Recent Developments in HER2-Directed Therapy in Breast Cancer

AbstractPurpose of ReviewThis review will discuss recent important trials for the treatment of HER2-positive breast cancer, emphasize ongoing areas of development, and highlight areas of unmet need.Recent FindingsAdvances for early-stage treatment have been driven by key clinical trials with pertuzumab, neratinib, and TDM-1. In the adjuvant setting, dual HER2 targeting with trastuzumab and pertuzumab has demonstrated modest improvement in disease-free survival. Neratinib also showed modest benefit in the extended adjuvant setting after prior trastuzumab. Finally, for patients who did not achieve pathologic complete response to neoadjuvant therapy, adjuvant therapy with TDM-1 showed significant disease-free survival benefit over trastuzumab. In advanced disease, neratinib appears to have activity beyond standard second line treatment. Promising compounds with early-phase data reviewed are tucatinib, margetuximab, and antibody-drug complexes. Immunotherapy in HER2-positive disease also has early-phase data. Endocrine therapy in combination with CDK4/6 inhibition and HER2-targeted therapy is in evaluation. Two areas of unmet need include CNS disease and disease treatment in the elderly population.SummaryIn the wake of recent practice changing clinical trials, HER2-directed therapy is rapidly evolving. Future advances in therapy are anticipated with ongoing studies.
Source: Current Breast Cancer Reports - Category: Cancer & Oncology Source Type: research

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Authors: Batoo S, Bayraktar S, Al-Hattab E, Basu S, Okuno S, Glück S Abstract With the introduction of anthracycline-based regimens, 5-year survival rates have significantly improved in patients with early-stage breast cancer. With the addition of trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor-2 (HER2), improvements in overall survival have been observed among patients with advanced HER2-positive disease. Subsequently, lapatinib, an orally bioavailable small molecule dual HER2- and EGFR/HER1-specific tyrosine kinase inhibitor, received Food and Drug Administration (FDA)...
Source: Journal of Carcinogenesis - Category: Cancer & Oncology Tags: J Carcinog Source Type: research
Breast cancer (BC) with overexpression and/or amplification of the Human Epidermal Growth Factor Receptor 2 (HER2-positive) represents 11-30% of all breast tumors[1]. HER2 positivity is defined today by immunohistochemistry (IHC) as complete and strong membrane staining (i.e. score of 3+) in ≥10% of cancer cells, and/or by in situ immunofluorescence (ISH) techniques as amplified using a HER2/CEP17 ratio cutoff of ≥ 2.0 and an average HER2 gene copy number ≥ 4.0 signals per cell[2]. This consensus definition is based on the methods and cutoffs used over the years in pivotal trials that led to the approval of trastu...
Source: Cancer Treatment Reviews - Category: Cancer & Oncology Authors: Tags: Systematic or Meta-analysis Studies Source Type: research
ConclusionIn the neoadjuvant setting, the pCR rate with the standard TCbHP  →  T-DM1+P regimen was numerically better than the TCbHP regimen alone and significantly better in patients with ER+. Personalization of the T-DM1+P regimen could serve as a reasonable approach to minimize toxicity while maintaining efficacy.Trial registration ID: UMIN-CTR: UMIN000014649.
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
ConclusionsDisease progression occurred intracranially more often than extracranially following resection of a solitary BCBM. In ER+ patients, postoperative hormonal therapy was associated with longer OS. Postoperative HER2-targeted therapy did not show survival benefit in HER2+ patients. These results should be validated in larger cohorts.
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
CONCLUSION: The Erk signaling pathway may be crucially involved in the differentiation induction of breast cancer cells in vitro and in vivo. Collectively, our results suggest that the combination can probably serve as promising candidates for the development of novel therapeutic approaches for different types of breast cancer. PMID: 31934280 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
Conclusions The effectiveness and safety results of eribulin as the first- or second-line treatment were favorable. Thus, these suggest eribulin may be a first-line treatment candidate for patients with HER2-negative advanced breast cancer in Japan.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research
ntamaria-Martinez Rüegg Membrane-associated guanylate kinase (MAGUK) with inverted domain structure-1 (MAGI1) is an intracellular adaptor protein that stabilizes epithelial junctions consistent with a tumor suppressive function in several cancers of epithelial origin. Here we report, based on experimental results and human breast cancer (BC) patients’ gene expression data, that MAGI1 is highly expressed and acts as tumor suppressor in estrogen receptor (ER)+/HER2− but not in HER2+ or triple negative breast cancer (TNBC). Within the ER+/HER2− subset, high MAGI1 expression associates...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Abstract Quadruple negative breast cancer (QNBC), lacking the expression of ER (estrogen receptor), PR (progesterone receptor), HER2 (human epidermal growth factor receptor-2) and AR (androgen receptor), was regarded as one breast cancer subtype with the worst prognosis. Recently, the molecular features of QNBC are not well understood. Different from AR-positive triple-negative breast cancer, QNBC is insensitive to conventional chemotherapeutic agents and has no efficient treatment targets. However, QNBC has been shown to express unique proteins that may be amenable to use in the development of targeted therapies....
Source: Breast Cancer - Category: Cancer & Oncology Authors: Tags: Breast Cancer Source Type: research
Condition:   HER2+/HR+ Breast Cancer Interventions:   Drug: ZW25;   Drug: Palbociclib;   Drug: Fulvestrant Sponsor:   Zymeworks Inc. Recruiting
Source: - Category: Research Source Type: clinical trials
Condition:   Advanced Breast Cancer Interventions:   Drug: Abemaciclib;   Drug: Aromatase Inhibitors Sponsor:   University of Milano Bicocca Not yet recruiting
Source: - Category: Research Source Type: clinical trials
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