Performance of the IBIS/Tyrer-Cuzick (TC) Model by race/ethnicity in the Women’s Health Initiative.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1503-1503
Author(s):  
Allison W. Kurian ◽  
Elisha Hughes ◽  
Ryan Bernhisel ◽  
Braden Probst ◽  
Jerry Lanchbury ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Assessment ◽  
Assessment Tool ◽  
Health Initiative ◽  
Menopausal Women ◽  
Race Ethnicity ◽  
Asian Pacific ◽  
Post Menopausal ◽  
Tc Model

1503 Background: The TC model, a breast cancer (BC) risk assessment tool based on family cancer history, reproductive and lifestyle factors is used to guide BC screening and prevention. TC was developed and validated largely in non-Hispanic White (NHW) women. We evaluated the calibration and discrimination of TC version 7.02 among racially/ethnically diverse post-menopausal women enrolled in the Women’s Health Initiative (WHI) clinical trials or observational study. Methods: WHI enrolled post-menopausal women from 1993-1998 and followed them prospectively for BC incidence. We included women aged ≤80 years at enrollment with no prior BC or mastectomy and with data required for TC, including weight, height, ages at menarche, first birth and menopause, menopausal hormone therapy use and family history of breast or ovarian cancer in first or second-degree relatives. Calibration was assessed by the ratio of observed BC cases to the number expected by TC (O/E), with expected cases calculated as the sum of cumulative hazards. We tested for differential discrimination by race/ethnicity (NHW, African American, Hispanic, Asian/Pacific Islander, Native American, other) using Cox regression. Time to BC was modeled using age, race/ethnicity, TC estimate (transformed by log of relative lifetime risk), and a term for interaction between race/ethnicity and TC estimate. Results: During the follow-up period (median 18.9 years, maximum 23.4 years), 6,836 new BC cases were diagnosed among 91,893 women. TC was well-calibrated overall (O/E 0.95) in NHW and African Americans, but over-estimated risk for Hispanics (O/E 0.75, Table). Results suggested good calibration for Asian/Pacific Islanders and Native Americans, but sample sizes were small. Discrimination did not differ significantly by race/ethnicity (two-sided p-value for interaction = 0.33). Conclusions: TC provided similar risk discrimination among post-menopausal women of different racial/ethnic groups over nearly 20 years of follow-up; however, it overestimated risk for Hispanics. Future studies in diverse populations are warranted, with need for a more accurate breast cancer risk assessment tool for Hispanics. [Table: see text]

Prevalence and penetrance of breast cancer-associated mutations identified by multiple-gene sequencing in the Women’s Health Initiative.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1513-1513
Author(s):  
Allison W. Kurian ◽  
Elisha Hughes ◽  
Ryan Bernhisel ◽  
Katie Larson ◽  
Jennifer Lee Caswell-Jin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Women's Health ◽  
Cancer Patients ◽  
Cancer Susceptibility ◽  
Breast Cancer Patients ◽  
Women's Health Initiative ◽  
Health Initiative ◽  
Menopausal Women ◽  
Post Menopausal ◽  
The Women’S Health Initiative

1513 Background: Next-generation sequencing enables rapid analysis of many inherited cancer susceptibility genes. Little is known about the prevalence and penetrance of pathogenic variants (PVs) in such genes among post-menopausal women with breast cancer, who comprise the majority of all breast cancer patients. Methods: The Women’s Health Initiative enrolled post-menopausal women from 1993-1998. We conducted a nested case-control study using banked DNA samples of 2,195 women who subsequently developed invasive breast cancer (cases) and 2,322 cancer-free controls. Sequenced genes were APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A (p16INK4a and p14ARF) , CHEK2, EPCAM, GREM1, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, POLD1, POLE, PTEN, RAD51C, RAD51D, SMAD4, STK11, and TP53. PV were defined using American College of Medical Genetics criteria. PV prevalence is reported as proportions and penetrance as the odds ratio (OR) and 95% confidence interval (CI) of PV versus none among cases versus controls. Results: Among cases, the median age at diagnosis was 73 years; 66% were White, 18% Black, 6% Hispanic, 6% Asian and 4% other. The prevalence of PVs in any gene was significantly higher in cases (6.61%, 95% CI 5.57-7.65%) versus controls (4.09%, 95% CI 3.29-4.90%). The prevalence of BRCA1/2 PVs was 1.2% in cases and 0.22% in controls. Among cases, the prevalence of PVs in other breast cancer-risk genes was 2.3% ( ATM, CDH1, BARD1, BRIP1, CHEK2, NBN, and PALB2 collectively), two-fold higher than PVs in BRCA1/2. Prevalence of BRCA1/2 PVs decreased with age among cases, while prevalence of ATM, CHEK2 and PALB2 PVs did not. Statistically significant ORs for breast cancer penetrance were observed for BRCA1 (5.43, 95% CI 1.19-51.52), BRCA2 (4.71, 95% CI 1.84-15.08), BARD1 (9.78, 95% CI 1.04-1295.87) and PALB2 (6.30, 95% CI 1.93-31.94). Conclusions: Approximately 7% of women diagnosed with post-menopausal breast cancer carry a PV in a cancer susceptibility gene. In contrast to studies of younger breast cancer patients, PVs in other breast cancer-related genes were two times more common than in BRCA1/2. Results may guide genetic testing of women with post-menopausal breast cancer.

