Triple negative breast cancers (TNBCs) were proved to be a heterogeneous disease with a wide spectrum of genomic alterations. TNBC is associated with early recurrence of disease and poor outcome. Recently next generation sequencing (NGS) is entering practice, whether multiple-gene changes have some relevance with TNBC, whether predict heterogeneity, prognostic or chemo-sensitivity of TNBC patients are worthy to be explored.
170 TNBC patients were invited to donate a research blood sample, including 100 patients unselected for family history of breast cancer and 70 patients with neo-adjuvant chemotherapy. For each patient, genomic DNA was extracted from peripheral-blood samples. NGS were used to sequence 115 genes that had cancer risk associations. Medical records were collected and patients were followed up.
Overall, 36 deleterious mutations were identified in 34 patients (20%). Of these, 9.4% had pathogenic mutations in the BRCA1 (5.9%) and BRCA2 (3.5%) genes in 170 patients. Twenty pathogenic variants were detected in other genes except for BRCA1/2 mutations, for a prevalence of 11.8%. The affected genes were PALB2(2.9%), ATM(1.8%), MUTYH(1.8%), BRIP1, CHEK2, GALNT12, HMMR, MSR1, NTRK1, RAD50, SDHC, VHL (0.6%one women).A total of 354 variants of uncertain significance(VUS) were identified in 115 genes among 170 participants.Participants carried an average of 1.6 VUS among 49 genes. Multiple-gene analysis suggests that TNBC patient with a pathogenic germline gene mutation and (or) has multiple-gene mutations has a poor outcome, however, neo-adjuvant chemotherapy is more sensitivity in these patients.
Pathogenic mutations associated with cancer or DNA repair pathways are present at high frequency in patients with TNBC unselected for family history of cancer. VUS is prevalent in TNBCs. TNBC patients with a high level of genomic instability have a relatively poor prognosis, however, sensitive to chemotherapy. Since then, additional studies are required to determine whether neo-adjuvant chemotherapy can improve survival of this group of TNBCs. These results suggest that multiple-gene sequencing may benefit TNBC patients.
Clinical trial identification
Legal entity responsible for the study
National Science and Technology Support Program(No. 2015BAI12B15)
All authors have declared no conflicts of interest.