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Breast cancer exhibits significant heterogeneity, manifesting in various subtypes that are critical in guiding treatment decisions. This study aimed to investigate the existence of distinct subtypes of breast cancer within the Asian population, by analysing the transcriptomic profiles of 934 breast cancer patients from a Malaysian cohort. Our findings reveal that the HR + /HER2- breast cancer samples display a distinct clustering pattern based on immune phenotypes, rather than conforming to the conventional luminal A-luminal B paradigm previously reported in breast cancers from women of European descent. This suggests that the activation of the immune system may play a more important role in Asian HR + /HER2- breast cancer than has been previously recognized. Analysis of somatic mutations by whole exome sequencing showed that counter-intuitively, the cluster of HR + /HER2- samples exhibiting higher immune scores was associated with lower tumour mutational burden, lower homologous recombination deficiency scores, and fewer copy number aberrations, implicating the involvement of non-canonical tumour immune pathways. Further investigations are warranted to determine the underlying mechanisms of these pathways, with the potential to develop innovative immunotherapeutic approaches tailored to this specific patient population.
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Neoplasias da Mama , Mutação , Fenótipo , Receptor ErbB-2 , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Povo Asiático/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Análise por Conglomerados , Estudos de Coortes , Variações do Número de Cópias de DNA , Sequenciamento do Exoma , Perfilação da Expressão Gênica , Malásia/epidemiologia , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Receptores de Progesterona/metabolismo , Receptores de Progesterona/genética , TranscriptomaRESUMO
INTRODUCTION: Regional analgesia techniques have been increasingly used for post-operative pain management following mastectomy. We aim to evaluate analgesic benefits of pectoral nerve (PECS2) block incorporated as part of the enhanced recovery after surgery (ERAS) protocol in patients undergoing mastectomy in University Malaya Medical Centre, Malaysia. MATERIAL AND METHODS: A single centre, cohort study evaluating 335 women who have undergone unilateral mastectomy between January 2017 and March 2020 in Malaysia. Regional anaesthesia were given pre-operatively via ultrasound guided pectoral and intercostal nerves block (PECSII). RESULTS: Utilization of regional anaesthesia increased from 11% in 2017 to 43% in 2020. Types and duration of surgeries were comparable. Opiod consumption was 3 mg lower in those who had PECS2 block ((27 [24-30] mg), in comparison with those who received general anaesthesia only (30 [26-34] mg), p < 0.001, and length of stay was half a day shorter in the regional anaesthesia group and these were statistically significant. However, pain score (2 [1-3]; 2 [1-3], p=0.719) and post-operative nausea and vomiting (PONV) (32.6-32.5%, p = 0.996) were similar. CONCLUSION: This study highlights the importance of PECS2 block as a component of ERAS protocol for mastectomy in an Asian hospital. This study also inferred that patients may be safely discharged within 24 h of surgery and therefore, same day surgery may be feasible in selected group of patients undergoing mastectomy and this could imply overall cost benefits.
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Neoplasias da Mama , Recuperação Pós-Cirúrgica Melhorada , Bloqueio Nervoso , Feminino , Humanos , Mastectomia/efeitos adversos , Neoplasias da Mama/cirurgia , Estudos de Coortes , Estudos Retrospectivos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controleRESUMO
Cascade testing for families with BRCA pathogenic variants is important to identify relatives who are carriers. These relatives can benefit from appropriate risk management and preventative strategies arising from an inherited increased risk of breast, ovarian, prostate, melanoma, and pancreatic cancers. Cascade testing has the potential to enable cost-effective cancer control even in low- and middle-income settings, but few studies have hitherto evaluated the psychosocial impact of cascade testing in an Asian population, where the cultural and religious beliefs around inheritance and destiny have previously been shown to influence perception and attitudes toward screening. In this study, we evaluated the short- and long-term psychosocial impact of genetic testing among unaffected relatives of probands identified through the Malaysian Breast Cancer Genetics Study and the Malaysian Ovarian Cancer Study, using validated questionnaires (Hospital Anxiety and Depression Scale and Cancer Worry Scale) administered at baseline, and 1-month and 2-year post-disclosure of results. Of the 305 unaffected relatives from 98 independent families who were offered cascade testing, 256 (84%) completed predictive testing and family history of cancers was the only factor significantly associated with uptake of predictive testing. We found that the levels of anxiety, depression, and cancer worry among unaffected relatives decreased significantly after result disclosure and remained low 2-year post-result disclosure. Younger relatives and relatives of Malay descent had higher cancer worry at both baseline and after result disclosure compared to those of Chinese and Indian descent, whereas relatives of Indian descent and those with family history of cancers had higher anxiety and depression levels post-result disclosure. Taken together, the results from this Asian cohort highlight the differences in psychosocial needs in different communities and inform the development of culture-specific genetic counseling strategies.
