Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Department of Surgical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Expert Rev Mol Diagn. 2023 May;23(5):431-443. doi: 10.1080/14737159.2023.2203815. Epub 2023 Apr 20.
Pathology-supported genetic testing (PSGT) enables transitioning of risk stratification from the study population to the individual.
We provide an overview of the translational research performed in postmenopausal breast cancer patients at increased risk of osteoporosis due to aromatase inhibitor therapy, as the indication for referral. Both tumor histopathology and blood biochemistry levels were assessed to identify actionable disease pathways using whole exome sequencing (WES).
The causes and consequences of inadequate vitamin D levels as a modifiable risk factor for bone loss were highlighted in 116 patients with hormone receptor-positive breast cancer. Comparison of lifestyle factors and WES data between cases with vitamin D levels at extreme upper and lower ranges identified obesity as a major discriminating factor, with the lowest levels recorded during winter. Functional polymorphisms in the vitamin D receptor gene contributed independently to therapy-related osteoporosis risk. In a patient with invasive lobular carcinoma, genetic counseling facilitated investigation of the potential modifying effect of a rare CDH1 variant co-occurring with BRCA1 c.66dup (p.Glu23ArgfsTer18).
Validation of PSGT as a three-pronged pharmacodiagnostics tool for generation of adaptive reports and data reinterpretation during follow-up represents a new paradigm in personalized medicine, exposing significant limitations to overcome.
病理学支持的基因检测（PSGT）使风险分层从研究人群转变为个体。
我们提供了在因芳香酶抑制剂治疗而患有骨质疏松风险增加的绝经后乳腺癌患者中进行的转化研究概述，作为转诊的指征。使用全外显子组测序（WES）评估肿瘤组织病理学和血液生化水平，以识别可操作的疾病途径。
116 例激素受体阳性乳腺癌患者中强调了维生素 D 水平作为可改变的骨质流失风险因素的原因和后果。对极端上下维生素 D 水平的病例进行生活方式因素和 WES 数据比较，确定肥胖是主要的区分因素，冬季记录到的水平最低。维生素 D 受体基因的功能多态性独立导致治疗相关骨质疏松症的风险增加。在一位患有浸润性小叶癌的患者中，遗传咨询促进了对罕见 CDH1 变异与 BRCA1 c.66dup（p.Glu23ArgfsTer18）共同发生的潜在修饰作用的研究。
验证 PSGT 作为生成适应性报告和在随访期间重新解释数据的三管齐下的药物诊断工具代表了个性化医学的新模式，揭示了需要克服的重大局限性。
