Cancer Research Malaysia, No. 1, Jalan SS12/1A, 47500, Subang Jaya, Malaysia.
University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
Nat Commun. 2020 Dec 22;11(1):6433. doi: 10.1038/s41467-020-20173-5.
Molecular profiling of breast cancer has enabled the development of more robust molecular prognostic signatures and therapeutic options for breast cancer patients. However, non-Caucasian populations remain understudied. Here, we present the mutational, transcriptional, and copy number profiles of 560 Malaysian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to breast tumours in Caucasian women, we show an increased prevalence of HER2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. We also observe elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst HER2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations.
乳腺癌的分子谱分析使乳腺癌患者的更强大的分子预后特征和治疗选择成为可能。然而，非白种人群的研究仍然不足。在这里，我们展示了 560 例马来西亚乳腺癌肿瘤的突变、转录和拷贝数图谱，并对亚洲和白种人女性乳腺癌进行了比较分析。与白种人女性的乳腺癌相比，我们发现 ER+亚洲乳腺癌中 HER2 富集的分子亚型更为普遍，TP53 体细胞突变的发生率更高。我们还观察到亚洲乳腺癌中免疫评分升高，提示对免疫检查点抑制剂有潜在的临床反应。虽然 HER2 亚型和丰富的免疫评分与生存改善相关，但 ER+肿瘤中存在 TP53 体细胞突变与生存较差相关。总之，这些人群差异揭示了改善对该疾病认识的机会，并为不同人群的精准医学奠定了基础。