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Neoplasias da Mama , Neoplasias Ovarianas , Masculino , Feminino , Humanos , Predisposição Genética para Doença , Depressão , Testes Genéticos/métodos , Ansiedade , Neoplasias Ovarianas/genética , Neoplasias da Mama/genética , Proteína BRCA1/genéticaRESUMO
The discovery of high-risk breast cancer susceptibility genes, such as Breast cancer associated gene 1 (BRCA1) and Breast cancer associated gene 2 (BRCA2) has led to accurate identification of individuals for risk management and targeted therapy. The rapid decline in sequencing costs has tremendously increased the number of individuals who are undergoing genetic testing world-wide. However, given the significant differences in population-specific variants, interpreting the results of these tests can be challenging especially for novel genetic variants in understudied populations. Here we report the characterization of novel variants in the Malaysian and Singaporean population that consist of different ethnic groups (Malays, Chinese, Indian, and other indigenous groups). We have evaluated the functional significance of 14 BRCA2 variants of uncertain clinical significance by using multiple in silico prediction tools and examined their frequency in a cohort of 7840 breast cancer cases and 7928 healthy controls. In addition, we have used a mouse embryonic stem cell (mESC)-based functional assay to assess the impact of these variants on BRCA2 function. We found these variants to be functionally indistinguishable from wild-type BRCA2. These variants could fully rescue the lethality of Brca2-null mESCs and exhibited no sensitivity to six different DNA damaging agents including a poly ADP ribose polymerase inhibitor. Our findings strongly suggest that all 14 evaluated variants are functionally neutral. Our findings should be valuable in risk assessment of individuals carrying these variants.
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Neoplasias da Mama , Animais , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/epidemiologia , Estudos de Coortes , Feminino , Genes BRCA2 , Predisposição Genética para Doença , Testes Genéticos , Humanos , Malásia , CamundongosRESUMO
PURPOSE: Mammographic density is a measurable and modifiable biomarker that is strongly and independently associated with breast cancer risk. Paradoxically, although Asian women have lower risk of breast cancer, studies of minority Asian women in predominantly Caucasian populations have found that Asian women have higher percent density. In this cross-sectional study, we compared the distribution of mammographic density for a matched cohort of Asian women from Malaysia and Caucasian women from Sweden, and determined if variations in mammographic density could be attributed to population differences in breast cancer risk factors. METHODS: Volumetric mammographic density was compared for 1501 Malaysian and 4501 Swedish healthy women, matched on age and body mass index. We used multivariable log-linear regression to determine the risk factors associated with mammographic density and mediation analysis to identify factors that account for differences in mammographic density between the two cohorts. RESULTS: Compared to Caucasian women, percent density was 2.0% higher among Asian women (p < 0.001), and dense volume was 5.7 cm3 higher among pre-menopausal Asian women (p < 0.001). Dense volume was 3.0 cm3 lower among post-menopausal Asian women (p = 0.009) compared to post-menopausal Caucasian women, and this difference was attributed to population differences in height, weight, and parity (p < 0.001). CONCLUSIONS: Our analysis suggests that among post-menopausal women, population differences in mammographic density and risk to breast cancer may be accounted for by height, weight, and parity. Given that pre-menopausal Asian and Caucasian women have similar population risk to breast cancer but different dense volume, development of more appropriate biomarkers of risk in pre-menopausal women is required.
