Abstract P5-13-04: Gene expression profiling of breast cancers between high and low Ki-67 after short-term preoperative hormone therapy among hormone receptor-positive / human epidermal growth factor receptor 2-negative breast cancers with high Ki-67
Authors: Kajiwara Yukiko , Iwamoto Takayuki , Otani Yusuke , Fujihara Miwa , Suzuki Yoko , Hatono Minami , Tsukioki Takahiro , Kawada Kengo , Kochi Mariko , Ikeda Hirokuni , Shien Tadahiko , Taira Naruto , Doihara Hiroyoshi 
Published: March 2020

Background In hormone receptor (HR)-positive / human epidermal growth factor receptor 2 (HER2)-negative breast cancers, high Ki-67 predicts poor prognosis. Recently, it has been reported that among breast cancers with high Ki-67, low Ki-67 after short-term preoperative hormone therapy (post Ki-67) might predict favorable prognosis compared to high post Ki-67 (SABCS 2017). However, the differences in gene expression profiling of breast cancers between high and low post Ki-67 among high Ki-67 before treatment are unclear. Therefore, this study aimed to clarify genetic differences in two groups and to explore novel therapeutic targets for the poor prognostic group after the treatment.

Methods

Seventy-seven patients with primary HR-positive / HER2-negative breast cancer who received an aromatase inhibitor for 2 weeks [NCBI Gene Expression Omnibus repository GSE80077:19 cases, GSE20181:58 cases] were enrolled in this study. Forty-five patients with high pre Ki-67 among them were stratified into two groups, high (H→H) and low (H→L) post Ki-67 after short-term preoperative hormone therapy. We compared gene expression profiling in two groups about the followings.

1) 3 genes (ESR1, PGR and ERBB2) related to classical clinical treatment strategy of breast cancer, immune- and inflammatory-related genes

2) 178 pathways (gene set analysis)

3) 41 genes that are targeted by FDA-approved drugs or have been investigated with clinical trials as molecular target agents for various malignant tumors including breast cancer

Results

1) TNF that is inflammatory-related gene were significantly overexpressed in H→L group (P=0.021). However, 3 genes related to clinical treatment of breast cancer and immune-related genes expression had no significant difference between two groups.

2) 5 gene sets (Tryptophan metabolism, Propanoate metabolism, beta-Alanine metabolism, SNARE interactions in vesicular transport and Nucleotide excision repair) were significantly upregulated in H→L group. (P ≤ 0.005)

3) 5 targeted genes (PARP, BRCA2, FLT4, CDK6 and PDCD1LG2) were significantly overexpressed in H→H group (P ≤ 0.05).

Conclusions

There were different gene expression and biological processes in two groups stratified by post-Ki67. In the future, it is necessary to seek new therapeutic strategies for poor prognostic group with high post-Ki67 in considerations of these differences.

Citation Format: Yukiko Kajiwara, Takayuki Iwamoto, Yusuke Otani, Miwa Fujihara, Yoko Suzuki, Minami Hatono, Takahiro Tsukioki, Kengo Kawada, Mariko Kochi, Hirokuni Ikeda, Tadahiko Shien, Naruto Taira, Hiroyoshi Doihara. Gene expression profiling of breast cancers between high and low Ki-67 after short-term preoperative hormone therapy among hormone receptor-positive / human epidermal growth factor receptor 2-negative breast cancers with high Ki-67 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-13-04.