Oncology
Endometrial Cancer
Endometrial Cancer Biomarkers
The endometrial cancer treatment landscape is rapidly evolving and is being driven, in part, by the incorporation of molecular biomarkers into everyday clinical practice. Data related to endometrial cancer biomarkers were presented at the Society of Gynecologic Oncology (SGO) 2025 Annual Meeting on Women’s Cancer.
<br>
Following these presentations, featured expert Bradley J. Monk, MD, FACS, FACOG, was interviewed by Conference Reporter Medical Director Lauren Weinand, MD. Dr Monk’s clinical perspectives on these findings are presented here.
Biomarkers are already changing the way we evaluate and treat endometrial cancer. Currently, we have multiple standard-of-care biomarkers. I think that every patient with endometrial cancer should be tested for mismatch repair deficiency (dMMR) because, in addition to providing therapeutic guidance for endometrial cancer, it is also helpful in screening for Lynch syndrome. Additional biomarkers include estrogen and progesterone receptor positivity, as well as TP53 expression. All these biomarkers can be evaluated through immunohistochemistry (IHC), as can HER2. HER2 is also now a biomarker ever since the landscape-changing US Food and Drug Administration (FDA) accelerated approval of trastuzumab deruxtecan for unresectable or metastatic HER2+ (IHC 3+) solid tumors. We also evaluate genetic markers of homologous recombination repair (HRR) deficiency (eg, BRCA1/BRCA2), which is generally associated with a poor prognosis, and POLE mutation, which is associated with a better prognosis. Unfortunately, many patients are not having their endometrial cancer appropriately molecularly profiled according to contemporary guidelines.
<br>
At the SGO 2025 Annual Meeting on Women’s Cancer, Kathleen N. Moore, MD, MS, gave an oral late-breaking abstract presentation on the phase 3 DUO-E trial, which focused on the impact of maintenance durvalumab in combination with olaparib and chemotherapy in the subset of enrolled patients with MMR-proficient (pMMR) endometrial cancer. The investigators found striking heterogeneity in the molecular biomarkers in the pMMR population, as well as some overlap. Among those with pMMR endometrial cancer, 21% had HRR gene mutations, 8% had BRCA mutations, and POLE mutations were rare, at 2%. In an exploratory post hoc analysis, it was suggested that, despite this molecular heterogeneity, the addition of maintenance olaparib to durvalumab, carboplatin, and paclitaxel enhances progression-free survival in the pMMR subpopulation compared with carboplatin and paclitaxel alone. The results of another exploratory post hoc analysis suggested a progression-free survival benefit with the addition of olaparib across a range of biomarkers and histologic subsets, including patients who had baseline-detectable circulating tumor DNA.
<br>
Finally, a poster presented by Ana Rosario Santos, MD, and colleagues at SGO 2025 compared vaginal quorum-sensing molecules, which are produced by the vaginal microbiome, present in vaginal swabs from a small number of women with low-grade endometrial cancer (n = 23), high-grade endometrial cancer (n = 13), or no cancer (n = 23) (poster 2203). This was interesting, but very preliminary. Researchers concluded that a larger sample size and correlation with clinicopathologic and demographic characteristics are needed.
Concin N, Creutzberg CL, Vergote I, et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Virchows Arch. 2021;478(2):153-190. doi:10.1007/s00428-020-03007-z
<br>
Hamilton CA, Pothuri B, Arend RC, et al. Endometrial cancer: a Society of Gynecologic Oncology evidence-based review and recommendations. Gynecol Oncol. 2021;160(3):817-826. doi:10.0116/j.ygyno.220.12.021
<br>
Leclerc J, Vermaut C, Buisine MP. Diagnosis of Lynch syndrome and strategies to distinguish Lynch-related tumors from sporadic MSI/dMMR tumors. Cancers (Basel). 2021;13(3):467. doi:10.3390/cancers13030467
<br>
Moore KN, Westin SN, Chon HS, et al. Durvalumab plus carboplatin/paclitaxel followed by durvalumab with/without olaparib in endometrial cancer: biomarkers, histological heterogeneity, baseline circulating tumor DNA levels, and efficacy in the DUO-E mismatch repair proficient subpopulation [scientific plenary I: IMPACTful trials: improving patient care]. Session presented at: Society of Gynecologic Oncology 2025 Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle, WA.
<br>
Santos AR, O’Connor G, Schlumbrecht M, Deo SK, George S, Daunert S. Identification of quorum sensing molecules in endometrial cancer: exploring vaginal microbiome interactions as a risk biomarker [poster 2203]. Poster presented at: Society of Gynecologic Oncology 2025 Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle, WA.
<br>
This information is brought to you by Engage Health Media and is not sponsored, endorsed, or accredited by the Society of Gynecologic Oncology.