Suitable trial designs and cohorts for preventive breast cancer agents
Cet article identifie les raisons expliquant la lente progression de la recherche dans la chimioprévention du cancer du sein
Effective chemoprevention of oestrogen receptor (ER)-positive breast cancer has been shown convincingly using several selective ER modulators and the aromatase inhibitor exemestane. Although these agents are well tolerated and the numbers needed-to-treat in the prevention setting are similar to other established preventive interventions, uptake has been poor in clinical practice because of difficulties in visualizing risk, predicting individual outcomes and measuring treatment benefit. In addition, new agents targeting ER-negative breast cancer are urgently needed. The development of new agents is hampered by the lack of suitable biomarkers and targets, as well as regulatory and financial considerations. Establishing breast cancer chemoprevention in standard clinical practice will require advances in many different fields, including biomarker research, the development of more powerful tools to predict and communicate the risks and benefits of treatments and establishing innovative trial designs. Furthermore, changes in regulatory procedures could reduce the size and cost of trials needed in the prevention setting. Identification of biomarkers for risk and efficacy that are easily accessible, such as blood-based biomarkers, will be key to future chemoprevention strategies. In this Review, we analyse past and current efforts in breast cancer chemoprevention in an attempt to explain why the field of breast cancer chemoprevention is progressing more slowly than was anticipated after early successes with tamoxifen. We identify some of the major obstacles to progress in this field and highlight the prospects for future research.
Nature Reviews Clinical Oncology , résumé, 2012