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A systematic review of dual targeting in HER2-positive breast cancer
Iben Kümler1, Malgorzata K Tuxen, Dorte Lisbet Nielsen
1Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
Background:
Human epidermal growth factor receptor 2 (HER2) is overexpresed in 15-20% of all breast cancers. Treatment with trastuzumab has led to an improved outcome and prolonged survival of HER2-positive breast cancer patients and today the drug is established as standard of care in both the adjuvant and metastatic settings. However, trastuzumab resistance is common and a major focus in the treatment of HER2-positive breast cancer has been developing therapeutic agents to either potentiate the effect of trastuzumab or to target cells which have become resistant to trastuzumab. The present review addresses efficacy and toxicity of dual targeting in HER2-positive breast cancer.
Materials And Methods:
A computer-based literature search was carried out using PubMed; data reported at international meetings and clinicaltrials.gov was included.
Results:
This paper describes efficacy and safety of lapatinib, pertuzumab or trastuzumab-DM1 in combination with trastuzumab in the (neo)adjuvant and metastatic settings. Furthermore, combinations of trastuzumab and drugs targeting the downstream pathway are described.
Conclusion:
Dual blockade is likely to represent a substantial advance for patients with HER2-positive breast cancer. However, the relevant subpopulation remains to be defined and side effects including cardiotoxicity might be a limiting factor to the use. There is an urgent need for prospective biomarker-driven trials to identify patients for whom dual targeting is cost-effective.
Insights
Dual targeting strategies show promise for HER2-positive breast cancer, combining trastuzumab with other agents to overcome resistance. Further research is needed to define patient populations and manage side effects like cardiotoxicity.
Area of Science:
- Oncology
- Cancer Therapeutics
- Molecular Biology
Background:
- Human epidermal growth factor receptor 2 (HER2) overexpression occurs in 15-20% of breast cancers.
- Trastuzumab is a standard treatment for HER2-positive breast cancer, improving outcomes but facing resistance.
- Developing agents to enhance trastuzumab efficacy or overcome resistance is a key research focus.
Purpose of the Study:
- To review the efficacy and toxicity of dual targeting strategies in HER2-positive breast cancer.
- To explore combinations of trastuzumab with other agents and downstream pathway inhibitors.
Main Methods:
- A literature search was conducted using PubMed.
- Data from international meetings and clinicaltrials.gov were included.
Main Results:
- The review covers the efficacy and safety of lapatinib, pertuzumab, and trastuzumab-DM1 in combination with trastuzumab.
- Combinations involving trastuzumab and drugs targeting downstream pathways are also discussed.
Conclusions:
- Dual blockade offers potential advancements for HER2-positive breast cancer patients.
- Identifying specific patient subpopulations and managing side effects like cardiotoxicity are crucial.
- Biomarker-driven trials are needed to determine cost-effectiveness.
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