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Povo Asiático , Densidade da Mama , Neoplasias da Mama/epidemiologia , População Branca , Neoplasias da Mama/etiologia , Estudos Transversais , Feminino , Humanos , Malásia/epidemiologia , Mamografia , Pessoa de Meia-Idade , Vigilância da População , Fatores de Risco , Suécia/epidemiologiaRESUMO
BACKGROUND: Inter-women and intra-women comparisons of mammographic density (MD) are needed in research, clinical and screening applications; however, MD measurements are influenced by mammography modality (screen film/digital) and digital image format (raw/processed). We aimed to examine differences in MD assessed on these image types. METHODS: We obtained 1294 pairs of images saved in both raw and processed formats from Hologic and General Electric (GE) direct digital systems and a Fuji computed radiography (CR) system, and 128 screen-film and processed CR-digital pairs from consecutive screening rounds. Four readers performed Cumulus-based MD measurements (n = 3441), with each image pair read by the same reader. Multi-level models of square-root percent MD were fitted, with a random intercept for woman, to estimate processed-raw MD differences. RESULTS: Breast area did not differ in processed images compared with that in raw images, but the percent MD was higher, due to a larger dense area (median 28.5 and 25.4 cm2 respectively, mean âdense area difference 0.44 cm (95% CI: 0.36, 0.52)). This difference in âdense area was significant for direct digital systems (Hologic 0.50 cm (95% CI: 0.39, 0.61), GE 0.56 cm (95% CI: 0.42, 0.69)) but not for Fuji CR (0.06 cm (95% CI: -0.10, 0.23)). Additionally, within each system, reader-specific differences varied in magnitude and direction (p < 0.001). Conversion equations revealed differences converged to zero with increasing dense area. MD differences between screen-film and processed digital on the subsequent screening round were consistent with expected time-related MD declines. CONCLUSIONS: MD was slightly higher when measured on processed than on raw direct digital mammograms. Comparisons of MD on these image formats should ideally control for this non-constant and reader-specific difference.
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Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Processamento de Imagem Assistida por Computador , Mamografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Metformin, an AMPK activator, has been reported to improve pathological response to chemotherapy in diabetic breast cancer patients. To date, its mechanism of action in cancer, especially in cancer stem cells (CSCs) have not been fully elucidated. In this study, we demonstrated that metformin, but not other AMPK activators (e.g. AICAR and A-769662), synergizes 5-fluouracil, epirubicin, and cyclophosphamide (FEC) combination chemotherapy in non-stem breast cancer cells and breast cancer stem cells. We show that this occurs through an AMPK-dependent mechanism in parental breast cancer cell lines. In contrast, the synergistic effects of metformin and FEC occurred in an AMPK-independent mechanism in breast CSCs. Further analyses revealed that metformin accelerated glucose consumption and lactate production more severely in the breast CSCs but the production of intracellular ATP was severely hampered, leading to a severe energy crisis and impairs the ability of CSCs to repair FEC-induced DNA damage. Indeed, addition of extracellular ATP completely abrogated the synergistic effects of metformin on FEC sensitivity in breast CSCs. In conclusion, our results suggest that metformin synergizes FEC sensitivity through distinct mechanism in parental breast cancer cell lines and CSCs, thus providing further evidence for the clinical relevance of metformin for the treatment of cancers.
