INTRODUCTION: Pregnancy-associated breast cancer (PABC) is described as breast cancer diagnosed within pregnancy or within 1 year postpartum. PABC is becoming more common due to delayed childbearing, with older maternal age increasing the likelihood of tumorigenesis coinciding with pregnancy. Our review aims to outline the important principles of managing PABC, and discusses future fertility implications, genetic testing and postnatal considera-tions that are not often considered in other existing reviews. METHOD: A literature search was conducted using PubMed, Cochrane and Google Scholar databases. RESULTS: A persistent breast mass in pregnant women should be evaluated with a breast ultrasound. Total mastectomy is the standard treatment in the first trimester. Chemotherapy is contraindicated in the first trimesters, but can be given in the second and third trimester, and stopped before 35 weeks. Radiotherapy should be delayed until delivery, and hormone receptor therapy is contraindicated in pregnancy. A multidisciplinary team involving an obstetrician, medical oncologist and other allied health professionals is crucial. Delivery should be planned as close to 37 weeks as possible, and at least 3 weeks after the last chemotherapy cycle. Vaginal delivery is preferred, and breastfeeding can resume 14 days after the last chemotherapy regime. CONCLUSION A breast mass in a pregnant woman should not be dismissed. PABC must be managed by multidisciplinary teams at tertiary medical centres with access to surgery and chemoradiation therapies. Management strategies must include safe manage-ment and delivery of the fetus, contraception and future fertility planning.
Humans ; Female ; Pregnancy ; Breast Neoplasms/diagnosis* ; Pregnancy Complications, Neoplastic/diagnosis* ; Mastectomy ; Delivery, Obstetric

INTRODUCTION: Risk-based screening (RBS) has emerged as a promising alternative to age-based cancer screening. However, evidence regarding real-world implementation outcomes remains fragmented. Thus, a systematic review was conducted to evaluate the implementation metho-dologies and outcomes of RBS programmes across different cancer types. METHODS: MEDLINE, Embase, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials and Scopus were systematically searched from their respective dates of inception up to 8 July 2024. Prospective and rando-mised controlled trials (RCTs), which implement the RBS of cancer in an asymptomatic population, or studies retrospectively evaluating the outcomes of the same were included. Geographic distribution, population characteristics, RBS methodology, diagnostic accuracy and clinical outcomes were narratively synthesised. RESULTS: Among the 33 included studies (i.e. 21 prospective cohort, 8 RCTs, 3 retrospective and 1 non-RCT), sample sizes ranged from 102 to 1,429,890 participants. Most RBS trials were conducted in China (n=7, 21.2%), followed by the Netherlands (n=4, 12.1%) then the US, Australia and Sweden (n=3, 9.8%). Studies predominantly examined colorectal (27.3%), breast (21.2%) and prostate cancer (18.2%). Three main stratification approaches emerged: algorithmic (48.5%), validated risk models (39.4%) and physician assessment (9.1%). Implementation outcomes showed higher uptake in moderate-risk (75.4%) compared to high-risk (71.3%) and low-risk groups (67.9%). Five studies demonstrated cost-effectiveness with increased quality-adjusted life years, while 12 studies showed superior or non-inferior cancer detection rates compared to traditional screening. CONCLUSION The RBS of cancer has the potential to optimise healthcare resource allocation while minimising harm and increasing receptiveness for patients. More work is needed to evaluate long-term outcomes prior to the scaling of RBS programmes.
Humans ; Early Detection of Cancer/methods* ; Neoplasms/diagnosis* ; Risk Assessment ; Mass Screening/methods*

Knowledge of an underlying genetic predisposition to cancer allows the use of personalised prognostic, preventive and therapeutic strategies for the patient and carries clinical implications for family members. Despite great progress, we identified six challenging areas in the management of patients with hereditary cancer predisposition syndromes and suggest recommendations to aid in their resolution. These include the potential for finding unexpected germline variants through somatic tumour testing, optimal risk management of patients with hereditary conditions involving moderate-penetrance genes, role of polygenic risk score in an under-represented Asian population, management of variants of uncertain significance, clinical trials in patients with germline pathogenic variants and technology in genetic counselling. Addressing these barriers will aid the next step forward in precision medicine in Singapore. All stakeholders in healthcare should be empowered with genetic knowledge to fully leverage the potential of novel genomic insights and implement them to provide better care for our patients.
Humans ; Singapore ; Genotype ; Neoplasms/therapy* ; Risk Factors ; Family

Genetic testing has the power to identify individuals with increased predisposition to disease, allowing individuals the opportunity to make informed management, treatment and reproductive decisions. As genomic medicine continues to be integrated into aspects of everyday patient care and the indications for genetic testing continue to expand, genetic services are increasingly being offered by non-genetic clinicians. The current complexities of genetic testing highlight the need to support and ensure non-genetic professionals are adequately equipped with the knowledge and skills to provide services. We describe a series of misdiagnosed/mismanaged cases, highlighting the common pitfalls in genetic testing to identify the knowledge gaps and where education and support is needed. We highlight that education focusing on differential diagnoses, test selection and result interpretation is needed. Collaboration and communication between genetic and non-genetic clinicians and integration of genetic counsellors into different medical settings are important. This will minimise the risks and maximise the benefits of genetic testing, ensuring adverse outcomes are mitigated.
Humans ; Missed Diagnosis ; Genetic Testing ; Educational Status ; Diagnosis, Differential ; Genotype

Background: Von Hippel–Lindau (VHL) syndrome is a dominantly inherited multisystem cancer syndrome caused by a heterozygous mutation in the VHL tumor suppressor gene. Previous studies suggested that similar populations of Caucasian and Japanese patients have similar genotype or phenotype characteristics. In this comprehensive study of East Asian patients, we investigated the genetic and clinical characteristics of patients with VHL syndrome. Methods: To create a registry of clinical characteristics and mutations reported in East Asian patients with VHL syndrome, we conducted a comprehensive review of English language and non?English language articles identi?fied through a literature search. Publications in Japanese or Chinese language were read by native speakers of the language, who then performed the data extraction. Results: Of 237 East Asian patients with VHL syndrome, 154 unique kindreds were identified for analysis. Analyzed by kindred, missense mutations were the most common (40.9%, 63/154), followed by large/complete deletions (32.5%, 50/154) and nonsense mutations (11.7%, 18/154). Compared with a previously reported study of both East Asian and non?East Asian patients, we found several key differences. First, missense and frameshift mutations in the VHL gene occurred less commonly in our population of East Asian patients (40.9% vs. 52.0%; P = 0.012 and 8.4% vs.13.0%; P < 0.001, respectively). Second, large/complete deletions were more common in our population of East Asian patients (32.5% vs. 10.5%; P < 0.001). Third, phenotypically, we observed that, in our population of East Asian patients with VHL syndrome, the incidence of retinal capillary hemangioblastoma was lower, whereas the incidence of renal cell carcinoma was higher. Conclusions: Evidence suggests that the genotypic and phenotypic characteristics of East Asian patients with VHL syndrome differ from other populations. This should be considered when making screening recommendations for VHL syndrome in Asia.