355 research outputs found
Breast Cancer Patient Navigation Program in a Resource-Constrained Health Care Setting in Asia
No full text Abstract 23 Background: Breast cancer incidence is rapidly increasing in Asia as a result of changes in life expectancy and lifestyle factors. In Malaysia, incidence is expected to double in the next decade and survival is poor (50% to 75%) because of late presentation and poor adherence to treatment. This burden is greater for women in underserved communities, but few studies have examined systematic approaches to reduce late presentation and poor treatment adherence. We sought to determine whether a patient navigation program (PNP) could be a community-based solution to improve outcomes of patients with breast cancer, particularly in a resource-constrained setting. Methods: PNP was implemented in a secondary hospital that serves a suburban area near Kuala Lumpur. A decision aid, which incorporated local key messages, was developed. Nurses and community workers in the program received skills training in navigation, communications, patient management, and resource identification and utilization. Data were retrieved from baseline questionnaires and a patient tracking system and was analyzed by using descriptive statistics. Results: In the first year of the program, 225 women were served, of whom 137 were patients with breast cancer. Compared with the prior year, more patients in the PNP received diagnoses within 14 days of their first visit (67.7% v 62.4%; P = .516) and had surgery within 28 days from diagnosis (68.4% v 61.3%; P = .487). There were also fewer reported patients who experienced default in the PNP (4.4% v 6.6%; P = .797). Conclusion: This 1-year evaluation showed that patient navigation is feasible in a resource-constrained setting, but longer follow-up is required to determine the impact on outcomes. Moving forward, we seek to increase the efficiency of patient navigation by increasing access to palliative care and improving interdepartment coordination and patient tracking systems. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Maheswari Jaganathan No relationship to disclose Dhiauddin Hai No relationship to disclose Nur Hidayati Zainal No relationship to disclose Nadia Rajaram No relationship to disclose Mohamed Yusof No relationship to disclose Soo-Hwang Teo Honoraria: AstraZeneca Consulting or Advisory Role: AstraZeneca Speakers' Bureau: AstraZeneca Research Funding: AstraZeneca Travel, Accommodations, Expenses: AstraZeneca </jats:sec
Current Status of the Management of Hereditary Breast and Ovarian Cancer in Asia: First Report by the Asian BRCA Consortium
No full textBackground: BRCAl/BRCA2 mutations are associated with an increased lifetime risk for hereditary breast and ovarian cancer (HBOC). Compared with the Western developed countries, genetic testing and risk assessment for HBOC in Asia are less available, thus prohibiting the appropriate surveillance, clinical strategies and cancer management. Methods: The current status of HBOC management in 14 Asian countries, including genetic counselling/testing uptakes and clinical management options, was reviewed. We analysed how economic factors, healthcare and legal frameworks, and cultural issues affect the genetic service availability in Asia. Results: In 2012, only an estimated 4,000 breast cancer cases from 14 Asian countries have benefited from genetic services. Genetic testing costs and the absence of their adoption into national healthcare systems are the main economic barriers for approaching genetic services.Training programmes, regional accredited laboratories and healthcare professionals are not readily available in most of the studied countries. A lack of legal frameworks against genetic discrimination and a lack of public awareness of cancer risk assessment also provide challenges to HBOC management in Asia. Condusions:The Asian BRCA Consortium reports the current disparities in genetic services for HBOC in Asia and urges the policy makers, healthcare sectors and researchers to address the limitations in HBOC management. (C) 2015 S. Karger AG, Base
Lif1p targets the DNA ligase Lig4p to sites of DNA double-strand breaks
No full textAbstractDNA ligases catalyse the joining of DNA single- and double-strand breaks. Saccharomyces cerevisiae Cdc9p is a homologue of mammalian DNA ligase I and is required for DNA replication, recombination and single-strand break repair. The other yeast ligase, Lig4p/Dnl4p, is a homologue of mammalian DNA ligase IV, and functions in the non-homologous end-joining (NHEJ) pathway of DNA double-strand break repair [1–4]. Lig4p interacts with Lif1p, the yeast homologue of the human ligase IV-associated protein, XRCC4 [5]. This interaction takes place through the carboxy-terminal domain of Lig4p and is required for Lig4p stability. We show that the carboxy-terminal interaction region of Lig4p is necessary for NHEJ but, when fused to Cdc9p, is insufficient to confer NHEJ function to Cdc9p. Also, Lif1p stimulates the in vitro catalytic activity of Lig4p in adenylation and DNA ligation. Nevertheless, Lig4p is inactive in NHEJ in the absence of Lif1p in vivo, even when Lig4p is stably expressed. We show that Lif1p binds DNA in vitro and, through in vivo cross-linking and chromatin immuno precipitation assays, demonstrate that it targets Lig4p to chromosomal DNA double-strand breaks. Furthermore, this targeting requires another key NHEJ protein, Ku
Abstract 4288: Inherited mutations in <i>BRCA1</i> and <i>BRCA2</i> in an unselected multi-ethnic cohort of Asian breast cancer patients and healthy controls from Malaysia
No full textAbstract
Background: BRCA1 and BRCA2 are significant cancer predisposition genes which have hitherto primarily been tested in breast cancer patients selected on the basis of age of onset of breast cancer and family history of breast and ovarian cancer. Given that only 40% of breast cancer occur in post-menopausal women in many Asian countries including Malaysia, compared to close to 80% in many Caucasian countries, the proportion of risk attributable to genetic factors is likely to be correspondingly higher in Asians. We sought to determine the prevalence of germline mutations in BRCA1 and BRCA2 in an unselected cohort of Asian breast cancer patients and healthy controls.
