Four genes by RT-PCR predicts distant relapse for women given adjuvant tamoxifen.
Desmedt C, Loi SM, Haibe-Kains B, Soree A, Lallemand F, Durbecq V,
Larsimont D, Tutt A, Ellis P, Gillett C, Ryder K, Harris A, Cardoso F,
Martiat PH, Piccart MJ, Sotiriou C
Background:
There have been many gene classifiers developed recently that claim to
predict clinical outcome better than currently used clinical factors.
Whilst microarray technology offers huge advantages in furthering our
knowledge of breast cancer biology, for present-day use, clinically
applicable and useful tools may need only the quantitative information
that is provided by genes that are already well known to convey
prognostic/predictive information in breast cancer.
Material and methods: Our aim
was to assess if the results of a
reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay for the
genes ER, PgR, HER2/Neu and Ki67 in frozen tissue could correlate with
distant disease recurrence in 175 breast cancer patients from 2
institutions treated with adjuvant tamoxifen only and followed for a
median of 9.4 years. All RT-PCR experiments were performed in duplicate.
Results: Adequate RT-PCR
profiles were obtained for 154 of 175 tumors. We constructed a score
from a linear combination of the coefficients from a multivariate Cox
analysis including the 4 genes (likelihood ratio test, overall
p-value<0.001) and the expression of those genes. When considering
the score as a binary variable with the median as cutoff, a hazard
ratio (HR) of 3.7 (95% CI: 1.8-7.6, p<0.001) was reached with 97%,
95% and 91% of the patients being distant metastasis free at 3, 5 and
10 years in the low risk group and 88%, 74% and 65% in the high risk
group respectively. In a Cox model that included the binary score and
traditional prognostic variables (tumor size, grade, age, nodal
status), the score was the only significant predictor of distant
metastasis at .05 level with a HR of 2.7 (95%CI: 1.2-6.2, p=0.019) and
tumor size was borderline significant (p=0.052). Similar HR were found
when considering the score as a continuous variable both in univariate
and multivariate analysis.
Discussion: We are currently
validating this score on a further 100 samples and comparing with
RT-PCR results on corresponding paraffin-embedded tumour tissue. A
comparison between RT-PCR and immunohistochemistry is also ongoing.
This simple test using the RT-PCR value of 4 genes could provide an
immediately applicable and cheap clinical tool that can assist
clinicians in discriminating high and low risk prognostic groups for
ER+ women treated with tamoxifen.