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Trifosfato de Adenosina/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Reparo do DNA/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/química , Proteínas Quinases Ativadas por AMP/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacologia , Antineoplásicos/metabolismo , Compostos de Bifenilo , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/metabolismo , Dano ao DNA/efeitos dos fármacos , Combinação de Medicamentos , Sinergismo Farmacológico , Células-Tronco Embrionárias/metabolismo , Epirubicina/metabolismo , Feminino , Fibroblastos/metabolismo , Fluoruracila/metabolismo , Glucose/metabolismo , Humanos , Ácido Láctico/metabolismo , Pulmão/citologia , Pironas/farmacologia , Ribonucleotídeos/farmacologia , Tiofenos/farmacologiaRESUMO
BACKGROUND: Vaginal examination to monitor labor progress is recommended at least every 4 hours, but it can cause pain and embarrassment to women. Trial data are limited on the best intensity for vaginal examination. Vaginal examination is not needed for oxytocin dose titration after an amniotomy has been performed and oxytocin infusion started. The Foley balloon commonly ripens the cervix without strong contractions. Amniotomy and oxytocin infusion are usually required to drive labor. OBJECTIVE: This study aimed to evaluate the first vaginal examination at 8 vs 4 hours after amniotomy-oxytocin after Foley ripening in multiparous labor induction. STUDY DESIGN: A randomized controlled trial was conducted from October 2021 to September 2022 at the University Malaya Medical Center, Kuala Lumpur, Malaysia. Multiparas at term were recruited at admission for labor induction. Participants were randomized to a first routine vaginal examination at 8 or 4 hours after Foley balloon ripening and amniotomy. Titrated oxytocin infusion was routinely commenced after amniotomy to initiate contractions. The 2 primary outcomes were the time from amniotomy to delivery (noninferiority hypothesis) and maternal satisfaction (superiority hypothesis). Data were analyzed using the Student t test, Mann-Whitney U test, and chi-square test (or Fisher exact test), as suitable for the data. RESULTS: A total of 204 women were randomized, 102 to each arm. Amniotomy to birth intervals were 4.97±2.47 hours in the 8-hour arm and 5.79±3.17 hours in the 4-hour arm (mean difference, -0.82; 97.5% confidence interval, -1.72 to 0.08; P=.041; Bonferroni correction), which were noninferior within the prespecified 2-hour upper margin, and the maternal satisfaction scores (11-point 0-10 numerical rating scale) with allocated labor care were 9 (interquartile range, 8-9) in the 8-hour arm and 8 (interquartile range, 7-9) in the 4-hour arm (P=.814). In addition, oxytocin infusion to birth interval difference was noninferior within the 97.5% confidence interval (-1.59 to 0.23) margin of 1.3 hours. Of the maternal outcomes, the amniotomy to first vaginal examination intervals were 3.9±1.8 hours in the 8-hour arm and 3.4±1.3 hours in the 4-hour arm (P=.026), and the numbers of vaginal examinations were 2.00 (interquartile range, 2.00-3.00) in the 8-hour arm and 3.00 (interquratile range, 2.00-3.25) in the 4-hour arm (P<.001). For the 8-hour arm, the first vaginal examination was less likely to be as scheduled and more likely to be indicated by sensation to bear down (P<.001), and the epidural analgesia rates were lower (13/102 participants [12.7%] in the 8-hour arm vs 28/102 participants [27.5%] in the 4-hour arm; relative risk, 0.46; 95% confidence interval, 0.26-0.84; P=.009). Other outcomes of the mode of delivery, indications for cesarean delivery, and delivery blood loss were not different. Neonatal outcomes were not different. CONCLUSION: Routine first vaginal examination at 8 hours compared with that at 4 hours was noninferior for the time to birth but did not improve maternal satisfaction.
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Amniotomia , Maturidade Cervical , Trabalho de Parto Induzido , Ocitócicos , Ocitocina , Humanos , Feminino , Trabalho de Parto Induzido/métodos , Gravidez , Adulto , Amniotomia/métodos , Ocitócicos/administração & dosagem , Ocitocina/administração & dosagem , Maturidade Cervical/fisiologia , Maturidade Cervical/efeitos dos fármacos , Malásia , Fatores de Tempo , Paridade , Satisfação do PacienteRESUMO
Triple-negative breast cancers (TNBCs) are a subset of breast cancers that have remained difficult to treat. A proportion of TNBCs arising in non-carriers of BRCA pathogenic variants have genomic features that are similar to BRCA carriers and may also benefit from PARP inhibitor treatment. Using genomic data from 129 TNBC samples from the Malaysian Breast Cancer (MyBrCa) cohort, we developed a gene expression-based machine learning classifier for homologous recombination deficiency (HRD) in TNBCs. The classifier identified samples with HRD mutational signature at an AUROC of 0.93 in MyBrCa validation datasets and 0.84 in TCGA TNBCs. Additionally, the classifier strongly segregated HRD-associated genomic features in TNBCs from TCGA, METABRIC, and ICGC. Thus, our gene expression classifier may identify triple-negative breast cancer patients with homologous recombination deficiency, suggesting an alternative method to identify individuals who may benefit from treatment with PARP inhibitors or platinum chemotherapy.
