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

J 2017

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

DUCHNOWSKA, Renata, Jeff SPERINDE, Bogumiła CZARTORYSKA-ARŁUKOWICZ, Paulina MYŚLIWIEC, John WINSLOW et. al.

Základní údaje

Originální název

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

Autoři

Vydání

Oncotarget, New York, Impact Journals, 2017, 1949-2553

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.168 v roce 2016

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.18632/oncotarget.22027

UT WoS

000419562500111

Klíčová slova anglicky

Breast cancer; HER2; Lapatinib; P95HER2; Trastuzumab

Štítky

EL OK, Excelence Science, MOÚ, MU, RIV, user

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 19. 3. 2021 13:04, Mgr. Tereza Miškechová

Anotace

V originále

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.

Návaznosti

LM2015090, projekt VaV

Název: Český národní uzel Evropské sítě infrastruktur klinického výzkumu (Akronym: CZECRIN)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CZECRIN - Český národní uzel Evropské sítě infrastruktur klinického výzkumu

Citovat

DUCHNOWSKA, Renata, Jeff SPERINDE, Bogumiła CZARTORYSKA-ARŁUKOWICZ, Paulina MYŚLIWIEC, John WINSLOW, Barbara RADECKA, Christos PETROPOULOS, Regina DEMLOVÁ, Marlena ORLIKOWSKA, Anna KOWALCZYK, Istvan LANG, Barbara ZIÓŁKOWSKA, Sylwia DĘBSKA-SZMICH, Monika MENDALSKA, Aleksandra GRELA- WOJEWODA, Anton ŻAWROCKI, Wojciech BIERNAT, Weidong HUANG a Jacek JASSEM. Predictive value of quantitative HER2, HER3 and p95HER2 levels in HER2-positive advanced breast cancer patients treated with lapatinib following progression on trastuzumab. Oncotarget. New York: Impact Journals, 2017, roč. 8, č. 61, s. 104149-104159. ISSN 1949-2553. Dostupné z: https://dx.doi.org/10.18632/oncotarget.22027.

@article{1402244,
   author = {Duchnowska, Renata and Sperinde, Jeff and CzartoryskaandArłukowicz, Bogumiła and Myśliwiec, Paulina and Winslow, John and Radecka, Barbara and Petropoulos, Christos and Demlová, Regina and Orlikowska, Marlena and Kowalczyk, Anna and Lang, Istvan and Ziółkowska, Barbara and DębskaandSzmich, Sylwia and Mendalska, Monika and Grelaand Wojewoda, Aleksandra and Żawrocki, Anton and Biernat, Wojciech and Huang, Weidong and Jassem, Jacek},
   article_location = {New York},
   article_number = {61},
   doi = {http://dx.doi.org/10.18632/oncotarget.22027},
   keywords = {Breast cancer; HER2; Lapatinib; P95HER2; Trastuzumab},
   language = {eng},
   issn = {1949-2553},
   journal = {Oncotarget},
   note = {Bez afiliace k MU.},
   title = {Predictive value of quantitative HER2, HER3 and p95HER2 levels in HER2-positive advanced breast cancer patients treated with lapatinib following progression on trastuzumab},
   url = {http://dx.doi.org/10.18632/oncotarget.22027},
   volume = {8},
   year = {2017}
}

TY  - JOUR
ID  - 1402244
AU  - Duchnowska, Renata - Sperinde, Jeff - Czartoryska-Arłukowicz, Bogumiła - Myśliwiec, Paulina - Winslow, John - Radecka, Barbara - Petropoulos, Christos - Demlová, Regina - Orlikowska, Marlena - Kowalczyk, Anna - Lang, Istvan - Ziółkowska, Barbara - Dębska-Szmich, Sylwia - Mendalska, Monika - Grela- Wojewoda, Aleksandra - Żawrocki, Anton - Biernat, Wojciech - Huang, Weidong - Jassem, Jacek
PY  - 2017
TI  - Predictive value of quantitative HER2, HER3 and p95HER2 levels in HER2-positive advanced breast cancer patients treated with lapatinib following progression on trastuzumab
JF  - Oncotarget
VL  - 8
IS  - 61
SP  - 104149-104159
EP  - 104149-104159
PB  - Impact Journals
SN  - 19492553
N1  - Bez afiliace k MU.
KW  - Breast cancer
KW  - HER2
KW  - Lapatinib
KW  - P95HER2
KW  - Trastuzumab
UR  - http://dx.doi.org/10.18632/oncotarget.22027
L2  - http://dx.doi.org/10.18632/oncotarget.22027
N2  - 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.
ER  -

DUCHNOWSKA, Renata, Jeff SPERINDE, Bogumiła CZARTORYSKA-ARŁUKOWICZ, Paulina MY$\backslash$'SLIWIEC, John WINSLOW, Barbara RADECKA, Christos PETROPOULOS, Regina DEMLOVÁ, Marlena ORLIKOWSKA, Anna KOWALCZYK, Istvan LANG, Barbara ZIÓŁKOWSKA, Sylwia DĘBSKA-SZMICH, Monika MENDALSKA, Aleksandra GRELA- WOJEWODA, Anton $\backslash$.ZAWROCKI, Wojciech BIERNAT, Weidong HUANG a Jacek JASSEM. Predictive value of quantitative HER2, HER3 and p95HER2 levels in HER2-positive advanced breast cancer patients treated with lapatinib following progression on trastuzumab. \textit{Oncotarget}. New York: Impact Journals, 2017, roč.~8, č.~61, s.~104149-104159. ISSN~1949-2553. Dostupné z: https://dx.doi.org/10.18632/oncotarget.22027.

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