ReviewMechanismInconclusiveLimited evidenceTier 3 · early human
Cells · Aug 2025 · review
uterine serous carcinomaendometrial cancerbreast cancer
This is a narrative review of HER2/neu as a signaling and therapeutic marker in uterine serous carcinoma (USC). It summarizes HER2 expression and amplification in USC, compares USC HER2 features to breast cancer, evaluates preclinical and clinical evidence for HER2-directed therapies (including monoclonal antibodies and ADCs), and discusses possible mechanisms of resistance.
Studied with: monoclonal antibodies, antibody-drug conjugates, chemotherapy.
Key findings
- HER2/neu coordinates cell growth and differentiation and when overexpressed and/or amplified its downstream tyrosine kinase can become constitutively activated, causing dysregulated gene transcription.
- HER2/neu has been successfully targeted in breast cancer with monoclonal antibodies and antibody-drug conjugates.
- Use of HER2-directed therapies in gynecologic malignancies has been slower, in part due to unique characteristics of HER2 protein expression and gene amplification in USC such as major heterogeneity and lack of apical staining compared to breast cancer.
- Optimal testing algorithms for HER2/neu status in USC may have important implications for developing targeted therapies.
- The review evaluates efficacy of HER2-directed therapies in both preclinical and clinical settings and discusses possible mechanisms of resistance.
Limitations: Narrative review rather than original experimental or systematic/meta-analytic data.; Abstract contains no quantitative results or study-level sample sizes.; Conclusions depend on heterogeneous preclinical and clinical studies in the literature rather than a single controlled dataset.; Field limitations noted (e.g., heterogeneity of HER2 expression in USC) may limit generalizability of testing and therapeutic approaches..
Reviews HER2/neu expression and the potential of HER2-directed therapies in uterine serous carcinoma, with attention to diagnostic testing and resistance.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMechanismReported positiveLimited evidenceTier 3 · early humann = 8
The American journal of surgical pathology · Apr 2025 · retrospective molecular cohort study
uterine serous carcinomaendometrial hyperplasia
Researchers identified 8 uterine serous carcinomas with concurrent endometrial hyperplasia and performed tumor-normal panel sequencing on the carcinoma and hyperplasia separately. In 7 of 8 paired cases the carcinoma and hyperplasia were clonally related and often shared TP53 mutations; one case was genetically unrelated and another shared only a single mutation. ARID1A mutations were more common in hyperplasia-associated USC than in atrophy-associated USC (43% vs 0%; P = 0.02).
Reported effects: cases_screened_with_sequencing_and_slides_available 267, n=267 · cases_with_sufficient_tissue_for_molecular_studies 8, n=8 · +5 more
Key findings
- Of 267 USCs with available sequencing and slides, 8 cases with concurrent carcinoma and hyperplasia had sufficient tissue for molecular study.
- In 7 of these 8 cases (87.5%), USC and hyperplasia were clonally related and shared multiple mutations.
- TP53 hotspot mutations were shared between carcinoma and hyperplasia in 4 cases (57% of the clonally related cases).
- In 1 case (USC4) the carcinoma and hyperplasia were genetically unrelated and the hyperplasia was TP53 wild-type.
- In another case (USC5) the carcinoma and TP53 wild-type hyperplasia shared 1 of 11 mutations and were distinct at the copy number level.
- ARID1A mutations were more prevalent in hyperplasia-associated USC than in atrophy-associated USC (43% vs. 0%; P = 0.02).
Limitations: Very small molecular cohort (only 8 cases with sufficient tissue) limits generalizability.; Retrospective selection of cases and requirement for sufficient tissue may introduce selection bias.; No functional experiments to demonstrate causality or biological consequences of shared mutations.; Clinical outcome data and broader validation cohorts are not reported in the abstract..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
ReviewMechanismMixed resultsLimited evidenceTier 4 · clinicaln = 95
Current oncology (Toronto, Ont.) · Apr 2025 · systematic review
uterine serous carcinoma
This systematic review searched PubMed/Medline and Cochrane through February 2025 and included 95 studies of uterine serous carcinomas. The authors report that these tumors are characterized by TP53 mutations and extensive copy number alterations and are commonly classified in the copy number-high/p53abn molecular group. The review identified 66 distinct molecular characteristics and new cancer signatures that may have prognostic significance and could inform tailored treatment strategies, though these findings require further validation.
