Abstract 5241: Association of polygenic risk scores with breast cancer risk among women with benign breast disease
Notice bibliographique
Résumé
Abstract Over one million biopsies are performed annually in the U.S. to evaluate suspicious breast lesions. Most biopsies lead to a diagnosis of benign breast disease (BBD) and these women have a 1.5- to fourfold increase in subsequent breast cancer (BC) risk compared with the general population. A polygenic risk score (PRS) including 313 common variants was developed to predict BC risk in the general population and has improved performance when added to existing BC prediction models. However, the value of PRS in risk prediction models among women with BBD has not been evaluated. To evaluate the role of the established PRS, BBD, and BC risk, we pooled data from 15,194 white women (6,706 BC cases and 8,488 controls) participating in five Breast Cancer Association Consortium case-control studies. BC risk associations were evaluated by self-reported BBD history and combinations of PRS expressed in tertiles using odds ratios (OR), considering the lowest category of PRS among women without BBD as the referent. Associations were also assessed in an independent case-cohort study (831 BC cases and 1,845 controls) using hazard ratios (HR). Among the case-control studies, the PRS was strongly associated with BC risk (OR=2.50 per standard deviation increase), and associations were similar in women with (OR=2.60) and without a history of BBD (OR=2.44, p-interaction=0.23). Women with BBD have a higher risk of BC than those without BBD within each level of PRS. Compared to women without BBD and in the lowest PRS category, those with BBD and PRS in the highest tertile had 5-fold increased odds of BC (OR = 5.38; 95% CI 4.73-6.13). Associations were similar in an independent case-cohort study. These findings indicate that BBD history and PRS are independent contributors to BC risk, and consideration of both simultaneously could improve breast cancer risk prediction. Future studies are needed to integrate PRS with other risk measures to refine absolute BC risk prediction among BBD patients. Associations of BC risk with combinations of PRS (tertiles) and history of BBD in five case-control studies and a case-cohort study from the Breast Cancer Association Consortium. Case-control studies Case-cohort study PRS score range History of BBD n BC cases n controls OR (95% CI)1 n BC cases n controls HR (95% CI)2 Tertile 1 (≤ -0.57) No 1009 2692 1.00 (Ref) 117 584 1.00 (Ref) Yes 508 902 1.54 (1.35-1.76) 69 163 2.05 (1.45-2.89) Tertile 2 (-0.58, -0.03) No 1469 2001 1.97 (1.78-2.17) 181 475 1.93 (1.48-2.51) Yes 760 798 2.65 (2.34-3.01) 108 170 2.99 (2.18-4.09) Tertile 3 (≥ -0.02) No 1910 1551 3.32 (3.01-3.67) 214 336 3.28 (2.52-4.26) Yes 1050 544 5.38 (4.73-6.13) 142 117 4.83 4.25-8.02) 1.Logistic regression analysis, adjusted for study site/genomic platform and age at enrollment. OR, odds ratio; CI, confidence interval.2.Cox proportional hazards regression analysis, accounting for the case-cohort study design and adjusted for age at enrollment. HR, hazard ratio; CI, confidence interval. Citation Format: Stacey J. Winham, Mark Sherman, Robert Vierkant, Bryan McCauley, Christopher Scott, Mia Gaudet, Melissa Troester, Sandhya Pruthi, Derek Radisky, Amy Degnim, Kristan Aronson, Rachel Murphy, Pascal Guenel, Therese Truong, Jenny Chang-Claude, Heiko Becher, Montserrat Garcia-Closas, Stephen Chanock, Thomas Ahearn, Xiaohong Yang, Doug Easton, Manjeet Bolla, Celine Vachon, Breast Cancer Association Consortium. Association of polygenic risk scores with breast cancer risk among women with benign breast disease. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5241.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».