Displaying publications 1 - 20 of 43 in total

Abstract:
Sort:
  1. Rahmat K, Ab Mumin N, Ng WL, Mohd Taib NA, Chan WY, Ramli Hamid MT
    Ultrasound Med Biol, 2024 Jan;50(1):112-118.
    PMID: 37839984 DOI: 10.1016/j.ultrasmedbio.2023.09.011
    OBJECTIVE: The aim of the work described here was to assess the performance of automated breast ultrasound (ABUS) as an adjunct to digital breast tomosynthesis (DBT) in the screening and diagnostic setting.

    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.

  2. Breast Cancer Association Consortium, Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, et al.
    N Engl J Med, 2021 02 04;384(5):428-439.
    PMID: 33471991 DOI: 10.1056/NEJMoa1913948
    BACKGROUND: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.

    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.).

  3. Ho WK, Hassan NT, Yoon SY, Yang X, Lim JMC, Binte Ishak ND, et al.
    Lancet Reg Health West Pac, 2024 Mar;44:101017.
    PMID: 38333895 DOI: 10.1016/j.lanwpc.2024.101017
    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).

  4. Syed Alwi SM, Narayanan V, Mohd Taib NA, Che Din N
    Support Care Cancer, 2022 Mar;30(3):2793-2801.
    PMID: 34841453 DOI: 10.1007/s00520-021-06686-9
    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.

  5. Dörk T, Peterlongo P, Mannermaa A, Bolla MK, Wang Q, Dennis J, et al.
    Sci Rep, 2019 08 29;9(1):12524.
    PMID: 31467304 DOI: 10.1038/s41598-019-48804-y
    Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
  6. Rajaram N, Lim ZY, Song CV, Kaur R, Mohd Taib NA, Muhamad M, et al.
    Psychooncology, 2019 01;28(1):147-153.
    PMID: 30346074 DOI: 10.1002/pon.4924
    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 

  7. Toh GT, Kang P, Lee SS, Lee DS, Lee SY, Selamat S, et al.
    PLoS One, 2008;3(4):e2024.
    PMID: 18431501 DOI: 10.1371/journal.pone.0002024
    BACKGROUND: In Asia, breast cancer is characterised by an early age of onset: In Malaysia, approximately 50% of cases occur in women under the age of 50 years. A proportion of these cases may be attributable, at least in part, to genetic components, but to date, the contribution of genetic components to breast cancer in many of Malaysia's ethnic groups has not been well-characterised.
    METHODOLOGY: Given that hereditary breast carcinoma is primarily due to germline mutations in one of two breast cancer susceptibility genes, BRCA1 and BRCA2, we have characterised the spectrum of BRCA mutations in a cohort of 37 individuals with early-onset disease (
  8. Tan MM, Ho WK, Yoon SY, Mariapun S, Hasan SN, Lee DS, et al.
    PLoS One, 2018;13(9):e0203469.
    PMID: 30216346 DOI: 10.1371/journal.pone.0203469
    BACKGROUND: Breast cancer risk factors have been examined extensively in Western setting and more developed Asian cities/countries. However, there are limited data on developing Asian countries. The purpose of this study was to examine breast cancer risk factors and the change of selected risk factors across birth cohorts in Malaysian women.

    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.

