Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

High HER2 intratumoral heterogeneity is a predictive factor for poor prognosis in Early-stage and Locally Advanced HER2-positive Breast Cancer

Tomonori Tanei
* ,
Shigeto Seno
ORCID logo ,
Yoshiaki Sota
ORCID logo ,
Kaori Abe
,
Nanae Masunaga
,
Masami Tsukabe
,
Tetsuhiro Yoshinami
,
Tomohiro Miyake
,
Masafumi Shimoda
,
Hideo Matsuda
ORCID logo ,
Kenzo Shimazu
Version 1 : Received: 20 February 2024 / Approved: 20 February 2024 / Online: 20 February 2024 (14:26:43 CET)

A peer-reviewed article of this Preprint also exists.

Tanei, T.; Seno, S.; Sota, Y.; Hatano, T.; Kitahara, Y.; Abe, K.; Masunaga, N.; Tsukabe, M.; Yoshinami, T.; Miyake, T.; Shimoda, M.; Matsuda, H.; Shimazu, K. High HER2 Intratumoral Heterogeneity Is a Predictive Factor for Poor Prognosis in Early-Stage and Locally Advanced HER2-Positive Breast Cancer. Cancers 2024, 16, 1062. Tanei, T.; Seno, S.; Sota, Y.; Hatano, T.; Kitahara, Y.; Abe, K.; Masunaga, N.; Tsukabe, M.; Yoshinami, T.; Miyake, T.; Shimoda, M.; Matsuda, H.; Shimazu, K. High HER2 Intratumoral Heterogeneity Is a Predictive Factor for Poor Prognosis in Early-Stage and Locally Advanced HER2-Positive Breast Cancer. Cancers 2024, 16, 1062.

Abstract

PURPOSE: Breast cancer tumors frequently have intratumor heterogeneity. Tumors with high intratumor heterogeneity have caused therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to poor prognosis for HER2-targeted adjuvant therapies resistance in primary breast cancers. METHODS: This study included patients with primary breast cancer (n = 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with HER2 gene copy number within a tumor sample. Those heterogeneity classified each tumor into the biphasic grade graph (high heterogeneity [HH]) group and the monophasic grade graph (low heterogeneity [LH]) group. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up. RESULTS: Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS: P < 0.001 (HH:63% vs LH:91% at 10 years), and OS: P = 0.012 (HH:78% vs LH:95% at 10 years). CONCLUSION: High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach of heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.

Keywords

Breast carcinoma, Intratumoral heterogeneity, HER2 gene expression, Prognosis, Breast Neoplasms

Subject

Biology and Life Sciences, Biology and Biotechnology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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