Introduction/Background In the era of personalized therapy, Human epidermal growth factor receptor 2 (HER2) targeting agent, such as Trastuzumab Deruxtecan (T-DXd) have shown promising efficacy with 75% overall response rate (ORR) in HER2 3+ patients. In our study, we investigated the expression level of HER2 in patients with ovarian cancer and its association with BRCA mutation and homologous recombination deficiency.

Methodology We conducted a retrospective review of electronic medical records for 216 patients newly diagnosed with advanced or recurrent ovarian cancers, assessing HER2 immunohistochemistry staining (IHC) and BRCA status results. The expression level of HER2 from IHC was validated by dedicated pathologists at the center and categorized as 0, 1+, 2+, or 3+ according to gastric cancer scoring system of HER2 in American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. Additionally, platinum sensitivity during the first line of chemotherapy was taken into account.

Results Patients were categorized as homologous recombination proficient (HRp), BRCA mutant (BRCAm), and homologous recombination deficiency without BRCA mutation (HRD). Only a subset of patients exhibited 2+ or 3+ expression of HER2 in each group; 28.3% from HRp, 28.8% from BRCAm, and 26.9% from HRD without significance (p-value 0.1784). Regarding platinum sensitivity, 19.7% of patients with HER2 IHC 0 or 1+ and 30.5% of patients with HER2 IHC 2+ or 3+ had platinum refractory disease (p-value 0.1356). On the aspect of progression-free survival, patients expressing HER2 IHC 3+ showed significantly poor prognosis than others (p-value 0.0079).

Conclusion Our findings indicate that status of homologous recombination and expression of HER2 is not related. However, some patients exhibiting HER2 IHC 2+ or 3+ showed platinum-resistant disease with poor prognosis. These individuals might benefit from treatment with HER2-targeting agents. Further study is needed to confirm efficacy of the agent in patients with HER2-amplified ovarian cancer.

Disclosures Consulting/advisory board to AstraZeneca, CanariaBio, Eisai, Genmab, GI Innovation, ImmunoGen, MSD, and Seagen

Funded research from Advenchen, Ascendis Pharma, Alkermes, AstraZeneca, BeiGene, BerGenBio, BMS, CanariaBio, Cellid, Clovis Oncology, Eisai, Genmab, GII, GSK, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, ONO, Regeneron, Roche, Seagen, Sutro, Synthon, and Takeda.