Background: Several targeted drugs have been recently approved for the treatment ofPIK3CA-mutated hormone receptor-positive (HR+)/HER2-negative (HER2−) breast cancer (BC). This study aimed at a comprehensive evaluation of the spectrum ofPIK3CAalterations in Russian BC patients. Methods: The tumor material from 1872 patients with ER+/HER2− BC was tested by a combination of PCR-based methods. Results: Mutations were detected in 693/1872 (37%) cases, including 46 BC with twoPIK3CAlesions. The three most common substitutions (E542K, E545K, and H1047R) were identified in 542/693 (78%)PIK3CA-mutated cases, while as many as 5.5–12% of identified mutations were not potentially detectable by common commercial kits. The study included patients of Slavic and non-Slavic ethnicities residing in regions with different climate conditions, however, these factors did not influence the distribution ofPIK3CAmutations. The presence ofPIK3CAvariants was associated with older patient age at diagnosis (p= 0.0002), smaller tumor size (p= 0.005), lower grade (p= 0.005), Ki67 <20% (p= 0.0001) and progesterone receptor-positive status (p= 0.002) at the initial disease diagnosis, and fewer distant metastases at the time of the detection of BC spread (p= 0.0001). In a subgroup of 413 BC patients who received adjuvant tamoxifen or aromatase inhibitors,PIK3CAmutations were not associated with resistance to either type of treatment. Conclusions: The results of this study highlight the need to extend thePIK3CAtesting beyond the hotspot regions of this gene. AlthoughPIK3CAalterations contribute to the pathogenesis of HR+/HER2− BC and represent a target for several novel drugs, they are not intrinsically associated with unfavorable clinical characteristics of this subtype of cancer disease.
背景：近年来，多种靶向药物已获批用于治疗PIK3CA突变的激素受体阳性（HR+）/人表皮生长因子受体2阴性（HER2-）乳腺癌。本研究旨在全面评估俄罗斯乳腺癌患者PIK3CA基因变异谱。方法：采用基于PCR的联合检测方法对1872例ER+/HER2-乳腺癌患者的肿瘤组织进行分析。结果：在693/1872例（37%）患者中检测到突变，其中46例乳腺癌存在双重PIK3CA变异。542/693例（78%）PIK3CA突变病例中发现了三种最常见替换（E542K、E545K和H1047R），而高达5.5-12%的已识别突变可能无法通过常规商业试剂盒检出。研究涵盖了居住在不同气候区域的斯拉夫与非斯拉夫族裔患者，但这些因素均未影响PIK3CA突变的分布特征。PIK3CA变异的存在与以下临床特征显著相关：确诊时年龄更大（p=0.0002）、肿瘤体积更小（p=0.005）、组织学分级更低（p=0.005）、Ki67<20%（p=0.0001）、孕激素受体阳性状态（p=0.002），且在乳腺癌扩散检测时远处转移灶更少（p=0.0001）。在413例接受他莫昔芬或芳香化酶抑制剂辅助治疗的乳腺癌亚组中，PIK3CA突变与两类治疗的耐药性均无关联。结论：本研究结果提示有必要将PIK3CA检测范围扩展至该基因的热点区域之外。尽管PIK3CA变异参与HR+/HER2-乳腺癌的发病机制，并成为多种新型药物的作用靶点，但其本质上与该癌症亚型的不良临床特征无内在关联。
肿瘤(癌症)患者之家