Pertuzumab: new hope for patients with HER2-positive breast cancer.
BACKGROUND
Human epidermal growth factor receptor 2 (HER2) overexpression is detected in approximately 15% to 20% of all breast cancers (BCs). A revolutionary change in the prognosis of this subgroup of patients has occurred since trastuzumab therapy was introduced into daily clinical practice. However, because trastuzumab resistance is common, new molecules with complementary and/or synergistic mechanisms of action have been developed. Pertuzumab is a new anti-HER2 humanized monoclonal antibody that prevents the formation of HER2 dimers.


METHODS
A computer-based literature search was carried out using PubMed (keywords: breast neoplasm, dimerization, HER-2, pertuzumab); data reported at international meetings are included.


RESULTS
This paper describes pertuzumab's mechanism of action, safety, and role in HER2-positive BCs. It also explores the role of pertuzumab as a single agent or combined with trastuzumab by reviewing data from preclinical research to ongoing clinical trials. Recently published trials, particularly the CLEOPATRA study, highlight the efficacy, tolerability, and increase in disease-free survival associated with this novel agent when combined with trastuzumab.


CONCLUSIONS
The pertuzumab and trastuzumab anti-HER2 dual blockade is likely to represent a substantial advance for patients with HER2-positive BCs and a new milestone on the way to personalized medicine.
Department of Medicine, Institute Jules Bordet, L'Université Libre de Bruxelles, Brussels; BrEAST Data Center, Institute Jules Bordet, l'Université Libre de Bruxelles, Brussels.
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M
Capelan
Department of Medicine, Institute Jules Bordet, L'Université Libre de Bruxelles, Brussels; Breast International Group (BIG), Brussels.
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L
Pugliano
Department of Medicine, Institute Jules Bordet, L'Université Libre de Bruxelles, Brussels; BrEAST Data Center, Institute Jules Bordet, l'Université Libre de Bruxelles, Brussels.
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E
De Azambuja
Department of Medicine, Institute Jules Bordet, L'Université Libre de Bruxelles, Brussels; BrEAST Data Center, Institute Jules Bordet, l'Université Libre de Bruxelles, Brussels.
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Bozovic
Department of Medicine, Institute Jules Bordet, L'Université Libre de Bruxelles, Brussels; Breast International Group (BIG), Brussels.
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KS
Saini
Department of Medicine, Institute Jules Bordet, L'Université Libre de Bruxelles, Brussels; Breast Cancer Translational Research Laboratory (BCTL) JC Heuson, Institut Jules Bordet, Brussels, Belgium.
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C
Sotiriou
Breast International Group (BIG), Brussels; Breast Cancer Translational Research Laboratory (BCTL) JC Heuson, Institut Jules Bordet, Brussels, Belgium.
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S
Loi
Department of Medicine, Institute Jules Bordet, L'Université Libre de Bruxelles, Brussels; Breast International Group (BIG), Brussels. Electronic address: martine.piccart@bordet.be.
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MJ
Piccart-Gebhart
D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019281:Dimerization; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D000068878:Trastuzumab
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C485206:pertuzumab