Background: The discordance in oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) status between primary and recurrent breast cancer is being intensively investigated and a large amount of data have been produced. However, results from different studies are heterogeneous and often conflicting. To highlight this issue, a meta-analysis of published data was performed. Methods: A literature search was performed using Medline, and all the studies published from 1983 to 2011 comparing changes in ER, PgR and/or HER2 status in patients with matched breast primary and recurrent tumours were included. We used random-effects models to estimate pooled discordance proportions. Results: We selected 48 articles, mostly reporting retrospective studies. Thirty-three, 24 and 31 articles were focused on ER, PgR and HER2 changes, respectively. A total of 4200, 2739 and 2987 tumours were evaluated for ER, PgR and HER2 discordance, respectively. The heterogeneity between study-specific discordance proportions was high for ER (I 2 = 91%, European Journal of Cancer (2014) 50, 277-289 A v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m ScienceDirectj o u r n a l h o m e p a g e : w w w . e j c a n c e r . c o m p < 0.0001), PgR (I 2 = 79%, p < 0.0001) and HER2 (I 2 = 77%, p < 0.0001). Pooled discordance proportions were 20% (95% confidence interval (CI): 16-35%) for ER, 33% (95% CI: 29-38%) for PgR and 8% (95% CI: 6-10%) for HER2. Pooled proportions of tumours shifting from positive to negative and from negative to positive were 24% and 14% for ER (p = 0.0183), respectively. The same figures were 46% and 15% for PgR (p < 0.0001), and 13% and 5% for HER2 (p = 0.0004). Conclusion: Our findings strengthen the concept that changes in receptor expression may occur during the natural history of breast cancer, suggesting clinical implications and a possible impact on treatment choice.

This study demonstrates that NGS analysis in mCRC is feasible, reveals high level of intra and intertumor heterogeneity, and identifies patients that might benefit of FOLFIRI plus cetuximab treatment.

The prognosis of patients with pancreatic cancer is extremely poor, and current systemic therapies provide marginal survival benefits for treated patients. The era of targeted therapies has offered a new avenue to search for potentially more effective strategies. Epidermal growth factor receptor (EGFR) is a member of the erbB/human epidermal growth factor receptor family of tyrosine kinases, which includes erbB2/HER2, erbB3/HER3 and erbB4/HER4. Epidermal growth factor receptor overexpression may be detected in up to 90% of pancreatic tumors. Two pharmacologic approaches have been successfully used to inhibit epidermal growth factor receptor function in cancer treatment: neutralizing monoclonal antibodies and small molecule tyrosine inhibitors. The randomized trials studying the addition of EGFR targeted agents to gemcitabine compared with gemcitabine alone have been disappointing, although results with the EGFR tyrosine kinase inhibitor erlotinib were statistically significant but clinically of marginal benefit. In this article, we review the epidermal growth factor receptor signaling network in pancreatic cancer, the strategies to increase the effectiveness of epidermal growth factor receptor inhibitors, and the clinical trials of these inhibitors in pancreatic cancer.