Germline breast cancer susceptibility gene mutations and breast cancer outcomes.

BACKGROUND: It is unclear whether germline breast cancer susceptibility gene mutations affect breast cancer related outcomes. We wanted to evaluate mutation patterns in 20 breast cancer susceptibility genes and correlate the mutations with clinical characteristics to determine the effects of these germline mutations on breast cancer prognosis. METHODS: The study cohort included 480 ethnic Chinese individuals in Taiwan with at least one of the six clinical risk factors for hereditary breast cancer: family history of breast or ovarian cancer, young age of onset for breast cancer, bilateral breast cancer, triple negative breast cancer, both breast and ovarian cancer, and male breast cancer. PCR-enriched amplicon-sequencing on a next generation sequencing platform was used to determine the germline DNA sequences of all exons and exon-flanking regions of the 20 genes. Protein-truncating variants were identified as pathogenic. RESULTS: We detected a 13.5% carrier rate of pathogenic germline mutations, with BRCA2 being the most prevalent and the non-BRCA genes accounting for 38.5% of the mutation carriers. BRCA mutation carriers were more likely to be diagnosed of breast cancer with lymph node involvement (66.7% vs 42.6%; P = 0.011), and had significantly worse breast cancer specific outcomes. The 5-year disease-free survival was 73.3% for BRCA mutation carriers and 91.1% for non-carriers (hazard ratio for recurrence or death 2.42, 95% CI 1.29-4.53; P = 0.013). After adjusting for clinical prognostic factors, BRCA mutation remained an independent poor prognostic factor for cancer recurrence or death (adjusted hazard ratio 3.04, 95% CI 1.40-6.58; P = 0.005). Non-BRCA gene mutation carriers did not exhibit any significant difference in cancer characteristics or outcomes compared to those without detected mutations. Among the risk factors for hereditary breast cancer, the odds of detecting a germline mutation increased significantly with having bilateral breast cancer (adjusted odds ratio 3.27, 95% CI 1.64-6.51; P = 0.0008) or having more than one risk factor (odds ratio 2.07, 95% CI 1.22-3.51; P = 0.007). CONCLUSIONS: Without prior knowledge of the mutation status, BRCA mutation carriers had more advanced breast cancer on initial diagnosis and worse cancer-related outcomes. Optimal approach to breast cancer treatment for BRCA mutation carriers warrants further investigation.

Clinical evaluation of percutaneous vertebroplasty for symptomatic adjacent vertebral compression fracture.

STUDY DESIGN: A retrospective study. OBJECTIVE: To evaluate the efficacy and safety of percutaneous vertebroplasty (PV) for treating patients with symptomatic osteoporotic vertebral compression fractures (VCFs) adjacent to lumbar instrumented circumferential fusion. SUMMARY OF BACKGROUND DATA: Few studies have investigated adjacent VCFs and their management after spinal fusion surgery for degenerative lumbar disease. PATIENTS AND METHODS: From January 2005 to July 2011, a total of 23 patients with lumbar instrumented circumferential fusion suffered from adjacent symptomatic osteoporotic VCFs. All of these patients received PV using polymethylmethacrylate bone cement augmentation in our institute. Radiography and magnetic resonance imaging were used for imaging studies. The visual analog scale and modified Brodsky criteria were used to compare clinical outcomes before and after surgery. The minimum follow-up period was 18 months (range, 18-45 mo). RESULTS: One level PV was performed in 18 patients and 2 levels were performed in 5 patients. The patients' visual analog scale scores improved by an average of 54.3 points after the procedure. Twenty patients returned to their preinjury activities of daily living. Lumbar lordosis was increased from 28.9 degrees before PV to 36.2 degrees after PV. The average restoration of the fractured vertebral body height was 14.0%. No surgery-related complications occurred except asymptomatic cement leakage in 4 patients. CONCLUSIONS: PV is a minimally invasive and effective procedure to treat patients with symptomatic osteoporotic VCFs adjacent to lumbar instrumented circumferential fusion.

Performance and Operational Feasibility of Epstein-Barr Virus-Based Screening for Detection of Nasopharyngeal Carcinoma: Direct Comparison of Two Alternative Approaches.