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Background: Breast cancer-related lymphedema (BCRL) is a debilitating chronic illness. Early management and prevention of disease progression rely on lymphedema monitoring and assessment. At present, lymphedema monitoring systems are costly and do not promote remote monitoring. Thus, a low-cost, portable, mobile-based bioimpedance lymphedema monitoring system (Mobilymph) was developed to ensure continuous lymphedema surveillance. Method and Results: Forty-five healthy and 100 BCRL participants were recruited in this study. Mobilymph bioimpedance measurement was validated with a Quadscan 4000 on healthy participants' arms. The interarm bioimpedance ratio was determined to evaluate the discriminatory capability of Mobilymph to detect BCRL. Mobilymph's bioimpedance results show no significant difference compared to Quadscan 4000. The interarm bioimpedance ratios were significantly different (p < 0.001), between participants in healthy and Stage 1, Stage 0 and Stage 1, and Stage 1 and Stage 2. Healthy and Stage 0 participants had similar interarm impedance ratios (p = 0.63). Conclusion: The bioimpedance results show that Mobilymph bioimpedance measurement is comparable to Quadscan 4000 and can detect BCRL arms. Thus, Mobilymph lymphedema monitoring system offers a feasible solution for early lymphedema diagnosis and treatment monitoring. Clinical trial registration number: MREC ID No.: 2020316-8181.
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This study aims to translate the BREAST-Q into Malay and validate it in breast cancer patients undergoing surgery. The English BREAST-Q was translated to Malay using the back-translation method. A total of 144 newly diagnosed breast cancer patients were sampled conveniently between December 2015 and November 2016. Test-retest was done after two to three weeks. Data were analyzed using SPSS and AMOS software. Content experts agreed the items in the Malay BREAST-Q were measuring the constructs appropriately. Internal consistencies were good for all items in each subscale (Cronbach's alpha = 0.83-0.95). The highest inter-item correlation for each item with at least one other item in the construct ranged from 0.47 to 0.90. The lowest corrected item-total correlation values ranged from 0.47 to 0.72. The test-retest analysis showed good reproducibility (intraclass correlation coefficient = 0.71-0.98). In exploratory factor analysis, the Kaiser-Meyer-Olkin values were excellent in all four subscales (0.76, 0.92, 0.91, and 0.86). For all subscales, the number of factors extracted cumulatively explained more than 50% of the variance. The Malay BREAST-Q demonstrated good reliability, face validity, content validity, and construct validity.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/cirurgia , Malásia , Reprodutibilidade dos Testes , Inquéritos e Questionários , Psicometria/métodosRESUMO
Soy intake is associated with lower breast cancer risk in observational studies concerning Asian women, however, no randomized controlled trials (RCT) have been conducted among Asian women living in Asia. This three-armed RCT assessed the effects of one-year soy isoflavone (ISF) intervention on mammographic density (MD) change among healthy peri- and postmenopausal Malaysian women. This study was registered at ClinicalTrials.gov (NCT03686098). Participants were randomized into the 100 mg/day ISF Supplement, 50 mg/day ISF Diet, or control arm, and assessed for change in absolute and relative dense area from digital mammograms conducted at enrolment and after 12 months, compared over time across study arms using Kruskal-Wallis tests. Out of 118 women enrolled, 91 women completed the intervention, while 27 women (23%) were lost in follow up. The ISF supplement arm participants observed a larger decline in dense area (−1.3 cm2), compared to the ISF diet (−0.5 cm2) and control arm (−0.8 cm2), though it was not statistically significant (p = 0.48). Notably, among women enrolled within 5 years of menopause; dense area declined by 6 cm2 in the ISF supplement arm, compared to <1.0 cm2 in the control arm (p = 0.13). This RCT demonstrates a possible causal association between soy ISF intake and MD, a biomarker of breast cancer risk, among Asian women around the time of menopause, but these findings require confirmation in a larger trial.
