Prognostic implications of HER2 in ovarian cancer: Associations with homologous recombination deficiency and folate receptor alpha expression

Abstract

Objective. We evaluated expression patterns of human epidermal growth factor receptor 2 (HER2) by histological subtype and key biomarkers in ovarian cancer (OC). Methods. We retrospectively analyzed 441 patients with primary or recurrent OC who underwent HER2 immunohistochemistry (IHC) at Yonsei Cancer Center. Association between histological subtype, HER2 and folate receptor alpha (FR alpha) expression, BRCA1/2 mutation or homologous recombination deficiency (HRD) status, and overall survival (OS) were evaluated. Results. HER2 2+/3+ were found in 104 patients (23.6 %), more frequent in mucinous (50.0 %) and clear cell carcinomas (51.2 %). Among 211 patients with high-grade serous carcinoma (HGSC) and known HRD status, HER2 2+/3+ tumors were more common in HRD (21.6 %) than in homologous recombination proficient (HRP) (6.9 %) patients. HER2 2+/3+ tumors were associated with poorer OS overall, with worse outcomes in HRD HGSC. Of 78 patients with sequential HER2 data, 34.6 % showed increased score during progression, correlating with a trend toward poorer OS. Concurrent HER2 2+/3+ and high FR alpha expression was observed in 9.4% of evaluable cases. Conclusions. HER2 overexpression is relatively common and had prognostically relevant in BRCA1/2-mutated/ HRD and in mucinous or clear cell OC. Further clinical trials are warranted to optimize use of HER2-and FR alpha targeted ADCs in these group.<br /> Published by Elsevier Inc.