scholarly journals The HER2 Receptor in Breast Cancer: Pathophysiology, Clinical Use, and New Advances in Therapy

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Zahi Mitri ◽  
Tina Constantine ◽  
Ruth O'Regan
Keyword(s):  
Breast Cancer ◽  
Cardiac Myocyte ◽  
Early Stage ◽  
Standard Of Care ◽  
Breast Cancers ◽  
Trastuzumab Resistance ◽  
Her2 Receptor ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Human epidermal growth factor receptor 2 (HER2) is overexpressed in around 20–30% of breast cancer tumors. It is associated with a more aggressive disease, higher recurrence rate, and increased mortality. Trastuzumab is a HER2 receptor blocker that has become the standard of care for the treatment of HER2 positive breast cancer. The effectiveness of Trastuzumab has been well validated in research as well as in clinical practice. The addition of Trastuzumab to standard of care chemotherapy in clinical trials has been shown to improve outcomes for early stage as well as metastatic HER2 positive breast cancer. The most clinically significant side effect of Trastuzumab is the risk of cardiac myocyte injury, leading to the development of congestive heart failure. The emergence of patterns of resistance to Trastuzumab has led to the discovery of new monoclonal antibodies and other targeted agents aimed at overcoming Trastuzumab resistance and improving survival in patients diagnosed with HER2 positive breast cancers.

Neratinib for the treatment of early-stage, hormone receptor-positive, HER2-overexpressed breast cancer

2020 ◽  
Vol 16 (17) ◽  
pp. 1165-1177
Author(s):  
Yolanda Jerez ◽  
Blanca Herrero ◽  
Marta Arregui ◽  
Blanca Morón ◽  
Miguel Martín ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Kinase Inhibitor ◽  
Early Stage ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Future Directions ◽  
Her2 Positive Breast Cancer ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

HER2-positive breast cancer accounts for 18–20% of all breast cancers. Despite significant advances and the currently available adjuvant treatments for management of the disease, approximately 25% of HER2-positive early-stage breast cancer patients show relapse and die. Neratinib is an irreversible tyrosine kinase inhibitor. Multiple studies have reported its significant antitumor activity in metastatic HER2-positive breast cancer. It is administered orally and has also been tested in the adjuvant setting. In this article, we present a comprehensive review of the pharmacokinetics and pharmacodynamics of neratinib as well as its clinical efficacy, with an emphasis on early HER2-positive breast cancer and suggestions for future directions for neratinib research.

scholarly journals The Changing Paradigm for the Treatment of HER2-Positive Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2081 ◽  
Author(s):  
Aena Patel ◽  
Nisha Unni ◽  
Yan Peng
Keyword(s):  
Breast Cancer ◽  
Targeted Therapies ◽  
Standard Of Care ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Her2 Positive Breast Cancer ◽  
Metastatic Setting ◽  
Treatment Paradigm ◽  
Positive Breast Cancer

For decades, HER2-positive breast cancer was associated with poor outcomes and higher mortality rates than other breast cancer subtypes. However, the advent of Trastuzumab (Herceptin) has significantly changed the treatment paradigm of patients afflicted with HER2-positive breast cancer. The discovery of newer HER2-targeted therapies, such as Pertuzumab (Perjeta), has further added to the armamentarium of treating HER2-positive breast cancers. This review highlights recent advancements in the treatment of HER2-positive diseases, including the newer HER2-targeted therapies and immunotherapies in clinical trials, which have paved (and will further update) the way for clinical practice, and become part of the standard of care in the neoadjuvant, adjuvant or metastatic setting.