PURPOSE: Two Epstein-Barr virus (EBV)-based testing approaches have shown promise for early detection of nasopharyngeal carcinoma (NPC). Neither has been independently validated nor their performance compared. We compared their diagnostic performance in an independent population. METHODS: We tested blood samples from 819 incident Taiwanese NPC cases (213 early-stage, American Joint Committee on Cancer version 7 stages I and II) diagnosed from 2010 to 2014 and from 1,768 controls from the same region, frequency matched to cases on age and sex. We compared an EBV antibody score using immunoglobulin A antibodies measured by enzyme-linked immunosorbent assay (EBV antibody score) and plasma EBV DNA load measured by real-time PCR followed by next-generation sequencing (NGS) among EBV DNA-positive individuals (EBV DNA algorithm). RESULTS: EBV antibodies and DNA load were measured for 2,522 (802 cases; 1,720 controls) and 2,542 (797 cases; 1,745 controls) individuals, respectively. Of the 898 individuals positive for plasma EBV DNA and therefore eligible for NGS, we selected 442 (49%) for NGS testing. The EBV antibody score had a sensitivity of 88.4% (95% CI, 86.1 to 90.6) and a specificity of 94.9% (95% CI, 93.8 to 96.0) for NPC. The EBV DNA algorithm yielded significantly higher sensitivity (93.2%; 95% CI, 91.3 to 94.9; P = 1.33 × 10-4) and specificity (98.1%; 95% CI, 97.3 to 98.8; P = 3.53 × 10-7). For early-stage NPC, the sensitivities were 87.1% (95% CI, 82.7 to 92.4) for the EBV antibody score and 87.0% (95% CI, 81.9 to 91.5) for the EBV DNA algorithm (P = .514). For regions with a NPC incidence of 20-100/100,000 person-years (eg, residents in southern China and Hong Kong), these two approaches yielded similar numbers needed to screen (EBV antibody score: 5,656-1,131; EBV DNA algorithm: 5,365-1,073); positive predictive values ranged from 0.4% to 1.7% and 1.0% to 4.7%, respectively. CONCLUSION: We demonstrated high sensitivity and specificity of EBV antibody and plasma EBV DNA for NPC detection, with slightly inferior performance of the EBV antibody score. Cost-effectiveness studies are needed to guide screening implementation.

Disparities in Access to Systemic Treatment for Breast Cancer in Thailand and Major Asian Territories.

PURPOSE: Breast cancer (BC) treatment has shifted from chemotherapy to targeted therapy. Several targeted agents have demonstrated an improvement in survival. Given that national healthcare resources were correlated with the cancer mortality-to-incidence ratio, we compared access to BC drugs in Thailand with that in other Asian countries. METHODS: BC experts involved in the Breast International Group (BIG)-Asia in six representative groups for countries or special administrative region (SAR) in Asia (Hong Kong SAR, Japan, Korea, Taiwan, Thailand, and Singapore) were invited to participate in the survey. The questionnaire addressed national health reimbursement schemes, molecular testing for early BC (EBC), availability and accessibility of BC drugs. Accessibility and reimbursement of the drugs were reported based on their listing as essential medicines in the World Health Organization Model List of Essential Medicines (WHO-EML) and their nomination as effective drugs in the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS). The study was approved by all participating BIG-Asia organizations in November 2021. RESULTS: Genomic tests for EBC were non-reimbursable in all surveyed territories. Reimbursement and co-payment of BC drugs vary between and within these regions (particularly Thailand). Most drugs in the WHO-EML and ESMO-MCBS (A/B for EBC and 4/5 for advanced BC) were accessible in all surveyed territories. However, the accessibility of effective but costly WHO-EML and ESMO-MCBS drugs was not uniform in Thailand. There was an evident disparity for individuals covered by the Thai Social Security/Universal Health Coverage schemes. CONCLUSION: Essential BC drugs are generally accessible in selected BIG-Asia countries or SAR. There is a disparity in accessing high-cost drugs in Thailand compared with other Asian territories.

Early application of extracorporeal membrane oxygenation in a patient with amniotic fluid embolism.

Amniotic fluid embolism occurs rarely but is a leading cause of maternal mortality. Regardless of emergent supportive medical treatment, it is associated with a very high mortality rate. Here, we present the case of a 33-year-old pregnant woman with amniotic fluid embolism, who sustained cardiac arrest and was rescued with early application of extracorporeal membrane oxygenation. The management of amniotic fluid embolism is to initially focus on rapid cardiopulmonary stabilization. Hemodynamic decompensation may be transient and recoverable within a few hours. Early application of extracorporeal membrane oxygenation should be considered in patients who are unresponsive to medical therapy before severe organ damage supervenes.

Birth asphyxia during general anesthesia for a morbidly obese parturient with gestational diabetes mellitus undergoing cesarean section--a case report.

A 26-year-old pregnant woman with a body mass index of 60 was scheduled for cesarean section at 36 weeks' gestation. She was found having affected with gestational diabetes mellitus and hypertension at 17 weeks of pregnancy. The blood glucose level as controlled by subcutaneous injection of insulin was maintained at the level of 110-140 mg/dL. Hypertension was also controlled by methyldopa and hydralazine with the systolic pressure maintaining at 140-180 mmHg during the pregnancy. Abnormal perfusion of umbilical artery without compromise of placental function was found twice by Doppler prenatal examination at gestation of 33 and 34 weeks respectively. The operation was performed under general anesthesia. However, apnea and low Apgar score of the neonate were noted. General anesthesia was thought as the root cause of this event at first. After a series of examination and management, hypoglycemia and uteroplacental perfusion insufficiency were considered as the causes of this morbidity. The neonate's condition was improved in 48 hr after close care.