Publications by authors named "Cheng H Yip"

Introduction: There is a lack of real-world evidence on direct comparisons between COVID-19 vaccines in multiethnic low- and middle-income settings. Cancer patients have an impaired vaccine response due to the disease itself or the effects of treatment. Hence, identifying the best vaccine to use for cancer patients is important.

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Breast cancer is one of the most common cancers in Malaysia. Recently, a new nomenclature was introduced for breast cancers with human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 1+, or 2+ with negative in situ hybridization (ISH), i.e.

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  • The Global Breast Cancer Initiative (GBCI), launched by WHO in 2023, focuses on improving early detection and management of breast cancer across 21 Asian countries.
  • A study investigated data availability for key performance indicators (KPIs) like stage at diagnosis and treatment completion by reviewing literature and national cancer reports.
  • Findings showed that only 57% of countries published relevant national cancer statistics, with significant differences from WHO estimates, and highlighted a strong link between early diagnosis, survival rates, and universal health coverage.
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Objectives: There is a lack of evidence-based guidelines for enhancing global surgical care delivery. We propose a set of recommendations to serve as a framework to guide surgical quality improvement and scale-up initiatives in low and middle income countries (LMICs).

Methods: From January-December 2019, we reviewed the available literature and their application toward LMIC settings.

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Purpose: Mammographic density (MD), after accounting for age and body mass index (BMI), is a strong heritable risk factor for breast cancer. Genome-wide association studies (GWAS) have identified 64 SNPs in 55 independent loci associated with MD in women of European ancestry. Their associations with MD in Asian women, however, are largely unknown.

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Soy intake is associated with lower breast cancer risk in observational studies concerning Asian women, however, no randomized controlled trials (RCT) have been conducted among Asian women living in Asia. This three-armed RCT assessed the effects of one-year soy isoflavone (ISF) intervention on mammographic density (MD) change among healthy peri- and postmenopausal Malaysian women. This study was registered at ClinicalTrials.

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  • - The study highlights the need for effective strategies to identify carriers of altered BRCA genes in Asian patients due to the growing use of poly (ADP-ribose) polymerase inhibitors for cancer treatment, which shows disparities in existing mutation prediction tools mainly designed for women of European descent.
  • - Researchers developed the Asian Risk Calculator, assessing 8,162 Asian breast cancer patients, which incorporated factors like age, ethnicity, tumor characteristics, and family history to predict the likelihood of carrying a pathogenic BRCA variant.
  • - The new model demonstrated improved accuracy and efficiency in identifying mutation carriers, reducing unnecessary referrals for genetic counseling, suggesting that tailored mutation prediction models are crucial for enhancing cancer genetics services in diverse populations.
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  • Rare germline genetic variants in specific genes are linked to increased breast cancer risk, but their impact on different subtypes of the disease is not fully understood.
  • The BRIDGES study analyzed data from 42,680 breast cancer patients and 46,387 controls, focusing on specific genetic mutations and their associations with tumor characteristics.
  • Results showed that certain gene variants (like RAD51C, RAD51D, and BARD1) are primarily linked to triple-negative breast cancer, while others (like CHEK2) are associated with various subtypes, indicating varied genetic influence on breast cancer types.
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  • Scientists are studying special gene changes (called PTVs) to see how they affect breast cancer in 8,852 Asian patients.
  • They found that having these gene changes is linked to more aggressive tumors, which are harder to treat.
  • Overall survival rates for patients with these gene changes were lower, suggesting that some genes might play a role in how long patients live after being diagnosed with breast cancer.
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Rare protein-truncating variants (PTVs) in PALB2 confer increased risk to breast cancer, but relatively few studies have reported the characteristics of tumours with PALB2 PTVs. In this study, we describe molecular characteristics of tumours with either germline or somatic alterations in PALB2. DNA from fresh frozen tumour tissues and matched peripheral blood lymphocytes for 560 breast cancer patients was subjected for whole-exome sequencing (WES), and RNA from tumour tissues was subjected to RNA sequencing (RNA-seq).

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Background: Rare protein-truncating variants (PTVs) in partner and localiser of BRCA2 () confer increased risk to breast cancer, but relatively few studies have reported the prevalence in South-East Asian populations. Here, we describe the prevalence of rare variants in in a population-based study of 7840 breast cancer cases and 7928 healthy Chinese, Malay and Indian women from Malaysia and Singapore, and describe the functional impact of germline missense variants identified in this population.

