Introduction/Background Low grade serous carcinoma (LGSC) is a subtype of ovarian cancer characterized by chemoresistance and a slow growth rate. Advances in HER2-targeted antibody drug conjugates (ADCs) have demonstrated efficacy in a variety of cancers. However, the significance of HER2 expression in LGSC, especially at low and ultralow levels, remains poorly characterized. This study aimed to stratify HER2 expression in LGSC to evaluate the feasibility of anti-HER2 ADCs in this context.

Methodology We conducted a restrospective analysis of 28 LGSC tissue specimens assessing HER2 expression by immunohistochemistry (IHC) using a validated, calibrated and routinely used assay. Interpretation of HER2 expression was aligned with ASCO/CAP breast cancer guidelines, with the addition of an « Ultralow » expression category. Fluorescence in situ Hybridization (FISH) was performed in applicable cases.

Results Among the 28 LGSC samples, no cases showed HER2 overexpression or amplification. Only one case was classified as HER2 score 2+ without amplification. Ten cases received a score of 1+, while 17 were scored 0. Notably, very low levels of staining wasp revalent, with 75% of tumors exhibiting some degree of positivity. The introduction of an Ultralow category for cases presenting any staining that did not meet the threshold for a 1+ score (accounting for 36% of the cohort) increased the proportion of tumors expressing some level of HER2 to 75%.

Conclusion This study evaluates HER2 IHC expression in LGSC through a refined lens, reflecting a recent shift in pathological assessment that places greater emphasis on the clinical implications of low and ultralow HER2 expression levels. Given the precedent for ADC efficacy, such as Trastuzumab Deruxtecan (T-DxD), in cancers with low HER2 expression, our findings suggests that LGSC patients could be candidates for clinical investigations for anti-HER2 ADCs. Other potential biomarkers such as TROP2 and FOLR1 expression will also be presented at the meeting.

Disclosures None.