Parkes Amanda, Arun Banu K, Litton Jennifer K
Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston Texas, USA.
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston Texas, USA.
Oncologist. 2017 Jun;22(6):655-666. doi: 10.1634/theoncologist.2016-0430. Epub 2017 May 3.
Hereditary breast cancer syndromes are associated with an increased risk of breast cancer and constitute a unique patient population, making up approximately 5%-10% of breast cancer cases in the United States. By virtue of the germline mutations that define these syndromes, invasive breast cancers in these patients have unique mechanisms that can be rationally targeted for therapeutic opportunities distinct from standard of care treatments in nongermline mutation associated breast cancers. This review intends to describe existing data on several of the most common hereditary breast cancer syndromes, including BRCA-related breast cancer syndrome, Li-Fraumeni syndrome, Cowden syndrome, Peutz-Jeghers syndrome, and hereditary diffuse gastric cancer syndrome, specifically focusing on rational therapeutics utilized in these distinct patient subgroups and completed or ongoing clinical trials evaluating their efficacy. By exploiting the distinct biologic features associated with these syndromes, tailored treatment strategies have the potential for improved efficacy and lower toxicity. Knowledge of the emergence of these targeted cancer therapies is critical for appropriate management in these patients, extending beyond treatment to highlight the need for appropriate genetic screening to allow for early recognition of these patients and therefore appropriate treatment.
Molecular testing allows for identification of germline mutations that place individuals at high risk for breast cancer and that are associated with distinct histopathology and molecular characteristics that define the invasive breast cancer cases that these patients develop. These unique characteristics may ultimately provide rational targets for systemic treatments with improvements in both morbidity and efficacy. Identification of patients with these germline mutations is important for not only appropriate screening and prophylaxis, but knowledge of therapies specifically targeting several of the most common hereditary breast cancer syndromes is essential to ensure appropriate treatment of invasive breast cancers in these patients.
遗传性乳腺癌综合征与乳腺癌风险增加相关，构成了一个独特的患者群体，在美国约占乳腺癌病例的5%-10%。由于定义这些综合征的种系突变，这些患者的浸润性乳腺癌具有独特的机制，可针对这些机制进行合理靶向治疗，从而获得与非种系突变相关乳腺癌的标准治疗不同的治疗机会。本综述旨在描述几种最常见的遗传性乳腺癌综合征的现有数据，包括与BRCA相关的乳腺癌综合征、李-佛美尼综合征、考登综合征、黑斑息肉综合征和遗传性弥漫性胃癌综合征，特别关注这些不同患者亚组中使用的合理治疗方法以及评估其疗效的已完成或正在进行的临床试验。通过利用与这些综合征相关的独特生物学特征，量身定制的治疗策略有可能提高疗效并降低毒性。了解这些靶向癌症治疗方法的出现对于这些患者的适当管理至关重要，不仅涉及治疗，还强调了进行适当基因筛查的必要性，以便早期识别这些患者并因此进行适当治疗。
分子检测能够识别使个体患乳腺癌风险增高的种系突变，这些突变与独特的组织病理学和分子特征相关，这些特征定义了这些患者所患的浸润性乳腺癌病例。这些独特特征最终可能为全身治疗提供合理靶点，从而改善发病率和疗效。识别具有这些种系突变的患者不仅对于适当的筛查和预防很重要，而且了解专门针对几种最常见遗传性乳腺癌综合征的治疗方法对于确保这些患者浸润性乳腺癌的适当治疗至关重要。
