Saikia Kandarpa Kumar, Panigrahi Manoj Kumar, Mehta Anurag, Kumar Dushyant
1Department of Bioengineering and Technology, Gauhati University, Assam, 781014 India.
2Rajiv Gandhi Cancer Institute and research Centre, New Delhi, 110085 India.
Indian J Surg Oncol. 2018 Sep;9(3):381-386. doi: 10.1007/s13193-018-0749-3. Epub 2018 May 3.
pathway is one of the important signaling pathways in cells, which is involved in cell proliferation, cell survival, motility, and growth. Mutation in gene negatively effects to anti-HER2 therapy in breast cancer patients. gene of HER2-positive breast cancers associated with reduced sensitivity to neoadjuvant therapy. In this study, we assessed the frequency of mutations and influence of mutations on patient survival in a series of HER2-positive breast cancer patients. mutations were assessed by pyrosequencing and next generation sequencing in 107 HER2-positive breast cancer patients of a tertiary Cancer Centre of India from Jan 2012 to Jun 2013 with minimum follow-up of 3 years. We found mutations in 26 tumors (24.2%) of which 5 were in exon 9, 20 were in exon 20, and 1 was in both exon 9 and 20. In exon 9, the mutation c.1634A>G was found in 4 cases and mutation c.1636C>A was found in 2 cases. In exon 20, the mutation c.3140A>G was found in 15 cases and c.3140A>T was found in 6 cases. The outcome between mutated versus wild type was significant showing value 0.014. Overall survival of mutation and treatment with herceptin, mutation with other chemotherapy treatment in both early breast cancer (EBC), and locally advanced breast cancer (LABC) showed significant value 0.037 and 0.044 respectively. In conclusion, we identified 24.2% somatic mutation of PIK3CA in HER2-positive breast cancer patients. PIK3CA mutation is significantly associated with ER-positive tumors. The frequency and distribution pattern reported in this study is similar to the global report. Overall survival of PIK3CA mutation is slightly lower but in patients who received herceptin with PIK3CA mutation showed better clinical outcome.
PIK3CA通路是细胞中重要的信号通路之一，参与细胞增殖、细胞存活、运动和生长。PIK3CA基因突变对乳腺癌患者的抗HER2治疗产生负面影响。HER2阳性乳腺癌的PIK3CA基因与新辅助治疗敏感性降低有关。在本研究中，我们评估了一系列HER2阳性乳腺癌患者中PIK3CA基因突变的频率以及PIK3CA基因突变对患者生存的影响。2012年1月至2013年6月期间，对印度一家三级癌症中心的107例HER2阳性乳腺癌患者进行了焦磷酸测序和下一代测序，以评估PIK3CA基因突变情况，这些患者的最短随访时间为3年。我们在26个肿瘤（24.2%）中发现了PIK3CA基因突变，其中5个在外显子9，20个在外显子20，1个在外显子9和20均有突变。在外显子9中，4例发现c.1634A>G突变，2例发现c.1636C>A突变。在外显子20中，15例发现c.3140A>G突变，6例发现c.3140A>T突变。PIK3CA突变型与野生型之间的结果具有显著性，P值为0.014。在早期乳腺癌（EBC）和局部晚期乳腺癌（LABC）中，PIK3CA基因突变患者接受赫赛汀治疗的总生存期以及PIK3CA基因突变联合其他化疗治疗的总生存期，P值分别为0.037和0.044，均具有显著性。总之，我们在HER2阳性乳腺癌患者中鉴定出24.2%的PIK3CA体细胞突变。PIK3CA突变与雌激素受体（ER）阳性肿瘤显著相关。本研究报道的频率和分布模式与全球报告相似。PIK3CA基因突变患者的总生存期略低，但接受赫赛汀治疗的PIK3CA基因突变患者显示出更好的临床结果。
