Abstract: The majority of patients with breast carcinoma receive
chemotherapy as a component of multimodality treatment. Over the
past decade, it has become increasingly more common to deliver
chemotherapy first, but this has raised new questions within all
disciplines of cancer management. However, the effect of cytotoxic
treatment cannot be predicted on individually specific basis, then
identification of tumor characteristics associated with tumor
therapeutic response and outcome is then of great clinical
interest. We studied 141 patients at Masaryk Memorial Cancer
Institute, who received neoadjuvant chemotherapy and/or
chemotherapy + radiotherapy (CHT/CHT+RT) between 1994--2002. Tumor
samples were taken prior to and after neoadjuvant therapy. We
quantified the response to therapy pathologically and determined
histological and molecular tumor characteristics (steroid
receptors, CEA, Ca 15-3). In addition to therapeutic response as
immediate outcome, event free survival (EFS) was examined as more
complex primary end-point of the study. Complete remission (CR)
has been achieved in 6.5%, partial remission (PR) in 49.6%, stable
disease (SD) in 26.2% and progression disease (PD) in 17.7%
patients. Patients were divided into two groups according to the
result of neoadjuvant therapy -- responders (CR+PR+SD, who
successfully underwent surgery), and risk group (patients with SD
or PD, who could not undergo surgery). Responders to neoadjuvant
CHT/CHT+RT regimens reached statistically significant better EFS
than non-responders, low tumor size (T2) and stage (II) categories
were confirmed as additional predictive factors not only for EFS
but for therapeutic response as well. The study primarily examined
predictive power of tumor markers as CEA, Ca 15-3, and steroid
receptors (ER/PR) and searched for their role in the prospective
evaluation of neoadjuvant therapy. We evaluated these factors as
potential predictors of EFS, independent in predictive power on
therapeutic response to neoadjuvant therapy. Diagnostically
valuable cut off points were proposed in ROC analysis for all
these markers. Responders to the neoadjuvant therapy with Ca 15-3
<23.0 kU/l, CEA <5.0 mg/l, estrogen receptors (ER) >5.0 fmol/mg or
both estrogen /progesterone receptors (ER/PR) positive had
statistically significantly better EFS in comparison to patients
with Ca 15-3 ż23.0 kU/l, CEA ż5.0 mg/l, ER Ă5.0 fmol/mg, or other
cases than patients double positive in ER/PR. Marker Ca 15-3
revealed significant predictive power even within the group of non-
responders, these patients with Ca 15-3 <23.0 kU/l had better EFS
as compared to patients with Ca 15-3 ż23.0 kU/l. Tumor size and
low stage proved predictive value for immediate response to
neoadjuvant therapy. Risk parameters for neoadjuvant therapy were
T4, stage III, namely if RT was necessary. Therapeutic response to
neoadjuvant therapy was independent on investigated molecular
parameters, but there was strong predictive association of Ca 15-
3, CEA and ER/PR receptors with event free survival development.
Diagnostically valuable cut-off points were proposed and validated
for sensitivity and specificity in ROC analysis.
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