Association of area- and volumetric-mammographic density and breast cancer risk in women of Asian descent: a case control study.

BACKGROUND: Mammographic density (MD) has been shown to be a strong and independent risk factor for breast cancer in women of European and Asian descent. However, the majority of Asian studies to date have used BI-RADS as the scoring method and none have evaluated area and volumetric densities in the same cohort of women. This study aims to compare the association of MD measured by two automated methods with the risk of breast cancer in Asian women, and to investigate if the association is different for premenopausal and postmenopausal women. METHODS: In this case-control study of 531 cases and 2297 controls, we evaluated the association of area-based MD measures and volumetric-based MD measures with breast cancer risk in Asian women using conditional logistic regression analysis, adjusting for relevant confounders. The corresponding association by menopausal status were assessed using unconditional logistic regression. RESULTS: We found that both area and volume-based MD measures were associated with breast cancer risk. Strongest associations were observed for percent densities (OR (95% CI) was 2.06 (1.42-2.99) for percent dense area and 2.21 (1.44-3.39) for percent dense volume, comparing women in highest density quartile with those in the lowest quartile). The corresponding associations were significant in postmenopausal but not premenopausal women (premenopausal versus postmenopausal were 1.59 (0.95-2.67) and 1.89 (1.22-2.96) for percent dense area and 1.24 (0.70-2.22) and 1.96 (1.19-3.27) for percent dense volume). However, the odds ratios were not statistically different by menopausal status [p difference = 0.782 for percent dense area and 0.486 for percent dense volume]. CONCLUSIONS: This study confirms the associations of mammographic density measured by both area and volumetric methods and breast cancer risk in Asian women. Stronger associations were observed for percent dense area and percent dense volume, and strongest effects were seen in postmenopausal individuals.

Evaluation of SNPs associated with mammographic density in European women with mammographic density in Asian women from South-East Asia.

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. METHOD: Using linear regression adjusting for age, BMI, and ancestry-informative principal components, we evaluated the associations of previously reported MD-associated SNPs with MD in a multi-ethnic cohort of Asian ancestry. Area and volumetric mammographic densities were determined using STRATUS (N = 2450) and Volpara™ (N = 2257). We also assessed the associations of these SNPs with breast cancer risk in an Asian population of 14,570 cases and 80,870 controls. RESULTS: Of the 61 SNPs available in our data, 21 were associated with MD at a nominal threshold of P value < 0.05, all in consistent directions with those reported in European ancestry populations. Of the remaining 40 variants with a P-value of association > 0.05, 29 variants showed consistent directions of association as those previously reported. We found that nine of the 21 MD-associated SNPs in this study were also associated with breast cancer risk in Asian women (P < 0.05), seven of which showed a direction of associations that was consistent with that reported for MD. CONCLUSION: Our study confirms the associations of 21 SNPs (19/55 or 34.5% out of all known MD loci identified in women of European ancestry) with area and/or volumetric densities in Asian women, and further supports the evidence of a shared genetic basis through common genetic variants for MD and breast cancer risk.

Characterisation of protein-truncating and missense variants in PALB2 in 15 768 women from Malaysia and Singapore.

BACKGROUND: Rare protein-truncating variants (PTVs) in partner and localiser of BRCA2 (PALB2) 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 PALB2 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. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays. RESULTS: PTVs in PALB2 were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2 were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks. CONCLUSION: Despite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2 PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.

Overlap of high-risk individuals predicted by family history, and genetic and non-genetic breast cancer risk prediction models: implications for risk stratification.

BACKGROUND: Family history, and genetic and non-genetic risk factors can stratify women according to their individual risk of developing breast cancer. The extent of overlap between these risk predictors is not clear. METHODS: In this case-only analysis involving 7600 Asian breast cancer patients diagnosed between age 30 and 75 years, we examined identification of high-risk patients based on positive family history, the Gail model 5-year absolute risk [5yAR] above 1.3%, breast cancer predisposition genes (protein-truncating variants [PTV] in ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, or TP53), and polygenic risk score (PRS) 5yAR above 1.3%. RESULTS: Correlation between 5yAR (at age of diagnosis) predicted by PRS and the Gail model was low (r=0.27). Fifty-three percent of breast cancer patients (n=4041) were considered high risk by one or more classification criteria. Positive family history, PTV carriership, PRS, or the Gail model identified 1247 (16%), 385 (5%), 2774 (36%), and 1592 (21%) patients who were considered at high risk, respectively. In a subset of 3227 women aged below 50 years, the four models studied identified 470 (15%), 213 (7%), 769 (24%), and 325 (10%) unique patients who were considered at high risk, respectively. For younger women, PRS and PTVs together identified 745 (59% of 1276) high-risk individuals who were not identified by the Gail model or family history. CONCLUSIONS: Family history and genetic and non-genetic risk stratification tools have the potential to complement one another to identify women at high risk.

