Breast cancer genetics and risk assessment: an overview for the clinician

Breast cancer is the most common cancer in women globally with enormous associated morbidity, mortality and economic impact. Prevention of breast cancer is a global public health imperative. To date, most of our global efforts have been directed at expanding population breast cancer screening programs for early cancer detection and not at breast cancer prevention efforts. It is imperative that we change the paradigm. As with other diseases, prevention of breast cancer starts with identification of individuals at high risk, and for breast cancer this requires improved identification of individuals who carry a hereditary cancer mutation associated with an elevated risk of breast cancer, and identification of others who are at high risk due to non-genetic, established modifiable and non-modifiable factors. This article will review basic breast cancer genetics and the most common hereditary breast cancer mutations associated with increased risk. We will also discuss the other non-genetic modifiable and non-modifiable breast cancer risk factors, available risk assessment models and an approach to incorporating screening for genetic mutation carriers and identifying high-risk women in clinical practice. A discussion of guidelines for enhanced screening, chemoprevention and surgical management of high-risk women is beyond the scope of this review.