Endpoints in advanced breast cancer: methodological aspects & clinical implications.

Breast cancer is an increasingly important public health problem in developing countries, with disproportionately high mortality. The increasing availability of active agents against advanced breast cancer makes the development of novel treatments and their choice in clinical practice progressively more complex. Furthermore, there is often a tension between the adequacy of endpoints used in clinical trials and the clinician's aim of improving survival and quality of life, the two most important therapeutic goals in advanced breast cancer. However, overall survival (OS) is no longer a suitable indicator of treatment efficacy within clinical trials in settings for which effective subsequent-line therapy exists. Conversely, progression-free survival (PFS) currently represents the most sensitive parameter to assess the efficacy of a new drug or combination in such settings. When coupled with a favourable toxicity profile and cost, the demonstration of an improved PFS may be enough evidence for the superiority of a treatment. Despite arguments favouring the use of PFS as a primary endpoint in clinical trials, clinicians who need to make sense of the available literature may be reluctant to use PFS as an indicator of clinical benefit when deciding among different therapeutic strategies for their patients. This choice is further complicated if one fails to distinguish between the use of an efficacy parameter as an indicator of therapeutic objective for individual patients and as a clinical trial endpoint. This brief review aims at helping clinicians in their daily need to interpret the literature and make informed treatment choices for patients with advanced breast cancer.