  9. Mohd Mujar NM, Dahlui M, Emran NA, Abdul Hadi I, Wai YY, Arulanantham S, et al.
    PLoS One, 2017;12(4):e0176394.
    PMID: 28448541 DOI: 10.1371/journal.pone.0176394
    Complementary and alternative medicine (CAM) is widely used among the breast cancer patients in Malaysia. Delays in presentation, diagnosis and treatment have been shown to impact the disease prognosis. There is considerable use of CAM amongst breast cancer patients. CAM use has been cited as a cause of delay in diagnosis and treatments in qualitative studies, however there had not been any confirmatory study that confirms its impact on delays. The purpose of this study was to evaluate whether the use of CAM among newly diagnosed breast cancer patients was associated with delays in presentation, diagnosis or treatment of breast cancer. This multi-centre cross-sectional study evaluating the time points of the individual breast cancer patients' journey from first visit, resolution of diagnosis and treatments was conducted in six public hospitals in Malaysia. All newly diagnosed breast cancer patients from 1st January to 31st December 2012 were recruited. Data were collected through medical records review and patient interview by using a structured questionnaire. Complementary and alternative medicine (CAM) was defined as the use of any methods and products not included in conventional allopathic medicine before commencement of treatments. Presentation delay was defined as time taken from symptom discovery to first presentation of more than 3 months. The time points were categorised to diagnosis delay was defined as time taken from first presentation to diagnosis of more than 1 month and treatment delay was defined as time taken from diagnosis to initial treatment of more than 1 month. Multiple logistic regression was used for analysis. A total number of 340 patients participated in this study. The prevalence of CAM use was 46.5% (n = 158). Malay ethnicity (OR 3.32; 95% CI: 1.85, 5.97) and not interpreting symptom as cancerous (OR 1.79; 95% CI: 1.10, 2.92) were significantly associated with CAM use. The use of CAM was associated with delays in presentation (OR 1.65; 95% CI: 1.05, 2.59), diagnosis (OR 2.42; 95% CI: 1.56, 3.77) and treatment of breast cancer (OR 1.74; 95% CI: 1.11, 2.72) on univariate analyses. However, after adjusting with other covariates, CAM use was associated with delays in presentation (OR 1.71; 95% CI: 1.05, 2.78) and diagnosis (OR 2.58; 95% CI: 1.59, 4.17) but not for treatment of breast cancer (OR 1.58; 95% CI: 0.98, 2.55). The prevalence of CAM use among the breast cancer patients was high. Women of Malay ethnicity and not interpreting symptom as cancerous were significantly associated with CAM use. The use of CAM is significantly associated with delay in presentation and resolution of diagnosis. This study suggests further evaluation of access to breast cancer care is needed as poor access may cause the use of CAM. However, since public hospitals in Malaysia are heavily subsidized and readily available to the population, CAM use may impact delays in presentation and diagnosis.
  10. Syed Alwi SM, Mazlan M, Mohd Taib NA, Che Din N, Narayanan V
    PLoS One, 2022;17(11):e0277056.
    PMID: 36395277 DOI: 10.1371/journal.pone.0277056
    OBJECTIVE: Chemotherapy-related cognitive impairment (CRCI) is a well-known phenomenon among breast cancer survivors. Cognitive impairment among breast cancer survivors can significantly affect their quality of life and ability to function independently. However, there is a lack of specific and focused cognitive intervention to improve their cognitive performances. This study aimed to develop a tailored cognitive intervention framework module by adapting the attention and memory interventions from the Cognitive Rehabilitation Manual of the Brain Injury Interdisciplinary Special Interest Group (BI-SIG) of the American Congress of Rehabilitation Medicine (ACRM) and incorporating them with the relevant exercises for cognitive rehabilitation for Malaysian breast cancer survivors with CRCI based on the consensus agreement of the expert panel.

    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.

  11. Padmanabhan H, Hassan NT, Wong SW, Lee YQ, Lim J, Hasan SN, et al.
    PLoS One, 2022;17(2):e0263675.
    PMID: 35167615 DOI: 10.1371/journal.pone.0263675
    There is an increasing number of cancer patients undertaking treatment-focused genetic testing despite not having a strong family history or high a priori risk of being carriers because of the decreasing cost of genetic testing and development of new therapies. There are limited studies on the psychosocial outcome of a positive result among breast cancer patients who are at low a priori risk, particularly in women of Asian descent. Breast cancer patients enrolled under the Malaysian Breast Cancer Genetic Study between October 2002 and February 2018 were tested for BRCA1, BRCA2 and PALB2 genes. All 104 carriers identified were invited by a research genetic counsellor for result disclosure. Of the 104 carriers, 64% (N = 66) had low a priori risk as determined by PENN II scores. Psychosocial, risk perception and health behaviour measures survey were conducted at baseline (pre-result disclosure), and at two to six weeks after result disclosure. At baseline, younger carriers with high a priori risk had higher Cancer Worry Scale scores than those with low a priori risk but all scores were within acceptable range. Around 75% and 55% of high a priori risk carriers as well as 80% and 67% of low a priori risk carriers had problems in the "living with cancer" and "children" psychosocial domains respectively. All carriers regardless of their a priori risk demonstrated an improved risk perception that also positively influenced their intent to undergo risk management procedures. This study has shown that with sufficient counselling and support, low a priori risk carriers are able to cope psychologically, have improved perceived risk and increased intent for positive health behaviour despite having less anticipation from a family history prior to knowing their germline carrier status.
  12. Wen WX, Allen J, Lai KN, Mariapun S, Hasan SN, Ng PS, et al.
    J Med Genet, 2018 02;55(2):97-103.
    PMID: 28993434 DOI: 10.1136/jmedgenet-2017-104947
    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.

