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FROM THE LITERATURE
Breast Cancer
How Many Prognostic Tests Do We Need?
The September 1, 2008 issue of the Journal of Clinical Oncology
(JCO) includes an article and an accompanying editorial that address prognostic
tests for breast cancer. For the reader, several questions immediately come to mind:
Is one test “better” than the other(s)? Should we develop more tests to cover all
of the various factors involved? Is there an “ideal” prognostic test for breast
cancer?
- Currently two independently validated prognostic tests are
widely used,
Adjuvant! Online and the Oncotype DXTM recurrence score (RS)
assay. Adjuvant! is a mathematical algorithm that provides an estimate of risk of
breast cancer (BC) related death at 10-year follow-up based on the tumor size, the
number of involved nodes, and estrogen receptor (ER) status. Estimates of the efficacy
of therapy are based primarily on the proportional risk reduction (PRR) analysis
from the Oxford overview. The 21-Gene RS Assay, a genomic classifier, provides individualized
risk estimates based on measurement of the expression of 16 cancer-related genes
and has the potential to more accurately identify individuals who benefit from chemotherapy.
- The trial by Goldstein et al compared these two very different prognostic
tests in a retrospective study of BC patients with hormone receptor (HR) positive
disease and zero to three positive axillary nodes who received contemporary chemohormonal
therapy. It should be noted that the study population is quite different from the
originally intended clinical target population (ER+, axillary node negative BC treated
with tamoxifen) for RS assay. Result: RS was a highly significant predictor of recurrence,
in both node (-) and node (+) disease (p<0.001 for both). RS also predicted recurrence
more accurately than clinical variables when integrated by an algorithm modeled
after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate
was only 5% or less for the estimated 46% of patients who have a low RS (<18).
The 21-Gene RS Assay may be useful to select low-risk patients for abbreviated chemotherapy
regimens or high-risk patients for more aggressive regimens or clinical trials evaluating
novel therapies.
- The most significant information from this trial is that RS and
Adjuvant! are independent of each other with a modest concordance, BUT within each
risk category defined by Adjuvant!, RS provided additional prognostic information
and vice-versa. For the 43% of those who were in the low Adjuvant! risk group, the
risk of recurrence was increased 2.6-fold and 4.0-fold respectively for intermediate
and high RS. For the 30% of patients in the intermediate Adjuvant! risk group, the
risk of recurrence was increased 9.6-fold and 5.8-fold respectively for intermediate
and high RS. For the 24% of patients in the high Adjuvant! risk group, only high
RS was associated with a significantly increased risk of relapse (2.6-fold). It
is also clear that Adjuvant! can also provide additional information for risk groups
defined by RS. Thus the best scenario for a patient is to have a low RS score and
low risk according to Adjuvant!. If either of the two shows poor risk, then the
risk of relapse appears to be increased.
- Lastly, this study also demonstrated a need to integrate RS and
Adjuvant! into a single prognostic algorithm. There are some technical hurdles to
overcome, but new trials to implement this strategy are underway. So which test
is better? A combined approach appears to provide the best of both worlds.
Goldstein LJ, et al. J Clin Oncol 26: 4063-4071, 2008
Paik S. J Clin Oncol 26: 4058-4059, 2008
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