A Case of Paraneoplastic Neurological Syndrome Associated with Breast Cancer Detected while Searching for the Cause of Involuntary Movement.

Our case involved a 66-year-old woman who noticed progressive asymmetric involuntary movement, difficulty speaking, and difficulty swallowing. The patient fractured her femur due to a lower extremity involuntary movement while walking. During the course of her treatment for the fracture, her neurological symptoms worsened. Approximately 2 months after becoming aware of her symptoms, she visited our clinic for evaluation of difficulty with unassisted walking and weight loss due to dysphagia. To identify the cause of her neurological symptoms, hematological examination, brain magnetic resonance imaging, single-photon emission computed tomography for cerebral blood flow, electroencephalography, and a somatosensory evoked potential test were conducted. Although the cause of her neurological symptoms could not be determined, computed tomography revealed the presence of breast cancer, which led us to suspect paraneoplastic neurological syndrome (PNS). After breast cancer treatment, her neurological symptoms improved simultaneously. Therefore, the patient was retrospectively diagnosed with PNS. We report a case of PNS whose neurological symptoms followed a subacute course and were relieved after breast cancer treatment.

Use of Liquid Biopsy to Detect PIK3CA Mutation in Metastatic Breast Cancer.

BACKGROUND: PIK3CA is associated with tumor progression, and the prevalence of PIK3CA mutation is high in breast cancer. Liquid biopsy offers convenient, noninvasive, and real-time insight into genetic alteration. In this study, we used liquid biopsy to detect PIK3CA mutations in patients with breast cancer. METHODS: We recruited patients with histologically confirmed breast cancer and distant metastases between April 2020 and September 2020. Circulating DNA was extracted from plasma (ctDNA) and exosomes (exoDNA). PIK3CA mutations (exons 9 and 20) were analyzed by droplet digital PCR. RESULTS: Of the 52 patients recruited, 16 had PIK3CA mutations in tumor tissue or blood: 9 had exon 9 mutations (E542K and E545K) and 8 had exon 20 mutations (H1047 L and H1047R). In 8 (15%) of the 52 patients, PIK3CA mutations were detected by liquid biopsies using ctDNA in 5 (9%), exoDNA in 6 (11%), and both ctDNA and exoDNA in 3 (6%). Of the 8 patients with PIK3CA mutations detected by liquid biopsies, 3 had no PIK3CA mutations in the primary tumors. CONCLUSIONS: PIK3CA mutations can be detected by liquid biopsy even in patients with no PIK3CA mutations in their primary tumors; thus, combination analysis using tissue and liquid biopsies can provide clinically useful information for patients with breast cancer.

Vascular Ehlers-Danlos Syndrome with a Novel Missense Mutation in COL3A1: A Man in His 50s with Aortic Dissection after Interventional Treatment for Hemothorax as the First Manifestation.

Type III collagen is the major protein in the walls of blood vessels and hollow organs; it is decreased in patients with vascular Ehlers-Danlos syndrome (EDS). A 52-year-old man was admitted for severe back pain, and right hemothorax was suspected by chest computed tomography. Immediately after embolization for bleeding bronchial artery, aortic dissection occurred and was treated conservatively in the intensive-care unit. Vascular EDS with a mutation of COL3A1 cDNA (c.3175G>A) was diagnosed. When vascular EDS is suspected, the patient should be treated prophylactically, and a genetic examination should be performed to confirm the diagnosis.

A Real-World Retrospective Cohort Study of Combined Therapy with Bevacizumab and Paclitaxel in Japanese Patients with Metastatic Breast Cancer.

OBJECTIVE: Combined therapy with bevacizumab and paclitaxel (BP regimen) as a first-line treatment has proven highly effective with good tolerance for patients with metastatic breast cancer (MBC). The objective of this study was to examine the efficacy and safety of the BP regimen for Japanese patients with MBC in real-world clinical settings. METHODS: From June 2012 through May 2014, we recruited 94 patients at 10 medical institutions. The primary endpoint was time to treatment failure (TTF), and the secondary endpoints were overall survival (OS) and safety. Objective response was assessed according to the Response Evaluation Criteria in Solid Tumors. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0-Japan Clinical Oncology Group. RESULTS: Nighty patients with MBC (mean 58 years, range: 34-80 years) were enrolled, and 60 (66.6%) and 52 (57.7%) had undergone prior chemotherapy as adjuvant treatment and treatment for MBC, respectively. Median TTF was 6.2 months (95% confidence interval [CI], 4.2-8.3 months), and median OS was 15.4 months (95% CI, 12.0-18.9 months). The overall response rate was 67.8% (95% CI: 57.1-77.2%). A total of 28 patients (31.1%) required a dose reduction of paclitaxel. Forty-five, 42, and 3 patients received the initial doses of 90, 80, and 60 mg/m2, respectively. Among patients who received the initial doses of 90 mg/m2, 13 patients (28.9%) unexpectedly required a dose reduction of ≥20 mg/m2. The BP regimen was discontinued for 66 (73.3%) of the 90 patients, 52 (57.7%) of whom experienced "disease progression." Grade 3/4 hematologic AEs developed in 51 patients (56.6%), with leukopenia and neutropenia in 16 patients (17.8%) and 21 patients (23.3%), respectively. Grade 3 nonhematologic AEs developed in 8 patients (8.9%), with the most common nonhematologic AE of peripheral neuropathy in 4 patients (4.4%). No Grade 4 nonhematologic AEs developed. Peripheral neuropathy [56 patients (62.2%) ], nail discoloration [53 patients (58.9%) ], and fatigue [51 patients (56.7%) ] were the most predominant AEs-the known AEs of paclitaxel. CONCLUSIONS: The BP regimen was active and well tolerated in the real-world clinical settings. As many as 28.9% of patients who received the initial dose of 90 mg/m2 required a dose reduction of paclitaxel by 20 mg/m2. Therefore, there is a need to find a therapeutic regimen that is less likely to result in dose reductions for patients with MBC who undergo a BP regimen using the initial paclitaxel dose of 90 mg/m2.