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Neoplasias da Mama , Isoflavonas , Feminino , Humanos , Densidade da Mama , Isoflavonas/farmacologia , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/prevenção & controle , MamografiaRESUMO
(1) Background: Differences in access to biomarker testing and cancer treatment in resource-limited settings may affect the clinical utility of the AJCC8 staging system compared to the anatomical AJCC7 system. (2) Methods: A total of 4151 Malaysian women who were newly diagnosed with breast cancer from 2010 to 2020 were followed-up until December 2021. All patients were staged using the AJCC7 and AJCC8 systems. Overall survival (OS) and relative survival (RS) were determined. Concordance-index was used to compare the discriminatory ability between the two systems. (3) Results: Migration from the AJCC7 to AJCC8 staging system resulted in the downstaging of 1494 (36.0%) patients and the upstaging of 289 (7.0%) patients. Approximately 5% of patients could not be staged using the AJCC8 classification. Five-year OS varied between 97% (Stage IA) and 66% (Stage IIIC) for AJCC7, and 96% (Stage IA) and 60% (Stage IIIC) for AJCC8. Concordance-indexes for predicting OS using the AJCC7 and AJCC8 models were 0.720 (0.694-0.747) and 0.745 (0.716-0.774), and for predicting RS they were 0.692 (0.658-0.728) and 0.710 (0.674-0.748), respectively. (4) Conclusions: Given the comparable discriminatory ability between the two staging systems in predicting the stage-specific survival of women with breast cancer in the current study, the continued use of the AJCC7 staging system in resource-limited settings seems pragmatic and justifiable.
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INTRODUCTION: Given that breast cancers in germline BRCA1 carriers are predominantly estrogen-negative and triple-negative, it has been suggested that women diagnosed with triple-negative breast cancer (TNBC) younger than 50 years should be offered BRCA1 testing, regardless of family cancer characteristics. However, the predictive value of triple-negative breast cancer, when taken in the context of personal and family cancer characteristics, is unknown. The aim of this study was to determine whether TNBC is a predictor of germline BRCA1 mutations, in the context of multiple predictive factors. METHODS: Germline mutations in BRCA1 and BRCA2 were analyzed by Sanger sequencing and multiple ligation-dependent probe amplification (MLPA) analysis in 431 women from the Malaysian Breast Cancer Genetic Study, including 110 women with TNBC. Logistic regression was used to identify and to estimate the predictive strength of major determinants. Estrogen receptor (ER) and phosphatase and tensin homologue (PTEN) status were assessed and included in a modified Manchester scoring method. RESULTS: Our study in an Asian series of TNBC patients demonstrated that 27 (24.5%) of 110 patients have germline mutations in BRCA1 (23 of 110) and BRCA2 (four of 110). We found that among women diagnosed with breast cancer aged 36 to 50 years but with no family history of breast or ovarian cancer, the prevalence of BRCA1 and BRCA2 mutations was similar in TNBC (8.5%) and non-TNBC patients (6.7%). By contrast, in women diagnosed with breast cancer, younger than 35 years, with no family history of these cancers, and in women with a family history of breast cancer, the prevalence of mutations was higher in TNBC compared with non-TNBC (28.0% and 9.9%; P = 0.045; and 42.1% and 14.2%; P < 0.0001, respectively]. Finally, we found that incorporation of estrogen-receptor and TNBC status improves the sensitivity of the Manchester Scoring method (42.9% to 64.3%), and furthermore, incorporation of PTEN status further improves sensitivity (42.9% to 85.7%). CONCLUSIONS: We found that TNBC is an important criterion for highlighting women who may benefit from genetic testing, but that this may be most useful for women with early-onset breast cancer (35 years or younger) or with a family history of cancers. Furthermore, addition of TNBC and PTEN status improves the sensitivity of the Manchester scoring method and may be particularly important in the Asian context, where risk-assessment models underestimate the number of mutation carriers.
