Research Papers:

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

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 and Jacek Jassem _

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Oncotarget. 2017; 8:104149-104159. https://doi.org/10.18632/oncotarget.22027

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Renata Duchnowska1, Jeff Sperinde2, Bogumiła Czartoryska-Arłukowicz3, Paulina Myśliwiec4, John Winslow2, Barbara Radecka5, Christos Petropoulos2, Regina Demlova6, Marlena Orlikowska7, Anna Kowalczyk8, Istvan Lang9, Barbara Ziółkowska10, Sylwia Dębska-Szmich11, Monika Merdalska12, Aleksandra Grela-Wojewoda13, Anton Żawrocki8, Wojciech Biernat8, Weidong Huang2 and Jacek Jassem8

1Military Institute of Medicine, Warsaw, Poland

2Monogram Biosciences, Integrated Oncology, Laboratory Corporation of America® Holdings, South San Francisco, CA, USA

3Białystok Oncology Center, Białystok, Poland

4Oncology Center, Zielona Góra, Poland

5Opole Oncology Center, Opole, Poland

6Masaryk Memorial Cancer Institute, Brno, Czech Republic

7Warmia and Masuria Oncology Center, Olsztyn, Poland

8Medical University of Gdańsk, Gdańsk, Poland

9National Institute of Oncology, Budapest, Hungary

10Regional Hospital, Wrocław, Poland

11Medical University of Łódź, Łódź, Poland

12Oncology Center, Kielce, Poland

13Oncology Institute, Kraków, Poland

Correspondence to:

Jacek Jassem, email: [email protected]

Keywords: breast cancer; trastuzumab; lapatinib; HER2; p95HER2

Received: August 13, 2017    Accepted: September 21, 2017    Published: October 24, 2017


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.

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