Therapy of metastatic breast cancer with humanized antibodies against the HER2 receptor protein

1999 ◽  
Vol 125 (8-9) ◽  
pp. 520-524 ◽  
Author(s):  
G. Schaller ◽  
N. Bangemann ◽  
C. Becker ◽  
H. Bühler ◽  
F. Opri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Receptor Protein ◽  
Her2 Receptor ◽  
Humanized Antibodies

scholarly journals Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive/HER2 receptor-negative metastatic breast cancer: a real-world multicentre Italian study

2021 ◽  
Vol 13 ◽  
pp. 175883592098765
Author(s):  
Raffaella Palumbo ◽  
Rosalba Torrisi ◽  
Federico Sottotetti ◽  
Daniele Presti ◽  
Anna Rita Gambaro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Real World ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Her2 Receptor ◽  
Treatment Line ◽  
Hormone Receptor Positive

Background: The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials. Patients and methods: This is a multicentre prospective real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary aim was the clinical benefit rate (CBR); secondary aims were the median PFS, overall survival (OS) and safety. Patients received palbociclib plus letrozole 2.5 mg (cohort A) or fulvestrant 500 mg (cohort B). Results: In total, 191 patients (92 in cohort A, 99 in cohort B) were enrolled and treated, and 182 were evaluable for the analysis. Median age was 62 years (range 47–79); 54% had visceral involvement; 28% of patients had previously performed one treatment line (including chemotherapy and ET), 22.6% two lines and 15.9% three. An overall response rate of 34.6% was observed with 11 (6.0%) complete responses and 52 (28.6%) partial responses. Stable disease was achieved by 78 patients (42.9%) with an overall CBR of 59.8%. At a median follow-up of 24 months (range 6–32), median PFS was 13 months without significant differences between the cohorts. When analysed according to treatment line, PFS values were significantly prolonged when palbociclib-based therapy was administered as first-line treatment (14.0 months), to decrease progressively in second and subsequent lines (11.7 and 6.7 months, respectively). Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively. Conclusions: Our data indicate that palbociclib plus ET is active and safe in HR+/HER2− MBC, also suggesting a better performance of the combinations in earlier treatment lines.

scholarly journals Trastuzumab for HER2-Positive Metastatic Breast Cancer: Clinical and Economic Considerations

2012 ◽  
Vol 6 ◽  
pp. CMO.S6460 ◽  
Author(s):  
Alwin Jeyakumar ◽  
Tallal Younis
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Drug Acquisition ◽  
Metastatic Breast ◽  
Her2 Receptor ◽  
Her2 Positive ◽  
Humanized Monoclonal Antibody ◽  
Clinical Benefits ◽  
Cellular Domain

Trastuzumab is a recombinant humanized monoclonal antibody that selectively targets the extra-cellular domain of the HER2 receptor. It was approved by the FDA in September 1998 as the first targeted therapy for HER2-positive metastatic breast cancer, and has since led to significant improvements in the overall prognosis for patients with HER2-positive metastatic disease. The favourable benefit/risk profile associated with palliative trastuzumab has been demonstrated in a number of clinical trials that examined trastusumab as monotherapy or in combination with chemotherapy, endocrine therapy and other HER2 targeted agents. The clinical benefits of trastuzumab, however should also be examined within the context of its significant drug acquisition costs. This review highlights the significant findings from the landmark clinical trials of trastuzumab for metastatic HER2-positive breast cancer, and the potential “value for money” associated with its use in clinical practice.

A Review of Trastuzumab-Based Therapy in Patients with HER2-positive Metastatic Breast Cancer

2009 ◽  
Vol 1 ◽  
pp. CMT.S35
Author(s):  
David N. Church ◽  
Chris G.A. Price
Keyword(s):  
Breast Cancer ◽  
Monoclonal Antibody ◽  
Metastatic Breast Cancer ◽  
Poor Prognosis ◽  
Chemotherapy Regimen ◽  
Metastatic Breast ◽  
Preclinical Studies ◽  
Breast Cancers ◽  
Her2 Receptor ◽  
Her2 Positive

The ERBB2 or HER2 receptor is overexpressed in 25% of breast cancers and is associated with poor prognosis. Trastuzumab, a monoclonal antibody targeting HER2 has been demonstrated to improve survival when combined with chemotherapy for the treatment of HER2 overexpressing metastatic breast cancer (MBC). Further studies have endeavoured to clarify the optimum chemotherapy regimen in combination with trastuzumab for MBC and its use together with novel biological agents. This review summarises these data together with preclinical studies exploring the mechanism of trastuzumab action and causes of drug resistance. The frequent incidence of brain metastases in patients on trastuzumab is highlighted, and data on the continuation of trastuzumab following CNS and non-CNS progression reviewed.