scholarly journals Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2922
Author(s):  
Ryan W. Holloway ◽  
Paola A. Marignani
Keyword(s):  
Breast Cancer ◽  
Treatment Strategies ◽  
Mtor Pathway ◽  
Breast Cancers ◽  
Her2 Receptor ◽  
Her2 Positive ◽  
Risk Of Recurrence ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Up to one third of all breast cancers are classified as the aggressive HER2-positive subtype, which is associated with a higher risk of recurrence compared to HER2-negative breast cancers. The HER2 hyperactivity associated with this subtype drives tumor growth by up-regulation of mechanistic target of rapamycin (mTOR) pathway activity and a metabolic shift to glycolysis. Although inhibitors targeting the HER2 receptor have been successful in treating HER2-positive breast cancer, anti-HER2 therapy is associated with a high risk of recurrence and drug resistance due to stimulation of the PI3K-Akt-mTOR signaling pathway and glycolysis. Combination therapies against HER2 with inhibition of mTOR improve clinical outcomes compared to HER2 inhibition alone. Here, we review the role of the HER2 receptor, mTOR pathway, and glycolysis in HER2-positive breast cancer, along with signaling mechanisms and the efficacy of treatment strategies of HER2-positive breast cancer.

scholarly journals Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials

2021 ◽  
Vol 22 (8) ◽  
pp. 1139-1150
Author(s):  
Rosie Bradley ◽  
Jeremy Braybrooke ◽  
Richard Gray ◽  
Robert Hills ◽  
Zulian Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Meta Analysis ◽  
Randomised Trials ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Influence of Anthropometric Characteristics in Patients With Her2-Positive Breast Cancer on Initial Plasma Concentrations of Trastuzumab

2017 ◽  
Vol 51 (11) ◽  
pp. 976-980 ◽  
Author(s):  
Jonathan González García ◽  
Fernando Gutiérrez Nicolás ◽  
Gloria Julia Nazco Casariego ◽  
José Norberto Batista López ◽  
Isaac Ceballos Lenza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Standard Dose ◽  
Plasma Concentrations ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Initial Plasma ◽  
Anthropometric Characteristics ◽  
Secondary Objective ◽  
Positive Breast Cancer

Background: Plasma concentrations of trastuzumab <20 µg/mL in patients with gastric cancer are associated with reduced progression-free and overall survival. In breast cancer treatment, this relationship has not yet been studied, but a suboptimal pharmacodynamic exposure to trastuzumab could be a reason for therapeutic failure of treatment of HER2-positive breast cancer. Objective: The objective of the present study was to determine the proportion of nonmetastatic HER2-positive breast cancers that do not reach a minimum plasma concentration ( Cmin) of 20 µg/mL after first drug administration, established as therapeutically effective in clinical trials. The secondary objective was to identify the physiological and anthropometric characteristics that determine interindividual pharmacokinetic variability. Methods: Serum concentrations of trastuzumab were assessed by ELISA on day 1 of the second cycle before administration of the second dose ( Cmin). Results: Of 19 patients included, 9 (47.4%) had a mean Cmin of 19.0 µg/mL (±12.1) after the first administration. Body mass index (BMI) and weight was the main variable that determined the achievement of therapeutic levels after the first administration. Thus, the proportion of patients reaching the target concentration was 89% when BMI was ≤30 kg/m2 but only 11% when BMI was >30 kg/m2 ( P < 0.01). Conclusions: The standard dose of 600 mg subcutaneous trastuzumab did not ensure adequate pharmacodynamic exposure from the first administration in 52% of patients, with weight and BMI being related to the plasma levels obtained.

scholarly journals Adjuvant breast cancer: (neo)adjuvant therapy for HER2-positive breast cancer

2019 ◽  
Vol 12 (4) ◽  
pp. 312-314 ◽  
Author(s):  
Christoph Suppan ◽  
Marija Balic
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Annual Meeting ◽  
Early Stage ◽  
Postoperative Treatment ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Adjuvant Breast Cancer ◽  
American Society ◽  
Positive Breast Cancer

Summary Early stage HER2-positive cancer outcomes have been substantially improved over the last two decades, but there is still some potential for improvement. Several studies on the preoperative/postoperative treatment of HER2-positive breast cancer were presented at the American Society of Clinical Oncology (ASCO) 2019 annual meeting.

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