Prevalence of PALB2 Mutations in Breast Cancer Patients in Multi-Ethnic Asian Population in Malaysia and Singapore

10.1371/journal.pone.0073638PLoS ONE88-POLN

Beyond diabetes: The role of metformin in non-muscle invasive bladder cancer

10.11622/smedj.2020121SINGAPORE MEDICAL JOURNAL2348-4

Cancer-specific methylation in the BRCA1 promoter in sporadic breast tumours

10.1007/s12032-010-9438-yMedical Oncology28164-6

Pedigrees of families with germline mutations in <i>PALB2</i>.

<p>(A) Family pedigree of BRC945, carrier of c.1037_1041delAAGAA [STOP358]. (B) Family pedigree of BRC859, carrier of c.2606delC [S869X]. (C) Family pedigree of BRC1126, carrier of c.1050delAACA [STOP353]. Index patients are indicated with an arrow while individuals affected with breast cancer are indicated with filled symbol. Date of birth (DOB) and age of diagnosis (in bracket) foraffected individuals are indicated. Deceased individuals are indicated with a slash.</p

Combinatorial hypofractionated radiotherapy and pembrolizumab in anaplastic thyroid cancer

Objective: Anaplastic thyroid cancer (ATC) is an aggressive disease associated with poor outcomes and resistance to therapies. Our study aim was to evaluate the activity of a combinatorial regimen of sandwich sequencing of pembrolizumab immunotherapy and hypofractionated radiotherapy (RT). Methods: In this case series, patients with ATC received hypofractionated RT (QUAD-shot) and intravenous pembrolizumab 200 mg every 3–4 weeks. Pembrolizumab was continued until disease progression or up till 24 months. Concurrent lenvatinib treatment was allowed. Primary endpoint was best overall response (BOR) and progression-free survival (PFS). Additionally, we performed immune profiling of circulating T cells in a responder to investigate the immune response to our combinatorial treatment. Results: At median follow-up of 32.6 months (IQR: 26.4–38.8), of a cohort of five patients, BOR was 80%; with two complete responses (CR) and two partial responses (PR). Patients who achieved CR remained disease-free at last follow-up. Median PFS was 7.6 months (IQR: 6.2–NR), and 1-year PFS and overall survival rate was 40% (95% CI: 13.7– 100) for both. Treatment was well-tolerated, with mostly grade 1–2 adverse events. Immune profiling of one partial responder revealed an increase in activated CD4 and CD8 T cells post-QUAD-shot RT, which was further enhanced during the maintenance phase of pembrolizumab. Conclusion: Herein, we report a case series of five patients with ATC, with two long-term survivors who were treated with surgical debulking followed by QUAD-shot RT and pembrolizumab, possibly due to synergy of local and systemic treatments in activating anti-tumour immunogenic cytotoxicity. This regimen warrants further investigation in a larger cohort of patients

Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers

10.1016/j.ajhg.2013.01.002American Journal of Human Genetics924489-503AJHG

Large-scale genotyping identifies 41 new loci associated with breast cancer risk

Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ~9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10−8). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility