Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Predictive value of quantitative HER2, HER3 and p95HER2 levels in HER2-positive advanced breast cancer patients treated with lapatinib following progression on trastuzumab

R. Duchnowska, J. Sperinde, B. Czartoryska-Arłukowicz, P. Myśliwiec, J. Winslow, B. Radecka, C. Petropoulos, R. Demlova, M. Orlikowska, A. Kowalczyk, I. Lang, B. Ziółkowska, S. Dębska-Szmich, M. Merdalska, A. Grela-Wojewoda, A. Żawrocki, W....

. 2017 ; 8 (61) : 104149-104159. [pub] 20171024

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc18000874

Lapatinib is a HER1 and HER2 tyrosine kinase inhibitor (TKI) approved in second line treatment of advanced or metastatic breast cancer following progression on trastuzumab-containing therapy. Biomarkers for activity of lapatinib and other TKIs are lacking. Formalin-fixed, paraffin-embedded primary tumor samples were obtained from 189 HER2-positive patients treated with lapatinib plus capecitabine following progression on trastuzumab. The HERmark® Breast Cancer Assay was used to quantify HER2 protein expression. HER3 and p95HER2 protein expression was quantified using the VeraTag® technology. Overall survival (OS) was inversely correlated with HER2 (HR = 1.9/log; P = 0.009) for patients with tumors above the cut-off positivity level by the HERmark assay. OS was significantly shorter for those with above median HER2 levels (HR = 1.7; P = 0.015) and trended shorter for those below the cut-off level of positivity by the HERmark assay (HR = 1.7; P = 0.057) compared to cases with moderate HER2 overexpression. The relationship between HER2 protein expression and OS was best captured with a U-shaped parabolic function (P = 0.004), with the best prognosis at moderate levels of HER2 protein overexpression. In a multivariate model including HER2, increasing p95HER2 expression was associated with longer OS (HR = 0.35/log; P = 0.027). Continuous HER3 did not significantly correlate with OS. Patients with moderately overexpressed HER2 levels and high p95HER2 expression may have best outcomes while receiving lapatinib following progression on trastuzumab. Further study is warranted to explore the predictive utility of quantitative HER2 and p95HER2 in guiding HER2-directed therapies.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc18000874
003      
CZ-PrNML
005      
20180116121253.0
007      
ta
008      
180116s2017 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.18632/oncotarget.22027 $2 doi
035    __
$a (PubMed)29262628
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Duchnowska, Renata $u Military Institute of Medicine, Warsaw, Poland.
245    10
$a Predictive value of quantitative HER2, HER3 and p95HER2 levels in HER2-positive advanced breast cancer patients treated with lapatinib following progression on trastuzumab / $c R. Duchnowska, J. Sperinde, B. Czartoryska-Arłukowicz, P. Myśliwiec, J. Winslow, B. Radecka, C. Petropoulos, R. Demlova, M. Orlikowska, A. Kowalczyk, I. Lang, B. Ziółkowska, S. Dębska-Szmich, M. Merdalska, A. Grela-Wojewoda, A. Żawrocki, W. Biernat, W. Huang, J. Jassem,
520    9_
$a Lapatinib is a HER1 and HER2 tyrosine kinase inhibitor (TKI) approved in second line treatment of advanced or metastatic breast cancer following progression on trastuzumab-containing therapy. Biomarkers for activity of lapatinib and other TKIs are lacking. Formalin-fixed, paraffin-embedded primary tumor samples were obtained from 189 HER2-positive patients treated with lapatinib plus capecitabine following progression on trastuzumab. The HERmark® Breast Cancer Assay was used to quantify HER2 protein expression. HER3 and p95HER2 protein expression was quantified using the VeraTag® technology. Overall survival (OS) was inversely correlated with HER2 (HR = 1.9/log; P = 0.009) for patients with tumors above the cut-off positivity level by the HERmark assay. OS was significantly shorter for those with above median HER2 levels (HR = 1.7; P = 0.015) and trended shorter for those below the cut-off level of positivity by the HERmark assay (HR = 1.7; P = 0.057) compared to cases with moderate HER2 overexpression. The relationship between HER2 protein expression and OS was best captured with a U-shaped parabolic function (P = 0.004), with the best prognosis at moderate levels of HER2 protein overexpression. In a multivariate model including HER2, increasing p95HER2 expression was associated with longer OS (HR = 0.35/log; P = 0.027). Continuous HER3 did not significantly correlate with OS. Patients with moderately overexpressed HER2 levels and high p95HER2 expression may have best outcomes while receiving lapatinib following progression on trastuzumab. Further study is warranted to explore the predictive utility of quantitative HER2 and p95HER2 in guiding HER2-directed therapies.
655    _2
$a časopisecké články $7 D016428
700    1_
$a Sperinde, Jeff $u Monogram Biosciences, Integrated Oncology, Laboratory Corporation of America Holdings, South San Francisco, CA, USA.
700    1_
$a Czartoryska-Arłukowicz, Bogumiła $u Białystok Oncology Center, Białystok, Poland.
700    1_
$a Myśliwiec, Paulina $u Oncology Center, Zielona Góra, Poland.
700    1_
$a Winslow, John $u Monogram Biosciences, Integrated Oncology, Laboratory Corporation of America Holdings, South San Francisco, CA, USA.
700    1_
$a Radecka, Barbara $u Opole Oncology Center, Opole, Poland.
700    1_
$a Petropoulos, Christos $u Monogram Biosciences, Integrated Oncology, Laboratory Corporation of America Holdings, South San Francisco, CA, USA.
700    1_
$a Demlova, Regina $u Masaryk Memorial Cancer Institute, Brno, Czech Republic.
700    1_
$a Orlikowska, Marlena $u Warmia and Masuria Oncology Center, Olsztyn, Poland.
700    1_
$a Kowalczyk, Anna $u Medical University of Gdańsk, Gdańsk, Poland.
700    1_
$a Lang, Istvan $u National Institute of Oncology, Budapest, Hungary.
700    1_
$a Ziółkowska, Barbara $u Regional Hospital, Wrocław, Poland.
700    1_
$a Dębska-Szmich, Sylwia $u Medical University of Łódź, Łódź, Poland.
700    1_
$a Merdalska, Monika $u Oncology Center, Kielce, Poland.
700    1_
$a Grela-Wojewoda, Aleksandra $u Oncology Institute, Kraków, Poland.
700    1_
$a Żawrocki, Anton $u Medical University of Gdańsk, Gdańsk, Poland.
700    1_
$a Biernat, Wojciech $u Medical University of Gdańsk, Gdańsk, Poland.
700    1_
$a Huang, Weidong $u Monogram Biosciences, Integrated Oncology, Laboratory Corporation of America Holdings, South San Francisco, CA, USA.
700    1_
$a Jassem, Jacek $u Medical University of Gdańsk, Gdańsk, Poland.
773    0_
$w MED00184852 $t Oncotarget $x 1949-2553 $g Roč. 8, č. 61 (2017), s. 104149-104159
856    41
$u https://pubmed.ncbi.nlm.nih.gov/29262628 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20180116 $b ABA008
991    __
$a 20180116121527 $b ABA008
999    __
$a ind $b bmc $g 1268269 $s 997536
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2017 $b 8 $c 61 $d 104149-104159 $e 20171024 $i 1949-2553 $m Oncotarget $n Oncotarget $x MED00184852
LZP    __
$a Pubmed-20180116

Najít záznam

Citační ukazatele

Možnosti archivace