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- Allaoui, Roni, et al.
(författare)
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Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Triple-negative (TN) breast cancers (ER â ' PR â ' HER2 â ') are highly metastatic and associated with poor prognosis. Within this subtype, invasive, stroma-rich tumours with infiltration of inflammatory cells are even more aggressive. The effect of myeloid cells on reactive stroma formation in TN breast cancer is largely unknown. Here, we show that primary human monocytes have a survival advantage, proliferate in vivo and develop into immunosuppressive myeloid cells expressing the myeloid-derived suppressor cell marker S100A9 only in a TN breast cancer environment. This results in activation of cancer-associated fibroblasts and expression of CXCL16, which we show to be a monocyte chemoattractant. We propose that this migratory feedback loop amplifies the formation of a reactive stroma, contributing to the aggressive phenotype of TN breast tumours. These insights could help select more suitable therapies targeting the stromal component of these tumours, and could aid prediction of drug resistance.
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| 2. |
- Morgan, G, et al.
(författare)
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Abstract P3-02-02: Concordance between immunohistochemical and gene-expression based subtyping of early breast cancer using core needle biopsies and surgical specimens - experices from SCAN-B
- 2018
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Ingår i: Cancer research. Supplement. - 1538-7445. ; 78:4
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Konferensbidrag (refereegranskat)abstract
- Introduction: Preoperative chemotherapy in early breast cancer increases the rate of breast preservation and provides prognostic information. Treatment decisions in these cases rely on biomarker assessments and subtyping from tissue acquired through core needle biopsies. Tumor heterogeneity and representativity are pit-falls when limited tissue is available. Biomarker expression may change considerably as a result of preoperative chemotherapy, and in a subset of cases a complete pathological response at time of surgery may even preclude any further assessment. Therefore, the reliability and reproducibility of biomarkers in base-line core biopsies are of utmost importance for patients treated with preoperative chemotherapy.Material and Methods: In an ongoing population-based study of early breast cancer, the SCAN-B (NCT02306096), patients were identified for whom an ultra-sound guided core needle biopsy was analyzed for biomarkers during primary clinical work-up and the patient was offered primary surgery as initial treatment. Clinical biomarker profiles including immunohistochemical (IHC) determinations of ER, PgR, HER2 and Ki67 were translated to subtypes according to modified St Gallen criteria (2013) and compared with paired samples from surgical specimens. In addition, tumor specimens for biomolecule extraction and RNA sequencing were collected fresh in RNAlater.Results: IHC data was available from 51 paired samples. The subtype distribution in core needle biopsies was DCIS in 1 case (2 %), LCIS in 1 case (2 %) Luminal A-like in 16 cases (31 %), Luminal B-like (HER2 negative) in 26 cases (51 %), Luminal B-HER2-like (HER2 positive) in 4 cases (8 %), HER2-positive (non-luminal) in 1 case (2 %) and triple negative (ductal) breast cancer in 2 cases (4 %). The subtype distribution in surgical specimens was DCIS in 0 case (0 %), LCIS in 1 case (2 %) Luminal A-like in 18 cases (35 %), Luminal B-like (HER2negative) in 23 cases (45 %), Luminal B--like (HER2 positive) in 6 cases (12 %), HER2-positive (non-luminal) in 1 case (2 %) and triple negative (ductal) breast cancer in 2 cases (4 %). Notably, 5/16 cases classified as Luminal A-like in the core needle biopsy were reclassified as Luminal B-like (HER2-negative) in the surgical specimen, whereas 9/26 cases classified as Luminal B-like (HER2-negative) in the core needle biopsy were reclassified as either Luminal A-like (7 cases) or Luminal B-like (HER2 positive) (2 cases) in the surgical specimen. In all instances, except one, transition between Luminal A-like and Luminal B-like was due to recorded Ki67 expression. One case that was classified as a DCIS in the core needle was reclassified as Luminal B-like (HER2 negative) at time of surgery.Discussion: In this limited material, discordance between evaluations regarding Luminal A-like and Luminal B-like was considerable. Especially the misclassification of primary HER2-positive breast cancer needs further evaluation. These findings may be caused by tumor heterogeneity, and highlight the risk of both over- and under-treatment upon biomarker assessment from core needle biopsies. Data from gene expression based subtype classifications will be presented during the meeting.
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