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 Late Administration of Trastuzumab Emtansine Might Lead to Loss of Chance for Better Outcome in Patients with HER2-Positive Metastatic Breast Cancer

Breast Care ◽  
2018 ◽  
Vol 13 (4) ◽  
pp. 277-283 ◽  
Author(s):  
Luis Manso ◽  
Alfonso Sanchez-Muñoz ◽  
Isabel Calvo ◽  
Yann Izarzugaza ◽  
Jessica Plata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Safety Data ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Optimal Sequence ◽  
Number Of Patients ◽  
Epidermal Growth

The optimal sequence of anti-human epidermal growth factor receptor 2 (HER2) therapies in metastatic breast cancer (MBC) is still undetermined. Physicians must therefore make decisions based on clinical trials and their own experience for the best treatment sequence in these patients. The objective of this review is to summarize the efficacy and safety data for trastuzumab emtansine (T-DM1) in patients with MBC. Additionally, the concept of ‘loss of chance for a better outcome' is investigated. It applies to patients who are not receiving the best possible treatment for their disease. Physicians should strive to offer the best possible care, although getting optimal results in each individual patient is not guaranteed. Lastly, the number of patients with MBC lost per treatment line is evaluated. We conclude that both concepts reinforce the importance of giving the most active treatments as soon as possible in the course of disease to secure the longest possible survival for HER2-positive MBC patients.

Metronomic Chemotherapy for Metastatic Breast Cancer

2021 ◽  
pp. 1-6
Author(s):  
Slavomir Krajnak ◽  
Marco J. Battista ◽  
Annette Hasenburg ◽  
Marcus Schmidt
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Metronomic Chemotherapy ◽  
Best Supportive Care ◽  
Chemotherapeutic Agents ◽  
Her2 Positive ◽  
Continuous Administration ◽  
Leading Role

Background: As disease control and quality of life play a leading role in metastatic breast cancer (MBC), metronomic chemotherapy (MCT) is gaining popularity alongside conventional chemotherapy (CCT) and targeted therapies. Summary: MCT, defined as continuous administration of low-dose chemotherapeutic agents, is accepted as a therapy that exerts its effects via immunomodulation, anti-angiogenesis and direct cytotoxic effects. Oral administration of MCT is safe, easy to handle, and allows for flexible drug dosing. Dose accumulations associated with non-tolerable side effects are rare, so the medication can be administered for longer periods of time. Patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic disease resistant to endocrine-based therapy and not requiring rapid tumor response are generally suitable for MCT. However, MCT may also be promising in patients with triple-negative and HER2-positive tumors without aggressive disease who prefer a lower toxicity profile compared to CCT. The most commonly used agents are cyclophosphamide (CTX), methotrexate (MTX), capecitabine (CAPE), and vinorelbine (VRL), whereby a combination of agents is frequently applied. Key Messages: Based on the growing body of evidence, MCT can be considered as a suitable treatment option in selected MBC patients. Nevertheless, there is an urgent need for randomized controlled trials comparing MCT with CCT, but also with best supportive care. Due to the multimodal mechanisms of action, the combination with targeted and immunological therapies may represent a new promising approach for the treatment of MBC.

Indium-111–Labeled Trastuzumab Scintigraphy in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

2006 ◽  
Vol 24 (15) ◽  
pp. 2276-2282 ◽  
Author(s):  
Patrick J. Perik ◽  
Marjolijn N. Lub-De Hooge ◽  
Jourik A. Gietema ◽  
Winette T.A. van der Graaf ◽  
M. Alexander de Korte ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Myocardial Uptake ◽  
Her2 Positive ◽  
Indium 111 ◽  
Epidermal Growth

