SAN ANTONIOLong-term disease-free survival in
node-positive, estrogen-receptor (ER)-positive postmenopausal breast cancer
patients is improved when hormonal therapy follows chemotherapy, according to a
10-year analysis of the Breast Cancer Intergroup of North America Trial 0100,
presented at the 27th Annual San Antonio Breast Cancer Symposium (abstract 37).
"In many cases, tamoxifen or other hormonal therapy alone is
not optimal," said Kathy S. Albain, MD, of Loyola University Chicago Stritch
School of Medicine, Maywood, Illinois. "This survival advantage is greatest
when tamoxifen follows chemotherapy, rather than being given concurrently."
Dr. Albain performed a 10-year follow-up analysis of 1,477
patients enrolled in INT 0100. A total of 550 patients received concurrent
chemohormonal therapy (CAFT) (cyclophosphamide, doxorubicin, fluorouracil,
tamoxifen); another 566 patients received sequential chemohormonal therapy (CAF-T);
and 361 patients received tamoxifen alone. Previous analyses showed superior
survival in the combined CAF + T arms vs tamoxifen alone, and with CAF-T vs
CAFT. The current study was the updated, mature outcomes analysis on the entire
study population, with additional analyses of biomarkers to explore whether
certain profiles can predict benefit from CAF.
Confirming the earlier findings, tamoxifen alone continued
to be inferior to the combined CAF + T arms for both disease-free and overall
survival, with adjusted hazard ratios of 1.31 and 1.21, respectively.
Concurrent CAFT was worse than sequential CAF-T for both disease-free and
overall survival (adjusted hazard ratios of 1.20 and 1.12, respectively).
Ten-year estimates of disease-free survival were 48% for
tamoxifen alone; 53% for concurrent chemohormonal therapy; and 60% for
sequential therapy. Ten-year overall survival estimates were 60%, 62%, and 68%,
The biomarker analysis contributed important new information
from this study population, which Dr. Albain cautioned was
hypothesis-generating and not yet ready for clinical use. From tissue available
from 782 patients, information was obtained on ER level positivity using
immunohistochemistry (IHC) by Allred score, mitotic and nuclear grade, HER2
status by IHC with Tab250 and CB11 or by FISH, and p53 expression.
In univariate analysis, significant adverse prognostic
factors for disease-free survival were HER2-positivity by IHC Tab250, four or
more positive nodes, larger tumor size, progesterone-receptor (PgR)-negative
status, high mitotic grade, and p53 positivity. A particularly favorable
prognostic group was women who were HER2 negative and PgR positive (P =
.003), she said. Factors that were not significantly prognostic included ER
positivity by various cutoffs, nuclear grade, and HER2 status by IHC CB11 or
Predictive factors for disease-free survival benefit from
CAF (adjusted hazard ratio) included HER2 positivity by IHC Tab250 (54%
improvement vs 22% with negative HER2 status); p53 positivity (56% vs 20% for
p53 negative); high nuclear grade (48% for grade 3 vs 7% for grade 1-2); and
low/intermediate ER score (score of 6-7) vs high ER score (score of 7-8) (44%
improvement vs no benefit for high ER score). None of these tests was
significant due to the small number of patients in the groups.
"We discovered that women with very high ER levels in their
tumors can probably avoid chemotherapy," she said, "but those with low or
intermediate levels benefit from it over and above tamoxifen."
High ER score was the only informative analysis in the
prediction of a benefit from the timing of tamoxifen in the two CAF arms. Those
with high ER levels had an improvement in disease-free survival with sequencing
(CAF-T), compared with CAFT, she said. There was no added benefit to CAF vs
tamoxifen alone in a favorable group with one to three positive nodes and HER2