Impact of hormone receptor status and distant recurrence-free interval on survival benefits from trastuzumab in HER2-positive metastatic breast cancer

Abstract

We sought to investigate the impact of hormone receptor (HR) status and distant recurrence-free interval (DRFI) on the degree of overall survival (OS) benefit from palliative trastuzumab-containing treatment in HER2-positive metastatic breast cancer (MBC). Here, we retrospectively identified 588 eligible HER2-positive patients with postoperative distant recurrence. DRFI of HR+HER2+ MBC patients (median: 30.7 months, IQR: 18.5–45.9, P < 0.001) was significant longer compared with HR−HER2+ patients. Patients were categorized into four subgroups based on HR status and palliative trastuzumab (trast+) received. The most superior outcome was observed in the HR+HER2+trast+ subgroup, with a median OS of 48.3 months. Moreover, DRFI > 24 months is an independent favourable prognostic factor for both HR−HER2+ patients (Hazard Ratio (HzR) = 0.55, 95% CI: 0.39–0.76, P < 0.001) and HR+HER2+ patients (HzR = 0.45, 95% CI: 0.32–0.64, P < 0.001). Upon further analysis of the interaction between trastuzumab and DRFI, the degree of trastuzumab benefits in HR−HER2+ MBC patients remained basically unchanged regardless of DRFI length. Unlikely, the degree in HR+HER2+ MBC patients decreased gradually along with DRFI extending, indicating that trastuzumab failed to translate into an OS benefit for late recurrent (DRFI > 5years) HR+HER2+ MBC patients.

MicroRNA-212-3p inhibits the Proliferation and Invasion of Human Hepatocellular Carcinoma Cells by Suppressing CTGF expression

“…CTGF also regulates KLF4 to trigger EMT in Kawasaki disease 30 . CTGF enhances ANGPT2 expression, a key element in tumor angiogenesis 31 . The suppression of CTGF expression appreciably decreases angiogenesis 31 and tumor growth 32 in vivo .…”

MiR-218 regulates epithelial–mesenchymal transition and angiogenesis in colorectal cancer via targeting CTGF

“…CTGF has also been reported to promote EMT process in Kawasaki disease by regulation of KLF4 [ 15 ]. In the process of angiogenesis, CTGF has been demonstrated to be the regulator of ANGPT2 expression, which is key factor for tumor angiogenesis [ 37 ]. Silencing CTGF expression significantly reduced tumor growth [ 7 ] and angiogenesis [ 37 ] in vivo.…”

“…In the process of angiogenesis, CTGF has been demonstrated to be the regulator of ANGPT2 expression, which is key factor for tumor angiogenesis [ 37 ]. Silencing CTGF expression significantly reduced tumor growth [ 7 ] and angiogenesis [ 37 ] in vivo. In this present study, CTGF was for the first time identified as the direct target of miR-218 by dual luciferase assay.…”

“…In breast cancer, studies have shown that CTGF cooperates with other genes to promote metastasis, and high level of CTGF correlated with advanced tumor stages [ 34 ]. In osteosarcoma, CTGF has been proved to facilitate angiogenesis by regulating miR-543/angiopoietin 2 signaling [ 37 ].…”

Prognostic role of distant disease-free interval from completion of adjuvant trastuzumab in HER2-positive early breast cancer: analysis from the ALTTO (BIG 2-06) trial

“…12 With a larger sample size, our analysis shows the important prognostic role In addition, our results provide further evidence on the different behaviour of HER2-positive tumours according to hormone receptor status. [13][14][15][16][17][18] As compared to patients with hormone receptor-positive disease, those with hormone receptor-negative tumours had higher likelihood to relapse within 12 months following completion of adjuvant trastuzumab and had poorer OS irrespective of TFI. These data further highlight the need to pursue in research efforts aiming to improve the outcomes of patients with metastatic HER2-positive disease with different approaches according to hormone receptor status.…”