Changes in Dietary Intake of Breast Cancer Survivors: Early Findings of a Malaysian Breast Cancer Prospective Cohort Study.

This study aimed to evaluate the changes in post-diagnosis dietary intake of breast cancer survivors. A total of 112 participants from the Malaysian Breast Cancer Survivorship Cohort study with dietary intake at one-year post-diagnosis (T1) and three-year post-diagnosis (T2) were included. A three-day food record was used to assess the dietary intake of breast cancer survivors. The participants' anthropometrical measurements were measured at both time points (n = 95). Notably, we found that around half of the participants were obese at both time points. Body weight and body mass index increased significantly between the two time points (P < 0.01). Most of the participants did not meet the Malaysian recommended nutrient intake for dietary fat, fiber, and calcium at both time points. The energy intake significantly decreased (from 1,596 kcal/day to 1,524 kcal/day, P = 0.028) within the survivors. Significant decreases were observed in the overall intakes of carbohydrates, total sugar, protein, fiber, and calcium (P < 0.05). Overall, many Malaysian breast cancer survivors remained overweight or obese and had suboptimal dietary intake even at three years post-diagnosis. These require more proactive dietary intervention with continuous monitoring and evaluation among breast cancer survivors for their survivorship care.

Predictors of health-related quality of life after completion of chemotherapy among Malaysian early-stage breast cancer survivors.

PURPOSE: Health-related quality of life (QoL) is an important outcome measure in breast cancer management. Evidence of QoL of breast cancer patients in lower and middle-income countries remains scarce. We examined the level of QoL, cognitive impairment, psychological distresses, and the predictors of QoL among multiethnic Malaysian early-stage breast cancer survivors 1 to 3 years following chemotherapy. METHODS: A total of 160 breast cancer survivors from the University of Malaya Medical Centre (UMMC) participated in this cross-sectional study. Their QoL was evaluated with the Malay version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) version 3.0. Cognitive functioning and psychological distress were evaluated using the Malay version of the Montreal Cognitive Assessment (MoCA-BM) and Hospital Anxiety and Depression Scale (HADS), respectively. Data analysis was performed with Pearson's correlation and multiple regression analyses. RESULTS: At 1- to 3-year post-chemotherapy, the mean EORTC QLQ-C30 global health status of the breast cancer survivors was relatively low (60.5 over 100, SD = 10.88). One-third (31.9%) of them demonstrated cognitive impairment, and another 3.2% showed moderate to severe anxiety levels. The significant predictors for global health status and functioning included age, psychological distresses, cognitive performance, fatigue, appetite loss, insomnia, pain, and constipation. CONCLUSION: Our breast cancer survivors demonstrated poor global health status. Health care providers and policymakers must strive to provide holistic intervention strategies to improve the multiple dimensions of QoL and the cognitive and psychological functioning of this vulnerable population.

A qualitative exploration: Dietary behaviour of Malaysian breast cancer survivors.

OBJECTIVE: This study aimed to explore the dietary practices and factors affecting Malaysian breast cancer survivors' dietary behaviours. METHODS: We conducted an in-depth qualitative interview on 20 participants from a cohort study. An ecological framework was used to construct the semi-structured topic guide. The interviews were audio-recorded and transcribed verbatim. Thematic analysis with theoretical saturation was used in data analysis. RESULTS: The participants were found to have variable dietary practices that either followed or did not follow dietary recommendations. The social environment was critical as most women relied on family and friends for food choices; additionally, individuals in charge of food preparation had to prepare food based on their family member preferences. Furthermore, individuals had difficulty sustaining healthy dietary changes during the acute survivorship phase due to a lack of health consciousness and difficulty in healthy food access. Notably, there was a lack of dietary guidance from health care professionals, especially dietitians, in long-term survivorship care. CONCLUSION: This study highlights the lack of breast cancer survivors' healthy diet and lifestyle knowledge. A holistic multidisciplinary approach involving individual, social, physical, and macro-level environmental elements are crucial to influencing healthy eating behaviours.

