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  1. Chong SC, Rajah R, Chow PL, Tan HC, Chong CM, Khor KY, et al.
    J Oncol Pharm Pract, 2022 Jun 13.
    PMID: 35698761 DOI: 10.1177/10781552221104773
    INTRODUCTION: Biosimilars confer significant cost-saving advantages and expand patients' access to biologic therapies in cancer care. In line with the increasing availability of antineoplastic biosimilars, it is pertinent to understand the oncologists' view on the adoption of biosimilars in their clinical practice. The study aimed to assess (i) the prevalence of biosimilar use, (ii) perception towards biosimilars, (iii) factors influencing the use of biosimilars and (iv) knowledge about biosimilars among Malaysian oncologists.

    METHODS: A cross-sectional survey was conducted among clinical oncologists and medical oncologists in Malaysia between January 2020 and February 2021 using a structured 31-item questionnaire.

    RESULTS: Among the 121 oncologists registered in the country, 36 responded (response rate  =  30%). A total of 64% of the respondents prescribed biosimilars either often or always. Most oncologists (72%) agreed or strongly agreed that switching will not have a significant effect on the treatment benefit, with lower percentages saying that they agreed or strongly agreed that it will not lead to the emergence of additional adverse effects (56%) or harmful immunogenicity (64%). Patients' preferences (40%) and the non-availability of biosimilars in hospitals (34%) are the major barriers cited to the prescribing of biosimilars. Cost differences and robust pharmacovigilance activities are the two most important factors that would influence the prescribing of biosimilars. The mean score of knowledge in biosimilar among respondents was 3.81 (± 0.86) out of a maximum possible score of 6.

    CONCLUSIONS: The identified gap in prescribing and the use of biosimilars among Malaysian oncologists warrant educational intervention and robust pharmacovigilance activities to facilitate the prescribing of biosimilars and ultimately increase the accessibility to biologics in cancer treatment.

  2. Ho PJ, Khng AJ, Loh HW, Ho WK, Yip CH, Mohd-Taib NA, et al.
    Genome Med, 2021 Dec 02;13(1):185.
    PMID: 34857041 DOI: 10.1186/s13073-021-00978-9
    BACKGROUND: Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent.

    METHODS: Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease.

    RESULTS: PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35-5.17], moderately vs well-differentiated 2.33 [1.56-3.49]), as well as luminal B [HER-] and triple-negative subtypes (vs luminal A 2.15 [1.58-2.92] and 2.85 [2.17-3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2-] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16-2.28]).

    CONCLUSIONS: PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions.

  3. Chaisson MJP, Sanders AD, Zhao X, Malhotra A, Porubsky D, Rausch T, et al.
    Nat Commun, 2019 04 16;10(1):1784.
    PMID: 30992455 DOI: 10.1038/s41467-018-08148-z
    The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We identify 818,054 indel variants (<50 bp) and 27,622 SVs (≥50 bp) per genome. We also discover 156 inversions per genome and 58 of the inversions intersect with the critical regions of recurrent microdeletion and microduplication syndromes. Taken together, our SV callsets represent a three to sevenfold increase in SV detection compared to most standard high-throughput sequencing studies, including those from the 1000 Genomes Project. The methods and the dataset presented serve as a gold standard for the scientific community allowing us to make recommendations for maximizing structural variation sensitivity for future genome sequencing studies.
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