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 language | English |
|---|---|
| Pages (from-to) | 699-706 |
| Number of pages | 8 |
| Journal | Expert Opinion on Pharmacotherapy |
| Volume | 14 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Apr 2013 |
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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 journal › Article
}
TY - JOUR
T1 - Epidermal growth factor receptor gene copy number may predict lapatinib sensitivity in HER2-positive metastatic breast cancer
AU - Fabi, Alessandra
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
PY - 2013/4
Y1 - 2013/4
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.
KW - EGFR amplification
KW - HER2
KW - HER3
KW - Lapatinib
KW - Metastatic breast cancer
UR - http://www.scopus.com/inward/record.url?scp=84875199261&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875199261&partnerID=8YFLogxK
U2 - 10.1517/14656566.2013.779672
DO - 10.1517/14656566.2013.779672
M3 - Article
C2 - 23472669
AN - SCOPUS:84875199261
VL - 14
SP - 699
EP - 706
JO - Expert Opinion on Pharmacotherapy
JF - Expert Opinion on Pharmacotherapy
SN - 1465-6566
IS - 6
ER -