Abstract P4-04-14: High mammographic density is associated with deposition of organised fibrillar collagen and increased stiffness in periductal breast stroma
Notice bibliographique
Résumé
Abstract Introduction High mammographic density (MD) in women is strongly associated with breast cancer risk. However the structural and compositional differences between dense and non-dense breast tissues are not well defined. We determined the relationship between MD, collagen deposition and fibril alignment, and tissue micro-stiffness, in similarly aged individuals without adjacent cancer. Methods Fresh tissue samples were collected from post-menopausal women undergoing breast screening. Collagen deposition and fibril organisation were analysed using light microscopy of wax-sections stained with H&E, Trichrome or Picrosirius Red (with polarising light), and quantified using ImageJ. Local tissue stiffness was measured using atomic force microscopy (AFM) of hydrated tissue. For AFM, 3 x 25 µm2 areas of each sample were indented at 400 equally spaced points with a 1 µm diameter spherical probe at a loading rate of 1 Hz (Reduced Modulus; YM). Results Volumetric MD (VolparaTM) was determined in 22 women (54-66y) undergoing risk-reducing surgery or mastectomy. Localised regions of elevated density, determined from digital mammograms, were isolated from patients of low and high overall MD, using a new collaborative workflow linking radiologist, surgeon, pathologist, and tissue biobank. All elevated-density regions contained considerable amounts of stromal connective tissue. However, there were significant differences in these regions from women with low vs high overall MD. Picrosirius Red staining of the localised areas of density revealed that the percentage organised fibrillar collagen content, particularly in the periductal breast stroma, strongly correlated with overall MD. AFM showed that the localised micro-stiffness of dense areas increased significantly in the breast stroma of patients with high overall MD (Volpara score > 15) compared with those of low overall MD (Volpara score < 5). Conclusions High MD is a significant risk factor for breast cancer, yet its molecular determinants in the normal, non-cancerous breast are poorly defined. We have shown that high MD is associated with more organised fibrillar collagen, leading to increased stiffness of the periductal breast stroma. Women with low and high MD all have regions with localised density, which contain both stromal connective tissue and epithelial ducts/lobules. However, our results show that these localised areas have differences in collagen organisation and tissue micro-mechanics. We now hypothesise that in the connective tissue of women with high MD, altered synthesis, deposition and turnover of stromal proteins alters the local biomechanical properties within the breast, providing a stiffer microenvironment, and contributing to cancer onset. Citation Format: Ashu Gandhi, Cliona C Kirwan, James C McConnell, Oliver V O'Connell, Michael J Sherratt, Charles H Streuli. High mammographic density is associated with deposition of organised fibrillar collagen and increased stiffness in periductal breast stroma [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 P4-04-14.
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 | 0,000 | 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,009 | 0,001 |
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 ».