Abstract P3-06-03: Quantitative p95HER2 and HER2 correlations with outcome in the FinHer trial
Authors: Sperinde Jeff , Huang Weidong , Vehtari Aki , Chenna Ahmed , Kellokumpu-Lehtinen Pirkko-Liisa , Winslow John , Bono Petri , Lie Yolanda , Weidler Jodi , Joensuu Heikki 
Published: May 2015

Background: Expression of p95HER2 (p95), a truncated form of the HER2 receptor that lacks the trastuzumab binding site but retains kinase activity, appears to be a prognostic biomarker for poor trastuzumab treatment outcome in HER2-positive metastatic breast cancer. The impact of p95 expression on trastuzumab treatment efficacy in early HER2-positive breast cancer is less clear. In the current study, p95 expression levels were measured in HER2-positive patients from the phase III FinHer adjuvant trastuzumab trial and correlated with treatment outcome.

Methods: In the FinHer phase III trial, 232 HER2-positive early breast cancer patients were randomized to receive 9-weeks of trastuzumab treatment versus no trastuzumab treatment (control). Quantitative p95 protein expression was measured in formalin-fixed paraffin-embedded samples using the p95 VeraTag® assay (Monogram Biosciences), specific for the M611 form of p95. Quantitative HER2 protein expression was measured using the HERmark® assay (Monogram Biosciences). Time to distant recurrence (TDR) was used as the primary outcome measure.

Results: Sufficient tissue was available to measure p95 in 192 HER2-positive patients randomized to receive chemotherapy vs chemotherapy plus trastuzumab. The chemotherapy only (n=97) and chemotherapy plus trastuzumab (n=95) arms were first analyzed separately. In the chemotherapy only arm, increasing log(p95) correlated with shorter TDR (HR = 2.0; p = 0.02) when stratified by hormone receptor status, nodal status and chemotherapy regimen. In the chemotherapy plus trastuzumab arm, increasing log(p95) was not correlated with a shorter TDR (HR = 0.58; p = 0.19). Log(HER2) was not significantly correlated with TDR in either arm. In a combined analysis of both treatment arms, log(p95) was significantly correlated with trastuzumab treatment outcome in a multivariate model that included hormone receptor status, nodal status, chemotherapy regimen, log(p95) and treatment arm. Subset analyses of hormone receptor positive and negative groups indicated that the interaction of p95 expression with trastuzumab treatment was largely driven by the hormone receptor negative subset.

Conclusions: In the FinHer phase III adjuvant breast cancer trial, HER2-positive patients with elevated breast tumor p95HER2 expression experienced poor outcomes when treated with chemotherapy alone, whereas patients with elevated p95 expression experienced the most benefit when trastuzumab was added to chemotherapy. The different influence between hormone receptor subsets of p95 expression on trastuzumab response resembles the effect of HER2 expression on trastuzumab response in the NSABP B-31 trial (JNCI 105:1782, 2013).

Citation Format: Jeff Sperinde, Weidong Huang, Aki Vehtari, Ahmed Chenna, Pirkko-Liisa Kellokumpu-Lehtinen, John Winslow, Petri Bono, Yolanda Lie, Jodi Weidler, Heikki Joensuu. Quantitative p95HER2 and HER2 correlations with outcome in the FinHer trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-03.