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dc.contributor.authorAzim, HA
dc.contributor.authorPeccatori, FA
dc.contributor.authorBrohee, S
dc.contributor.authorBranstetter, D
dc.contributor.authorLoi, S
dc.contributor.authorViale, G
dc.contributor.authorPiccart, M
dc.contributor.authorDougall, WC
dc.contributor.authorPruneri, G
dc.contributor.authorSotiriou, C
dc.date.accessioned2021-02-12T00:24:04Z
dc.date.available2021-02-12T00:24:04Z
dc.date.issued2015-02-21
dc.identifierpii: s13058-015-0538-7
dc.identifier.citationAzim, H. A., Peccatori, F. A., Brohee, S., Branstetter, D., Loi, S., Viale, G., Piccart, M., Dougall, W. C., Pruneri, G. & Sotiriou, C. (2015). RANK-ligand (RANKL) expression in young breast cancer patients and during pregnancy. BREAST CANCER RESEARCH, 17 (1), https://doi.org/10.1186/s13058-015-0538-7.
dc.identifier.issn1465-5411
dc.identifier.urihttp://hdl.handle.net/11343/260581
dc.description.abstractINTRODUCTION: RANKL is important in mammary gland development during pregnancy and mediates the initiation and progression of progesterone-induced breast cancer. No clinical data are available on the effect of pregnancy on RANK/RANKL expression in young breast cancer patients. METHODS: We used our previously published dataset of 65 pregnant and 130 matched young breast cancer patients with full clinical, pathological, and survival information. 85% of patients had available transcriptomic data as well. RANK/RANKL expression by immunohistochemistry using H-score on the primary tumor and adjacent normal tissue was performed. We examined the difference in expression of RANK/RANKL between pregnant and non-pregnant patients and their association with clinicopathological features and prognosis. We also evaluated genes and pathways associated with RANK/RANKL expression on primary tumors. RESULTS: RANKL but not RANK expression was more prevalent in the pregnant group, both on the tumor and adjacent normal tissue, independent of other clinicopathological factors (both P <0.001). 18.7% of pregnant and 5.3% of non-pregnant patients had tumors showing ≥10% of cells with 3+ RANKL expression. RANKL expression was significantly higher in progesterone receptor-positive, and luminal A-like tumors, with negative correlation with Ki-67 (all P <0.001). On the contrary, RANK expression was higher in triple negative tumors (P <0.001). Using false discovery rate <0.05, 151 and 1,207 genes were significantly correlated with tumor-expressed RANKL and RANK expression by immunohistochemistry, respectively. High RANKL expression within primary tumor was associated with pathways related to mammary gland development, bone resorption, T-cell proliferation and regulation of chemotaxis, while RANK expression was associated with immune response and proliferation pathways. At a median follow-up of 65 months, neither RANK nor RANKL expression within tumor was associated with disease free survival in pregnant or non-pregnant group. CONCLUSIONS: Pregnancy increases RANKL expression both in normal breast and primary tumors. These results could guide further development of RANKL-targeted therapy.
dc.languageEnglish
dc.publisherBMC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleRANK-ligand (RANKL) expression in young breast cancer patients and during pregnancy
dc.typeJournal Article
dc.identifier.doi10.1186/s13058-015-0538-7
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.affiliation.facultyCollected Works
melbourne.source.titleBreast Cancer Research
melbourne.source.volume17
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1070736
melbourne.contributor.authorLoi, Sherene
dc.identifier.eissn1465-542X
melbourne.accessrightsOpen Access


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