use of tumor markers in testicular, prostate, colorectal, breast, and ...

Tumor Markers in Breast Cancer 49
NACB Breast Cancer Panel Recommendation 7:
Gene Expression Profiling, as Determined by
Microarray, for Predicting Outcome
None of the microarray-based gene signatures currently
available should be routinely used for predicting patient
outcome [LOE, III; SOR, B].
Oncotype DX Test
Oncotype DX (Genomic Health, Redwood City, CA) is a
multigene assay that quantifies the likelihood of breast cancer
recurrence in women with newly diagnosed, early stage breast
cancer (for review, see ref (391). Rather than using microarray
technology, this test uses RT-PCR to measure the expression
21 genes (16 cancer associated and five control genes).
Based on the expression of these genes, a recurrence score (RS)
was calculated that predicted low, intermediate and high risk
of distant metastasis for ER-positive patients, treated with adjuvant
tamoxifen (392). The RS was prospectively validated in
an independent population of lymph node–negative ER-positive
patients treated with adjuvant tamoxifen, as part of the
National Surgical Adjuvant Breast and Bowel Project trial B14
(392). In this validation study, the RS was an independent predictor
of patient outcome. The independent prognostic impact
of the RS was later confirmed in a population-based case-control
study (393). While a low RS predicted good outcome in
patients treated with adjuvant tamoxifen, a high RS was found
to be associated with favourable outcome in patients treated
with either neoadjuvant or adjuvant chemotherapy (394, 395).
A particular advantage of this test is that it may be carried out
on formal-fixed paraffin-embedded tissue.
Currently, the RS is undergoing prospective validation as
part of the Trial Assigning Individualized Options for Treatment
trial (396). In this trial, patients with intermediate RS are being
randomly assigned to receive hormone therapy alone or hormone
therapy plus chemotherapy. The aim is to establish if adjuvant
chemotherapy improves survival in the group of patients
with the intermediate score. Also, in this trial, patients with low
RS after tamoxifen therapy will receive endocrine treatment
while those with high RS will be given chemotherapy and hormone
therapy.
NACB Breast Cancer Panel Recommendation 8:
Oncotype DX Test for Predicting Outcome
The Oncotype DX test may be used for predicting recurrence
in lymph node–negative, ER-positive patients receiving
adjuvant tamoxifen. Patients predicted to have a good
outcome may be able to avoid having to undergo treatment
with adjuvant chemotherapy [LOE, I/II; SOR, A].
The Oncotype DX test may also be used to predict benefit
from adjuvant chemotherapy (CMF or methotrexate
and 5-fluorouracil) in node-negative, ER-positive patients
(ie, patients with high recurrence score appear to derive
greater benefit from chemotherapy than those with low
scores) [LOE, III; SOR, B].
KEY POINTS: TUMOR MARKERS
IN BREAST CANCER
The best-validated markers in breast cancer are all tissue based
and include ER, PR, HER-2, uPA, and PAI-1. Assay of ER,
PR, and HER-2 is now mandatory for all newly diagnosed
breast cancer patients. The measurement of uPA and PAI-1,
although technically and clinically validated (361-363, 366,
367), is not presently in widespread clinical use, mainly due
to the requirement of a minimum amount of fresh or freshly
frozen tissue. Assay of these proteins however, may be used to
aid the selection of lymph node–negative breast cancer patients
who do not need adjuvant chemotherapy. Similarly, the
Oncotype DX test may be used for predicting recurrence in
lymph node–negative, ER-positive patients receiving adjuvant
tamoxifen. Although widely used in postoperative surveillance
and monitoring therapy in advanced disease, the clinical value
of CA 15-3, and other serum markers has not yet been validated
by a level I evidence study.