti, I, Vici, P, Marino, M, Gori, S, Botti, C, Malaguti, P, Cognetti, F & Mottolese, M 2013, 'Epidermal growth factor receptor gene copy number may predict lapatinib sensitivity in HER2-positive metastatic breast cancer', Expert Opinion on Pharmacotherapy, vol. 14, no. 6, pp. 699-706. https://doi.org/10.1517/14656566.2013.779672
Fabi, Alessandra ; Merola, Roberta ; Ferretti, Gianluigi ; Di Benedetto, Anna ; Antoniani, Barbara ; Ercolani, Cristiana ; Nisticò, Cecilia ; Papaldo, Paola ; Ciccarese, Mariangela ; Sperduti, Isabella ; Vici, Patrizia ; Marino, Mirella ; Gori, Stefania ; Botti, Claudio ; Malaguti, Paola ; Cognetti, Francesco ; Mottolese, Marcella. / Epidermal growth factor receptor gene copy number may predict lapatinib sensitivity in HER2-positive metastatic breast cancer. In: Expert Opinion on Pharmacotherapy. 2013 ; Vol. 14, No. 6. pp. 699-706.
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AU - Merola, Roberta

AU - Ferretti, Gianluigi

AU - Di Benedetto, Anna

AU - Antoniani, Barbara

AU - Ercolani, Cristiana

AU - Nisticò, Cecilia

AU - Papaldo, Paola

AU - Ciccarese, Mariangela

AU - Sperduti, Isabella

AU - Vici, Patrizia

AU - Marino, Mirella

AU - Gori, Stefania

AU - Botti, Claudio

AU - Malaguti, Paola

AU - Cognetti, Francesco

AU - Mottolese, Marcella

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N2 - Objective: Lapatinib, a dual HER2/EGFR tyrosine kinase inhibitor (TKI), associated to capecitabine represents the treatment of choice in HER2-positive metastatic breast cancer (BC) patients in progression after trastuzumab-based therapy. Though lapatinib-based therapy prolongs the time to progression, its efficacy is often limited by the development of drug resistance. It is aimed to evaluate novel biomarkers predictive of lapatinib response, we analyzed EGFR protein and gene status in a series of 50 metastatic HER2-positive BC patients. Methods: Lapatinib was given at 1250 mg/day continuously and capecitabine at 2000 mg/m2/day every 3 weeks. EGFR protein expression and gene copy number (GCN) were assessed by immunohistochemistry and FISH, respectively. Receiver operating curve (ROC) analysis identified the value of > 3.36 EGFR copies/nucleus as the cut-off point able to discriminate responders versus non-responders. Results: A statistical significant correlation between EGFR GCN value > 3.36 and response to lapatinib (p = 0.01) was found. Cox regression analysis further supported these findings evidencing that HER2 score 3+ and EGFR GCN increase are positive predictor factors of lapatinib response. Conclusions: Though further investigations are needed to confirm these findings, EGFR GCN could be a suitable screening to identify the subset of BC patients particularly responsive to the dual TKI lapatinib.

AB - Objective: Lapatinib, a dual HER2/EGFR tyrosine kinase inhibitor (TKI), associated to capecitabine represents the treatment of choice in HER2-positive metastatic breast cancer (BC) patients in progression after trastuzumab-based therapy. Though lapatinib-based therapy prolongs the time to progression, its efficacy is often limited by the development of drug resistance. It is aimed to evaluate novel biomarkers predictive of lapatinib response, we analyzed EGFR protein and gene status in a series of 50 metastatic HER2-positive BC patients. Methods: Lapatinib was given at 1250 mg/day continuously and capecitabine at 2000 mg/m2/day every 3 weeks. EGFR protein expression and gene copy number (GCN) were assessed by immunohistochemistry and FISH, respectively. Receiver operating curve (ROC) analysis identified the value of > 3.36 EGFR copies/nucleus as the cut-off point able to discriminate responders versus non-responders. Results: A statistical significant correlation between EGFR GCN value > 3.36 and response to lapatinib (p = 0.01) was found. Cox regression analysis further supported these findings evidencing that HER2 score 3+ and EGFR GCN increase are positive predictor factors of lapatinib response. Conclusions: Though further investigations are needed to confirm these findings, EGFR GCN could be a suitable screening to identify the subset of BC patients particularly responsive to the dual TKI lapatinib.

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