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/m(2)/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.
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/m(2)/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.
Authors: H J Lee; A N Seo; E J Kim; M H Jang; Y J Kim; J H Kim; S-W Kim; H S Ryu; I A Park; S-A Im; G Gong; K H Jung; H J Kim; S Y Park Journal: Br J Cancer Date: 2014-10-28 Impact factor: 7.640
Authors: Renata Duchnowska; Jeff Sperinde; Bogumiła Czartoryska-Arłukowicz; Paulina Myśliwiec; John Winslow; Barbara Radecka; Christos Petropoulos; Regina Demlova; Marlena Orlikowska; Anna Kowalczyk; Istvan Lang; Barbara Ziółkowska; Sylwia Dębska-Szmich; Monika Merdalska; Aleksandra Grela-Wojewoda; Anton Żawrocki; Wojciech Biernat; Weidong Huang; Jacek Jassem Journal: Oncotarget Date: 2017-10-24
Authors: Brian Godman; Alexander E Finlayson; Parneet K Cheema; Eva Zebedin-Brandl; Inaki Gutiérrez-Ibarluzea; Jan Jones; Rickard E Malmström; Elina Asola; Christoph Baumgärtel; Marion Bennie; Iain Bishop; Anna Bucsics; Stephen Campbell; Eduardo Diogene; Alessandra Ferrario; Jurij Fürst; Kristina Garuoliene; Miguel Gomes; Katharine Harris; Alan Haycox; Harald Herholz; Krystyna Hviding; Saira Jan; Marija Kalaba; Christina Kvalheim; Ott Laius; Sven-Ake Lööv; Kamila Malinowska; Andrew Martin; Laura McCullagh; Fredrik Nilsson; Ken Paterson; Ulrich Schwabe; Gisbert Selke; Catherine Sermet; Steven Simoens; Dominik Tomek; Vera Vlahovic-Palcevski; Luka Voncina; Magdalena Wladysiuk; Menno van Woerkom; Durhane Wong-Rieger; Corrine Zara; Raghib Ali; Lars L Gustafsson Journal: BMC Med Date: 2013-08-13 Impact factor: 8.775
Authors: Jennifer J Wheler; Barbara A Parker; Jack J Lee; Johnique T Atkins; Filip Janku; Apostolia M Tsimberidou; Ralph Zinner; Vivek Subbiah; Siqing Fu; Richard Schwab; Stacy Moulder; Vicente Valero; Maria Schwaederle; Roman Yelensky; Vincent A Miller; M Philip J Stephens; Funda Meric-Bernstam; Razelle Kurzrock Journal: Oncotarget Date: 2014-05-15