Abstract P4-04-12: Both metabolic syndrome and statin use are more common in women with breast inflammation
Bibliographic record
Abstract
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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".