Purpose The cardiac and antineoplastic effects of trastuzumab may be related to specific uptake of trastuzumab in myocardium and tumor tissue, respectively. We evaluated whether indium-111 (111In) –labeled trastuzumab scintigraphy can predict cardiotoxicity and identify tumor lesions. In addition, we evaluated whether plasma markers for cardiac dysfunction can be used to predict cardiotoxicity. Patients and Methods Patients with human epidermal growth factor receptor 2 (HER2) –positive metastatic breast cancer underwent gamma camera imaging from 15 minutes to 7 days after injection of 150 MBq 111In–diethylenetriamine penta-acetic acid anhydride (DTPA) –trastuzumab, after loading-dose trastuzumab, and after once-a-week trastuzumab doses for 11 weeks, and concomitant paclitaxel once every 3 weeks. Cardiac assessments were performed before treatment, and after four and six cycles. Plasma N-terminal probrain natriuretic peptide (NT-proBNP) and serum troponin I were measured with immunoassay. Results Fifteen of the 17 patients were available for cardiac and tumor uptake analysis. On the first scan, myocardial 111In-DTPA-trastuzumab uptake was observed in one patient with pre-existing cardiac arrhythmias, who did not develop heart failure during treatment. Severe cardiotoxicity occurred in three patients, without initial myocardial uptake, whereas one showed weak myocardial uptake after four cycles. The detection rate of single tumor lesions was 45%. New tumor lesions were discovered in 13 of 15 patients. Pretreatment plasma NT-proBNP levels were higher in patients with than without heart failure (mean, 534 [standard deviation, 236] v 105 [standard deviation, 79] ng/L; P = .009). Conclusion Radiolabeled trastuzumab scintigraphy was not valuable in predicting trastuzumab-related cardiotoxicity in metastatic breast cancer patients, but can identify HER2-positive tumors. Measurement of plasma NT-proBNP is promising regarding prediction of trastuzumab-related cardiotoxicity.

scholarly journals Potential biomarkers of long-term benefit from single-agent trastuzumab or lapatinib in HER2-positive metastatic breast cancer

2013 ◽  
Vol 8 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Filippo Montemurro ◽  
Aleix Prat ◽  
Valentina Rossi ◽  
Giorgio Valabrega ◽  
Jeff Sperinde ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Term Benefit ◽  
Potential Biomarkers

Quantitative HER2 measurement and PI3K mutation profile in matched primary and metastatic breast cancer tissues.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 614-614
Author(s):  
Weidong Huang ◽  
Jonathan F. Lara ◽  
Richard Michaelson ◽  
Xiu Sun ◽  
Pierfranco Conte ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Catalytic Domain ◽  
Pik3ca Mutation ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Her2 Positive ◽  
Pik3ca Mutations ◽  
Meta Analyses ◽  
Negative Conversion

614 Background: HER2 status of primary breast cancer (PBC) is routinely used to determine systemic treatment for metastatic breast cancer (MBC) patients. Discordance rates of HER2 status between PBC and MBC range from 5.5% to 29% based on published meta-analyses. The clinical benefit of re-assessing HER2 in MBC tissues remains controversial. In this study, we measured quantitative HER2 expression in matched PBC and MBC tissues and correlated changes of HER2 with mutations in the catalytic domain of PI3 kinase(PIK3CA). Methods: Total HER2 protein expression (H2T) was quantified by the HERmark assay in 41 matched PBC and MBC formalin-fixed, paraffin-embedded specimens. PIK3CA mutation status in exons 9 (E545K and E542K) and 20 (H1047R) was determined using a validated pyrosequencing assay. Results: MBC samples included 5 lymph node, 13 viscera, 6 brain, and 17 soft tissue lesions (N=41). 27 (66%) cases showed higher H2T in MBC than in matched PBC; and 14 (34%) cases had higher H2T in PBC than in matched MBC, indicating an overall increase of H2T in matched MBC lesions (fold change 0.25-17.57; p=0.005, paired Wilcoxon rank sum test). HER2 positive conversion (HERmark negative/equivocal in PBC, but positive in matched MBC) was found in 6 (15%) cases, while HER2 negative conversion (HERmark positive in PBC, but negative/equivocal in matched MBC) was seen in 2 (5%) cases. HER2 status was unchanged in 33 (80%) cases. PIK3CA mutations were detected in 13 (32%) of PBC and 19 (46%) of MBC samples. Among the HER2 positive conversion cases, PIK3CA mutation was identified in 50% (3/6) PBC and 67% (4/6) MBC, compared to 0% (0/2, PBC or MBC) in the HER2 negative conversion cases. Among cases with unchanged HER2 status, PIK3CA mutation was observed in 30% (10/33) PBC and 42% (14/33) MBC. Conclusions: Quantitative HER2 assessment revealed a 20% discordance in HER2 status between matched PBC and MBC tissues, with more frequent conversion from low HER2 in PBC to high HER2 in MBC. PIK3CA mutation was observed more frequently in patients who converted from HER2 negative PBC to HER2 positive MBC. These results suggest that re-assessment of biomarkers in MBC tissues may better inform the selection of therapeutic options for patients with MBC.

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