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  • American Society of Clinical Oncology (ASCO)  (3)
  • 1
    Online Resource
    Online Resource
    Constitutional BRCA1 methylation and risk of incident triple-negative breast cancer and high-grade serous ovarian cancer.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 10509-10509
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 10509-10509
    Abstract: 10509 Background: About 25% of all triple-negative breast cancer (TNBC) and 10–20% of high-grade serous ovarian cancers (HGSOC) harbor BRCA1 promoter methylation. While constitutional BRCA1 promoter methylation has been observed in normal tissues of some individuals, the potential role of normal tissue methylation as a risk factor for incident TNBC or HGSOC risk is unknown. Methods: The objective of this study was to assess potential correlation between white blood cell (WBC) BRCA1 promoter methylation and subsequent risk of incident TNBC and HGSOC. To do so, we analyzed samples from women participating in the Women’s Health Initiative (WHI) study who had not been diagnosed with either breast or ovarian cancer prior to study entrance. A total of n = 636 women developing incident TNBC and 509 women developing incident HGSOC were matched with cancer-free controls (n = 1838 and 2979) in a nested case-control design. Cancers were confirmed after central medical record review. Blood samples, collected at entry, were analyzed for BRCA1 promoter methylation by massive parallel sequencing. Associations between BRCA1 methylation and incident TNBC and incident HGSOC were analyzed by unconditional logistic regression. Results: Age at entry was 62 (median; range 50 to 79) years, with median interval to diagnosis of 9 (TNBC) and 10 (HGSOC) years. The presence of methylated BRCA1 alleles was significantly associated with higher risk of incident TNBC (OR 2.44, 95% CI 1.79–3.33; P 〈 .001) and incident HGSOC (OR 1.87, 95% CI 1.32–2.61; P 〈 .001). Restricting analyses to individuals with 〉 5 years between sampling and cancer diagnosis yielded similar results ( 〉 5 years; TNBC: OR 2.53, 95% CI 1.81–3.54; P 〈 .001; HGSOC: OR 1.81, 95% CI 1.21–2.63; P =.003). Across individuals, methylation was not haplotype-specific, arguing against an underlying cis-acting factor. Within individuals, BRCA1 methylation was observed on the same allele, indicating clonal expansion from a single methylation event. Conclusions: Constitutional normal tissue BRCA1 promoter methylation is significantly associated with risk of incident TNBC and HGSOC with implications for prediction of these cancers not associated with germline mutations. These findings warrant further research to determine if constitutional methylation of tumor suppressor genes are pan-cancer risk factors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.10509
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    Estrogen Alone in Postmenopausal Women and Breast Cancer Detection by Means of Mammography and Breast Biopsy
    American Society of Clinical Oncology (ASCO) ; 2010
    In:  Journal of Clinical Oncology Vol. 28, No. 16 ( 2010-06-01), p. 2690-2697
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 28, No. 16 ( 2010-06-01), p. 2690-2697
    Abstract: As the influence of estrogen alone on breast cancer detection is not established, we examined this issue in the Women's Health Initiative trial, which randomly assigned 10,739 postmenopausal women with prior hysterectomy to conjugated equine estrogen (CEE; 0.625 mg/d) or placebo. Methods Screening mammography and breast exams were performed at baseline and annually. Breast biopsies were based on clinical findings. Effects of CEE alone on breast cancer detection were determined by using receiver operating characteristic (ROC) analyses of mammogram performance. Results After a 7.1-year mean follow-up, fewer invasive breast cancers were diagnosed in the CEE than in the placebo group, but the difference was not statistically significant. Use of CEE alone increased mammograms with short-interval follow-up recommendations (cumulative, 39.2% v 29.6.3%; P 〈 .001) but not abnormal mammograms (ie, those suggestive of or highly suggestive of malignancy; cumulative, 7.3% v 7.0%; P = .41). Breast biopsies were more frequent in the CEE group (cumulative, 12.5% v 10.7%; P = .004) and less commonly diagnosed as cancer (8.9% v 15.8%, respectively, with positive biopsies; P = .04). Mammographic breast cancer detection in the CEE group was significantly compromised only in the early years of use. Conclusion CEE alone use for 5 years results in approximately one in 11 and one in 50 women having otherwise avoidable mammograms with short-interval follow-up recommendations or breast biopsies, respectively. Although the breast biopsies on CEE were less commonly diagnosed as cancer, breast cancer detection was not substantially compromised. These findings differ from estrogen-plus-progestin use, for which significantly increased abnormal mammograms and a compromise in breast cancer detection are seen.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2009.24.8799
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2010
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
  • 3
    Online Resource
    Online Resource
    Insulin, Physical Activity, and Caloric Intake in Postmenopausal Women: Breast Cancer Implications
    American Society of Clinical Oncology (ASCO) ; 2004
    In:  Journal of Clinical Oncology Vol. 22, No. 22 ( 2004-11-15), p. 4507-4513
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 22, No. 22 ( 2004-11-15), p. 4507-4513
    Abstract: Increased physical activity and programs to reduce body mass index (BMI) with both increased physical activity and decreased caloric intake have been proposed to reduce insulin as a potential mediator of breast cancer and other chronic diseases. However, there are few data on the relative contribution of physical activity, caloric intake, and BMI to fasting insulin levels. Materials and Methods An ethnically diverse subsample of 2,996 mostly healthy postmenopausal women with no prior cancer history was randomly identified from the 161,809 participants in the Women's Health Initiative clinical trials and observational study. Information was collected on diet, recreational physical activity, and anthropometrics including BMI. Fasting insulin levels were determined. Using a cross-sectional design, insulin levels were then compared across quintiles of caloric intake and physical activity in linear regression model analyses controlled for BMI and other factors. Results Lower BMI (P 〈 .0001), higher levels of physical activity (P 〈 .0001), and lower caloric intake (P 〈 .02) were all independently associated with significantly lower mean fasting insulin levels throughout the range of observed values. Insulin levels of 8.74 μU/mL ± 4.16 SD were seen in the highest physical activity and lowest caloric intake quintile compared with insulin levels of 15.08 μU/mL ± 16.32 SD in the lowest physical activity and highest caloric intake quintile (P 〈 .0001). Conclusion These findings suggest that reduction in BMI achieved by increasing physical activity, reducing caloric intake, or both, should lower insulin levels, providing support for clinical trials evaluating insulin level change and breast cancer risk.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2004.04.119
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2004
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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