|
Chemosensitivity
and
stratification by a five monoclonal antibody immunohistochemistry test
in the
NSABP B14 and B20 trials.
Clin
Cancer Res 2008
Oct 15; 14(20): 6602-9
Douglas T. Ross1,
Chung-yeul Kim2, Gong Tang3,5,
Olga L. Bohn2,
Rodney A. Beck7, Brian Z. Ring1,
Robert S. Seitz7,
Soonmyung Paik2, Joseph P. Costantino3,5
and Norman
Wolmark4,6
1 Applied Genomics, Inc., Burlingame,
California; 2 Division
of Pathology and 3 Biostatistical Center, 4
National
Surgical Adjuvant Breast and Bowel Project; 5
Department of
Biostatistics, Graduate School of Public Health, University of
Pittsburgh; 6
Allegheny General Hospital, Pittsburgh, Pennsylvania; and 7
Applied
Genomics, Inc., Huntsville, Alabama
ABSTRACT
PURPOSE: To
test the association
between risk stratification and outcome in a prospectively designed,
blinded
retrospective study using tissue arrays of available paraffin blocks
from the
estrogen receptor-expressing, node-negative samples from the National
Surgical
Adjuvant Breast and Bowel Project B14 and B20 tamoxifen and
chemotherapy
trials.
EXPERIMENTAL
DESIGN: Tissue arrays
were stained by immunohistochemistry targeting p53, NDRG1, SLC7A5,
CEACAM5, and
HTF9C. Risk stratification was done using predefined scoring rules,
algorithm
for combining scores, and cutoff points for low-risk, moderate-risk,
and
high-risk patient strata. RESULTS: In a univariate Cox model, this test
was
significantly associated with recurrence-free interval [HR, 1.3 (95%
confidence
interval, 1.1-1.6); P = 0.006]. In a multivariate model it contributed
information independent of age, tumor size, and menopausal status (P =
0.007).
The Kaplan-Meier estimates of the proportion of recurrence-free after
10 years
were 73%, 86%, and 85% for the high-risk, moderate-risk, and low-risk
groups (P
= 0.001). The Kaplan-Meier estimates of the
breast-cancer-specific-death rate
were 23%, 10%, and 9% (P < 0.0001). Exploratory analysis in
patients
>/=60 years old showed Kaplan-Meier estimates of the proportion
of
recurrence-free of 78%, 89%, and 92%. Both high-risk and low-risk
groups showed
significant improvement on treatment with cytotoxic chemotherapy.
CONCLUSIONS:
Immunohistochemistry
using five monoclonal antibodies assigns breast cancer patients to a
risk index
that was significantly associated with clinical outcome among the
estrogen
receptor-expressing, node-negative tamoxifen-treated patients. It seems
that
the test may be able to identify patients who have greater absolute
benefit
from adjuvant chemotherapy compared with unstratified patient
populations.
Exploratory analysis suggests that this test will be most useful in
clinical
decision making for postmenopausal patients.
 |
 |
| |
(.4
MB PDF) |
|
