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. 2017 Jun 27;8:15916. doi: 10.1038/ncomms15916

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Copyright © 2017, The Author(s)

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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(a) Alterations in Rb and cyclin E RNA levels in tumours from patients with breast (n=817), ovary (n=557), lung (n=230), pancreas (n=178), colon (n=379) or prostate (n=333) cancer taken from the TCGA database. (b) Percentage of breast cancer patients exhibiting alterations in Rb and LMWE as determined via immunohistochemical staining of tumour samples from the NCI patient cohort (n=879). (c) Proportion of 109 breast patients treated with palbociclib with Rb+/LMW−, Rb+/LMWE+ or Rb−/LMWE+ status and their disease progression (response to palbociclib). (d,e) Kaplan–Meier curves showing PFS duration (in months) among 109 patients with advanced ER+ breast cancer classified on the basis of their tumoral expression of Rb and cyclin E (d) and separated based on letrozole and fulvestrant (e). Survival curves were censored at disease progression or date of last follow-up. (f) Representative images from immunohistochemical analysis of Rb and LMWE in tumours from patients with ER+ breast cancer treated with palbociclib, classified on the basis of response. Scale bars equal 50 μm and insert scale bars equal 20 μm. (g) C-index of the multivariate cox model with progesterone receptor, prior therapy for metastatic disease only (without Rb) and the addition of Rb and LMWE.