ABCB1, FCGR2A, and FCGR3A polymorphisms in patients with HER2-positive metastatic breast cancer who were treated with first-line taxane plus trastuzumab chemotherapy.

Abstract

OBJECTIVE:

The aim of this study was to elucidate clinical implications of ABCB1, FCGR2A, and FCGR3A polymorphisms in patients with HER2-positive metastatic breast cancer (MBC) after taxane plus trastuzumab (TH) chemotherapy.

METHODS:

Using genomic DNA samples extracted from mononuclear cells of consecutive patients with HER2-positive MBC who received first-line TH, we analyzed five polymorphisms (ABCB1 1236C>T, ABCB1 2677G>T/A, ABCB1 3435C>T, FCGR2A 131H/R, and FCGR3A 158V/F) and then correlated them with the response rate, progression-free survival (PFS), overall survival (OS), and adverse events of patients.

RESULTS:

A total of 57 women were analyzed. The median age was 46 years (range 27-72). ABCB1 2677T carriers had a longer PFS (p = 0.037) along with a tendency toward a longer OS (p = 0.057). ABCB1 3435CC genotype carriers had a shorter PFS (p = 0.039) along with a tendency toward a shorter OS (p = 0.093). In combined analysis, PFS was significantly longer in ABCB1 1236CC and/or 2677TT carriers compared to the others (p = 0.006). FCGR2A 131H/R and FCGR3A 158V/F polymorphisms were not significantly associated with response rate, PFS, and OS.

CONCLUSIONS:

Our data support that ABCB1 polymorphisms may predict PFS after first-line TH chemotherapy in patients with HER2-positive MBC. In contrast, FCGR2A 131H/R and FCGR3A 158V/F polymorphisms could not predict treatment outcomes.

• Authors: Ji-Won Kim, Jee Hyun Kim, Seock-Ah Im, Yu Jung Kim, Hye-Suk Han, Jin-Soo Kim, Sae-Won Han, Yoon Kyung Jeon, Do-Youn Oh, Wonshik Han, Tae-You Kim, In Ae Park, Dong-Young Noh, Yung-Jue Bang
• Journal: Oncology (Oncology) Vol. 83 Issue 4 Pg. 218-27 ( 2012) ISSN: 1423-0232 [Electronic] Switzerland
• PMID: 22906996 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 S. Karger AG, Basel.

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antibodies, Monoclonal, Humanized
• DNA, Neoplasm
• FCGR2A protein, human
• FCGR3A protein, human
• Receptors, IgG
• Taxoids
• Docetaxel
• Receptor, ErbB-2
• Trastuzumab
• Paclitaxel

Topics

• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy, genetics, mortality)
• DNA, Neoplasm (genetics)
• Docetaxel
• Female
• Follow-Up Studies
• Humans
• Immunoenzyme Techniques
• Middle Aged
• Neoplasm Metastasis
• Paclitaxel (administration & dosage)
• Polymerase Chain Reaction
• Polymorphism, Genetic (genetics)
• Prognosis
• Receptor, ErbB-2 (metabolism)
• Receptors, IgG (genetics)
• Survival Rate
• Taxoids (administration & dosage)
• Trastuzumab