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ABSTRACT: S-Phase Fraction and DNA Ploidy in 633 T1T2 Breast Cancers:
A Standardized Flow Cytometric Study
[04/19/2001; Clinical Cancer Research]
The lack of a standardized methodology for quantifying DNA ploidy
and S-phase fraction (SPF) by flow cytometry is hindering routine
use of these markers in breast cancer management. In a retrospective
clinical multicenter study, we validated a standardized flow
cytometry protocol. We tested 633 frozen T1T2, N0N1, M0 breast
tumors obtained in four institutions. Cell preparation was standardized,
and precise rules for data interpretation were followed. Three
SPF classes were defined on the basis of tertiles after adjustment
for ploidy. DNA aneuploidy was observed in 61.0% of cases.
No
significant difference was observed among centers. Aneuploidy
and high SPF were associated with large tumor size, node involvement,
high histological grade, and hormone receptor negativity. In
the overall population (median follow-up, 69 months), patients
with medium and high SPF values had shorter disease-free survival
(DFS) than those with low SPF values (P < 0.0001). Ploidy
had no significant influence. By Cox analysis, SPF, pN, and estrogen
receptor status were independent predictors of DFS (P = 0.0002,
P = 0.001, and P = 0.05).
In node-negative patients, SPF was
the only predictor of DFS (P = 0.01), whereas in node-positive
patients, the risk of relapse increased with both high SPF (P
= 0.003) and estrogen receptor negativity (P = 0.004). Low SPF
values distinguished grade II tumors with a particularly good
outcome.
Our results strongly support the use of SPF in multicenter
studies and clinical trials and suggest that node-negative patients
with slowly proliferating tumors do not require systemic adjuvant
therapy.
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