Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The natural history of HER2-positive breast cancer has progressively improved since the introduction of the first anti-HER2 directed therapy (trastuzumab). Trastuzumab has significantly increased survival of patients with HER2-positive metastatic breast cancer and, after the standardization of the use of this drug in the adjuvant setting in 2005, has also avoided many disease recurrences and, consequently, saved many lives. Later on, the introduction of lapatinib offered new choices for patients with advanced HER2-positive breast cancer, although the drug has failed to show a clear efficacy in the adjuvant setting. New promising drugs have been approved to broaden the horizon of HER2-positive breast cancer such as pertuzumab or T-DM1, but we need new options to further improve the management of these diseases. In this review, we cover new strategies that are currently under evaluation for the treatment of patients with HER2-positive breast cancer, including new tyrosine kinase inhibitors (neratinib, ONT-380), new antibody-drug conjugates targeting HER2 (MM-302), and new indications of already approved drugs (T-DM1), as well as the potential dual combinations of anti-HER2 therapy with phosphoinositide 3-kinase/mTOR or cell cycle inhibitors (palbociclib, abemaciclib). Last but not least, we briefly review a new paradigm of emerging approaches that involve the host immune response, HER2 breast cancer vaccines, and other immune strategies, including immune checkpoint inhibition.
...
PMID:Emerging Therapeutic Options for HER2-Positive Breast Cancer. 2724 72

Human Epidermal Growth Factor Receptor 2-positive breast cancer (HER2+ BC) is defined by increased amplification of the ERBB2/neu oncogene and/or overexpression of its associated HER2 transmembrane receptor protein. HER2+ BC represents approximately 15-20% of breast cancer, and it is independently associated with a higher grade, more aggressive phenotype, and worse prognosis. With the advent of trastuzumab, the prognostic landscape for HER2+ BC patients has considerably improved. However, both de novo and acquired resistance to trastuzumab remain a significant obstacle for many patients, requiring novel therapies for further clinical benefit. Over the last two decades, there has been extraordinary progress in the development of HER2+ BC treatment regimens, with extensions into HER2-amplified gastroesophageal junction cancer via the NCI-MATCH precision medicine trial program (NCT02465060). Trastuzumab, pertuzumab, T-DM1, and lapatinib are commonly recommended as a single agent (along with chemotherapy) or in combinations of anti-HER2 agents in neoadjuvant, adjuvant and metastatic settings according to National Comprehensive Cancer Network (NCCN) guidelines. Currently, the combination of trastuzumab, pertuzumab, and taxane chemotherapy are first-line for HER2+/HR- metastatic breast cancer with potential breakthrough therapies such as trastuzumab-deruxtecan (DS-8201a), margetuximab and tucatinib (ONT-380) on the horizon. Furthermore, recent clinical trials have demonstrated the potential utility of hormone receptor status, PAM-50 luminal intrinsic subtype, PD-L1, and TIL as predictive biomarkers for response to HER2+ therapies. We briefly introduce the origin of HER2, the invention of trastuzumab, and the classification of HER2+ BC. Each HER2-targeted therapy is then presented by indication, mechanism of action, and relevant clinical trials with subsequent elaboration and contextualization within clinical settings with an epilogue of potential future biomarkers for clinical use in HER2+ BC. We summarize the most significant and updated research in clinical practice relevant to HER2+ BC management and highlight the clinical status of upcoming anti-HER2 agents as well as immunotherapy drugs in combination with anti-HER2 agents.
 ...
PMID:The trastuzumab era: current and upcoming targeted HER2+ breast cancer therapies. 3236 85