Mika Okazawa-Sakai

Current management of hereditary cancer syndromes in ovarian and endometrial cancer: a Japanese study

Abstract Background To evaluate the current state of hereditary cancer syndrome management in patients with ovarian and endometrial cancer and to identify the barriers to uptake of genetic testing. Methods We conducted a cross-sectional multicenter study at five regional cancer centers in Japan, including 229 patients with ovarian cancer and 454 with endometrial cancer treated between January 2021 and December 2022. We assessed the proportion of patients who received information about hereditary cancer syndromes from gynecologists, underwent genetic counseling with genetic experts, and completed genetic testing; in addition, we explored the barriers to testing uptake. Results Among patients with ovarian cancer, 152 (66.4%) received information about hereditary cancer syndromes from their gynecologists, with 61 (26.6%) subsequently receiving genetic counseling and 58 (25.3%) undergoing genetic testing. By contrast, patients with endometrial cancer demonstrated markedly lower rates: only 76 (16.7%) received initial information, 22 (5.3%) accessed genetic counseling, and 13 (2.9%) completed genetic testing. Among patients who received information about hereditary cancer syndromes from their gynecologists, 38% with ovarian cancer and 14% with endometrial cancer underwent genetic testing. Among patients identified as high-risk for hereditary cancer syndromes through tumor profiling, 27.6% (8/29) with ovarian cancer and 70.6% (12/17) with endometrial cancer did not undergo genetic testing. Patient disinterest was the primary barrier to genetic testing among high-risk individuals. Conclusions The barriers to uptake of genetic testing arise primarily from inadequate provider communication and patient disinterest in hereditary cancer syndromes.

Frequency and clinical features of deficient mismatch repair in ovarian clear cell and endometrioid carcinoma

To clarify the frequency of deficient mismatch repair (dMMR) in Japanese ovarian cancer patients, we examined microsatellite instability (MSI) status and immunohistochemistry (IHC) subtypes, including endometrioid carcinoma (EMC), clear cell carcinoma (CCC), or a mixture of both (Mix). We registered 390 patients who were diagnosed with EMC/CCC/Mix between 2006 and 2015 and treated at seven participating facilities. For 339 patients confirmed eligible by the Central Pathological Review Board, MSI, IHC, and MutL homolog 1 methylation analyses were conducted. The tissues of patients with Lynch syndrome (LS)-related cancer histories, such as colorectal and endometrial cancer, were also investigated. MSI-high (MSI-H) status was observed in 2/217 CCC (0.9%), 10/115 EMC (8.7%), and 1/4 Mix (25%). Additionally, loss of MMR protein expression (LoE-MMR) was observed in 5/219 (2.3%), 16/115 (14.0%), and 1/4 (25%) patients with CCC, EMC, and Mix, respectively. Both MSI-H and LoE-MMR were found significantly more often in EMC (p<0.001). The median (range) ages of patients with MMR expression and LoE-MMR were 54 (30-90) and 46 (22-76) (p=0.002), respectively. In the multivariate analysis, advanced stage and histological type were identified as prognostic factors. The dMMR rate for EMC/CCC was similar to that reported in Western countries. In Japan, it is assumed that the dMMR frequency is higher because of the increased proportion of CCC.

Gut microbiome associated with PARP inhibitor efficacy in patients with ovarian cancer

To investigate an association between the gut microbiome and efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer. This study conducted fecal microbiome analysis (16S rRNA gene sequencing) and circulating tumor DNA (ctDNA) profiling for ovarian cancer patients who underwent PARPi maintenance therapy. Fecal and blood samples were collected at the baseline and the progressive disease (PD) or last follow-up. The relative abundance of gut microbes and progression-free survival (PFS) were analyzed using linear discriminant analysis of effect size and the Cox proportional hazard model according to Baseline samples were available from 23 High fecal composition of