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The article focuses on the androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. According to the authors, treatment for advanced or metastatic prostate cancer has relied on androgen-deprivation therapy (ADT) for the past 50 years. At present, few treatment options offer effective relief for patients who develop resistance to ADT. Here the authors describe described how prostate cancer growth is stimulated in response to androgens, and consequently how ADT acts to combat this. They also explain how modifications to the androgen receptor (AR) via mutations, amplification and phosphorylation may affect the development of androgen escape.

Overdiagnosis, and thus overtreatment, are inevitable consequences of most screening programmes; identification of ways of minimising the impact of overdiagnosis demands new prospective research, in particular the need to separate clinically relevant lesions that require active treatment from those that can be safely left alone or monitored and only need treated if they change characteristics. Breast cancer screening has led to a large increase in ductal carcinoma in situ (DCIS) diagnoses. This is a widely heterogeneous disease and most DCIS detected through screening is of high cytonuclear grade and therefore likely to be important clinically. However, the historic practice of surgical treatment for all DCIS is unlikely to be optimal for lower risk patients. A clearer understanding of how to manage DCIS is required. This article describes the background and development of ‘The low risk’ DCIS trial (LORIS), a phase III trial of surgery versus active monitoring. LORIS will determine if it is appropriate to manage women with screen detected or asymptomatic, low grade and intermediate grade DCIS with low grade features, by active monitoring rather than by surgical treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background: Multiple studies suggest better efficacy of chemotherapy in invasive ductal breast carcinomas (IDC) than invasive lobular breast carcinomas (ILC). However, data on efficacy of adjuvant endocrine therapy regimens and histological subtypes are sparse. This study assessed endocrine therapy efficacy in IDC and ILC. The influence of semi-quantitative oestrogen receptor (ER) expression by Allred score was also investigated. Methods: Dutch and Belgian patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial were randomized to exemestane (25mg daily) alone or following tamoxifen (20mg daily) for 5years. Inclusion was restricted to IDC and ILC patients. Histological subtype was assessed locally; ER expression was centrally reviewed according to Allred score (ER-poor (<7; n =235); ER-rich (⩾7; n =1789)). Primary end-point was relapse-free survival (RFS), which was the time from randomization to disease relapse. Findings: Overall, 2140 (82%) IDC and 463 (18%) ILC patients were included. RFS was similar for both endocrine treatment regimens in IDC (hazard ratio (HR) for exemestane was 0.83 (95%confidence interval (CI) 0.67–1.03)), and ILC (HR 0.69 (95%CI 0.45–1.06)). Irrespective of histological subtype, patients with ER-rich Allred scores allocated to exemestane alone had an improved RFS (multivariable HR 0.71 (95%CI 0.56–0.89)). In contrast, patients with ER-poor Allred scores allocated to exemestane had a worse RFS (multivariable HR 2.33 (95%CI 1.32–4.11)). Significant effect modification by ER-Allred score was confirmed (multivariable p =0.003). Interpretation: Efficacy of endocrine therapy regimens was similar for IDC and ILC. However, ER-rich patients showed superior efficacy to upfront exemestane, while ER-poor patients had better outcomes with sequential therapy, irrespective of histological subtype, emphasising the relevance of quantification of ER expression. Funding: The Dutch/Belgian TEAM trial is supported by an unrestricted research grant from Pfizer. The sponsors have in no way influenced the design and conduct of the study, collection, management, analysis and interpretation of the data and preparation, review or approval of the manuscript. [Copyright &y& Elsevier]