Reported effects: included_studies 95 · distinct_molecular_characteristics 66
Key findings
- Uterine serous carcinomas are an aggressive minority of endometrial cancers.
- These tumors are characterized by mutations in TP53 and extensive copy number alterations and are primarily classified in the copy number-high/p53abn molecular prognostic group.
- The systematic review searched PubMed/Medline and Cochrane databases through February 2025 and included 95 studies.
- A total of 66 distinct molecular characteristics and new cancer signatures with potential prognostic impact were identified across the included studies.
- Authors suggest these molecular findings may inform clinical practice and aid development of tailored treatment strategies for patients with uterine serous carcinoma.
Limitations: Review limited to English-language articles (English-only search was performed).; Systematic review format reported; no pooled meta-analytic effect sizes or patient-level pooled estimates are presented in the abstract.; Prognostic markers and new signatures identified across multiple studies may be heterogeneous and require independent validation before clinical application.; Abstract does not report the quality assessment of included studies or patient-level sample sizes..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
ReviewMechanismMixed resultsModerate evidenceTier 4 · clinical
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · Mar 2025 · Review
uterine serous carcinomauterine carcinosarcoma
This is a narrative review summarizing recent evidence on molecular classification, biomarkers, and new treatment approaches for uterine serous carcinoma and uterine carcinosarcoma. The authors highlight biomarkers such as HER2, TP53, and mismatch repair deficiency/microsatellite instability, discuss circulating tumor DNA and precision-based treatment options, and note survival disparities for non-Hispanic Black and other underserved minority patients. They conclude that continuing to prioritize biomarker-driven therapies and developing novel treatments through clinical trials — integrated with surgery and cytotoxic chemotherapy — is necessary.
Reported effects: proportion_of_cases 15% · proportion_of_deaths 50%
Key findings
- Uterine serous carcinoma and uterine carcinosarcoma are rare but account for a disproportionate share of endometrial cancer deaths.
- These subtypes have a high likelihood of metastasis and multisite recurrence and are biologically distinct from other endometrial cancers.
- The review analyzes the role of biomarkers including HER2, TP53, and mismatch repair deficiency/microsatellite instability and their influence on treatment strategies and surveillance.
- Circulating tumor DNA (ctDNA) is discussed as a potential tool.
- Novel precision-based treatment options are described and the authors call for continued development of biomarker-driven therapies through clinical trials.
- Disparate survival outcomes for non-Hispanic Black and other underserved minority patients are identified, and strategies to improve their outcomes are discussed.
Limitations: Narrative review rather than primary research; no new experimental or trial data presented in the abstract.; Abstract provides no methods, search strategy, or inclusion criteria (potential selection bias).; Rare tumor subtypes mean available evidence is likely limited and heterogeneous (implicit limitation).; No quantitative synthesis (meta-analysis) or new clinical outcome data reported in the abstract..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
ReviewMixed resultsLimited evidenceTier 4 · clinical
Medicina (Kaunas, Lithuania) · Dec 2024 · literature review
uterine serous carcinoma (serous endometrial carcinoma)endometrial cancer
This literature review summarizes current HER2-directed therapies for HER2-positive uterine serous (serous endometrial) carcinoma. The authors note that about one-third of serous endometrial cancers overexpress HER2 or have ERBB2 amplification and that clinical trials combining chemotherapy with anti-HER2 agents (mainly trastuzumab, alone or with pertuzumab) have shown promising results and been incorporated into international guidelines. The review also describes ongoing research into antibody–drug conjugates and tyrosine kinase inhibitors and highlights that acquired resistance and other unmet needs remain.
Studied with: chemotherapy, pertuzumab.
