Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women. Patients diagnosed with early stage generally have better survival. However, disease free survival differed significantly for different molecular subtypes. Understanding the genetic alterations of early-stage breast cancer may help to identify patients at high risk for relapse.
We retrospectively reviewed genetic profiling of 53 early-stage breast cancer samples in our institute. Surgical specimens were analyzed using hybridization capture-based NGS ER-seq method, white blood cells as control, which enables simultaneously assess single-nucleotide variants (SNV), insertions/deletions (indel), rearrangements and somatic copy-number variation(CNV) of 1021 genes.
Fifty-three surgical specimens from 51 female patients with early-stage breast cancer were analyzed, including two bilateral primary breast cancers with different molecular subtypes. There were 29 HR+/HER2-, 6 HER2+, 6 HR+/HER2+ and 12 TNBC. The median diagnosis age was 43(range 31-67). In addition to TP53, there were 16 genes carried actionable mutations identified (details in table). The most frequently mutant genes were TP53 and PIK3CA, in all molecular subtypes. Among PIK3CA mutations, the H1047R/L were tested in all subtypes. Other gene alterations were highly heterogeneous in different molecular subtypes. HRAS or KRAS mutation was always identified with other genes. For instance, HRAS/PIK3CA and KRAS/AKT1 concurrent in 2 HR+/HER2-, KRAS/PIK3CA concurrent in 1 TNBC. Interestingly, for the two bilateral primary breast cancers, one patient had no overlapping mutation in 2 samples within total 6 variants, the other one only had common HER2 CNV in 2 samples within total 13 variants. sc, somatic mutation; gm, germline mutation.
Signaling Pathways Genetic Alterations HR+/ HER2-(29) HER2 + (6) HR+/ HER2 + (6) TNBC(12) p53 TP53 14 5 4 11 PI3K/AKT/mTOR PIK3CA 12 3 1 3 AKT1 6 - - - PTEN 3 - - - NF1 1 - - - FLCN 1 - - - Homologous recombination repair BRCA1(gm) - - - 1 BRCA1(sc) - 1 - - BRCA2(gm) 2 - - - BRCA2(sc) - 1 - - ATM(gm) - - 1 - Ras/Raf/MAPK HRAS 1 - - - KRAS 1 - - 1 Cell cycle RB1 1 - - - CDKN2A 1 - - - CCND1 1 - - - RTKs FGFR1 1 - 1 - HER2 CNV - 4 5 - EGFR CNV - - - 1
sc, somatic mutation; gm, germline mutation.
Genetic alterations were highly heterogeneous in different molecular subtypes of early-stage breast cancers. And this may contribute to the different relapse risk.
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All authors have declared no conflicts of interest.