24 research outputs found
Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers
Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as
Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers
Abstract
Introduction
More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers.
Methods
We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement.
Results
The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC)â=â0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICCâ=â0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICCâ=â0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P <10â6 in the analyses by PR status, HER2 status, TN phenotype, morphologic subtypes, histological grade and nodal involvement.
Conclusions
Differences in associations of common BC susceptibility alleles between BRCA1 and BRCA2 carriers and the general population are explained to a large extent by differences in the prevalence of ER-positive and ER-negative tumors. Estimates of the risks associated with these variants based on population-based studies are likely to be applicable to mutation carriers after taking ER status into account, which has implications for risk prediction
The Burden of Breast Cancer Predisposition Variants Across The Age Spectrum Among 10 000 Patients.
BACKGROUND/OBJECTIVES: Women diagnosed with breast cancer (BC) at an older age are less likely to undergo genetic cancer risk assessment and genetic testing since the guidelines and referrals are biased toward earlier age at diagnosis. Thus, we determined the prevalence and type of pathogenic cancer predisposition variants among women with a history of BC diagnosed at the ageâof 65 years or older vs younger than 65âyears.
DESIGN: Prospective registration cohort.
SETTING: The Clinical Cancer Genomics Community Research Network, including 40 community-based clinics in the United States and 5 in Latin America.
PARTICIPANTS: Women with BC and genetic testing results.
MEASUREMENTS: Sociodemographic characteristics, clinical variables, and genetic profiles were compared between women aged 65 years and older andâthose younger than 65âyears at BC diagnosis.
RESULTS: Among 588 women diagnosed with BC and aged 65âyears and older and 9412 diagnosed at younger than 65âyears, BC-associated pathogenic variants (PVs) were detected in 5.6% of those aged 65 years and older (nâ=â33) and 14.2% of those younger than 65âyears (nâ=â1340) (Pâ\u3câ.01). PVs in high-risk genes (eg, BRCA1 and BRCA2) represented 81.1% of carriers among women aged 65âyears and older (nâ=â27) and 93.1% of those younger than 65âyears (nâ=â1248) (Pâ=â.01). BRCA2 PVs represented 42.4% of high-risk gene findings for those aged 65âyears and older, whereas BRCA1 PVs were most common among carriers younger than 65âyears (49.7%). PVs (nâ=â7) in moderate-risk genes represented 21.2% for carriers aged 65 years and older and 7.3% of those younger than 65 years (nâ=â98; Pâ\u3câ.01). CHEK2 PVs were the most common moderate-risk gene finding in both groups.
CONCLUSION: Clinically actionable BC susceptibility PVs, particularly in BRCA2 and CHEK2, were relatively prevalent among older women undergoing genetic testing. The significant burden of PVs for older women with BC provides a critical reminder to recognize the full spectrum of eligibility and provide genetic testing for older women, rather than exclusion based on chronological age alone. J Am Geriatr Soc 67:884-888, 2019
Supplementary Material for: Beurteilung und Förderung der arbeitsbezogenen Selbstwirksamkeitserwartung in der Psychotherapie: Ergebnisse einer SekundÀranalyse einer randomisiert-kontrollierten Studie
Hintergrund: Arbeitsbezogene Selbstwirksamkeitserwartungen (aSW) gelten als PrĂ€diktor fĂŒr eine erfolgreiche RĂŒckkehr an den Arbeitsplatz bei Arbeitnehmenden mit psychischen Störungen. Spezifische Interventionen zur FördeÂrung der aSW existieren bislang jedoch nicht. In der vorliegenden SekundĂ€ranalyse wurde untersucht, ob ein neu entwickeltes kognitiv-imaginatives aSW-Modul geeignet erscheint, (1) imaginative BewĂ€ltigungserfahrungen zu erzeugen, (2) reale BewĂ€ltigungsbestrebungen vorzubereiÂten (Verhaltensrelevanz; VR) und (3) die aSW zu adressieren. Methoden: Das aSW-Modul wurde im Rahmen einer arÂbeitsplatzbezogenen Kurzzeitintervention durchgefĂŒhrt und videographiert (N = 22). Die aSW und Indikatoren fĂŒr imaginative BewĂ€ltigungserfahrungen (IB) sowie fĂŒr die VR wurden anhand der Videoaufzeichnungen durch unabhĂ€ngige Beurteiler:innen eingeschĂ€tzt. ZusĂ€tzlich erfolgten Selbstbeurteilungen der aSW vor Behandlungsbeginn und zum Zeitpunkt des aSW-Moduls. Ergebnisse: Alle IB-Indikatoren (Kooperation, Lebhaftigkeit, emotionale Beteiligung, kognitive FlexibilitĂ€t) waren eher hoch ausgeprĂ€gt. BezĂŒglich der VR-Indikatoren zeigte sich, dass Erkenntnisgewinne modeÂrat, Intentionen fĂŒr VerhaltensĂ€nderungen eher hoch und die Identifikation von erfolgreichen Modellen gering ausgeprĂ€gt waren. Die Fremdberichte der aSW korrelierten mit der selbstberichteten aSW vor Behandlungsbeginn (r = 0,47, p = 0,025) und wĂ€hrend des aSW-Moduls (r = 0,51, p = 0,014). Schlussfolgerung: Im aSW-Modul wurden (1) imaginative BewĂ€ltigungserfahrungen erzeugt, (2) Intentionen fĂŒr VerhaltensĂ€nderungen gefördert und (3) selbstwirkÂsamÂkeitsÂrelevante Kognitionen aktiviert. Es erscheint geeignet zur kognitiv-motivationalen Vorbereitung von BewĂ€ltigungsbestrebungen. Forschungsbedarf besteht hinsichtlich der Effekte des Interventionsmoduls auf reale BewĂ€ltigungsÂerfahrungen und die Entwicklung der aSW