Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care Poster Display session

210P - Genetic Alterations of Early-Stage Breast Cancers by next-generation sequencing (NGS)

Presentation Number
210P
Lecture Time
12:45 - 12:45
Speakers
  • Yan Xu (Chongqing, CN)
Location
Hall A3 - Poster Area Networking Hub, ICM M√ľnchen, Munich, Germany
Date
22.10.2018
Time
12:45 - 13:45

Abstract

Background

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.

Methods

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.

Results

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.

Signaling PathwaysGenetic AlterationsHR+/ HER2-(29)HER2  + (6)HR+/ HER2 + (6)TNBC(12)
p53TP53145411
PI3K/AKT/mTORPIK3CA12313
AKT16---
PTEN3---
NF11---
FLCN1---
Homologous recombination repairBRCA1(gm)---1
BRCA1(sc)-1--
BRCA2(gm)2---
BRCA2(sc)-1--
ATM(gm)--1-
Ras/Raf/MAPKHRAS1---
KRAS1--1
Cell cycleRB11---
CDKN2A1---
CCND11---
RTKsFGFR11-1-
HER2 CNV-45-
EGFR CNV---1

sc, somatic mutation; gm, germline mutation.

Conclusions

Genetic alterations were highly heterogeneous in different molecular subtypes of early-stage breast cancers. And this may contribute to the different relapse risk.

Legal entity responsible for the study

Geneplus-Beijing.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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