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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2017

01-08-2017 | Preclinical study

Impact of serum HER2, TIMP-1, and CAIX on outcome for HER2+ metastatic breast cancer patients: CCTG MA.31 (lapatinib vs. trastuzumab)

Authors: Diep Ho, Jessica Huang, Judith-Anne W. Chapman, Kim Leitzel, Suhail M. Ali, Lois Shepherd, Wendy R. Parulekar, Catherine E. Ellis, Rocco J. Crescnzo, Liting Zhu, Shakeel Virk, Dora Nomikos, Samuel Aparicio, Karen A. Gelmon, Walter P. Carney, Allan Lipton

Published in: Breast Cancer Research and Treatment | Issue 3/2017

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Abstract

Background

The lapatinib–taxane combination led to shorter PFS than trastuzumab–taxane in HER2+ metastatic breast cancer. We investigated the prognostic and predictive effects of pretreatment serum HER2, CAIX, and TIMP-1.

Methods

MA.31 accrued 652 patients; 537 (82%) were centrally confirmed HER2+. Biomarkers were categorized for univariate and multivariable predictive investigations with a median cut-point, ULN cut-points (15 ng/ml for HER2; 506 pg/ml for CAIX; 454 pg/ml for TIMP-1), and custom cut-points (30 and 100 ng/ml for HER2). Stratified step-wise forward Cox multivariable analysis examined continuous and categorical effects of biomarkers on PFS in the ITT and central HER2+ populations; central HER2+ biomarker results are shown.

Results

Serum was banked for 472 (72%) of 652 patients. Higher serum HER2 (>median; >15; >30; or >100 ng/ml; p = 0.05–0.002); higher CAIX (>median; >506 pg/ml; p = 0.02; p = 0.001); and higher TIMP-1 (> median; > 454 pg/ml; p = 0.001; p = 0.02) had shorter univariate PFS. In multivariable analysis, higher continuous TIMP-1 was associated with significantly shorter PFS: HR = 1.001 (95% CI = 1.00–01.002; p = 0.004). Continuous serum HER2 and CAIX were not significantly associated with PFS. HER2 of 15 ng/ml or higher had shorter PFS (p = 0.02); higher categorical CAIX had shorter PFS (p = 0.01–0.08). Interaction terms of HER2, CAIX, and TIMP-1 with treatment were not significant; the predictive test power was low.

Conclusions

Higher levels of serum TIMP-1, CAIX, and HER2 were significant prognostic biomarkers of shorter PFS. We found no significant interaction between serum biomarkers and response to lapatinib versus trastuzumab. Evaluation of TIMP-1 and CAIX-targeted therapy in addition to HER2-targeted therapy appears warranted in patients with elevated serum levels of these biomarkers.
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Metadata
Title
Impact of serum HER2, TIMP-1, and CAIX on outcome for HER2+ metastatic breast cancer patients: CCTG MA.31 (lapatinib vs. trastuzumab)
Authors
Diep Ho
Jessica Huang
Judith-Anne W. Chapman
Kim Leitzel
Suhail M. Ali
Lois Shepherd
Wendy R. Parulekar
Catherine E. Ellis
Rocco J. Crescnzo
Liting Zhu
Shakeel Virk
Dora Nomikos
Samuel Aparicio
Karen A. Gelmon
Walter P. Carney
Allan Lipton
Publication date
01-08-2017
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2017
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4273-x

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