Key findings
- Approximately one-third of patients with serous endometrial carcinoma may overexpress HER2/neu protein and/or show c-erBb2 (ERBB2) gene amplification.
- HER2-directed treatments, especially trastuzumab alone or combined with pertuzumab and chemotherapy, have shown promising results in clinical trials and have been incorporated into international guidelines.
- Antibody-drug conjugates and tyrosine kinase inhibitors targeting HER2 are under active investigation in endometrial cancer.
- Acquired resistance to HER2-targeted therapies is an important unresolved problem in endometrial cancer and its mechanisms are mostly unknown.
- Research is exploring earlier use of HER2-directed therapy in this disease.
Limitations: This is a literature review and does not present new primary experimental or trial data.; The abstract does not state this is a systematic review, so selection and synthesis methods are not described in the abstract.; No quantitative effect sizes or detailed trial outcome data are presented in the abstract.; Mechanistic understanding of acquired resistance in endometrial cancer is reported as largely unknown..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalReported positiveLimited evidenceTier 3 · early humann = 10
BMC cancer · Dec 2024 · retrospective cohort
Trastuzumab-deruxtecan-t-dxdTrastuzumab-deruxtecanendometrial neoplasmsovarian neoplasmscervical neoplasmsuterine carcinosarcomauterine leiomyosarcomauterine serous carcinomaovarian carcinosarcomahigh-grade serous ovarian carcinomamucinous ovarian carcinomasquamous cervical carcinoma This retrospective single-center study identified 10 patients with HER2-expressing (IHC 2+/3+) recurrent or metastatic gynecological cancers who received trastuzumab deruxtecan (5.4 mg/kg IV every 3 weeks). The cohort had a median progression-free survival of 5.4 months (95% CI 0.8-9.8). Five patients had a partial response, one had stable disease at 12 weeks, and four had disease progression at initial assessment. Clinical benefit was observed mainly in tumors with HER2 IHC 3+.
Reported effects: median PFS 5.4 mo [0.8–9.8], n=10 · partial responses 5, n=10 · +2 more
Key findings
- 10 patients with recurrent/metastatic HER2-expressing gynecological malignancies were treated with T-DXd.
- Histologies included uterine neoplasms (n=5), cervical squamous carcinoma (n=1) and ovarian cancers (n=4).
- Median age was 65.4 years (25th-75th percentile, 58.1-75.2 years).
- HER2 by IHC: 5 patients were 3+ and 5 patients were 2+.
- Median number of prior therapy lines was 4 (range 2-6); 2 uterine serous carcinoma patients were pretreated with trastuzumab and 4 patients had prior immunotherapy.
- Dose: T-DXd 5.4 mg/kg IV every 3 weeks until progression/toxicity.
- Median progression-free survival (PFS) in the cohort was 5.4 months (95% CI 0.8-9.8 months).
- Responses: 5 patients had partial response (including 2 previously treated with trastuzumab), 1 patient had stable disease at 12 weeks, 4 patients had disease progression at initial assessment.
- Most patients who derived clinical benefit had HER2 IHC 3+ expression.
Limitations: Retrospective, single-center design; Very small sample size (n=10); No control or comparator arm; Heterogeneous mix of gynecologic histologies; Heavily pre-treated population limits generalizability; Limited/absent reporting of safety or adverse event data in the abstract; Potential selection and reporting bias inherent to retrospective series.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMechanismReported negativeLimited evidenceTier 3 · early humann = 289
Frontiers in oncology · Oct 2024 · retrospective cohort genomic analysis
endometrial adenocarcinomauterine serous carcinoma
This single-institution retrospective study analyzed FoundationOne CDx genomic results from 289 patients with advanced or recurrent endometrial adenocarcinoma (January 2017–August 2022). Uterine serous carcinoma (USC) was more common among Black patients and CCNE1 amplification was more frequent in Black versus White patients; tumors with CCNE1 amplification had a high rate of progression within 12 months of first-line platinum and were associated with shorter median overall survival. PI3K/AKT/mTOR pathway mutations were reported less frequently in Black patients but that difference did not reach statistical significance in this report.
