Abstract P2-11-17: Expression levels of some genes associated with tumor shrinkage by neoadjuvant endocrine therapy were paradoxically related with poor prognosis in patients with ER-positive/HER2-negative operable breast cancer
Authors: Goto-Yamaguchi Lisa , Ibusuki-Yamamoto Mutsuko , Takeno Masako , Fujiki Yositaka , Tomiguchi Mai , Sueta Aiko , Yamamoto Yutaka 
Published: March 2020

Purpose: We previously published that the expression levels of 5 genes (ADCK2, CUL2, FAM13A, KRAS, LILRA2) related to tumor shrinkage by neoadjuvant endocrine therapy (NAET) were identified though the gene expression profiles (Goto-Yamaguchi L et al, Breast Cancer Res Treat. 72:353-362,2018). In this study, we examined whether expression levels of these 5 genes were associated with prognosis in patients with ER-positive/HER2-negative operable breast cancer.

Methods: Formalin-fixed paraffin embedded tumor tissues before systemic treatment were provided by 273 patients with ER-positive/HER2-negative operable breast cancer receiving standard of care at our institute from June 2000 to January 2011. We examined gene expression levels of these 5 genes determined by real time-quantitative PCR using RNA extracted from the tumor samples. We analyzed the prognostic impact of these 5 genes in terms of relapse-free survival (RFS) and breast cancer-specific survival (BCSS). We also study the relationship between 5 genes expression and clinic-pathological factors.

Results: Median follow-up time was 106 months. Among 5 genes, high expression levels of ADCK2 and CUL2 were significantly related with poor PFS (log-rank test, ADCK2: p=0.022, CUL2: p0.045) but not BCSS. On the other hand, high levels of FAM13A expression were significantly poor BCSS (log-rank test, p=0.042) but not RFS. Expression of KRAS and LILRA2 were not any correlation with prognosis. Multivariate analysis in terms of RFS revealed that ADCK2 was an independent prognostic factor (HR 2.26, 95%CI 1.04 to 5.07, p = 0.038). In addition, multivariate analysis in terms of BCSS revealed that FAM13A (HR 15.6, 95%CI 2.36 to 316.0, p = 0.0029), nodal status (HR 8.22, 95%CI 1.57 to 62.9, p=0.012) and PgR (HR 0.14, 95%CI 0.0068 to 0.93, p=0.042) were independent prognostic factors. Expression of ADCK2 and CUL2 were not associated with any clinic-pathological factors such as menopausal status, tumor size, nodal status, expression levels of ER and PgR, nuclear grade and ki67 labeling index. FAM13A expression was positively correlated with ki67 labeling index (chi-square test, p=0.0007).

Conclusion: Despite the genes associated with tumor shrinkage by NAET, ADCK2, CUL2 and FAM13A among the genes were positively correlated with poor prognosis. This paradoxical phenomenon showed that endpoint of short-term endocrine therapy such as tumor shrinkage may not be reflect that of long-term endocrine therapy such as PFS and BCSS.

Citation Format: Lisa Goto-Yamaguchi, Mutsuko Ibusuki-Yamamoto, Masako Takeno, Yositaka Fujiki, Mai Tomiguchi, Aiko Sueta, Yutaka Yamamoto. Expression levels of some genes associated with tumor shrinkage by neoadjuvant endocrine therapy were paradoxically related with poor prognosis in patients with ER-positive/HER2-negative operable breast cancer [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 P2-11-17.