scholarly journals Responses: Re: Treatment of Human Epidermal Growth Factor Receptor 2-Overexpressing Breast Cancer Xenografts With Multiagent Human Epidermal Growth Factor Receptor-Targeted Therapy

2007 ◽  
Vol 99 (21) ◽  
pp. 1645-1646
Author(s):  
T. J. Powles ◽  
S. Ashley ◽  
I. E. Smith ◽  
M. Dowsett
2013 ◽  
Vol 31 (14) ◽  
pp. 1726-1731 ◽  
Author(s):  
Mothaffar F. Rimawi ◽  
Ingrid A. Mayer ◽  
Andres Forero ◽  
Rita Nanda ◽  
Matthew P. Goetz ◽  
...  

Purpose We previously reported the eradication of human epidermal growth factor receptor 2 (HER2)– amplified human xenografts in mice by inhibition of the HER2 pathway with lapatinib and trastuzumab to block all homo- and heterodimer signaling as well as by blockade of estrogen receptor (ER) when expressed. In this clinical trial, we sought to translate these findings to patients using targeted therapy without chemotherapy. Patients and Methods Women with stages II to III HER2-positive breast cancers were eligible. They received trastuzumab once per week (4 mg/kg loading, then 2 mg/kg) and lapatinib 1000 mg once per day for 12 weeks. Women with ER-positive tumors also received letrozole (plus a luteinizing hormone–releasing hormone [LHRH] agonist if premenopausal). Pathologic response was assessed by ER status. Biopsies were obtained at baseline, weeks 2 and 8, and time of surgery. Results Sixty-six patients were enrolled, and 64 were eligible and evaluable for response. Median tumor size was 6 cm (range, 1.5 to 30 cm). Adverse events were mainly grades 1 to 2 (GI, 63%; skin, 46%). Grade 3 metabolic, GI, and liver (18%; 12 patients) and grade 4 liver toxicities (one patient) were also observed. Overall, in-breast pathologic complete response (pCR; ypT0-is) was 27% (ER positive, 21%; ER negative, 36%). The rate of low-volume residual disease (ypT1a-b) was 22% (ER positive, 33%; ER negative, 4%). Conclusion In patients with locally advanced HER2-positive breast cancer, our approach of targeted therapy only resulted in a high pCR rate without chemotherapy. Our data support the hypothesis that selected patients with HER2-positive tumors may not need chemotherapy, and more-complete blockade of HER receptors and ER is an effective strategy worthy of further study.


2018 ◽  
Vol 4 (Supplement 3) ◽  
pp. 27s-27s ◽  
Author(s):  
Nita S. Nair ◽  
Sudeep Gupta ◽  
Jaya Ghosh ◽  
Sangeeta Desai ◽  
Vani Parmar ◽  
...  

Purpose In a previous retrospective audit from our institution, access to human epidermal growth factor receptor 2 (HER2) –targeted therapy (H2T) in patients registered and treated in 2008 was reported, wherein only 38 (8.61%) of 441 patients received some form of H2T. Three developments occurred in subsequent years that potentially affected access to H2T at our institution—that is, a patient access program supported by the innovator pharmaceutical company, a generous philanthropic donor, and the use of biosimilars. Methods To evaluate the cumulative impact of these developments on access to trastuzumab, we reviewed access to H2T in a recent cohort of patients with breast cancer registered in at our institution. Results In 2016, 4,717 new patients with breast cancer were registered at our institution. Among these patients, HER2 3+ expression by immunohistochemistry or fluorescent in situ hybridization (FISH) was reported in 828 patients (22.77%). Assuming the same 33.22% amplification rate in the 343 patients who did not undergo FISH testing, there were potentially 114 more patients with HER2-amplified tumors. Thus, the final number of HER2-overexpressing/-amplified tumors is estimated to be 942 in 2016 (729 HER2 immunohistochemistry 3+, 99 known FISH amplified, and 114 estimated FISH amplified). Of these 942 patients, 13 were not deemed suitable for H2T and 94 did not follow-up for additional treatment at our institution. The remaining 835 patients were eligible to receive H2T and were analyzed for access to this treatment. Overall, 444 (53.2%) of these 835 patients received trastuzumab for durations that ranged from 12 weeks to 12 months in the (neo)adjuvant setting or other durations in the metastatic setting. This is in contrast to the previously reported 8.61% use of H2T in the cohort of patients registered in 2008. Conclusion We suggest that other institutions, especially public hospitals that treat underprivileged patients, make concerted efforts to increase access to potentially curative treatments, such as trastuzumab, using targeted programs and philanthropic support, and consider using a shorter duration of 12 weeks of trastuzumab to improve patient outcomes. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc . No COIs from the authors.


BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e035802
Author(s):  
Qiancheng Hu ◽  
Xin Wang ◽  
Ye Chen ◽  
Xiaofen Li ◽  
Ting Luo ◽  
...  

IntroductionControversy regarding optimum duration of trastuzumab treatment remains in patients with human epidermal growth factor receptor-2 (HER2) positive early breast cancer. The objective of applying network meta-analysis (NMA) is to integrate existing evidence based on direct and indirect comparisons of efficacy and safety, and then to determine the duration of trastuzumab treatments with the greatest impact on therapeutic outcomes in HER2-positive early breast cancers.Methods and analysisElectronic searching of trastuzumab treatments for early breast cancer by titles and abstracts will be conducted for the period from inception to 16 June 2019 in PubMed, Cochrane Library, Embase and ClinicalTrils.gov, as well as the annual meetings of San Antonio Breast Cancer Symposium (SABCS), European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) online archives. The outcomes of interest are overall survival, disease-free survival, acceptability, cardiotoxicities and grade 3 to 4 non-haematological toxicities. Two independent reviewers will screen and extract eligible data based on the inclusion and exclusion criteria, and then assess the risk of bias and evidence quality of individual studies using Cochrane Collaboration’s tool and Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The heterogeneity, transitivity and inconsistency of NMA will be evaluated. In addition, we will perform subgroup and sensitivity analyses to assess the robustness and reliability of findings in our NMA.Ethics and disseminationEthics approval is not required for our NMA. Findings from our NMA will be submitted as peer-reviewed journal manuscripts and international conference reports.Trial registration numberCRD42019139109.


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