The Cyclin D1 (CCND1) A870G polymorphism predicts clinical outcome to lapatinib
and capecitabine in HER2-positive metastatic breast cancer.
Author(s): Labonte MJ, Wilson PM, Yang D, Zhang W, Ladner RD, Ning Y, Gerger A, Bohanes PO,
Benhaim L, El-Khoueiry R, El-Khoueiry A, Lenz HJ.
Affiliation(s): Department of Medicine, University of Southern California, Los Angeles, CA, USA.
Publication date & source: 2012, Ann Oncol. , 23(6):1455-64
BACKGROUND: Lapatinib plus capecitabine emerged as an efficacious therapy in
metastatic breast cancer (mBC). We aimed to identify germline single-nucleotide
polymorphisms (SNPs) in genes involved in capecitabine catabolism and human
epidermal receptor signaling that were associated with clinical outcome to assist
in selecting patients likely to benefit from this combination.
PATIENTS AND METHODS: DNA was extracted from 240 of 399 patients enrolled in
EGF100151 clinical trial (NCT00078572; clinicaltrials.gov) and SNPs were
successfully evaluated in 234 patients. The associations between SNPs and
clinical outcome were analyzed using Fisher's exact test, Kaplan-Meier curves,
log-rank tests, likelihood ratio test within logistic or Cox regression model, as
appropriate.
RESULTS: There were significant interactions between CCND1 A870G and clinical
outcome. Patients carrying the A-allele were more likely to benefit from
lapatinib plus capecitabine versus capecitabine when compared with patients
harboring G/G (P = 0.022, 0.024 and 0.04, respectively). In patients with the
A-allele, the response rate (RR) was significantly higher with lapatinib plus
capecitabine (35%) compared with capecitabine (11%; P = 0.001) but not between
treatments in patients with G/G (RR = 24% and 32%, respectively; P = 0.85). Time
to tumor progression (TTP) was longer in patients with the A-allele treated with
lapatinib plus capecitabine compared with capecitabine (median TTP = 7.9 and 3.4
months; P < 0.001), but not in patients with G/G (median TTP = 6.1 and 6.6
months; P = 0.92).
CONCLUSION: Our findings suggest that CCND1A870G may be useful in predicting
clinical outcome in HER2-positive mBC patients treated with lapatinib plus
capecitabine.
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