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).
METHODS: This cross-sectional study of women who underwent DBT and ABUS from December 2019 to March 2022 included opportunistic and targeted screening cases, as well as symptomatic women. Breast density, Breast Imaging Reporting and Data System categories and histopathology reports were collected and compared. The PPV3 (proportion of examinations with abnormal findings that resulted in a tissue diagnosis of cancer), biopsy rate (percentage of biopsies performed) and cancer detection yield (number of malignancies found by the diagnostic test given to the study sample) were calculated.
RESULTS: A total of 1089 ABUS examinations were performed (age range: 29-85 y, mean: 51.9 y). Among these were 909 screening (83.5%) and 180 diagnostic (16.5%) examinations. A total of 579 biopsies were performed on 407 patients, with a biopsy rate of 53.2%. There were 100 (9.2%) malignant lesions, 30 (5.2%) atypical/B3 lesions and 414 (71.5%) benign cases. In 9 cases (0.08%), ABUS alone detected malignancies, and in 19 cases (1.7%), DBT alone detected malignancies. The PPV3 in the screening group was 14.6%.
CONCLUSION: ABUS is useful as an adjunct to DBT in the opportunistic screening and diagnostic setting.
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, 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
METHODS: A total of 12,901 breast cancer cases and 12,583 controls from 12 case-control studies were included in our pooled analysis. HLA imputation was performed using SNP2HLA on 10,886 quality-controlled variants within the 15-55 Mb region on chromosome 6. HLA alleles (n = 175) with info scores greater than 0.8 and frequencies greater than 0.01 were included (resolution at two-digit level: 71; four-digit level: 104). We studied the associations between HLA alleles and breast cancer risk using logistic regression, adjusting for population structure and age. Associations between HLA alleles and the risk of subtypes of breast cancer (ER-positive, ER-negative, HER2-positive, HER2-negative, early-stage, and late-stage) were examined.
RESULTS: We did not observe associations between any HLA allele and breast cancer risk at P
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.
OBJECTIVE: To characterize tumors associated with BC susceptibility genes in large-scale population- or hospital-based studies.
DESIGN, SETTING, AND PARTICIPANTS: The multicenter, international case-control analysis of the BRIDGES study included 42 680 patients and 46 387 control participants, comprising women aged 18 to 79 years who were sampled independently of family history from 38 studies. Studies were conducted between 1991 and 2016. Sequencing and analysis took place between 2016 and 2021.
EXPOSURES: Protein-truncating variants and likely pathogenic missense variants in ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53.
MAIN OUTCOMES AND MEASURES: The intrinsic-like BC subtypes as defined by estrogen receptor, progesterone receptor, and ERBB2 (formerly known as HER2) status, and tumor grade; morphology; size; stage; lymph node involvement; subtype-specific odds ratios (ORs) for carrying protein-truncating variants and pathogenic missense variants in the 9 BC susceptibility genes.
RESULTS: The mean (SD) ages at interview (control participants) and diagnosis (cases) were 55.1 (11.9) and 55.8 (10.6) years, respectively; all participants were of European or East Asian ethnicity. There was substantial heterogeneity in the distribution of intrinsic subtypes by gene. RAD51C, RAD51D, and BARD1 variants were associated mainly with triple-negative disease (OR, 6.19 [95% CI, 3.17-12.12]; OR, 6.19 [95% CI, 2.99-12.79]; and OR, 10.05 [95% CI, 5.27-19.19], respectively). CHEK2 variants were associated with all subtypes (with ORs ranging from 2.21-3.17) except for triple-negative disease. For ATM variants, the association was strongest for the hormone receptor (HR)+ERBB2- high-grade subtype (OR, 4.99; 95% CI, 3.68-6.76). BRCA1 was associated with increased risk of all subtypes, but the ORs varied widely, being highest for triple-negative disease (OR, 55.32; 95% CI, 40.51-75.55). BRCA2 and PALB2 variants were also associated with triple-negative disease. TP53 variants were most strongly associated with HR+ERBB2+ and HR-ERBB2+ subtypes. Tumors occurring in pathogenic variant carriers were of higher grade. For most genes and subtypes, a decline in ORs was observed with increasing age. Together, the 9 genes were associated with 27.3% of all triple-negative tumors in women 40 years or younger.
CONCLUSIONS AND RELEVANCE: The results of this case-control study suggest that variants in the 9 BC risk genes differ substantially in their associated pathology but are generally associated with triple-negative and/or high-grade disease. Knowing the age and tumor subtype distributions associated with individual BC genes can potentially aid guidelines for gene panel testing, risk prediction, and variant classification and guide targeted screening strategies.
METHODS: Data of 3,100 Malaysian women with nonmetastatic breast cancer diagnosed between 2010 and 2017 were analyzed. Adherence to the Malaysian Clinical Practice Guidelines for Management of Breast Cancer second Edition was measured. Outcomes comprised overall survival and event-free survival.
