HER2-targeted treatment for older patients with breast cancer: An expert position paper from the International Society of Geriatric Oncology

Publication date: Available online 22 June 2019Source: Journal of Geriatric OncologyAuthor(s): Etienne Brain, Philippe Caillet, Nienke de Glas, Laura Biganzoli, Karis Cheng, Lissandra Dal Lago, Hans WildiersAbstractHER2-positive (HER2+) breast cancer (BC) affects older women nearly as frequently as younger ones. Many older patients have cardiovascular comorbidity and risk greater toxicity from therapy. Treatment therefore requires careful consideration, especially since trials include few patients over 65 and so provide limited guidance. A multidisciplinary task force of the International Society of Geriatric Oncology conducted a literature review to make specific recommendations. In the absence of impaired left ventricular ejection fraction, older patients with HER2+ advanced or metastatic BC (MBC) should receive HER2-targeted therapy adjusted to their general condition. Although trastuzumab combined with pertuzumab and docetaxel or paclitaxel is recommended first-line in fit patients, taxanes are difficult in vulnerable ones, making a better-tolerated chemotherapy partner highly desirable. Hormonal therapy with anti-HER2 treatment is an alternative with hormone sensitive tumours. T-DM1 is the standard for fit trastuzumab- and taxane-exposed patients. Lapatinib activity differs from trastuzumab and causes more side effects and drug interactions that are at higher risk in older patients. For fit HER2+ early BC (EBC) patients, chemotherapy plus one year trastuzumab is standard...
Source: Journal of Geriatric Oncology - Category: Cancer & Oncology Source Type: research

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Abstract The failure to treat and control the growth of metastases is the main cause of death in breast cancer (BC) patients. Compared to the traditional method of analyzing circulating tumor DNA (ctDNA), capturing intact circulating tumor cells (CTCs) allows us to more accurately characterize mutations and identify suitable targeted therapies. We used CellCollector to collect peripheral CTCs. Thirty metastatic breast cancer (MBC) patients were enrolled, and 17 were analyzed with next-generation sequencing (NGS) methods. Clinical characteristics were analyzed along with the CTCs enumeration and detection rates. Wh...
Source: Neoplasma - Category: Cancer & Oncology Authors: Tags: Neoplasma Source Type: research
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Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
In this study, we conducted a systematic analysis to determine the regulation of TUBB3 expression in breast cancer metastases to the brain and strategically target these metastases using vinorelbine (VRB), a drug approved by the U.S. Food and Drug Administration (FDA). We found that human epidermal growth factor receptor 2 (HER2) signaling regulates TUBB3 expression in both trastuzumab-sensitive and trastuzumab-resistant neoplastic cells. We further discovered that bromodomain and extra-terminal domain (BET) inhibition increases TUBB3 expression, rendering neoplastic cells more susceptible to apoptosis by VRB. Orthotopic x...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research
Mechanisms driving tumor progression from less aggressive subtypes to more aggressive states represent key targets for therapy. We identified a subset of luminal A primary breast tumors that give rise to HER2-enriched (HER2E) subtype metastases, but remain clinically HER2 negative (cHER2–). By testing the unique genetic and transcriptomic features of these cases, we developed the hypothesis that FGFR4 likely participates in this subtype switching. To evaluate this, we developed 2 FGFR4 genomic signatures using a patient-derived xenograft (PDX) model treated with an FGFR4 inhibitor, which inhibited PDX growth in vivo....
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Conditions:   Breast Cancer;   Brain Metastases;   HER2-positive Breast Cancer;   CNS Disease Interventions:   Drug: Tucatinib;   Drug: Pembrolizumab;   Drug: Trastuzumab Sponsors:   Reva Basho;   Merck Sharp & Dohme Corp.;   Seattle Genetics, Inc. Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Abstract Prior to the introduction of trastuzumab, the first targeted anti-HER2 agent, in 1998, patients diagnosed with HER2-positive breast cancer felt like they were being handed a death sentence. Despite treatment with aggressive chemotherapy, their tumors recurred faster, more often spread to brain and liver, and were associated with higher rates of death than HER2-negative tumors. HER2-positive breast cancer was also more prevalent in younger patients, making the diagnosis even more devastating. However, in the 1980s, cancer researcher Axel Ullrich, PhD, and oncologist Dennis Slamon, MD, PhD, recognized that ...
Source: Oncology (Williston Park, N.Y.) - Category: Cancer & Oncology Authors: Tags: Oncology (Williston Park) Source Type: research
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Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Clinical Source Type: research
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Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Endo Takabe We generated a 4-gene score with genes upregulated in LM2-4, a metastatic variant of MDA-MB-231 (DOK 4, HCCS, PGF, and SHCBP1) that was strongly associated with disease-free survival (DFS) in TCGA cohort (hazard ratio [HR]>1.2, p < 0.02). The 4-gene score correlated with overall survival of TCGA (HR = 1 .44, p < 0 .001), which was validated with DFS and disease-specific survival of METABRIC cohort. The 4-gene score was able to predict worse survival or clinically aggressive tumors, such as high Nottingham pathological grade and advanced cancer staging. High score was associated wit...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Poster Session Abstracts Source Type: research
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