  13. Lee DS, Meiser B, Mariapun S, Hassan T, Yip CH, Mohd Taib NA, et al.
    J Genet Couns, 2021 Jun;30(3):720-729.
    PMID: 33245177 DOI: 10.1002/jgc4.1360
    The vast majority of studies assessing communication of BRCA1/2 results with relatives and family uptake of BRCA1/2 testing have been conducted in Western societies, and a dearth of studies have been conducted in Asia among relatives of diverse carriers of pathogenic BRCA1/2 germline variants. This study aimed to present rates of BRCA1/2 result disclosure by probands and probands' motivators and barriers of family communication and predictive testing uptake among eligible relatives. It also examined patterns of disclosure and testing uptake among different types of relatives. Eighty-seven carriers with either breast or ovarian cancer, who had previously been found to be carriers of a pathogenic variant in BRCA1/2, were interviewed over the phone using a semi-structured interview guide. Fifty-six percent of patients were Chinese, 21% were Indian, and 23% were Malay. It was found that 62.0% of eligible first- and second-degree relatives were informed by the proband about the testing result and that 11.5% of eligible first- and second-degree relatives had genetic testing. First-degree relatives were more likely to have been informed and tested compared to second-degree relatives, as were sisters compared to brothers. The low rates of family communication and testing uptake documented in this study suggest that interventions should focus on encouraging probands to inform male and second-degree relatives and targeting such relatives to increase informed decisions and accessibility to testing. Promotion strategies should be culturally sensitive to optimize outcomes.
  14. Yang X, Leslie G, Doroszuk A, Schneider S, Allen J, Decker B, et al.
    J Clin Oncol, 2020 03 01;38(7):674-685.
    PMID: 31841383 DOI: 10.1200/JCO.19.01907
    PURPOSE: To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized.

    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.

  15. Syed Alwi SM, Narayanan V, Mohd Taib NA, Che Din N
    J Clin Exp Neuropsychol, 2021 07;43(5):534-545.
    PMID: 34369307 DOI: 10.1080/13803395.2021.1945539
    Introduction: Breast cancer survivors frequently develop cognitive impairment following chemotherapy which can significantly hamper their well-being, ability to function independently, and overall quality of life. Evidence of cognitive functioning in breast cancer survivors from lower and middle-income countries remains scarce. We examined the prevalence of cognitive impairment among Malaysian multiethnic early-stage breast cancer survivors one to three years post-chemotherapy.Methods: This cross-sectional study included 160 breast cancer survivors from the University Malaya Medical Center (UMMC). The cognitive assessments used included the Montreal Cognitive Assessment (MoCA-BM), the Rey Auditory and Verbal Learning Test (RAVLT-BM), and the digit span and arithmetic of the Working Memory Index (WMI) of Wechsler Adult Intelligence Scale-IV (WAIS-IV). Data were analyzed using independent sample t-tests and Pearson's correlation.Results: Our breast cancer survivors demonstrated poor performances in MoCA-BM (31.9%) RAVLT-BM, recall (53.8%), and WMI of WAIS-IV (51.3%) with 30.6% of them performed poorly in all three cognitive tests administered. There were no significant mean group differences in cognitive performances between <24 months after chemotherapy and ≥24 months after chemotherapy.Conclusions: A high proportion of breast cancer survivors exhibited poor performances in the cognitive assessments. Cognitive rehabilitation programmes tailored to the needs of these survivors should be incorporated into cancer care management.
  16. Wong JHD, Zaili Z, Abdul Malik R, Bustam AZ, Saad M, Jamaris S, et al.
    J Appl Clin Med Phys, 2021 Aug;22(8):139-147.
    PMID: 34254425 DOI: 10.1002/acm2.13338
    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.

  17. Zainal NZ, Ng CG, Wong A, Andrew B, Mohd Taib NA, Low SY
    J Taibah Univ Med Sci, 2021 Aug;16(4):497-503.
    PMID: 34408606 DOI: 10.1016/j.jtumed.2021.01.013
    Objective: This study aims to determine the prevalence of depression, trait anxiety, and social support among women suspected of breast cancer (BC) and to investigate the association of these factors with the diagnosis of BC.

    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.

  18. Song CV, Yip CH, Mohd Taib NA, See MH, Teoh LY, Monninkhof EM, et al.
    JCO Glob Oncol, 2022 Mar;8:e2100314.
    PMID: 35245099 DOI: 10.1200/GO.21.00314
    PURPOSE: Addressing unwarranted clinical variation in oncology practices is expected to lead to improved cancer outcomes. Particularly, the application and impact of treatment guidelines on breast cancer outcomes are poorly studied in resource-limited settings. We measured adherence to a set of locally developed adjuvant treatment guidelines in a middle-income setting. Importantly, the impact of guidelines adherence on survival following breast cancer was determined.

    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.

  19. Mohd Mujar NM, Dahlui M, Emran NA, Hadi IA, Yan YW, Arulanantham S, et al.
    JCO Glob Oncol, 2022 Mar;8:e2100250.
    PMID: 35286134 DOI: 10.1200/GO.21.00250
    PURPOSE: The aim of this study is to determine the pathway that women follow for Breast Cancer Care (BCC) and the time intervals from symptom discovery to treatment initiation and to develop a quality matrix framework.

    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.

  20. Breast Cancer Association Consortium, Mavaddat N, Dorling L, Carvalho S, Allen J, González-Neira A, et al.
    JAMA Oncol, 2022 Mar 01;8(3):e216744.
    PMID: 35084436 DOI: 10.1001/jamaoncol.2021.6744
    IMPORTANCE: Rare germline genetic variants in several genes are associated with increased breast cancer (BC) risk, but their precise contributions to different disease subtypes are unclear. This information is relevant to guidelines for gene panel testing and risk prediction.

    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.

Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links