Methods: Women diagnosed with invasive breast cancer recruited from University Malaya Medical Centre between October 2002 and April 2015, and Sime Darby Medical Centre between September 2012 and April 2015 [n=2,592]. Eligible control subjects were recruited from women attending an opportunistic mammography screening programme at University Malaya Medical Centre between January 2014 and April 2015, and Sime Darby Medical Centre between October 2011 and April 2015 [n=2,851]. Amplicon-based targeted sequencing of exonic and proximal splice site junction regions of 31 known and probable breast cancer susceptibility genes were performed on Fluidigm Access Array system, with sequencing conducted on the Illumina HiSeq2500 platform. Variant calling was performed as per GATK recommended best practices with UnifiedGenotyper using the default parameters except -minIndelFrac 0.05. Variants were annotated with ANNOVAR and variants with MAF &gt;1% as reported in population databases were filtered out. Nonsense, frameshift indels, and splice site variants were presumed to be deleterious.
Results: Overall, 111 distinct mutations (50 BRCA1 and 61 BRCA2) were identified in 143 carriers (70 BRCA1 and 73 BRCA2) among breast cancer patients, and 11 carriers (5 BRCA1 and 6 BRCA2) were identified among healthy controls. Germline carriers were more likely to be younger, have family history of breast and/or ovarian cancer, have higher grade tumours and for BRCA1 carriers, they were more likely to have breast cancers which are negative for estrogen receptor and ERBB2 receptor. Notably, 45% of breast cancer patients fulfilled the NCCN guidelines for recommendation for genetic counseling and genetic testing, and of these, 80% of carriers fulfill the NCCN guidelines. Taken together, our results show that ~5% of Asian breast cancer patients have pathogenic mutations in BRCA1 or BRCA2, and that germline testing can be cost-effectively delivered to Asian women by focusing primarily on women with early onset breast cancer in the presence of family history of breast and ovarian cancers.