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Proteína BRCA1/genética , PTEN Fosfo-Hidrolase/genética , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idade de Início , Proteína BRCA2/genética , Sequência de Bases , Neoplasias da Mama/genética , Feminino , Testes Genéticos , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Mutação , Receptores de Estrogênio/genética , Análise de Sequência de DNA , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
INTRODUCTION: Breast cancer patients in low- and middle-income countries often present at an advanced stage. This qualitative study elicited views regarding the challenges and opportunities for breast cancer screening and early detection among women in a low-income semi-rural community in Segamat district, Malaysia. METHODS: Individual semi-structured interviews with 22 people (health professionals, cancer survivors, community volunteers and member from a non-governmental organization) and four focus group discussions (n = 22 participants) with women from a local community were conducted. All participants were purposively sampled and female residents registered with the South East Asia Community Observatory aged ≥40 years were eligible to participate in the focus group discussions. Data were transcribed verbatim and analyzed using thematic analysis. RESULTS: The thematic analysis illuminated barriers, challenges and opportunities across six domains: (i) personal experiences and barriers to help-seeking as well as financial and travel access barriers; (ii) primary care challenges (related to delivering clinical breast examination and teaching breast-self-examination); (iii) secondary care challenges (related to mammogram services); (iv) disconnection between secondary and primary care breast cancer screening pathways; and (v) opportunities to improve breast cancer early detection relating to community civil service society activities (i.e. awareness raising, support groups, addressing stigma/embarrassment and encouraging husbands to support women) and vi) links between public healthcare personnel and community (i.e. improving breast self-examination education, clinical breast examination provision and subsidised mammograms). CONCLUSION: The results point to a variety of reasons for low uptake and, therefore, to the complex nature of improving breast cancer screening and early detection. There is a need to adopt a systems approach to address this complexity and to take account of the socio-cultural context of communities in order, in turn, to strengthen cancer control policy and practices in Malaysia.
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Neoplasias da Mama , Detecção Precoce de Câncer , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Malásia/epidemiologia , Pesquisa Qualitativa , População RuralRESUMO
PURPOSE: With the development of poly (ADP-ribose) polymerase inhibitors for treatment of patients with cancer with an altered BRCA1 or BRCA2 gene, there is an urgent need to ensure that there are appropriate strategies for identifying mutation carriers while balancing the increased demand for and cost of cancer genetics services. To date, the majority of mutation prediction tools have been developed in women of European descent where the age and cancer-subtype distributions are different from that in Asian women. METHODS: In this study, we built a new model (Asian Risk Calculator) for estimating the likelihood of carrying a pathogenic variant in BRCA1 or BRCA2 gene, using germline BRCA genetic testing results in a cross-sectional population-based study of 8,162 Asian patients with breast cancer. We compared the model performance to existing mutation prediction models. The models were evaluated for discrimination and calibration. RESULTS: Asian Risk Calculator included age of diagnosis, ethnicity, bilateral breast cancer, tumor biomarkers, and family history of breast cancer or ovarian cancer as predictors. The inclusion of tumor grade improved significantly the model performance. The full model was calibrated (Hosmer-Lemeshow P value = .614) and discriminated well between BRCA and non-BRCA pathogenic variant carriers (area under receiver operating curve, 0.80; 95% CI, 0.75 to 0.84). Addition of grade to the existing clinical genetic testing criteria targeting patients with breast cancer age younger than 45 years reduced the proportion of patients referred for genetic counseling and testing from 37% to 33% (P value = .003), thereby improving the overall efficacy. CONCLUSION: Population-specific customization of mutation prediction models and clinical genetic testing criteria improved the accuracy of BRCA mutation prediction in Asian patients.
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Neoplasias da Mama , Neoplasias Ovarianas , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Estudos Transversais , Feminino , Genes BRCA2 , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/genéticaRESUMO
This study aims to test the psychometric properties of the Malay, English, and Chinese 9-Item Shared Decision Making Questionnaire (SDM-Q-9) in breast cancer patients making treatment decisions. The original German SDM-Q-9 was translated to Malay using the back-translation method. A total of 222 newly diagnosed breast cancer patients making treatment decisions were sampled conveniently from three breast clinics between August 2015 and February 2016. A total of 66 patients answered the SDM-Q-9 in Malay, 87 in English, and 69 in Chinese. Data were analyzed using SPSS and AMOS software. SDM-Q-9 demonstrated good reliability in the three translations. All the items correlated well except for Item 1 in English. The factor loadings were within acceptable range except for Item 1 in Malay, Items 1 and 2 in English, and Items 7 and 9 in Chinese SDM-Q-9. However, no items were deleted in accordance with experts' opinions and the previous SDM-Q-9 validation studies. The Malay, English, and Chinese SDM-Q-9 demonstrated good reliability and validity.
