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

Abstract

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.

摘要

乳腺癌是全球女性最常见的癌症, 其发病率、死亡率和经济影响巨大。预防乳腺癌是全球公共卫生的当务之急。迄今为止, 我们在全球范围内的大部分努力都是针对扩大人群乳腺癌筛查计划, 进行早期癌症检测, 而不是乳腺癌预防工作。我们必须改变这种模式。与其他疾病一样, 预防乳腺癌从识别高危个体开始, 对于乳腺癌, 这需要更好地识别携带与乳腺癌高风险相关的遗传性癌症突变的个体, 并识别由于非遗传、既定的可改变和不可改变的因素而处于高风险的其他人。本文将对乳腺癌的基本遗传学和与风险增加相关的最常见的遗传性乳腺癌突变进行综述。我们还将讨论其他非遗传修饰和不可改变的乳腺癌风险因素、可用的风险评估模型, 以及在临床实践中纳入基因突变携带者筛查和识别高危女性的方法。对高危妇女强化筛查、化学预防和外科治疗指南的讨论超出了本综述的范围。

Keywords:

• Breast cancer
• hereditary cancer mutation
• genetics
• risk assessment

Potential conflict of interest

Nil.

Source of funding

Nil.