Abstract P2-09-28: New quantitative diagnostic method by fluorescence nanoparticle for HER2 positive breast cancer treated with neoadjuvant lapatinib and trastuzumab: The Neo LaTH study (JBCRG-16TR)
Authors: Tada H , Miyashita M , Gonda K , Watanabe M , Suzuki A , Watanabe G , Harada N , Sato A , Hamanaka Y , Masuda N , Toi M , Ohno S , Bando H , Ishiguro H , Inoue K , Yamamoto N , Kuroi K , Ohuchi N , Ishida T 
Published: February 2018

Abstract
Background: HER2 (human epidermal growth factor receptor 2) testing performed by IHC (immunohistochemical) methods and FISH (fluorescence in situ hybridization) is semi-quantitative. Exact quantification of HER2 is needed to predict which patients are more or less likely to response to anti HER2 therapy. To improve the method for cancer patients' HER2 status, we developed a novel fluorescence IHC method using new fluorescence nanoparticle. The fluorescent intensity of this new nanoparticles, termed phosphor-integrated dot (PID), was approximately 100-fold brighter than that of Quantum dots. Because of its increased brightness and analyzing technology, this PID-based fluorescent IHC(IHC-PIC) has an ability of quantifying the biomarker protein in the cancer tissue sample at single particle level. In this study, the primary objective was to investigate if pathological complete response (pCR) rate in HER2- positive breast cancer treated by trastuzumab and lapatinib containing neoadjuvant systemic therapy would depend on the level of HER2, EGFR, HER3, Ki67, ER and PgR protein quantified by this new method.
Methods: The Neo-LaTH study is a randomized phase II multicenter trial evaluating the efficacy and safety of lapatinib and trastuzumab followed by lapatinib and trastuzumab plus weekly paclitaxel with or without prolongation of anti-HER2 therapy prior to chemotherapy (18 weeks vs. 6 weeks). The primary endpoint was the comprehensive pCR rate. We evaluated the HER2, EGFR, HER3, Ki67, ER and PgR amount by nano-patho method using PID in formalin-fixed paraffin-embedded core biopsy samples taken at diagnosis retrospective analysis. Univariate and multivariate analyses were performed to determine the association between pCR and variables, including HER2, EGFR, HER3, Ki67, ER and PgR nano-patho score and clinicopathological factors including histological grade, tumor status, nodal status and HER2 FISH ratio.
Results: A total of 96 tumor samples from patients were used for the present analysis.The pCR rate was 60.4%. We obtained the images of only PID signal by the image analyses, and calculated the number of PID particles in a cell and defined it as IHC-PID score that reflects the level of HER2, EGFR, HER3, Ki67, ER and PgR protein expression in cancer cells. Univariate analysis showed that HER2 IHC-PID score(p&lt;0.0001), ER IHC-PID score(p=0.009) and PgR IHC-PID score(p=0.019) were associated with pCR and multivariate analysis showed that HER2 IHC-PID score was significantly associated with pCR (adjusted odds ratio, 0.990 [95% CI, 0.984–0.996]; P &lt; .0001).
Conclusion: We successfully performed the quantitative IHC-PID for HER2, EGFR, HER3, Ki67, ER and PgR. And we propose using HER2 IHC-PID score as a predictive factor for trastuzumab and lapatinib containing neoadjuvant systemic therapy. This quantitative diagnostic method would be expected to contribute to the development of a molecular therapeutic strategy.
Citation Format: Tada H, Miyashita M, Gonda K, Watanabe M, Suzuki A, Watanabe G, Harada N, Sato A, Hamanaka Y, Masuda N, Toi M, Ohno S, Bando H, Ishiguro H, Inoue K, Yamamoto N, Kuroi K, Ohuchi N, Ishida T. New quantitative diagnostic method by fluorescence nanoparticle for HER2 positive breast cancer treated with neoadjuvant lapatinib and trastuzumab: The Neo LaTH study (JBCRG-16TR) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-09-28.