Reported effects: cohort size and racial composition, n=289 · USC proportion of tested tumors 26.3%, n=289 · +7 more
Key findings
- Total cohort: 289 patients (29.4% Black, 52.6% White).
- USC comprised 26.3% (76 of 289) of tested tumors; of USC tumors, 33 of 76 (44%) were Black.
- USC occurred more frequently in Black patients (33 of 85 [38.8%] Black patients compared to 30 of 152 [19.7%] White patients, p<0.05).
- Among USC, CCNE1 amplification occurred more frequently in Black patients than in White patients (12 of 33 [36.36%] vs 2 of 30 [6.67%], p<0.05).
- PI3K/AKT/mTOR pathway mutations occurred less frequently among Black USC patients (16 of 33 [48.5%] vs 26 of 33 [86.7%], p=0.17).
- Among patients with CCNE1 amplification, 73.3% (11 of 15) progressed on or within 12 months of first-line platinum-based therapy.
- CCNE1 amplification was associated with shorter median overall survival (97.3 months vs 44.3; HR (95%CI): 7.1 (10.03, 59.4) p< 0.05).
Limitations: Single-institution, retrospective design which may introduce selection bias.; Small subgroup sizes for key comparisons (e.g., 15 patients with CCNE1 amplification), limiting precision.; Abstract does not report multivariable adjustment for potential confounders.; Some subgroup denominators and statistical reporting in the abstract appear inconsistent, which may affect interpretation..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMechanismReported positiveLimited evidenceTier 3 · early humann = 18
Cell death & disease · Aug 2024 · Single-cell RNA sequencing of 18 human endometrial cancer samples across multiple pathological types, with patient-derived organoid drug testing and in vitro validation experiments
endometrial canceruterine clear cell carcinomaendometrioid endometrial carcinomauterine serous carcinoma
The authors performed single-cell RNA sequencing on 18 endometrial cancer samples across different pathological subtypes to map tumor-cell and microenvironment heterogeneity. They report pathology-specific tumor cell programs (immune-, proliferation-, or metabolism-modulating) and distinct microenvironment compositions, identified candidate drugs for each pathological group and confirmed drug activity in patient-derived organoids, and validated oncogenic effects of SOD2+ inflammatory cancer-associated fibroblasts in vitro. These findings provide descriptive molecular and cellular maps that may guide future, but not yet clinical, personalized approaches.
Reported effect: n_samples 18, n=18
Key findings
- scRNA-seq was performed on 18 endometrial cancer samples from multiple pathological types.
- Cancer cells showed pathology-associated hallmarks: immune-modulating in uterine clear cell carcinoma (UCCC), proliferation-modulating in well-differentiated endometrioid endometrial carcinoma (EEC-I), and metabolism-modulating in uterine serous carcinoma (USC).
- Cancer cells from UCCC exhibited the greatest heterogeneity among the groups studied.
- Potential effective drugs were predicted for each pathological group and their effectiveness was confirmed using patient-derived endometrial cancer organoids.
- Tumor microenvironment differences: normal endometrium had prognostically favorable CD8+ cytotoxic T cells and NK cells, whereas tumors were dominated by CD4+ regulatory T cells, CD4+ exhausted T cells, and CD8+ exhausted T cells.
- CXCL3+ macrophages with an M2 signature and angiogenesis association were found exclusively in tumors.
- Epithelium-specific CAFs (eCAFs) predominated in EEC-I while SOD2+ inflammatory CAFs (iCAFs) predominated in UCCC.
- The oncogenic effects of SOD2+ iCAFs were validated in vitro.
Limitations: Relatively small sample size (18 samples) limits generalizability.; Observational single-cell profiling: no prospective clinical outcome data or in vivo validation reported.; Drug effectiveness was confirmed in patient-derived organoids (ex vivo) but not in patients or animal models.; In vitro validation of SOD2+ iCAFs does not establish causality in vivo or clinical relevance.; Abstract does not report specific drug names, doses, or safety data..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text