Decision-making for Risk-reducing Salpingo-oophorectomy (RRSO) in Southeast Asian BRCA Mutation Carriers With Breast Cancer: A Qualitative Study.

BACKGROUND: The uptake of risk-reducing salpingo-oophorectomy (RRSO) in Asian countries is variable despite being the most effective option for ovarian cancer risk reduction in BRCA mutation carriers. Exploration of factors which may impact the RRSO decision-making of BRCA mutation carriers from Malaysia, a developing country in Southeast Asia, was undertaken. METHODS: In-depth interviews with 28 Malaysian BRCA mutation carriers with a history of breast cancer were conducted in addition to observing their RRSO decision-making consultations in the clinic. RESULTS: The decision-making considerations among the carriers were centered around the overarching theme of "Negotiating cancer risk and womanhood priorities," with the following themes: (1) risk perception, (2) self-preservation, (3) motherhood obligation, and (4) the preciousness of marriage. Cognitive knowledge of BRCA risk was often conceptualized based on personal and family history of cancer, personal beliefs, and faith. Many women reported fears that RRSO would affect them physically and emotionally, worrying about the post-surgical impact on their motherhood responsibilities. Nevertheless, some reported feeling obliged to choose RRSO for the sake of their children. For some, their husband's support and approval were critical, with emotional well-being and sexuality reportedly perceived as important to sustaining married life. Despite reporting hesitancy toward RRSO, women's decisions about choosing this option evolved as their priorities changed at different stages of life. CONCLUSIONS: Recognizing during clinic encounters with Malaysian women that RRSO decision-making involves negotiating the likelihood of developing cancer with the societal priorities of being a woman, mother, and wife may serve to support their decision-making.

Attitudes and training needs of oncologists and surgeons in mainstreaming breast cancer genetic counseling in a low-to-middle income Asian country.

With the advent of poly-ADP-ribose polymerase inhibitor (PARPi) therapies, the focus of genetic testing for breast, ovarian, and other cancers has shifted from risk management to treatment decision-making in high-resource settings. Due to the shortage of genetic counselors worldwide, alternative ways of delivering genetic counseling have been explored, including training nongenetics healthcare professionals (NGHPs) to provide genetic counseling. However, little is known about the feasibility of adopting such models in healthcare settings with insufficient specialists, where population health literacy is low and where access to new therapies may be limited. In this study, we evaluated the attitudes, considerations, and self-efficacy of oncologists, breast surgeons, and general surgeons in mainstreaming breast cancer genetic counseling in Malaysia, a middle-income Asian country with a universal healthcare system. We developed a 32-item survey via a modified Delphi method, which was then distributed via a purposive and network sampling approach. While 77% of respondents expressed interest in providing breast cancer genetic counseling, 85% preferred to refer patients directly to genetic services for genetic counseling and testing. The main considerations for mainstreaming were the cost of genetic testing and PARPi therapy, as well as the availability of support from genetics professionals. Respondents reported a lack of confidence in communicating genetic risk, particularly to patients with poor health literacy, and in the clinical management of patients with variants of uncertain significance. Our results highlight the urgent need to train more NGHPs in providing genetic counseling and testing in low-to-middle income countries, and suggest that the mainstay for genetic counseling in this setting may be for risk management rather than access to PARPi therapy.

Evaluation of skin dose and skin toxicity in patients undergoing intraoperative radiotherapy for early breast cancer.