Citation Format: Wei Xiong Wen, Kah Nyin Lai, Jamie Allen, Craig Luccarini, Shivaani Mariapun, Cheng Har Yip, Nur Aishah Mohd Taib, Alison Dunning, Douglas Easton, Soo Hwang Teo. Inherited mutations in BRCA1 and BRCA2 in an unselected multi-ethnic cohort of Asian breast cancer patients and healthy controls from Malaysia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4288. doi:10.1158/1538-7445.AM2017-4288</jats:p
Abstract 1740: Lifestyle determinants of mammographic density in Asian and Caucasian populations: A comparative analysis
No full textAbstract Mammographic density is an independent risk factor for breast cancer and has been shown to differ among populations with varying risk to breast cancer. We sought to compare the distribution of known breast cancer risk factors between an Asian and a Caucasian population, and to determine if the variations in mammographic density between Asian and Caucasian populations can be attributed to the differences in the distribution of these risk factors. 2948 women with no personal history of breast cancer attending an opportunistic screening program in Malaysia (MyMammo) were included in the analysis. Participants were age and BMI matched to 8837 women of the Karolinska Mammography Project for Risk Reduction of Breast Cancer (KARMA) study in Sweden. For analyses involving mammographic density, a subset of Malaysian women with available raw FFDM images (n = 1501) and matched Swedish women (n = 4501) were included for analysis. Volume-based mammographic density measurements for both cohorts were measured using an automated method (Volpara). Descriptive statistics were used to describe the distribution of breast cancer risk factors and mammographic density measures between the two cohorts. General linear models and stepwise selection method were used to determine the risk factors associated with mammographic density within each cohort. Most of the anthropometric, reproductive and lifestyle risk factors examined were differentially distributed between the two cohorts. There was a significantly greater proportion of postmenopausal Swedish women (56%) compared to Malaysian women (51%). Hormone replacement therapy and oral contraceptive ever use was substantially higher among Swedish women (24% and 73%) than Malaysian women (14% and 29%). Mean dense volume was not significantly different between the two cohorts, but Swedish women had a significantly higher mean non-dense volume and lower percent volumetric density compared to Malaysian women. However, pre-menopausal Malaysian women had statistically significant higher dense volume than Swedish women (mean dense volume of 73.9cm3 compared to 70.4cm3). Among post-menopausal women, Malaysian women had significantly lower dense volume than Swedish women (mean dense volume of 54.7cm3 compared to 57.5cm3). In multivariable analyses, age, BMI and parity were associated with dense volume in both cohorts, but regular alcohol intake, height, changes in body shape over time, and menopausal status were only significantly associated with dense volume for Swedish women. In an age and BMI matched cohort, pre-menopausal Asian women had significantly higher dense volume than Caucasian women, whereas, post-menopausal Asian women had lower dense volume than Caucasian women. Population differences in height, body shape changes over time, and alcohol intake could explain, in part, the variation seen in mammographic density, and potentially breast cancer risk, across populations. Citation Format: Nadia Rajaram, Shivaani Mariapun, Mikael Eriksson, Jose Tapia, Pui Yoke Kwan, Weang Kee Ho, Faizah Harun, Nor Aishah Mohd Taib, Per Hall, Soo-Hwang Teo. Lifestyle determinants of mammographic density in Asian and Caucasian populations: A comparative analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1740
Differences in the DNA-Binding Properties of the Hmg-Box Domains of HMG1 and the Sex-Determining Factor SRY
No full textAbstract P2-06-02: A randomized controlled trial of soy isoflavone intake on mammographic density among Malaysian women
No full textAbstract Introduction: Soy intake is associated with lower breast cancer risk in observational studies of Asian women, but clinical trials of soy isoflavone (ISF) supplements report no effect on biomarkers of breast cancer risk among Caucasian women. To date, there are no such trials among Asian women living in Asia. We conducted a three-armed, randomized controlled trial (RCT) to assess the effects of one-year intervention of soy isoflavone supplements (100mg/day) or soy isoflavones through diet (50mg/day) on mammographic density (MD) change among peri- and postmenopausal Malaysian women. Methodology: Healthy women between 45-65 years old were enrolled between November 2018 and December 2019 at a private tertiary hospital in Malaysia. Women were randomly assigned into the 100mg/day ISF Supplement arm, 50mg/day ISF Diet arm, or Control arm. Dense area was assessed from digital mammograms conducted at enrolment and after 12 months. We compared absolute and relative change in dense area over the study period by study arm using Kruskal Wallis tests. Results: Of the 118 women who received the intervention, 91 women completed the study whilst 27 women (23%) were lost to follow up. After 12 months of intervention, women in the ISF Supplement arm observed a marginally larger decline in dense area (-1.3cm2), compared to women in the ISF Diet arm (-0.5cm2) and Control arm (-0.8cm2), but this difference was not statistically significant (p=0.479). Notably, these effects appear to be stronger and limited to women who enrolled within 5 years of menopause, where up to 6cm2 decline in MD was observed in the ISF Supplement arm, compared to < 1.0cm in the Control arm (p=0.131). Conclusion: This RCT demonstrates a possible causal association between soy ISF intake and lower breast cancer risk among Asian women, specifically around the time of menopause, but these findings will require confirmation in a larger trial. Citation Format: Nadia Rajaram, Beverley Yap, Mikael Eriksson, Shivaani Mariapun, Lee Mei Tan, Hamizah Saat, Evelyn Ho, Nur Aishah Mohd Taib, Geok Lin Khor, Cheng Har Yip, Weang Kee Ho, Per Hall, Soo Hwang Teo. A randomized controlled trial of soy isoflavone intake on mammographic density among Malaysian women [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-06-02
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