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Pertuzumab

About: Pertuzumab is a research topic. Over the lifetime, 1453 publications have been published within this topic receiving 73219 citations. The topic is also known as: 2C4 Antibody & MOAB 2C4.


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Journal ArticleDOI
TL;DR: The results suggest that the TRAS + PER combination may be effective in T-DM1-resistant cancer cells where HER2 overexpression is maintained and suppressed tumor growth in the OE19bTDR xenograft model compared with each single agent.
Abstract: Trastuzumab emtansine (T-DM1) is the standard treatment in the current second-line therapy of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. However, a useful therapy after T-DM1 resistance has not been established. In this study, we established two different HER2-positive T-DM1-resistant cancer cells and evaluated the antitumor effect of trastuzumab in combination with pertuzumab (TRAS + PER). Single-cell-cloned OE19 and BT-474 cells were cultured with increasing concentrations of T-DM1 to generate T-DM1-resistant OE19bTDR and BT-474bTDR cells, respectively. HER2 expression was assessed by immunohistochemistry. Multidrug resistance proteins (MDR1 and MRP1) were evaluated by real-time polymerase chain reaction and western blotting. Intracellular trafficking of T-DM1 was examined by flow cytometry and immunofluorescence staining. Efficacy of TRAS + PER was evaluated by cell proliferation assay, HER3 and AKT phosphorylation, caspase 3/7 activity, and antitumor activity. HER2 expression of both resistant cells was equivalent to that of the parent cells. Overexpression of MDR1 and MRP1 was observed and affected the T-DM1 sensitivity in the OE19bTDR cells. Abnormal localization of T-DM1 into the lysosomes was observed in the BT-474bTDR cells. In BT-474bTDR cells, TRAS + PER inhibited the phosphorylation of AKT involved in HER2–HER3 signaling, and apoptosis induction and cell proliferation inhibition were significantly higher with TRAS + PER than with the individual drugs. TRAS + PER significantly suppressed tumor growth in the OE19bTDR xenograft model compared with each single agent. The results suggest that the TRAS + PER combination may be effective in T-DM1-resistant cancer cells where HER2 overexpression is maintained.

4 citations

Journal ArticleDOI
29 Dec 2022-Cancers
TL;DR: In this article , the authors evaluated 22 patients diagnosed with HER2-positive breast cancer, who underwent combination treatment with trastuzumab, pertussumab and docetaxel, and they monitored their cardiac profiles through radionuclide ventriculography and cardiac-biomarker measurements both at the beginning of their treatment and after 6 months of therapy.
Abstract: Simple Summary Breast cancer is the most frequently diagnosed cancer in women, causing over 500,000 deaths worldwide. Human epidermal growth factor receptor 2 is overexpressed in roughly 15–20% of the breast cancer cases diagnosed nowadays, denoting poor prognoses. However, the presence of this receptor in tumoral cells provided patients with the opportunity for treatment with HER2 inhibitors, which have well-documented clinical benefits but still present variable grades of cardiotoxicity. We evaluated 22 patients, diagnosed with HER2-positive breast cancer, who underwent combination treatment with trastuzumab, pertuzumab and docetaxel, and we monitored their cardiac profiles through radionuclide ventriculography and cardiac-biomarker measurements both at the beginning of their treatment and after 6 months of therapy. Our results confirmed the good cardiac safety profile of this therapeutic scheme while also suggesting use of radionuclide ventriculography and dosing of NT-proBNP and ST2-IL33R for early detection of cardiac impairment. Abstract (1) Background: The aim of our study was to determine whether monitoring cardiac function through RNV and cardiac biomarkers could predict the cardiac impact of combined therapy with trastuzumab, pertuzumab and docetaxel, which are regularly used nowadays to treat HER2-positive breast cancer. (2) Methods: This prospective monocentric study included 22 patients, diagnosed with HER2-positive breast cancer, who had their LVEFs and cardiac biomarkers evaluated both at the beginning of their treatment and after 6 months. Among all of the enrolled patients, two blood specimens were collected to assess circulating cardiac biomarkers. RNV was performed in each patient after “in vivo” radiolabeling of the erythrocytes. The obtained results were then statistically correlated. (3) Results: The average LVEF decrease between the two time points was approximately 4%. Of the five biomarkers we considered in this paper, only NT-proBNP correlated with the LVEF values obtained both in the baseline study and after 6 months of follow-up (r = −0.615 for T0 and r = −0.751 for T1, respectively). ST2/IL-33R proved statistically significant at the T1 time point (r = −0.547). (4) Conclusions: A combination of LVEF, NT-proBNP and ST2/IL-33R assessment may be useful for early detection of cardiac impairment in breast cancer patients treated with trastuzumab, pertuzumab and docetaxel.

4 citations

Journal ArticleDOI
TL;DR: The results confirm that HRs expression impacts the clinical behavior and novel treatment‐related outcomes of HER2‐positive tumors when treatment sequences are considered, and multivariate analysis showed thatHRs expression had no effect on PFS and OS.
Abstract: We analyzed data from 738 HER2-positive metastatic breast cancer (mbc) patients treated with pertuzumab-based regimens and/or T-DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression-free survival at first-line (mPFS1) was 12 months. Pertuzumab as first-line conferred longer mPFS1 compared to other first-line treatments (16 vs. 9 months, p = 0.0001), regardless of IHC subtype. Median PFS in second-line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T-DM1 compared to other agents (7 vs. 6 months, p = 0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs; p = 0.17), while a trend emerged for tumors with one HR (p = 0.05). Conversely, PFS2 gain was significant in HRs-negative tumors (p = 0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T-DM1 in second-line after pertuzumab were significantly lower compared to pertuzumab-naive patients (p = 0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p = 0.02 and p = 0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment-related outcomes of HER2-positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor pathways in HER2-positive (mbc) patients.

4 citations

Journal ArticleDOI
TL;DR: Tailored therapies are a step forward in improving patients' prognosis and key points in the intracellular signal transduction pathways relevant for cell proliferation, apoptosis and the angiogenesis/metastasis process, represent possible targets for new target-specific agents.
Abstract: Metastatic breast cancer (MBC) remains an incurable disease. The aims of treatment include tumour shrinkage, symptom control, delay of disease progression and prolongation of survival while maintaining an acceptable quality of life. In the last decade, a decline in mortality has been observed. Combination chemotherapy generally provides some survival advantage over single-agent chemotherapy. Taxanes and antimetabolites are among the most effective agents, providing a balance between efficacy and tolerability. Increasing numbers of patients are receiving adjuvant anthracycline and taxane therapy. In these patients, treatment options include cytotoxic agents not used in adjuvant treatment, re-challenge with anthracycline and taxanes, or new targeted agents such as pertuzumab, lapatinib or bevacizumab. Biology of the disease at cell level plays a major role in treatment choice. Key points in the intracellular signal transduction pathways relevant for cell proliferation, apoptosis and the angiogenesis/metastasis process, represent possible targets for new target-specific agents. Tailored therapies are a step forward in improving patients' prognosis.

4 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023372
2022307
2021158
2020144
2019143
2018130