To confirm that stage III BRCA1-like breast cancer (BC) is highly sensitive to ... number profile of a breast tumor is similar to that of BRCA1 mutated BCs.3.
San Antonio Breast Cancer Symposium December 5-9, 2017 OT2-07-08
Substantially Improving the cure rate of high-risk BRCA1-like breast cancer patients with personalized therapy (SUBITO). An international randomized phase III trial.
- Revival of High-Dose Chemotherapy?SB Vliek, A Jager, M Jongen-Lavrencic, JP Lotz, A Gonçalves, M Graeser, U Nitz, IAM Mandjes, MJ Holtkamp, M Schot, VP Retel, EJ Kuip, ANM Wymenga, IR Konings, VCG Tjan-Heijnen, JR Kroep, CP Schrӧder, E van der Wall, SC Linn
Study conduct
Objective
• Homologous recombination (HR) is essential for error-free repair of DNA double strand breaks. • DNA double strand breaks (DSB) are for example caused by alkylating chemotherapy .1 • In absence of HR, DSBs are repaired by more error prone DNA repair mechanisms, like nonhomologous end joining. Extensive damage will lead to genomic instability and cell death.2 • HR deficiency (HRD) causes genomic instability with a typical profile of DNA copy number aberrations as seen in BC patients with a BRCA1 or BRCA2 germline mutation (gBRCAm).3 • The BRCA1-like test, a biomarker for HRD, calculates the probability that the genomic copy number profile of a breast tumor is similar to that of BRCA1 mutated BCs.3 • The BRCA1-like test is positive in a small percentage of estrogen receptor positive, and in > 50% of triple negative BCs.
High or intermediate dose IACT for BRCA-like BC? Table 1: Evidence from retrospective analyses Publication
N (BRCA-like)
population
High Dose regiment
Control
Adjusted Hazard Ratio
P-value
Vollebergh et al. Br Canc Res; 2014
249 (81)
>4 lymph nodes (LN) (RCT, Netherlands)
cyclophosphamide, thiotepa, carboplatin Followed by auto-SCT
FE90C
0.19
10 lymph nodes OR Premenopausal + 3-9 LN OR stage II-III with ER(Heidelberg)
epirubicin, ifosfamide, carboplatin Followed by auto-SCT
CMF, (F)AC/EC
0.15
Schouten et al. Int J Canc; 2016
143 (26)
>9 lymph nodes (WSG-AM 01)
(tandem) epirubicin, cyclophosphamide, thiotepa Followed by auto-SCT
AC-CMF dose dense
0.19
Lymph node positive (GAIN)
epirubicin, paclitaxel, cyclophosphamide No auto-SCT
EC-TX
1.26
van Rossum et al. 163 Br Canc Res Tr; (119) 2017
(overall survical)