scholarly journals Risk assessment in precapillary pulmonary hypertension: a comparative analysis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Thomas Sonnweber ◽  
Eva-Maria Schneider ◽  
Manfred Nairz ◽  
Igor Theurl ◽  
Günter Weiss ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Pulmonary Hypertension ◽  
High Risk ◽  
Risk Stratification ◽  
Risk Prediction ◽  
Mortality Risk ◽  
Assessment Tool ◽  
Risk Models ◽  
Non Invasive

Abstract Background Risk stratification is essential to assess mortality risk and guide treatment in patients with precapillary pulmonary hypertension (PH). We herein compared the accuracy of different currently used PH risk stratification tools and evaluated the significance of particular risk parameters. Methods We conducted a retrospective longitudinal observational cohort study evaluating seven different risk assessment approaches according to the current PH guidelines. A comprehensive assessment including multi-parametric risk stratification was performed at baseline and 4 yearly follow-up time-points. Multi-step Cox hazard analysis was used to analyse and refine risk prediction. Results Various available risk models effectively predicted mortality in patients with precapillary pulmonary hypertension. Right-heart catheter parameters were not essential for risk prediction. Contrary, non-invasive follow-up re-evaluations significantly improved the accuracy of risk estimations. A lack of accuracy of various risk models was found in the intermediate- and high-risk classes. For these patients, an additional evaluation step including assessment of age and right atrium area improved risk prediction significantly. Discussion Currently used abbreviated versions of the ESC/ERS risk assessment tool, as well as the REVEAL 2.0 and REVEAL Lite 2 based risk stratification, lack accuracy to predict mortality in intermediate- and high-risk precapillary pulmonary hypertension patients. An expanded non-invasive evaluation improves mortality risk prediction in these individuals.

scholarly journals 82P Risk factors for breast cancer: A case-control study among post-menopausal women in Pakistan

2016 ◽  
Vol 27 ◽  
pp. ix24
Author(s):  
N.A. Jadoon ◽  
M. Hussain ◽  
F.U. Sulehri ◽  
A. Zafar ◽  
A. Ijaz
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Case Control Study ◽  
Case Control ◽  
Menopausal Women ◽  
Post Menopausal ◽  
Control Study

scholarly journals Endogenous hormones and risk of invasive breast cancer in pre- and post-menopausal women: findings from the UK Biobank

2021 ◽  
Author(s):  
Sandar Tin Tin ◽  
Gillian K. Reeves ◽  
Timothy J. Key
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Invasive Breast Cancer ◽  
Cox Regression ◽  
Menopausal Status ◽  
Endogenous Hormones ◽  
Uk Biobank ◽  
Menopausal Women ◽  
Post Menopausal

Abstract Background Some endogenous hormones have been associated with breast cancer risk, but the nature of these relationships is not fully understood. Methods UK Biobank was used. Hormone concentrations were measured in serum collected in 2006–2010, and in a repeat subsample (N ~ 5000) in 2012–13. Incident cancers were identified through data linkage. Cox regression models were used, and hazard ratios (HRs) corrected for regression dilution bias. Results Among 30,565 pre-menopausal and 133,294 post-menopausal women, 527 and 2,997, respectively, were diagnosed with invasive breast cancer during a median follow-up of 7.1 years. Cancer risk was positively associated with testosterone in post-menopausal women (HR per 0.5 nmol/L increment: 1.18; 95% CI: 1.14, 1.23) but not in pre-menopausal women (pheterogeneity = 0.03), and with IGF-1 (insulin-like growth factor-1) (HR per 5 nmol/L increment: 1.18; 1.02, 1.35 (pre-menopausal) and 1.07; 1.01, 1.12 (post-menopausal); pheterogeneity = 0.2), and inversely associated with SHBG (sex hormone-binding globulin) (HR per 30 nmol/L increment: 0.96; 0.79, 1.15 (pre-menopausal) and 0.89; 0.84, 0.94 (post-menopausal); pheterogeneity = 0.4). Oestradiol, assessed only in pre-menopausal women, was not associated with risk, but there were study limitations for this hormone. Conclusions This study confirms associations of testosterone, IGF-1 and SHBG with breast cancer risk, with heterogeneity by menopausal status for testosterone.

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