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.

Basic information

Original name

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

Authors

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.168 in 2016

Organization unit

Faculty of Medicine

DOI

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

UT WoS

000419562500111

Keywords in English

Breast cancer; HER2; Lapatinib; P95HER2; Trastuzumab

Abstract

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.

Links

LM2015090, research and development project

Name: Český národní uzel Evropské sítě infrastruktur klinického výzkumu (Acronym: CZECRIN)

Investor: Ministry of Education, Youth and Sports of the CR

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 and 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, vol. 8, No 61, p. 104149-104159. ISSN 1949-2553. Available from: 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 and 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, vol.~8, No~61, p.~104149-104159. ISSN~1949-2553. Available from: https://dx.doi.org/10.18632/oncotarget.22027.

Detailed Information on Publication Record