Combining Fulvestrant with Low-Dose Capecitabine is Effective and Tolerable in Woman with Metastatic Breast Cancer.

Although the use of endocrine therapy in combination with intravenous chemotherapy has not been standardized, the combination of fulvestrant and chemotherapy may be promising. A 62-year-old woman came to our hospital's outpatient clinic with extensive ascites. Approximately 10 years earlier, she had undergone mastectomy and sentinel lymph node biopsy. Pathologically invasive lobular carcinoma, with a maximum diameter of 28 mm, had been diagnosed in the left breast. The cancer had a histological grade of 2, was positive for estrogen receptor (95% or more positive cells), and was negative for both progesterone receptor (less than 1% positive cells) and human epidermal growth factor receptor 2. For 5 years the patient underwent adjuvant endocrine therapy with tamoxifen and then with anastrozole. Four years 2 months after adjuvant endocrine therapy had been completed, she felt abdominal distention, and her symptoms gradually worsened. A series of intensive examinations indicated that the invasive lobular carcinoma had metastasized to the peritoneum, pleura, uterus, and bone. Aromatase inhibitor was administered as a first-line therapy for the metastatic disease and was accompanied by denosumab injected every 28 days. For 2 months after the start of treatment with anastrozole, the ascites did not decrease and tumor markers increased. Because anastrozole had not been effective, fulvestrant (500 mg) and low-dose capecitabine (500 mg) were administered for the first 21 days of a 28-day cycle; this regimen had been shown by a phase 2 trial to be effective and tolerable in patients with metastatic breast cancer. The patient felt an improvement in abdominal distention, and the tumor markers decreased 2 weeks after the start of this combination therapy. By 10 months after the start of the combined therapy the ascites had decreased and pleural effusion had completely disappeared. The uterine wall became thinner, and the endometrial cavity became smaller. Tumor markers continued decreasing. No adverse events were observed. The combination of fulvestrant and low-dose capecitabine is promising because of its efficacy and tolerability for the treatment of patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer.

Vascular invasion in triple-negative carcinoma of the breast identified by endothelial lymphatic and blood vessel markers.

The aim of this study was to determine lymph vessel invasion (LVI) and blood vessel invasion (BVI) using established biological markers and clinicopathological findings for triple-negative breast carcinoma. We reviewed all 202 cases of primary breast carcinoma that were surgically resected at Saitama Medical Center, Saitama Medical School, between 2006 and 2009. Tumor tissue was immunostained for estrogen receptor, progesterone receptor, Her2/neu, D2-40, and CD34. Among these, 26 cases of triple-negative carcinoma were reported retrospectively. The results were compared with those of 176 cases of non-triple-negative carcinomas that were included as controls. The frequency of LVI examined by hematoxylin and eosin and D2-40 (triple negative, 7 of 26; non-triple negative, 61 of 176) was not significantly different, and neither was BVI examined by HE, Elastica van Gieson, CD34 (triple negative, 2 of 26; non-triple negative, 16 of 176), and lymph node metastasis (triple negative 9 of 26, non-triple negative, 65 of 176). However, a specific pattern of distant metastasis with a high frequency of visceral metastases was detected in triple-negative carcinoma cases (triple negative, 6 of 26; non-triple negative, 8 of 176). Our findings show that triple-negative carcinoma of the breast may have a distinct biological behavior.

Basal cytokeratin expression in relation to biological factors in breast cancer.

The objective of this study was to determine the predictive impact of several established tumor biological markers and clinicopathological findings for basal-like carcinoma. Expression was determined by immunohistochemistry using antibodies to cytokeratins 5/6, 14, and 17, and the cases were divided into basal-like carcinoma and non basal-like carcinoma. These subgroups were compared in terms of biological markers (HER2, estrogen receptor, progesterone receptor, Ki-67, P-53, and P-glycoprotein) and clinicopathological behavior. Of the 49 basal-like carcinoma cases, 25(51.0%) were P-53-positive, whereas 100 (35.9%) of the 278 non basal-like carcinoma cases were P-53-positive. A high ratio of nuclear Ki-67 expression was detected in 39 (79.6%) of 49 basal-like carcinoma cases and was significantly more common than in non basal-like carcinoma cases (81/278, 29.1%). P-glycoprotein expression was identified in 29 (59.2%) of 49 basal-like carcinomas but only 85 (30.6%) of 278 non basal-like carcinomas. We observed high levels of P-53, Ki-67, and P-glycoprotein, with the reduction or loss of estrogen receptor, progesterone receptor, and HER2 being more obvious, in basal-like carcinomas than in non basal-like carcinomas. Our findings provide further evidence that basal-like carcinoma has different mechanisms of histogenesis.