ABCB1, FCGR2A, and FCGR3A polymorphisms in patients with HER2-positive metastatic breast cancer who were treated with first-line taxane plus trastuzumab chemotherapy.
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.
Department of Internal Medicine, Seoul National University College of Medicine, Korea.
Ji-Won
JW
Kim
Jee Hyun
JH
Kim
Seock-Ah
SA
Im
Yu Jung
YJ
Kim
Hye-Suk
HS
Han
Jin-Soo
JS
Kim
Sae-Won
SW
Han
Yoon Kyung
YK
Jeon
Do-Youn
DY
Oh
Wonshik
W
Han
Tae-You
TY
Kim
In Ae
IA
Park
Dong-Young
DY
Noh
Yung-Jue
YJ
Bang
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D004273:DNA, Neoplasm / Q000235:genetics; D000077143:Docetaxel; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D017452:Receptors, IgG / Q000235:genetics*; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D061067:Antibodies, Monoclonal, Humanized; D004273:DNA, Neoplasm; D000077143:Docetaxel; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D017452:Receptors, IgG; D043823:Taxoids; D000068878:Trastuzumab; C513055:ABCB1 protein, human; C445323:FCGR2A protein, human; C496124:FCGR3A protein, human