PURPOSE: This study aims to evaluate in vivo skin dose delivered by intraoperative radiotherapy (IORT) and determine the factors associated with an increased risk of radiation-induced skin toxicity. METHODOLOGY: A total of 21 breast cancer patients who underwent breast-conserving surgery and IORT, either as IORT alone or IORT boost plus external beam radiotherapy (EBRT), were recruited in this prospective study. EBT3 film was calibrated in water and used to measure skin dose during IORT at concentric circles of 5 mm and 40 mm away from the applicator. For patients who also had EBRT, the maximum skin dose was estimated using the radiotherapy treatment planning system. Mid-term skin toxicities were evaluated at 3 and 6 months post-IORT. RESULTS: The average skin dose at 5 mm and 40 mm away from the applicator was 3.07 ± 0.82 Gy and 0.99 ± 0.28 Gy, respectively. Patients treated with IORT boost plus EBRT received an additional skin dose of 41.07 ± 1.57 Gy from the EBRT component. At 3 months post-IORT, 86% of patients showed no evidence of skin toxicity. However, the number of patients suffering from skin toxicity increased from 15% to 38% at 6 months post-IORT. We found no association between the IORT alone or with the IORT boost plus EBRT and skin toxicity. Older age was associated with increased risk of skin toxicities. A mathematical model was derived to predict skin dose. CONCLUSION: EBT3 film is a suitable dosimeter for in vivo skin dosimetry in IORT, providing patient-specific skin doses. Both IORT alone and IORT boost techniques resulted in similar skin toxicity rates.

Patient-reported outcome measures among breast cancer survivors: A cross-sectional comparison between Malaysia and high-income countries.

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. METHODS: Breast cancer patients were recruited from three Malaysian hospitals between June and November 2017. We compared the proportion of patients who rated PROs as very important (scored 7-9 on a 9-point Likert scale) between Malaysian patients and data collected from patients in HICs via the ICHOM questionnaire development process, using logistic regression. A two-step cluster analysis explored differences in PROs among Malaysian patients. RESULTS: The most important PROs for both cohorts were survival, overall well-being, and physical functioning. Compared with HIC patients (n = 1177), Malaysian patients (n = 969) were less likely to rate emotional (78% vs 90%), cognitive (76% vs 84%), social (72% vs 81%), and sexual (30% vs 56%) functioning as very important outcomes (P < 0.001). Cluster analysis suggests that older, parous, Malaysian women, who were less likely to have received breast reconstructive surgery, were more likely to rate body image and satisfaction with the breast as very important outcomes. CONCLUSION: Taking into account the differences in PROs by cultural and socioeconomic settings could improve patient expectation of services and refine the assessment of cancer care outcomes.

Inherited mutations in BRCA1 and BRCA2 in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia.

BACKGROUND: Genetic testing for BRCA1 and BRCA2 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. METHODS: Germ line DNA from a hospital-based study of 2575 unselected patients with breast cancer and 2809 healthy controls were subjected to amplicon-based targeted sequencing of exonic and proximal splice site junction regions of BRCA1 and BRCA2 using the Fluidigm Access Array system, with sequencing conducted on a Illumina HiSeq2500 platform. Variant calling was performed with GATK UnifiedGenotyper and were validated by Sanger sequencing. RESULTS: Fifty-five (2.1%) BRCA1 and 66 (2.6%) BRCA2 deleterious mutations were identified among patients with breast cancer and five (0.18%) BRCA1 and six (0.21%) BRCA2 mutations among controls. One thousand one hundred and eighty-six (46%) patients and 97 (80%) carriers fulfilled the National Comprehensive Cancer Network guidelines for genetic testing. CONCLUSION: Five per cent of unselected Asian patients with breast cancer carry deleterious variants in BRCA1 or BRCA2. While current referral guidelines identified the majority of carriers, one in two patients would be referred for genetic services. Given that such services are largely unavailable in majority of low-resource settings in Asia, our study highlights the need for more efficient guidelines to identify at-risk individuals in Asia.

Physical activity and mammographic density in an Asian multi-ethnic cohort.