RESULTS: Guideline adherence for chemotherapy, radiotherapy, hormonal therapy, and targeted therapy were 61.7%, 79.2%, 85.1%, and 26.2%, respectively. Older age was generally associated with lower adherence to guidelines. Compared with patients who were treated according to treatment guidelines, overall survival and event-free survival were substantially lower in patients who were not treated accordingly; hazard ratios for all-cause mortality were 1.69 (95% CI, 1.29 to 2.22), 2.59 (95% CI, 1.76 to 3.81), 3.08 (95% CI, 1.94 to 4.88), and 4.48 (95% CI, 1.98 to 10.13) for chemotherapy, radiotherapy, hormone therapy, and targeted therapy, respectively. Study inferences remain unchanged following sensitivity analyses.
CONCLUSION: Our study findings appear to suggest that adherence to treatment guidelines that have been adapted for resource-limited settings may still provide effective guidance in improving breast cancer outcomes.
METHODS: A retrospective cohort study was conducted at six tertiary centers in Malaysia. All women with newly diagnosed breast cancer were interviewed, and a medical records review was conducted using a structured questionnaire. The BCC timeliness framework showed that the total time between a woman discovering their first breast changes and the date of initial treatment was divided into three distinct intervals: presentation interval, diagnostic interval, and treatment interval. Four diagnosis subintervals, referral, biopsy, report, and diagnosis resolution intervals, were also looked into.
RESULTS: The BCC timeliness framework was used to capture important time points. The median total time, presentation interval, diagnostic interval, and treatment interval were 4.9 months (range, 1 month to 10 years), 2.4 months (range, 7 days to 10 years), 26 days (range, 4 days to 9.3 months), and 21 days (range, 1 day to 7.2 months), respectively. Meanwhile, the median time for the diagnosis subinterval of referral, biopsy, report, and diagnosis resolution was 8 days (range, 0 day to 8 months), 0 day (range, 0 day to 20 days), 7 days (range, 3 days to 3.5 months), and 4 days (range, 1 day to 1.8 months), respectively.
CONCLUSION: The BCC timeliness framework is based on the current sequenced trajectory of the BCC journey. Clarity in the measurement of timeliness provides a standardized language for monitoring and outcome research. It can serve as a quality indicator for community and hospital-based breast cancer programs.
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.
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.
METHODS AND ANALYSIS: The Delphi consensus technique was conducted online to review and evaluate the framework module. A panel of experts, including rehabilitation medicine physicians, occupational therapists, and clinical psychologists in Malaysia, was invited to participate in this study. For each round, the expert consensus was defined as more than 90% of the expert panel agreeing or strongly agreeing with the proposed items.
RESULTS: A total of 33 practitioners completed the three Delphi rounds. 72.7% of the expert panel have been practising in their relevant clinical fields for more than six years (M = 10.67, SD = 5.68). In Round 1, 23% of the experts suggested that the framework module for attention training required further improvements, specifically in the language (M = 1.97, SD = 0.75) and instructions (M = 2.03, SD = 0.71) provided. In Round 2, 15% of the experts recommended additional changes in the instruction (M = 2.15, SD = 0.67) for attention training. Amendments made to the framework module in line with the recommendations provided by the experts resulted in a higher level of consensus, as 94% to 100% of the experts in Round 3 concluded the framework module was suitable and comprehensive for our breast cancer survivors. Following the key results, the objectives were practical, and the proposed approaches, strategies, and techniques for attention and memory training were feasible. The clarity of the instructions, procedures, verbatim transcripts, and timeframe further enhanced the efficacy and utility of the framework module.
CONCLUSIONS: This study found out that the cognitive intervention framework module for breast cancer survivors with cognitive impairment following chemotherapy can be successfully developed and feasible to be implemented using Delphi technique.
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.
Methods: A cross-sectional study was conducted on 745 women who presented with breast symptoms in a university breast clinic in Malaysia. Participants were instructed to respond to self-report questionnaires on depression, trait anxiety, and social support while they were waiting for assessment of their suspected BC. The final diagnoses of these patients were traced one month after examining their medical records. Descriptive statistics were performed to examine the socio-demographic and clinical characteristics of all participants. A multiple regression analysis was carried out to determine the association of the abovementioned factors with the diagnosis of BC.
Results: The analysis showed that BC was diagnosed in 109 (14.6%), benign breast disease (BBD) in 550 (73.8%), and healthy breast (HB) in 86 (11.5%) women. The prevalence of depression was 53.2% in women with BC, 53.6% in women with BBD, and 60.5% in women with HB prior to diagnosis. The prevalence of trait anxiety was 33%. Mean scores for trait anxiety were 42.2 ± 9.0 and 41.8 ± 9.1 for the BC group and BBD group, respectively. The level of perceived social support was similar in all three groups.
Conclusion: We found no significant difference in depression, trait anxiety, and social support among women with newly diagnosed BC, BBD, and HB in women with breast symptoms while undergoing diagnostic evaluation. A longitudinal study is essential to establish the association between chronic mental stress and BC.
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.