TP53 and/or BRCA1 Mutations Based on CtDNA Analysis as Prognostic Biomarkers for Primary Triple-Negative Breast Cancer.

Precise biomarkers for predicting the therapeutic efficacy of molecularly targeted drugs are limited at the protein level; thus, it has been important to broadly scrutinize individual cancer driver gene mutations for effective cancer treatments. Multiplex cancer genome profiling can comprehensively identify gene mutations that are therapeutic targets using next-generation sequencing (NGS). In addition, circulating tumor DNA (ctDNA) is a DNA fragment released into the blood by tumor cell-derived cell death or apoptosis. Liquid biopsy with ctDNA is a novel clinical test for identifying genetic mutations in an entire population noninvasively, in real-time, and heterogeneously. Although there are several reports on ctDNA, fewer have evaluated ctDNA with NGS before an initial treatment for breast cancer patients. Therefore, we examined whether analyzing tumor-associated gene mutations in primary breast cancer based on ctDNA could serve as a biomarker for prognosis and optimal treatment selection. Ninety-five primary breast cancer patients treated at our department from January 2017 to October 2020 were included. Pretreatment plasma samples were subjected to NGS analysis of ctDNA, and correlations with patients' clinicopathological characteristics were evaluated. Fifty-nine (62.1%) patients were positive for ctDNA. ctDNA tended to be positive in hormone receptor-negative, and TP53 (34%), BRCA1 (20%), and BRCA2 (17%) gene mutations were more frequent. Regarding recurrence-free survival, the prognosis was poor in the TP53 and/or BRCA1 mutation-positive groups, especially in triple-negative breast cancer (TNBC) patients. In conclusion, the results of this study indicate that ctDNA with liquid biopsy could identify the poor prognosis group before treatment among TNBC patients and for those for whom optimal treatment selection is desirable; additionally, optimal treatment could be selected according to the ctDNA analysis results.

Granulomatous/sarcoid-like reactions in the setting of programmed cell death-1 inhibition: a potential mimic of disease recurrence.

Nivolumab and pembrolizumab are humanized IgG4 monoclonal antibodies against programmed cell death 1 (PD-1). Although these agents are effective in treating advanced melanoma, non-small-cell lung carcinoma, and other types of cancers, various adverse events have been reported. Cutaneous adverse events are particularly prevalent and, while granulomatous/sarcoid-like reactions are uncommon, they are increasingly recognized as immune-related adverse events associated with immune checkpoint inhibitors. Herein, we report two cases of granulomatous/sarcoid-like reaction with foreign material, mimicking metastatic malignancy after PD-1 inhibitor treatment. Clinicians should be aware of the existence of cutaneous lesions and perform biopsy if needed to prevent misdiagnosis and unnecessary adjustments to immunotherapy.

Eruptive squamous cell carcinoma in a patient treated with concomitant pembrolizumab and imiquimod.

Pembrolizumab, a humanized monoclonal antibody against programmed cell death 1, is used for various malignant neoplasms. Toll-like receptor (TLR) agonists, specifically targeting the TLR9 subfamily (TLR7-9), are treatment options for solid tumors and hematological malignancies. We experienced a case of eruptive squamous cell carcinoma (SCC) in a patient treated concomitantly with pembrolizumab and imiquimod, a TLR7 agonist. A 75-year-old woman who was given a diagnosis of bladder cancer with lung metastasis received pembrolizumab for 3 months when she was referred to our department for the evaluation of skin rashes on her hands. Her skin lesions were diagnosed as well-differentiated SCC and treated with topical imiquimod. Two months after the start of imiquimod, more than 10 reddish papules appeared on her hands. The histological diagnosis of a new plaque was the same as an earlier biopsy. We herein describe this case in detail and provide a published work review.

Usefulness of three-dimensional transesophageal echocardiography for diagnosis of hemolytic anemia due to inverted internal felt strip after surgery for aortic dissection.

Felt strips are widely used for reinforcement of the aortic stump in surgery for aortic dissection (AD). Postoperative hemolytic anemia (HA) due to an inverted internal felt strip at the aortic stump fixation for AD is extremely rare. A 70-year-old woman underwent ascending aorta replacement for acute type A AD, where both proximal and distal anastomotic sites were reinforced with Teflon felt strips. A week later, macroscopic hematuria and HA emerged. Three-dimensional transesophageal echocardiography (3D-TEE) demonstrated that the proximal inner felt strip turned up and protruded into the aortic inner lumen. At redo surgery, which was performed 2 weeks after the initial surgery, the findings of 3D-TEE were confirmed, and the inverted internal felt strip was replaced with a bovine pericardial strip. The findings of HA disappeared immediately after the second surgery. 3D-TEE is a very informative, valuable modality for accurate diagnosis that leads to a safe surgery.