BACKGROUND: Physical activity is a modifiable lifestyle factor associated with reduced breast cancer risk. Mammographic density is a strong, independent risk factor for breast cancer, and some breast cancer risk factors have been shown to modify mammographic density. However, the effect of physical activity on mammographic density, studied predominantly among Caucasians, has yielded conflicting results. In this study, we examined, in an Asian population, the association between physical activity and mammographic density. METHODS: We conducted a cross-sectional study of 2,377 Malaysian women aged 40-74 years. Physical activity information was obtained at screening mammogram and mammographic density was measured from mammograms by the area-based STRATUS method (n = 1,522) and the volumetric Volpara™ (n = 1,200) method. Linear regression analyses were performed to evaluate the association between physical activity and mammographic density, adjusting for potential confounders. RESULTS: We observed that recent physical activity was associated with area-based mammographic density measures among postmenopausal women, but not premenopausal women. In the fully adjusted model, postmenopausal women with the highest level of recent physical activity had 8.0 cm2 [95% confidence interval: 1.3, 14.3 cm2] lower non-dense area and 3.1% [0.1, 6.3%] higher area-based percent density, compared to women with the lowest level of recent physical activity. Physical activity was not associated to volumetric mammographic density. CONCLUSIONS: Our findings suggest that the beneficial effects of physical activity on breast cancer risk may not be measurable through mammographic density. Future research is needed to identify appropriate biomarkers to assess the effect of physical activity on breast cancer risk.

Characterization of BRCA1 and BRCA2 variants in multi-ethnic Asian cohort from a Malaysian case-control study.

BACKGROUND: Genetic testing for BRCA1 and BRCA2 has led to the accurate identification of individuals at higher risk of cancer and the development of new therapies. Approximately 10-20% of the genetic testing for BRCA1 and BRCA2 leads to the identification of variants of uncertain significance (VUS), with higher proportions in Asians. We investigated the functional significance of 7 BRCA1 and 25 BRCA2 variants in a multi-ethnic Asian cohort using a case-control approach. METHODS: The MassARRAY genotyping was conducted in 1,394 Chinese, 406 Malay and 310 Indian breast cancer cases and 1,071 Chinese, 167 Malay and 255 Indian healthy controls. The association of individual variant with breast cancer risk was analyzed using logistic regression model adjusted for ethnicity, age and family history. RESULTS: Our study confirmed BRCA2 p.Ile3412Val is presented in >2% of unaffected women and is likely benign, and BRCA2 p.Ala1996Thr which is predicted to be likely pathogenic by in-silico models is presented in 2% of healthy Indian women suggesting that it may not be associated with breast cancer risk. Single-variant analysis suggests that BRCA1 p.Arg762Ser may be associated with breast cancer risk (OR = 7.4; 95% CI, 0.9-62.3; p = 0.06). CONCLUSIONS: Our study shows that BRCA2 p.Ile3412Val and p.Ala1996Thr are likely benign and highlights the need for population-specific studies to determine the likely functional significance of population-specific variants. Our study also suggests that BRCA1 p.Arg762Ser may be associated with increased risk of breast cancer but other methods or larger studies are required to determine a more precise estimate of breast cancer risk.

Germline APOBEC3B deletion is associated with breast cancer risk in an Asian multi-ethnic cohort and with immune cell presentation.

BACKGROUND: APOBEC3B is a cytosine deaminase implicated in immune response to viral infection, cancer predisposition and carcinogenesis. Germline APOBEC3B deletion is more common in East Asian women and confers a modest risk to breast cancer in both East Asian and Caucasian women. Analysis of tumour samples from women of European descent has shown that germline APOBEC3B deletion is associated with an increased propensity to develop somatic mutations and with an enrichment for immune response-related gene sets. However, this has not been examined in Asian tumour samples, where population differences in genetic and dietary factors may have an impact on the immune system. METHODS: In this study, we determined the prevalence of germline APOBEC3B deletion and its association with breast cancer risk in a cross-sectional hospital-based Asian multi-ethnic cohort of 1451 cases and 1442 controls from Malaysia. We compared gene expression profiles of breast cancers arising from APOBEC3B deletion carriers and non-carriers using microarray analyses. Finally, we characterised the overall abundance of tumour-infiltrating immune cells in breast cancers from TCGA and METABRIC using ESTIMATE and relative frequency of 22 immune cell subsets in breast cancers from METABRIC using CIBERSORT. RESULTS: The minor allelic frequency of APOBEC3B deletion was estimated to be 0.35, 0.42 and 0.16 in female populations of Chinese, Malay and Indian descent, respectively, and that germline APOBEC3B deletion was associated with breast cancer risk with odds ratios of 1.23 (95 % CI: [1.05, 1.44]) for one-copy deletion and 1.38 (95 % CI: [1.10, 1.74]) for two-copy deletion compared to women with no deletion. Germline APOBEC3B deletion was not associated with any clinicopathologic features or the expression of any APOBEC family members but was associated with immune response-related gene sets (FDR q values < 0.05). Analysis of breast cancers from METABRIC revealed breast cancers from APOBEC3B deletion carriers to have significantly higher abundance of tumour-infiltrating immune cells (P < 0.001). CONCLUSIONS: Taken together, our data suggests that tumour-infiltrating immune cells may be an important feature of breast cancers arising in women with APOBEC3B germline deletion, and that this may be of particular interest in Asian women where the germline deletion is more common.

