HER2 expression in ovarian cancer: Its relationship with HRD status, and other biomarkers

BackgroundHuman epidermal growth factor receptor 2 (HER2) targeting agents are promising not only for breast cancer but also for other solid tumors with HER2 overexpression. However, HER2 status in ovarian cancer (OC) remains underexplored. This study aims to explore HER2 expression in OC and its relationship with other markers.MethodsWe conducted a retrospective review of electronic medical records for 373 patients diagnosed with newly advanced or recurrent OC, assessing HER2 immunohistochemistry staining (IHC) and homologous recombination deficiency (HRD) status. HER2 expression levels from IHC, validated by dedicated pathologists, were categorized as 0, 1+, 2+, or 3+ using the gastric cancer scoring system of HER2 in ASCO/CAP guidelines. Additionally, IHC results of mismatch repair (MMR) protein expression, and folate receptor alpha (FRα) were evaluated.Results2+ or 3+ (3+) HER2 expression rates by IHC were 17.6% (5.1%) in high-grade serous carcinoma (HGSC), 45.2% (9.7%) in clear cell, 50.0% (28.6%) in mucinous, and 30.4% (4.3%) in other subtypes (p-value <0.001). In the HGSC cohort, 2+ or 3+ (3+) HER2 expression was 22.0% (2.9%) in BRCAmut, 19.3% (4.8%) in BRCAwtHRD, and 4.4% (2.2%) in HRP cases (p-value 0.022). Poorer overall survival was noted in patients with HGSC expressing 2+ or 3+ HER2, especially in BRCAmut and BRCAwtHRD subgroups (p=0.04). Among 40 patients with high expression of FRα and 8 with MMR deficiency, only 5 and 1, respectively, exhibited 2+ or 3+ HER2 expression. Parenchymal metastasis showed higher percentage of 2+ or 3+ HER2 levels than ovarian or intra-abdominal tumors (35.8% vs. 24.8% and 27.4%). Table: 765P Others: sarcoma, poorly differentiated carcinoma, etc. HER2 HGSC Endometrioid Clear cell Mucinous Others 0 184 (62.4%) 6 (60.0%) 10 (32.3%) 5 (35.7%) 14 (60.9%) 1+ 59 (20.0%) 3 (30.0%) 7 (22.6%) 2 (14.3%) 2 (8.7%) 2+ 37 (12.5%) 1 (10.0%) 11 (35.5%) 3 (21.4%) 6 (26.1%) 3+ 15 (5.1%) 0 (0.0%) 3 (9.7%) 4 (28.6%) 1 (4.3%) ConclusionsOur study provides comprehensive information on HER2 expression in OC, significantly higher in non-HGSC types, and associated with poor outcomes in HGSC. This highlights the importance of targeted therapy in BRCAmut or HRD OC, emphasizing that HER2 targeting agents are a viable option following failure to PARP inhibitors.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureJ. Lee: Financial Interests, Personal and Institutional, Advisory Board, DP-02: AstraZeneca; Financial Interests, Personal and Institutional, Other, Lecture: Eisai, Roche, Takeda; Financial Interests, Personal and Institutional, Advisory Board, MK4830-002: MSD; Financial Interests, Personal and Institutional, Advisory Board, FLORA-5: CanariaBio; Financial Interests, Personal and Institutional, Advisory Board, GEN1046-05: Genmab; Financial Interests, Personal and Institutional, Advisory Board, GI-101: GII; Financial Interests, Personal and Institutional, Advisory Board, MIRASOL: ImmunoGen; Financial Interests, Personal and Institutional, Advisory Board, SGNTV-03: Seagen; Financial Interests, Personal and Institutional, Advisory Board, DDriver302: MERCK; Financial Interests, Personal and Institutional, Advisory Board, REFRaME-01: Sutro; Financial Interests, Institutional, Other: Advenchen, Ascendis Pharma, Beigene, BergenBio, BioNTech, BMS, Corcept, Cellid, CKD, Clovis Oncology, Genemedicine, GSK, Janssen, Kelun, Mersana, Novartis, Onconic Therapeutics, ONO, Regeneron, Synthon. All other authors have declared no conflicts of interest.