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Aim: Tamoxifen (TAM) is widely used in adjuvant endocrine therapy for invasive breast cancer as a selective estrogen modulator, but this treatment has a risk of developing endometrial malignancy. However, hysteroscopic findings during or after TAM treatment are unclear. The aim of this study is to examine the association between hysteroscopic patterns and malignant histological findings during or after treatment with TAM. Methods: The subjects were patients who received TAM after surgery for breast cancer and underwent hysteroscopy at our institution from January 2016 to December 2019. Clinicopathological factors and hysteroscopic findings were collected from medical records and investigated retrospectively. Histologically, atypical endometrial hyperplasia, endometrial cancer, and carcinosarcoma were classified as malignant diseases. Results: A total of 26 patients were eligible for the study. Hysteroscopic findings included an irregular surface of the endometrium (n = 3, 11.5%), atypical vessels (n = 10, 38.5%), papillary structure (n = 3, 11.5%), and polypoid structure (n = 18, 69.2%). Histological examination revealed malignancy in six patients (23.0%). The percentage of atypical vessels in patients with malignancies was significantly higher than that in patients with a normal endometrium or benign lesion (100% vs. 20%, p = 0.0009). The sensitivity and specificity of atypical vessels in hysteroscopy for diagnosis of malignant diseases were 100% and 80%, respectively. Conclusions: Hysteroscopic findings of atypical vessels may be useful for prediction of malignant diseases in patients treated with TAM. [ABSTRACT FROM AUTHOR]

ARID1A mutation is frequently found in clear cell ovarian cancer (CCC) and endometrioid ovarian cancer (EC). Anti-PD-1 monotherapy has been found to have limited efficacy in epithelial ovarian cancer; however, anti-PD-1 therapy showed significant clinical benefit in some CCC. We sought to define the relationship of ARID1A mutation/ARID1A expression to the immunogenic profile of different histologic subtypes of ovarian cancer. We performed next-generation sequencing of 160 cancer-related genes. Also, we analyzed the immunohistochemical status of ARID1A, PD-L1, and CD8 with survival in different histologic subtypes of ovarian cancer in a total of 103 cases. ARID1A mutation was found in 0% of the high-grade serous ovarian cancer (HGSC) (n = 36), 41.5% of the CCC (n = 41), 45.0% of the EC (n = 20), and 33.3% of the mucinous ovarian cancer (MC) (n = 6) cases. ARID1A loss was found in 19.4% of the HGSC, 75.6% of the CCC, 60.0% of the EC and 0% of the MC cases. ARID1A mutation was found to be associated with high PD-L1 (p < 0.001) or CD8 levels (p < 0.001) in CCC but not in other histologic subtypes. Meanwhile, ARID1A loss was associated with high PD-L1 or CD8 levels in CCC (p < 0.001) and HGSC (p < 0.001) but not in EC and MC. In addition, ARID1A mutation was associated with high tumor mutation burden in CCC (p = 0.006). ARID1A mutation/ARID1A expression is associated with immune microenvironmental factors in CCC but not in EC. ARID1A status can be a biomarker for selecting candidates for immune checkpoint blockade in CCC. • ARID1A mutation was identified in 41.5 and 45.0% of clear cell and endometrioid ovarian cancer patients, respectively. • ARID1A mutation/ARID1A loss is associated with positive PD-L1 or CD8 levels in clear cell ovarian cancer. • ARID1A mutation is associated with a high tumor mutation burden in clear cell ovarian cancer. [ABSTRACT FROM AUTHOR]

Purpose: To find genetic variants that predicted toxicity and/or efficacy of paclitaxel plus carboplatin combination therapy (TC therapy)., Patients and Methods: In a retrospective case-control study, we analyzed 320 patients who had received TC therapy for gynecological cancers (ovarian, fallopian tube, peritoneal, uterine, and cervical cancers) and collected their germline DNA. We performed a comprehensive pharmacogenomic analysis using a targeted resequencing panel of 100 pharmacogenes. For 1,013 variants passing QC, case-control association studies and survival analyses were conducted., Results: GSTP1 rs1695 showed the smallest p value for hematotoxicity association, and the 105 Ile wild type allele had a significantly higher risk of severe hematotoxicity (neutropenia G4, thrombocytopenia ≥ G3 and anemia ≥ G3) than the 105 Val allele (p=0.00034, odds ratio=5.71 (95% confidence interval:1.77-18.44)). Next, we assessed 5-year progression-free survival (PFS) and overall survival (OS) in 56 advanced ovarian cancer patients who received tri-weekly TC as a first-line chemotherapy. Patients with the 105 Ile/ 105 Ile genotype showed significantly better PFS (p=0.00070) and OS (p=0.0012) than those with the 105 Ile/ 105 Val or 105 Val/ 105 Val genotype., Conclusion: Our study indicates that the GSTP1 rs1695 105 Ile/ 105 Ile genotype is associated with both severe hematotoxicity and high efficacy of TC therapy, identifying a possible prognostic indicator for patients with TC therapy., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.