The updated network meta-analysis of neoadjuvant therapy for HER2-positive breast cancer

2018 ◽  
Vol 62 ◽  
pp. 9-17 ◽  
Author(s):  
Ayako Nakashoji ◽  
Tetsu Hayashida ◽  
Takamichi Yokoe ◽  
Hinako Maeda ◽  
Tomoka Toyota ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Meta Analysis ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

A network meta-analysis assessing the comparative effectiveness of neoadjuvant therapy for HER2-positive breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11598-e11598
Author(s):  
Aiko Nagayama ◽  
Tetsu Hayashida ◽  
Koji Okabayashi ◽  
Hiromitsu Jinno ◽  
Maiko Takahashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Neoadjuvant Therapy ◽  
Meta Analysis ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Dual Targeting ◽  
Significant Difference ◽  
Cancer Multiple ◽  
Positive Breast Cancer

e11598 Background: The growing number of anti-HER2 agents suggests the eventual need for defining the optimal choice of neoadjuvant therapy for HER2-positive breast cancer. Multiple-treatments meta-analysis synthesizes information from a network of trials and combines direct and indirect evidence on the relative effectiveness. An indirect estimate of the benefit of A over B can be obtained by comparing trials of A v C with trials of B v C. In this study, we assessed the efficacy and safety of neoadjuvant therapy for HER2-positive breast cancer by conducting the direct and indirect comparisons from multiple RCTs. Methods: The primary outcome of the study was the number of the patients who achieved pathological complete response (pCR) defined as no invasive residual in breast or node. Secondary objectives were the number of patients who completed the treatment as planned and adverse events including diarrhea, neutropenia, cardiac events and skin disorder. Results: We identified 1047 articles by database search and 10 studies met our criteria. A total of 2247 patients in 7 different treatment arms were assessed; chemotherapy (CT) alone, CT with single or dual anti-HER2 agents and dual anti-HER2 agents without CT. Anti-HER2 agents evaluated were trastuzumab (T-mab), lapatinib, pertuzumab (P-mab). There was no significant difference between dual targeting treatment arms (CT + T-mab + lapatinib v CT + T-mab + P-mab, OR; 1.11, [0.42-2.86], p=0.41), however, lapatinib reduced the treatment completion mainly due to adverse events. Patients in dual targeting arms had significantly higher incidence of pCR than in other treatment arms. (CT + T-mab + P-mab v CT + T-mab, OR; 2.29, [1.02-5.02], p=0.02) Surface under the cumulative ranking probability curve (SUCRA) also indicated that CT + T-mab + P-mab had the highest probability of being the best treatment arm for pCR followed by CT + T-mab + lapatinib and CT + T-mab. Conclusions: This study provides evidence that combining two anti-HER2 agents with chemotherapy are the most effective treatment arms. Considering the cost and limited medical resources, CT + T-mab showed a well-balanced profile for efficacy, completion and safety.

scholarly journals Efficacy and safety of neoadjuvant therapy for HER2-positive early breast cancer: a network meta-analysis

2021 ◽  
Vol 13 ◽  
pp. 175883592110069
Author(s):  
Jie Zhang ◽  
Yushuai Yu ◽  
Yuxiang Lin ◽  
Shaohong Kang ◽  
Xinyin Lv ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Combination Chemotherapy ◽  
Target Therapy ◽  
Meta Analysis ◽  
Her2 Positive ◽  
Single Target ◽  
Dual Target ◽  
Better Than ◽  
Positive Breast Cancer

