Abstract
This study aimed to clarify the genetic difference between Korean triple-negative breast cancer (TNBC) and other breast cancer (BC) subtypes. TNBC was defined as the absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2) amplification. DNA panel of the Ion Torrent Oncomine Comprehensive Assay (OCA) v3 was performed to identify somatic alteration in 48 specimens. In a total of 102 alterations (37 nonsense, 35 missense, 8 frameshift and 22 amplifications), 30 nucleotide alterations (24 nonsense, 1 missense, and 5 frameshift) were newly identified. The eight most commonly altered genes were PIK3CA, TP53, ERBB2, BRCA2, FANCD2, AKT1, BRCA1, and FANCA. TNBC had significantly lower mutation frequency in PIK3CA (TNBC vs. hormone receptor-positive and HER2-negative BC [HRPBC], p = 0.009), but higher mutation frequency in TP53 (TNBC vs. HRPBC, p = 0.036; TNBC vs. hormone receptor-positive and HER2- positive BC [HHPBC], p = 0.004). TNBC showed frequently higher Ki-67 expression than any positive BC (p = 0.004) due to HRPBC (p < 0.001). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 appears at a younger age (52.2 ± 7.6 years), compared to other subtypes (63.7 ± 11.0 years). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 may be related to relatively early onset BCThese findings demonstrate the genomic heterogeneity between TNBC and other BC subtypes and could present a new approach for molecular targeted therapy in TNBC patients.
Highlights
Breast cancer (BC) is the most frequently diagnosed cancer (11.6%) and the leading cause of cancer death (6.6%) among women worldwide [1]
Similar to previous studies [14,22,23], our study demonstrated that TP53 is the most commonly mutated gene, but PIK3CA mutation is rare in triple-negative breast cancer (TNBC)
Our study demonstrates that TNBC with high Ki-67/unmutated PIK3CA/
Summary
Breast cancer (BC) is the most frequently diagnosed cancer (11.6%) and the leading cause of cancer death (6.6%) among women worldwide [1]. The lack of expression of HR and HER2 amplification in TNBC makes it an orphan disease when considering standard therapeutic regimens for BC. An alternative classification divides TNBC into basal-like 1 (BL1), BL2, mesenchymal, and luminal androgen receptor [5]. Even though these subgroups can be further stratified through multi-omics approaches [6], they are largely unknown. Inherited mutations in the BRCA1 and BRCA2 genes as tumor suppressor lead to basal-like BC [7], and many TNBC with intact BRCA1/2 are classified as BRCAness lesions [8]. Combined loss of the TP53 was identified in 30 to 40% of sporadic TNBC [9]
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