Abstract A23: Plasma osteoprotegerin and breast cancer risk in BRCA1 and BRCA2 mutation carriers
Notice bibliographique
Résumé
Abstract Background: There is emerging evidence to suggest that progesterone-mediated upregulation of the receptor activator of nuclear factor κ β (RANK)/RANK ligand (RANKL) signaling pathway plays a critical role in mammary gland epithelial cell proliferation, mammary stem cell expansion and carcinogenesis. Of relevance for women at a high risk of developing breast cancer due to an inherited BRCA mutation, are recent findings showing that circulating levels of osteoprotegerin (OPG) (an endogenous decoy receptor for RANKL and thus inhibitor of RANK/RANKL-mediated signaling) are lower in women with a BRCA1 or BRCA2 mutation compared to non-carriers. Whether low OPG concentrations contribute to the high breast cancer risk in this population is unknown. If so, a therapeutic intervention that mimics the action of OPG might be used for primary prevention. We evaluated the relationship between plasma OPG and breast cancer risk among women with a BRCA1 or BRCA2 mutation in a prospective study. Methods: Baseline blood samples were available from 206 BRCA mutation carriers with no previous history of cancer. Plasma OPG concentrations were measured using a commercial enzyme-linked immunosorbent assay (ELISA) and categorized dichotomously as high vs. low based on the median of the entire cohort. The cumulative incidence of breast cancer by baseline plasma OPG concentration was estimated using Kaplan-Meier survival analysis. Results: Over a mean follow-up period of 6.5 years (range 0.1-18.8 years), 18 incident cases of primary invasive breast cancer were observed in the cohort. Women who developed breast cancer had significantly lower mean baseline OPG concentrations (90.59 pg/ml [range 4.2-205.7 pg/ml]) compared to the OPG concentrations of women who did not develop breast cancer ((117.9 pg/ml [7.4-547.7]) (P = 0.04). BRCA mutation carriers with low baseline OPG concentrations (< 95 pg/ml) had a significantly higher risk of developing breast cancer compared to those with high baseline OPG concentrations (≥95 pg/ml). After ten years of follow-up, the cumulative incidence of breast cancer among women with low OPG concentrations was 21% compared to 9% among women with high OPG concentrations (P-log rank test = 0.046). There was no evidence of effect modification by menopausal status or BRCA mutation type. After multivariate adjustment, women with high plasma OPG had a significantly decreased risk of developing breast cancer, compared to women with low OPG (HR = 0.25; 95%CI 0.08-0.78; P = 0.02). Conclusions: Our preliminary data suggest that low OPG concentrations are associated with an increased risk of breast cancer in BRCA1 and BRCA2 mutation carriers. These data support the potential for targeting of the RANKL pathway as a plausible cancer prevention strategy among women with germline BRCA mutations. Additional analyses with a larger sample size are underway and may help inform strategies of personalized prevention. These findings will not only further our understanding of the progesterone/OPG/RANKL pathway in breast cancer development, but will improve our identification of high-risk populations that can be targeted by prevention options that are currently available (i.e., denosumab) to simultaneously prevent breast cancer development and maintain bone health (particularly after salpingo-oophorectomy). Citation Format: Leonardo Salmena, Lovisa Oden, Shana Kim, Mohammad Akbari, Ping Sun, Steven Narod, Joanne Kotsopoulos. Plasma osteoprotegerin and breast cancer risk in BRCA1 and BRCA2 mutation carriers. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr A23.
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 | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 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) | 0,003 | 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 ».