Abstract P4-04-12: Both metabolic syndrome and statin use are more common in women with breast inflammation
Notice bibliographique
Résumé
Abstract Background: Metabolic syndrome is associated with increased breast cancer (BC) risk. After menopause, obesity is associated with increased risk of hormone receptor (HR)-positive breast cancer. We demonstrated an obesity → inflammation → aromatase axis in breast white adipose tissue (WAT) where inflammation is defined by the presence of crown-like structures (CLS) consisting of a dead or dying adipocyte encircled by macrophages. CLS in the breast (CLS-B) are associated with elevated body mass index (BMI), postmenopausal status, increased adipocyte size, and increased tissue levels of proinflammatory mediators and aromatase. As obesity is a component of the metabolic syndrome and is associated with inflammation, we compared levels of relevant circulating factors in women with and without breast WAT inflammation. Methods: We prospectively collected paired WAT and fasting serum and plasma from women undergoing mastectomy at MSKCC. WAT inflammation was detected by CD68 immunohistochemistry to identify CLS-B by light microscopy. Plasma levels of glucose, insulin, hsCRP, leptin, adiponectin, and IL-6 were measured by ELISA. Serum levels of total cholesterol, triglycerides (TG), HDL and LDL cholesterol were determined. Insulin resistance (IR) was assessed using fasting plasma glucose and insulin levels via the updated Homeostasis Model Assessment (HOMA2-IR). Associations between CLS-B and clinicopathologic features, including medication usage, were analyzed by logistic regression and Fisher’s exact test. Differences in serum/plasma endpoints between subjects with and without CLS-B were evaluated using Student t-test and nonparametric Wilcoxon rank-sum test. Results: From 11/2011 – 3/2013 we accrued 100 patients (pts); median age 47 years (range 27 – 70). Overall, CLS-B were found in 52/100 (52%) pts: 18/19 (95%) obese pts, 17/33 (52%) overweight pts, and 17/48 (35%) normal BMI pts. A clinical diagnosis of dyslipidemia was present in 14/52 (27%) pts with CLS-B and 1/48 (2%) pts without CLS-B (P<0.001). CLS-B were found in 10/11 (91%) statin users, but in only 42/89 (47%) non-users (P=0.008). Fasting glucose, insulin, LDL, TG, leptin, hsCRP, and IL-6 levels were higher in pts with CLS-B (Table). HOMA2-IR was greater in pts with CLS-B (mean 0.63 ±0.34) versus those without CLS-B (mean 0.46 ±0.23; P=0.006). Fasting level, mean (SD)No CLS-B, N=48CLS-B +, N=52PGlucose, mg/dL73.2 (8.0)84.3 (37.6)0.04Insulin, mU/L4.3 (2.1)5.6 (2.9)0.01LDL cholesterol, mg/dL105.9 (31.0)119.4 (32.4)0.04HDL cholesterol, mg/dL71.9 (15.8)62.1 (16.1)0.003Triglycerides, mg/dL69.2 (26.3)104.9 (50.6)<0.001Leptin, pg/mL12.0 (10.1)22.6 (19.7)<0.001Adiponectin, ng/mL13.7 (5.2)10.4 (5.4)0.002hsCRP, ng/mL1.0 (1.4)2.3 (2.7)0.003 Conclusions: Breast WAT inflammation, which we have previously linked to increased aromatase activity, is associated with biochemical changes that occur in the metabolic syndrome, a risk factor for BC. Statin use is more common in patients with breast WAT inflammation and metabolic syndrome. Clinically, statin use may be a surrogate identifier of a population that is at increased baseline risk of BC. These findings may account for the variability in results of prior studies examining statin use and breast cancer risk due to elevated risk in users compared to non-users. Citation Format: Neil M Iyengar, Ayca Gucalp, Xi K Zhou, Louise R Howe, Patrick G Morris, Dilip Giri, Kotha Subbaramaiah, Priya Bhardwaj, Samuel S Park, Michael Pollak, Monica Morrow, Clifford A Hudis, Andrew J Dannenberg. Both metabolic syndrome and statin use are more common in women with breast inflammation [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-12.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».