Recurrent mutation testing of BRCA1 and BRCA2 in Asian breast cancer patients identify carriers in those with presumed low risk by family history.

Although the breast cancer predisposition genes BRCA1 and BRCA2 were discovered more than 20 years ago, there remains a gap in the availability of genetic counselling and genetic testing in Asian countries because of cost, access and inaccurate reporting of family history of cancer. In order to improve access to testing, we developed a rapid test for recurrent mutations in our Asian populations. In this study, we designed a genotyping assay with 55 BRCA1 and 44 BRCA2 mutations previously identified in Asian studies, and validated this assay in 267 individuals who had previously been tested by full sequencing. We tested the prevalence of these mutations in additional breast cancer cases. Using this genotyping approach, we analysed recurrent mutations in 533 Malaysian breast cancer cases with <10 % a priori risk, and found 1 BRCA1 (0.2 %) and 5 BRCA2 (0.9 %) carriers. Testing in a hospital-based unselected cohort of 532 Singaporean breast cancer cases revealed 6 BRCA1 (1.1 %) and 3 BRCA2 (0.6 %) carriers. Overall, 2 recurrent BRCA1 and 1 BRCA2 mutations in Malays, 3 BRCA1 and 2 BRCA2 mutations in Chinese and 1 BRCA1 mutation in Indians account for 60, 24 and 20 % of carrier families, respectively. By contrast, haplotype analyses suggest that a recurrent BRCA2 mutation (c.262_263delCT) found in 5 unrelated Malay families has at least 3 distinct haplotypes. Taken together, our data suggests that panel testing may help to identify carriers, particularly Asian BRCA2 carriers, who do not present with a priori strong family history characteristics.

Factors associated with return to work of breast cancer survivors: a systematic review.

BACKGROUND: The breast cancer survival rate is the highest among all types of cancers, and survivors returning to work after completing treatment is extremely important in regards to economy and rehabilitation. The aim of this systematic review study is to identify the prevalence of breast cancer survivors who return to work (RTW) and the factors associated to RTW. METHODS: A computer based literature search was carried out. "PubMed, Cochrane Library, Embase, Web of Science, and Science Direct" databases were searched systematically. Our search strategy identified a total of 12,116 papers of which 26 studies met the inclusion criteria and quality assessment. These were original papers published between January 2003 and January 2013. RESULTS: The trends in RTW differ among countries for the breast cancer survivors. The time to RTW after successful cancer treatment also varies among the countries and by ethnicity. The prevalence of the RTW varies from 43% to 93% within one year of diagnosis. The prevalence of the RTW for the Netherland is the lowest in the world (43%). The United States survivors showed the highest RTW (93%) within 12 months of the diagnosis. Numerous barriers and facilitators were identified as factors that affect RTW. For instance, socio-demographic factors such as education and ethnicity; treatment oriented factors such as chemotherapy; work related factors such as heavy physical work; disease related factors such as poor health condition and fatigue; and psychological factors such as depression and emotional distress, act as barriers of RTW. In contrast, social, family, employer support, and financial independency emerge as key facilitators in enabling breast cancer survivors to return and continue work. CONCLUSION: Minimising these identified barriers and strengthening these facilitators could further improve the work condition and increase the percentage of RTW among the breast cancer survivors.

Exploring novel protein-based biomarkers for advancing breast cancer diagnosis: A review.

