Targeting HER2 Positive Breast Cancer with Chemopreventive Agents

Wahler, J.; Suh, Nanjoo

doi:10.1007/s40495-015-0040-z

Cited by 26 publications

(15 citation statements)

References 132 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a result, HER2 receptor is overexpressed in HER2+ BC patients up to 20 times more than in normal tissues 6. This overexpression is involved in the cell proliferation maintenance, avoiding apoptosis and in favoring cell spreading and metastasis formation 7.…”

Section: Introductionmentioning

confidence: 99%

Theranostic application of miR-429 in HER2+ breast cancer

et al. 2020

View full text Add to dashboard Cite

Human epidermal growth factor receptor 2 (HER2) is overexpressed/amplified in one third of breast cancers (BCs), and is associated with the poorer prognosis and the higher metastatic potential in BC. Emerging evidences highlight the role of microRNAs (miRNAs) in the regulation of several cellular processes, including BC.Methods: Here we identified, by in silico approach, a group of three miRNAs with central biological role (high degree centrality) in HER2+ BC. We validated their dysregulation in HER2+ BC and we analysed their functional role by in vitro approaches on selected cell lines and by in vivo experiments in an animal model.Results: We found that their expression is dysregulated in both HER2+ BC cell lines and human samples. Focusing our study on the only upregulated miRNA, miR-429, we discovered that it acts as an oncogene and its upregulation is required for HER2+ cell proliferation. It controls the metastatic potential of HER2+ BC subtype by regulating migration and invasion of the cell.Conclusions: In HER2+ BC oncogenic miR-429 is able to regulate HIF1α pathway by directly targeting VHL mRNA, a molecule important for the degradation of HIF1α. The overexpression of miR-429, observed in HER2+ BC, causes increased proliferation and migration of the BC cells. More important, silencing miR-429 succeeds in delaying tumor growth, thus miR-429 could be proposed as a therapeutic probe in HER2+ BC tumors.

show abstract

Section: Introductionmentioning

confidence: 99%

Theranostic application of miR-429 in HER2+ breast cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Currently, several treatments targeting HER2 are approved, which include monoclonal antibodies and small molecule inhibitors of receptor kinases or their combinations with chemotherapeutic agents [ 3 , 4 ]. Trastuzumab (Herceptin; Genentech, South San Francisco, CA, USA) was the first monoclonal antibody developed to target HER2.…”

Section: Introductionmentioning

confidence: 99%

Combination of lapatinib with isothiocyanates overcomes drug resistance and inhibits migration of HER2 positive breast cancer cells

Kaczyńska

Herman-Antosiewicz

2016

Breast Cancer

View full text Add to dashboard Cite

BackgroundLapatinib is a commonly used drug that interrupts signaling from the epidermal growth factor receptors, EGFR and HER2/neu. Long-term exposure to lapatinib during therapy eliminates cells that are sensitive to the drug; however, at the same time it increases probability of lapatinib-resistant cell selection. The aim of this study was to verify whether combinations of lapatinib with one of isothiocyanates (sulforaphane, erucin or sulforaphene), targeting different levels of HER2 signaling pathway, exert stronger cytotoxic effect than therapy targeting the receptor only, using heterogeneous populations consisting of lapatinib-sensitive and lapatinib-resistant breast cancer cells.MethodsLapatinib-sensitive HER2 overproducing SKBR-3 breast cancer cells and their lapatinib-resistant derivatives were combined at different proportions to simulate enrichment of cancer cell population in a drug-resistant fraction during lapatinib therapy. Effects of treatments on cell survival (MTT), apoptosis induction (PARP cleavage), prosurvival signaling (p-Akt, p-S6) as well as cell motility (wound healing assay) and invasion (Boyden chamber assay) were investigated.ResultsCombination of lapatinib with any of isothiocyanates significantly decreased cell viability and inhibited migration of populations consisting of different amounts of drug-sensitive and drug-resistant cells. In case of population entirely composed of lapatinib-resistant cells the most effective was combination of lapatinib with erucin which decreased cell viability and motility, phosphorylation of Akt, S6 and VEGF level more efficiently than each agent alone.ConclusionsCombination of lapatinib and isothiocyanates, especially erucin, might be considered as an effective treatment reducing metastatic potential of breast cancer cells, even these with the drug resistance phenotype.

show abstract

“…Human epidermal growth factor receptor 2 (HER2) is a transmembrane protein that plays a key role in the regulation of cell growth, apoptosis, and differentiation, so overactivity of HER2 will lead to malignant biological behavior in the breast [1]. HER2 gene amplification and/or protein overexpression occurs in approximately 25–30% of invasive breast cancer [2, 3].…”

Section: Introductionmentioning

confidence: 99%

HER2 double-equivocal breast cancer in Chinese patients: a high concordance of HER2 status between different blocks from the same tumor

Liu

Shi

et al. 2019

Breast Cancer Res Treat

View full text Add to dashboard Cite

PurposeHuman epidermal growth factor receptor 2 (HER2) status is both an independent prognostic factor and a predictive factor for the efficacy of targeted therapy for breast cancer, so it is critical to accurately detect HER2 protein expression and/or gene amplification. According to the recommendations of the 2013 American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) guidelines for HER2 breast cancer testing, an additional test should be pursued on a different block from the same tumor as one of the options for patients with immunohistochemistry (IHC) 2+ and a HER2/CEP17 ratio of < 2.0 with an average HER2 signals per tumor cell of ≥ 4.0 and < 6.0 by reflex test using dual-probe fluorescence in situ hybridization (FISH) (double-equivocal HER2). Our aim in this study is to explore the consistency of HER2 status between the two blocks.MethodsWe retrospectively analyzed 5685 primary invasive breast cancers between April 2015 and January 2019 from Peking Union Medical College Hospital. For cases with double-equivocal HER2 revealed in initial blocks, HER2 gene status was evaluated by FISH in a different block from the same tumor. The FISH score was interpreted according to the 2013 ASCO/CAP guidelines for HER2 testing.ResultsIn our cohort of 5685 specimens, the overall HER2 IHC3+, 2+, 1+ and 0 cases were 20.5%, 31.8%, 28.3%, and 19.5%, respectively. Then, 13.7%, 66.3%, and 20.0% of HER2 amplification, non-amplification, and equivocation rates were found, respectively, in IHC2+ patients (n = 1777) by reflex FISH assay. For specimens with double-equivocal HER2 (n = 333), HER2 status was assessed in another block from the same tumor by FISH and then the frequency of HER2 positive, negative, and equivocation was estimated at 5.7%, 22.5%, and 71.8%, respectively. Because double-equivocal HER2 cases are classified in the HER2 negative category by the 2018 ASCO/CAP HER2 testing guidelines, only 1.3% (19/1511) of HER2 positive patients were determined through additional HER2 testing in another block from the HER2 negative population.ConclusionsHER2 status in different blocks from the same tumor in primary invasive breast cancer was highly concordant. Our data supported the recommendation of the 2018 ASCO/CAP HER2 testing guidelines in breast cancer to remove the suggestion for additional HER2 testing using another block contained in the previous version.

show abstract

Targeting HER2 Positive Breast Cancer with Chemopreventive Agents

Cited by 26 publications

References 132 publications

Theranostic application of miR-429 in HER2+ breast cancer

Theranostic application of miR-429 in HER2+ breast cancer

Combination of lapatinib with isothiocyanates overcomes drug resistance and inhibits migration of HER2 positive breast cancer cells

HER2 double-equivocal breast cancer in Chinese patients: a high concordance of HER2 status between different blocks from the same tumor

Contact Info

Product

Resources

About