Aims: Currently, there are many approaches available for neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer that improve therapeutic efficacy but are also controversial. We conducted a two-step Bayesian network meta-analysis (NMA) to compare odds ratios (ORs) for pathologic complete response (PCR) and safety endpoints. Methods: The Cochrane Central Register of Controlled Trials, PubMed, Embase, and online abstracts from the American Society of Clinical Oncology and San Antonio Breast Cancer Symposium were searched comprehensively and systematically. Phase II/III randomised clinical trials for targeted therapy in at least one arm were included. Results: A total of 9779 published manuscripts were identified, and 36 studies including 10,379 patients were finally included in our analysis. The NMA of PCR showed that dual-target therapy is better than single-target therapy and combination chemotherapy is better than monochemotherapy. However, anthracycline did not bring extra benefits, whether combined with dual-target therapy or single-target therapy. On the other hand, the addition of endocrine therapy in the HER2-positive, hormone receptor (HR)-positive subgroup might have additional beneficial effects but without significant statistical difference. By performing a conjoint analysis of the PCR rate and safety endpoints, we found that ‘trastuzumab plus pertuzumab’ and ‘T-DM1 containing regimens’ were well balanced in terms of efficacy and toxicity in all target regimens. Conclusion: In summary, trastuzumab plus pertuzumab-based dual-target therapy with combination chemotherapy regimens showed the highest efficacy of all optional regimens. They also achieved the best balance between efficacy and toxicity. As our study showed that anthracycline could be replaced by carboplatin, we strongly recommended TCbHP as the preferred choice for neoadjuvant treatment of HER2-positive breast cancer. We also look forward to the potential value of T-DM1 in improving outcomes, which needs further study in future trials.

scholarly journals UCP-2 inhibitor enhanced the efficacy of trastuzumab against HER2 positive breast cancer cells

2021 ◽  
Author(s):  
Jun Hua ◽  
Zhe Zhang ◽  
Lili Zhang ◽  
Yan Sun ◽  
Yuan Yuan
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Neoadjuvant Therapy ◽  
Needle Biopsy ◽  
Breast Cancer Cells ◽  
Her2 Positive ◽  
Trastuzumab Treatment ◽  
Her2 Positive Breast Cancer ◽  
Trastuzumab Therapy ◽  
Positive Breast Cancer

Abstract Purpose This study aimed to investigate the possibility of UCP-2 inhibitor in reducing acquired resistance of trastuzumab to improve the outcome of patients receiving trastuzumab therapy by exploring the relationship between UCP-2 expression and HER2 signaling pathway and examining whether UCP-2 expression was modulated by trastuzumab treatment. Methods 32 women diagnosed with primary HER2-positive breast cancer were recruited in this study. Needle biopsy was obtained from patients before they received at least four cycles neoadjuvant therapy containing trastuzumab in combination with chemotherapy. Surgical tumor biopsy was obtained during surgical procedure after the neoadjuvant therapy. Levels of HER2 phosphorylation and UCP-2 expression were detected by immunohistochemistry (IHC) and compared between tumor needle biopsy tissue and surgical tumor samples of these patients, as well as in BT474 breast cancer cells before and after trastuzumab treatment. HER2-selective phosphorylation/kinase activity inhibitor ONT-380 was used to identify the correlation between HER2 phosphorylation level and UCP-2 expression. UCP-2 inhibitor Genipin was then used to evaluate the apoptosis index in BT474 cells treated with trastuzumab. Results UCP-2 expression was significantly elevated in surgical tumor samples from breast cancer patients receiving trastuzumab in a neoadjuvant setting. We further confirmed our findings in HER2-positive BT474 cell line and found that trastuzumab treatment induced phosphorylation of HER2 and the overexpression of UCP-2, and the latter can be reversed by HER2 selective kinase inhibitor ONT-380. Moreover, UCP-2 inhibitor Genipin significantly enhanced the proliferation suppression effects of trastuzumab and markedly promoted apoptosis. Conclusion Taken together, our study identified UCP-2 as a novel therapeutic target for HER2 positive breast cancer and UCP-2 inhibitor may have great potential to enhance the response rate and efficacy of trastuzumab therapy.

scholarly journals Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials

2021 ◽  
Vol 22 (8) ◽  
pp. 1139-1150
Author(s):  
Rosie Bradley ◽  
Jeremy Braybrooke ◽  
Richard Gray ◽  
Robert Hills ◽  
Zulian Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Meta Analysis ◽  
Randomised Trials ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer
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