This review provides a contemporary examination of the evolving landscape of breast cancer (BC) diagnosis, focusing on the pivotal role of novel protein-based biomarkers. The overview begins by elucidating the multifaceted nature of BC, exploring its prevalence, subtypes, and clinical complexities. A critical emphasis is placed on the transformative impact of proteomics, dissecting the proteome to unravel the molecular intricacies of BC. Navigating through various sources of samples crucial for biomarker investigations, the review underscores the significance of robust sample processing methods and their validation in ensuring reliable outcomes. The central theme of the review revolves around the identification and evaluation of novel protein-based biomarkers. Cutting-edge discoveries are summarised, shedding light on emerging biomarkers poised for clinical application. Nevertheless, the review candidly addresses the challenges inherent in biomarker discovery, including issues of standardisation, reproducibility, and the complex heterogeneity of BC. The future direction section envisions innovative strategies and technologies to overcome existing challenges. In conclusion, the review summarises the current state of BC biomarker research, offering insights into the intricacies of proteomic investigations. As precision medicine gains momentum, the integration of novel protein-based biomarkers emerges as a promising avenue for enhancing the accuracy and efficacy of BC diagnosis. This review serves as a compass for researchers and clinicians navigating the evolving landscape of BC biomarker discovery, guiding them toward transformative advancements in diagnostic precision and personalised patient care.

Age-specific breast and ovarian cancer risks associated with germline BRCA1 or BRCA2 pathogenic variants - an Asian study of 572 families.

Background: Clinical management of Asian BRCA1 and BRCA2 pathogenic variants (PV) carriers remains challenging due to imprecise age-specific breast (BC) and ovarian cancer (OC) risks estimates. We aimed to refine these estimates using six multi-ethnic studies in Asia. Methods: Data were collected on 271 BRCA1 and 301 BRCA2 families from Malaysia and Singapore, ascertained through population/hospital-based case-series (88%) and genetic clinics (12%). Age-specific cancer risks were estimated using a modified segregation analysis method, adjusted for ascertainment. Findings: BC and OC relative risks (RRs) varied across age groups for both BRCA1 and BRCA2. The age-specific RR estimates were similar across ethnicities and country of residence. For BRCA1 carriers of Malay, Indian and Chinese ancestry born between 1950 and 1959 in Malaysia, the cumulative risk (95% CI) of BC by age 80 was 40% (36%-44%), 49% (44%-53%) and 55% (51%-60%), respectively. The corresponding estimates for BRCA2 were 29% (26-32%), 36% (33%-40%) and 42% (38%-45%). The corresponding cumulative BC risks for Singapore residents from the same birth cohort, where the underlying population cancer incidences are higher compared to Malaysia, were higher, varying by ancestry group between 57 and 61% for BRCA1, and between 43 and 47% for BRCA2 carriers. The cumulative risk of OC by age 80 was 31% (27-36%) for BRCA1 and 12% (10%-15%) for BRCA2 carriers in Malaysia born between 1950 and 1959; and 42% (34-50%) for BRCA1 and 20% (14-27%) for BRCA2 carriers of the same birth cohort in Singapore. There was evidence of increased BC and OC risks for women from >1960 birth cohorts (p-value = 3.6 × 10-5 for BRCA1 and 0.018 for BRCA2). Interpretation: The absolute age-specific cancer risks of Asian carriers vary depending on the underlying population-specific cancer incidences, and hence should be customised to allow for more accurate cancer risk management. Funding: Wellcome Trust [grant no: v203477/Z/16/Z]; CRUK (PPRPGM-Nov20∖100002).

Natural language processing in narrative breast radiology reporting in University Malaya Medical Centre.

Radiology reporting is narrative, and its content depends on the clinician's ability to interpret the images accurately. A tertiary hospital, such as anonymous institute, focuses on writing reports narratively as part of training for medical personnel. Nevertheless, free-text reports make it inconvenient to extract information for clinical audits and data mining. Therefore, we aim to convert unstructured breast radiology reports into structured formats using natural language processing (NLP) algorithm. This study used 327 de-identified breast radiology reports from the anonymous institute. The radiologist identified the significant data elements to be extracted. Our NLP algorithm achieved 97% and 94.9% accuracy in training and testing data, respectively. Henceforth, the structured information was used to build the predictive model for predicting the value of the BIRADS category. The model based on random forest generated the highest accuracy of 92%. Our study not only fulfilled the demands of clinicians by enhancing communication between medical personnel, but it also demonstrated the usefulness of mineable structured data in yielding significant insights.