RESUMO
Purpose@#Pyrotinib is a newly-developed irreversible pan-ErbB receptor tyrosine kinase inhibitor. This study reported the first real-world data of pyrotinib-based therapy in metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), focusing on efficacy in lapatinib-treated patients and in brain metastasis. @*Materials and Methods@#One hundred thirteen patients with metastatic HER2-positive BC treated with pyrotinib-based therapy in Fudan University Shanghai Cancer Center under non-clinical trial settings from September 1, 2018 to March 1, 2019 were included. @*Results@#Over half patients have received more than two lines of systematic therapy and exposed to two or more kinds of anti-HER2 agents. Most patients received a combined therapy, commonly of pyrotinib plus capecitabine, or vinorelbine or trastuzumab. Median progression-free survival (PFS) was 6.3 months (range, 5.54 to 7.06 months) and objective response rate (ORR) was 29.5%, with two patients (1.9%) achieving complete response. Lapatinib-naïve patients had significantly longer PFS than lapatinib-treated patients (9.0 months vs. 5.4 months, p=0.001). ORR for lapatinib-treated patients was 23.2%. Thirty-one of 113 patients have brain metastasis. Median PFS was 6.7 months and intracranial ORR was 28%. For patients without concurrent radiotherapy and/or brain surgery, the ORR was very low (6.3%). But for patients receiving concurrent radiotherapy and/or brain surgery, the ORR was 66.7%, and three patients achieved complete response. Most common adverse event was diarrhea. @*Conclusion@#Pyrotinib-based therapy demonstrated promising effects in metastatic HER2-positive BC and showed activity in lapatinib-treated patients. For patients with brain metastasis, pyrotinib-based regimen without radiotherapy showed limited efficacy, but when combined with radiotherapy it showed promising intracranial control.
RESUMO
Bone metastasis is common for advanced breast cancer, and can cause pathologic fractures, hypercalcemia, spinal cord compression and other skeletal-related events. The life quality of patients with bone metastasis will be seriously affected. But for now, the mechanism of breast cancer bone metastasis is not clear. As a result, there are no effective and targeted treatments, except the locoregional therapy such as radiation therapy and surgery. Therefore, this review focuses on the molecular mechanisms of breast cancer bone metastasis in order to lay a foundation for further research of effective targeted therapy. Firstly, in this review, a complex succession of invasion-metastasis cascade in bone metastasis is expounded, and the positive feedback “vicious cycle” promoting the milignant proliferation of tumor cells is expatiated. Then the estrogen receptor mediating mechanism of bone metastasis is discussed. In the end, the recent advances in clinical research of breast cancer bone metastasis and the forward future research directions are summarized.