Methods: Mutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels.

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The discovery of high-risk breast cancer susceptibility genes, such as Breast cancer associated gene 1 (BRCA1) and Breast cancer associated gene 2 (BRCA2) has led to accurate identification of individuals for risk management and targeted therapy. The rapid decline in sequencing costs has tremendously increased the number of individuals who are undergoing genetic testing world-wide. However, given the significant differences in population-specific variants, interpreting the results of these tests can be challenging especially for novel genetic variants in understudied populations.

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Background: Primary breast angiosarcoma is a rare malignancy with non-specific clinical and radiological findings.

Case Report: A 30-year-old lady presented with left breast pain and lumpiness for over one year. She has had several breast ultrasounds (US) and was treated for acute mastitis and abscess.

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  • The study aimed to determine the age-specific relative and absolute cancer risks for breast cancer and other associated cancers in individuals with germline pathogenic variants (PVs), as previous research in this area was limited.
  • The researchers analyzed data from 524 families across 21 countries and found significant associations between PVs and increased risks of female breast cancer, ovarian cancer, pancreatic cancer, and male breast cancer, with no increased risk for prostate or colorectal cancer.
  • The results emphasize the importance of a specific gene as a significant risk factor for breast cancer and highlight the need to incorporate these findings into cancer risk prediction models for better understanding and management.
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Historically, breast cancer risk prediction models are based on mammographic density measures, which are dichotomous in nature and generally categorize each voxel or area of the breast parenchyma as 'dense' or 'not dense'. Using these conventional methods, the structural patterns or textural components of the breast tissue elements are not considered or ignored entirely. This study presents a novel method to predict breast cancer risk that combines new texture and mammographic density based image features.

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Objectives: Patient-reported outcomes (PROs) in high-income countries (HICs) suggest that physical, emotional, and psychological needs are important in cancer care. To date, there have been few inconsistent descriptions of PROs in low-income and middle-income Asian countries. Using a standard questionnaire developed by the International Consortium for Health Outcomes Measurement (ICHOM), we compared the perceived importance of PROs between patients in Malaysia and those in HICs and between clusters of Malaysian women.

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Background: Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis.

Methods: We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC).

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Background: Genetic testing for and is offered typically to selected women based on age of onset and family history of cancer. However, current internationally accepted genetic testing referral guidelines are built mostly on data from cancer genetics clinics in women of European descent. To evaluate the appropriateness of such guidelines in Asians, we have determined the prevalence of germ line variants in an unselected cohort of Asian patients with breast cancer and healthy controls.

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Over the past 20 years, high-penetrance pathogenic mutations in genes BRCA1, BRCA2, TP53, PTEN, STK11 and CDH1 and moderate-penetrance mutations in genes CHEK2, ATM, BRIP1, PALB2, RAD51C, RAD50 and NBN have been identified for breast cancer. In this study, we investigated whether there are additional variants in these 13 genes associated with breast cancer among women of Asian ancestry. We analyzed up to 654 single nucleotide polymorphisms (SNPs) from 6269 cases and 6624 controls of Asian descent included in the Breast Cancer Association Consortium (BCAC), and up to 236 SNPs from 5794 cases and 5529 controls included in the Shanghai Breast Cancer Genetics Study (SBCGS).

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  • This study looked at breast cancer patients in Singapore and Malaysia to see who responds well to a specific type of chemotherapy before surgery.
  • It found that only a small percentage (4.4%) of patients got this treatment, and those who had a complete response (meaning no cancer left) had better chances of survival.
  • Women with certain cancer characteristics, like higher tumor grades or negative estrogen receptors, had higher rates of complete response and did better overall, especially when treated with a type of chemotherapy called taxane.
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Background: Approximately 100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS). The utility of these variants in breast cancer risk prediction models has not been evaluated adequately in women of Asian ancestry.

Methods: We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry.

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Genome-wide association studies (GWASs) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). With data for 3,365 genotyped and imputed SNPs across a 1 Mb region (positions 44,394,495-45,364,167; NCBI build 37), we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen-receptor-positive (ER) breast cancer (per-g allele OR ER = 1.

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Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.

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