Assuntos
Neoplasias da Mama , Tomada de Decisão Compartilhada , Aminoacridinas , Neoplasias da Mama/terapia , China , Tomada de Decisões , Feminino , Humanos , Malásia , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
ABSTRACT: Pre-operative status of axillary lymph node (ALN) in early breast cancer is usually initially assessed by pre-operative ultrasound, followed by ultrasound-guided needle biopsy (UNB) confirmation. Patients with positive nodal status will undergo axillary lymph node dissection (ALND), while those with negative nodal status will have sentinel lymph node biopsy. ALND is associated with higher morbidity than Sentinel lymph node biopsy. The objective of this study is to determine if axillary ultrasound alone without UNB is predictive enough to assign patients to ALND and to identify ultrasound features that are significantly associated with pathologically positive ALN.383 newly diagnosed primary breast cancer patients between 2012 and 2014, and who had undergone pre-operative axillary ultrasound in University Malaya Medical Centre with a complete histopathology report of the axillary surgery were retrospectively reviewed. ALN was considered positive if it had any of these features: cortical thickening >â3âmm, loss of fatty hilum, hypoechoic solid node, mass-like appearance, round shape and lymph node size >â5âmm. Post-operative histopathological reports were then analyzed for nodal involvement.The overall sensitivity, specificity, and accuracy of pre-operative axillary ultrasound in detecting diseased nodes were 45.5%, 80.7%, and 60.3% respectively. The positive (PPV) and negative predictive values were 76.5% and 51.8%. Round shape, loss of fatty hilum and mass-like appearance had the highest PPVs of 87%, 83% and 81.6% respectively and significant odds ratios (ORs) of 5.22 (95% confidence interval [CI]: 1.52 - 17.86), ORs of 4.77 (95% CI: 2.62 - 8.70) and ORs of 4.26 (95% CI: 2.37 - 7.67) respectively (P-valueâ<â.05). Cortical thickness of >â3âmm was identified to have low PPV at 69.1%, ORs of 1.71 (95% CI: 0.86 - 3.41, Pâ=â.126).There are features on axillary ultrasound that confer high PPV for axillary involvement i.e. round shape, loss of fatty hilum, and mass-like appearance. In a low resource setting, these features may benefit from ALND without further pre-operative biopsies. However, pre-operative UNB for features with low PPV that is, cortical thickness >â3âmm should be considered to obviate the unnecessary morbidity associated with ALND.
Assuntos
Axila/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Excisão de Linfonodo , Ultrassonografia , Feminino , Humanos , Biópsia Guiada por Imagem , Malásia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
ABSTRACT: To evaluate the clinical and imaging findings of papillary breast neoplasm and review the pathologic correlation at a tertiary center.Retrospective study of patients diagnosed with benign and malignant papillary lesions between 2008 to 2018. 147 patients were identified with histology diagnosis of papillary lesions. The clinical, imaging, and pathological characteristics were reviewed.Patient cohort included 147 women diagnosed with papillary lesions (mean age at diagnosis 53.8âyears) and were divided into 3 histology groups (benign, atypical, and malignant). Common clinical presentations were breast lump (nâ=â60) and nipple discharge (nâ=â29), 48 patients were asymptomatic.Only 37 were detected as a mass lesion on mammogram. The presence of mass lesion on mammogram was the most common feature in all 3 papillary lesion groups, and with the presence of asymmetric density, were the 2 mammographic features significantly associated (Pâ<â.05) with malignancy.All lesions were detected on ultrasound. The most common sonographic features for all 3 groups were the presence of a mass and irregular shape. Among all the sonographic features assessed, larger size, presence of vascularity and absence of dilated ducts were significantly associated (Pâ<â.05) with malignancy.Feature pattern recognition of the variety of benign, atypical and malignant papillary neoplasm on ultrasound and mammogram, with emphasis on size, presence of vascularity and dilated ducts on ultrasound and presence of mass, and architectural distortion on mammogram, is important in the assessment of patients with suspected ductal lesions to facilitate optimal treatment and surgical care.