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: An unmatched hospital based case-control study was conducted from October 2002 to December 2016 in Selangor, Malaysia. A total of 3,683 cases and 3,980 controls were included in this study. Unconditional logistic regressions, adjusted for potential confounding factors, were conducted. The breast cancer risk factors were compared across four birth cohorts by ethnicity.
RESULTS: Ever breastfed, longer breastfeeding duration, a higher soymilk and soy product intake, and a higher level of physical activity were associated with lower risk of breast cancer. Chinese had the lowest breastfeeding rate, shortest breastfeeding duration, lowest parity and highest age of first full term pregnancy.
CONCLUSIONS: Our study shows that breastfeeding, soy intake and physical activity are modifiable risk factors for breast cancer. With the increasing incidence of breast cancer there is an urgent need to educate the women about lifestyle intervention they can take to reduce their breast cancer risk.
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: 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: 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: 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.
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: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity.
RESULTS: Protein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants.
CONCLUSIONS: The results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.).
METHODS: We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes.
RESULTS: We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 × 10-2). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer.
CONCLUSION: These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.
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.
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.
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
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.