Metastatic breast cancer: A regional audit of HER2 testing and trastuzumab access

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6097-6097
Author(s):  
P. Scullin ◽  
A. T. Drake ◽  
V. M. Coyle ◽  
J. J. McAleer
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Her2 Receptor ◽  
Her2 Positive ◽  
Her2 Testing ◽  
Number Of Patients

6097 Background: Clinical trials have clearly established that patients receiving taxane-based chemotherapy for metastatic breast cancer (MBC) should be treated with trastuzumab if their tumour is shown to overexpress the human epidermal growth factor receptor 2 (HER2) receptor. This is based on median survival gains for patients with HER2 positive tumours treated with trastuzumab plus taxane chemotherapy compared to taxane alone. Methods: Patients commencing chemotherapy for MBC in Northern Ireland in 2004 were identified from pharmacy records. Their case notes were retrospectively reviewed to determine whether patients in routine clinical practice had HER2 testing and trastuzumab treatment if indicated. Results: One hundred and fifty six patients commenced chemotherapy, of whom 145(93%) had HER2 testing. In 69(44%) patients the HER2 result was already available at the time of this relapse. In the remaining 76(49%) patients the result became available in a median of 41.5 (range 0–368) days. Of those tested, 48 patients (33%) were HER2 positive (immuno-histochemistry 3+ or fluorescence in situ hybridization positive). Thirty eight of these patients were treated with trastuzumab, either as a single agent or in combination with chemotherapy. There were valid reasons for trastuzumab omission in 7 of 10 patients not given trastuzumab (4 given first line anthracycline-based regimen, 1 had cardiac dysfunction, 1 had extensive lung metastastes and 1 was unfit for treatment). The data were examined for variations in chemotherapy and trastuzumab use across the 4 health boards which comprise the region. The number of patients commencing chemotherapy ranged from 6.9 to 11.4 patients per 100,000 population indicating a significantly different utilisation (p<0.001). Conclusions: In our region 145 of 156 patients who received chemotherapy for MBC were tested for overexpression of the HER2 receptor (93%). Of those patients who were eligible to receive trastuzumab 31 out of 34 (91%) received trastuzumab. There were inequalities in the region regarding chemotherapy for MBC and the time required to obtain a HER2 result averaged 41.5 days. Testing of HER2 status at time of original diagnosis would streamline management of metastatic disease. No significant financial relationships to disclose.

scholarly journals Measuring HER2-Receptor Expression In Metastatic Breast Cancer Using [68Ga]ABY-025 Affibody PET/CT

Theranostics ◽  
2016 ◽  
Vol 6 (2) ◽  
pp. 262-271 ◽  
Author(s):  
Jens Sörensen ◽  
Irina Velikyan ◽  
Dan Sandberg ◽  
Anders Wennborg ◽  
Joachim Feldwisch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Receptor Expression ◽  
Her2 Receptor ◽  
Pet Ct

Detection of trastuzumab (T) level in human serum using quartz crystal microbalance (QCM) piezo-immunosensors by immobilization of a HER2 mimotope-derived synthetic peptide and its potential application in breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 628-628
Author(s):  
Mohammad Muhsin Chisti ◽  
Yuqin Shang ◽  
Alaa Muslimani ◽  
Pankaj R Singh ◽  
Ray Mernaugh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Monoclonal Antibodies ◽  
Human Serum ◽  
Synthetic Peptide ◽  
Metastatic Breast ◽  
Receptor Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Her2 Receptor ◽  
Assay Sensitivity ◽  
First Time

628 Background: Varied clinico-pathological response to monoclonal antibodies like T has been reported either due to presence of antibodies, rapid clearance or low density of target receptor/antigens. This demands need for an assay to monitor serum T therapeutic levels to ensure appropriate dosage. Enzyme-linked immunosorbent assay (ELISA) is still the most widely used technique to detect T level in human serum which is expensive and time consuming. For the first time, we established a platform to detect T level by using a small (<2.2 kDa), inexpensive, highly stable HER2 mimotope-derived synthetic peptide immobilized on the surface of a gold quartz electrode. Methods: HER2 mimotope was used as a substitute for the HER2 receptor protein in QCM assays to detect T level. The validation samples were prepared from the standard T solution in 10% human serum at three concentrations (10, 20 and 40 ug/ml). The changes in frequencies (ΔF) of sera from 3 female patients , 61, 32 and 44 years old , with ER/PR positive, HER2/neu positive metastatic breast cancer were obtained by calculating the differences between frequency shifts in pre and post T infusion.T level was calculated by equation, (ΔF +1.0022) ÷ 0.9997 μg / ml. Results: We showed that assay sensitivity was dependent upon the amino acids used to tether and link the peptide to the sensor surface and the buffers used. QCM assay was capable of detecting T serum level as low as 0.038 nM (linear operating range of 0.038–0.859 nM). T levels of 3 patients were 43.34, 121.96 and 193.18 μg /ml corresponding to pre and post infusion ΔF of 3.33, 11.19 and 18.31 respectively. The time frame of assay was 20-30 minutes. These results were in concordance with previously published results using ELISA. Conclusions: For the first time, we have established a low cost, highly sensitive, fast, synthetic peptide based QCM assay which could be used as a basis for developing a new generation of affinity-based Immunosensor assays to monitor serum levels of T and other monoclonal antibodies, helping physicians to determine the clinical efficacy of these drugs and ensuring appropriate dosages.

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