A systematic review of dual targeting in HER2-positive breast cancer

Iben Kümler; Malgorzata K Tuxen; Dorte Lisbet Nielsen

doi:10.1016/j.ctrv.2013.09.002

A systematic review of dual targeting in HER2-positive breast cancer

Iben Kümler, Malgorzata K Tuxen, Dorte Lisbet Nielsen

Department of Clinical Medicine

108 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Cancer Treatment Reviews
Volume	40
Issue number	2
Pages (from-to)	259-270
Number of pages	12
ISSN	0305-7372
DOIs	https://doi.org/10.1016/j.ctrv.2013.09.002
Publication status	Published - Mar 2014

Keywords

Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols
Breast Neoplasms
Clinical Trials as Topic
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic
Humans
Maytansine
Molecular Targeted Therapy
Neoadjuvant Therapy
Protein Kinase Inhibitors
Protein-Tyrosine Kinases
Quinazolines
Quinolines
Receptor, ErbB-2
Sirolimus
TOR Serine-Threonine Kinases
Treatment Outcome
Tumor Markers, Biological
Up-Regulation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ctrv.2013.09.002

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title = "A systematic review of dual targeting in HER2-positive breast cancer",

abstract = "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.",

keywords = "Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Clinical Trials as Topic, Disease-Free Survival, Female, Gene Expression Regulation, Neoplastic, Humans, Maytansine, Molecular Targeted Therapy, Neoadjuvant Therapy, Protein Kinase Inhibitors, Protein-Tyrosine Kinases, Quinazolines, Quinolines, Receptor, ErbB-2, Sirolimus, TOR Serine-Threonine Kinases, Treatment Outcome, Tumor Markers, Biological, Up-Regulation",

author = "Iben K{\"u}mler and Tuxen, {Malgorzata K} and Nielsen, {Dorte Lisbet}",

year = "2014",

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doi = "10.1016/j.ctrv.2013.09.002",

language = "English",

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AU - Kümler, Iben

AU - Tuxen, Malgorzata K

AU - Nielsen, Dorte Lisbet

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N2 - 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.

AB - 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.

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KW - Disease-Free Survival

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KW - Humans

KW - Maytansine

KW - Molecular Targeted Therapy

KW - Neoadjuvant Therapy

KW - Protein Kinase Inhibitors

KW - Protein-Tyrosine Kinases

KW - Quinazolines

KW - Quinolines

KW - Receptor, ErbB-2

KW - Sirolimus

KW - TOR Serine-Threonine Kinases

KW - Treatment Outcome

KW - Tumor Markers, Biological

KW - Up-Regulation

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SN - 0305-7372

VL - 40

SP - 259

EP - 270

JO - Cancer Treatment Reviews

JF - Cancer Treatment Reviews

IS - 2

ER -

A systematic review of dual targeting in HER2-positive breast cancer

Abstract

Keywords

UN SDGs

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