HER2 expression in an endometrial cancer cohort

Trastuzumab deruxtecan, a HER2 antibody drug conjugate (ADC), is active in HER2 expressing gynecologic cancers. This study aims to determine the proportion of endometrial cancers (EC) that are HER2 expressing and eligible for these ADCs.

This was a retrospective, single-institution study of patients who underwent surgery for EC over 18 months. Clinical HER2 testing consisted of HER2 IHC and reflex FISH for select 2+ IHC. The outcome of interest was the proportion of patients with HER2 expressing tumors by IHC (1+, 2+, 3+). Chi-square tests of independence were performed to examine relationships between categorical variables and HER2 expression.

Two hundred forty-nine patients with newly diagnosed EC underwent hysterectomy. Forty-four patients were diagnosed at advanced stage (III/IV) and 203 at early stage (I/II). HER2 IHC was performed on 220 tumors. One hundred thirty-one (59.5 %) had HER2 expression by and 67 (30.5 %) were 2+ or 3+. HER2 expressing tumors were more likely to be advanced stage (25.3 % vs 10.5 %; χ² (1, N = 220) = 7.40, p = 0.0065), non-endometrioid histology (34.3 % vs 14.0, χ² (1, N = 220) = 11.20, p = 0.008), and p53 aberrant (27.6 % vs 12.8 %, χ² (2, N = 217) = 6.7, p = 0.035) than HER2 0 tumors.

In this retrospective study, 60 % of newly diagnosed EC patients were HER2 expressing by IHC. One-third of unselected EC were HER2 2+ or 3+ and would potentially qualify for current NCCN listed HER2 directed ADCs. HER2 expression was distributed across all histologic and molecular EC subtype suggesting that all endometrial tumors should undergo HER2 IHC testing.