DNA flow cytometry but not telomerase activity as predictor of disease-free survival in pT1-2/N0/G2 breast cancer.
OBJECTIVE
In the subgroup of patients with node-negative (N0) moderately differentiated (G2) breast cancer, the clinical decision of giving adjuvant therapy is critical. The aim of this study was to investigate the prognostic value of biomarkers (DNA flow cytometry and telomerase activity in correlation with routinely used estrogen receptors (ER) and HER oncoprotein) in pT1-2/N0/G2 breast cancer, for improving therapeutic management.


METHODS
The series involved 135 patients with pT1-2/N0/G2 breast cancer and median follow-up of 58.5 months. DNA ploidy and S-phase fraction (SPF) (<or=5%; 5-10%; >10%) were assessed on frozen samples. Telomerase activity, ER and c-erbB-2 expression were analyzed by standardized immunohistochemistry techniques. A Cox regression analysis was performed for prognostic evaluation.


RESULTS
Aneuploidy significantly correlated with high SPF and lack of ER, while high SPF showed significant correlations with high telomerase activity, c-erbB-2 overexpression and absence of ER. Kaplan-Meier curves showed significant differences for ploidy and SPF in relation with disease-free survival (DFS) and overall survival (OS), and a statistical trend for ER. By Cox regression analysis, DNA aneuploidy (RR = 16.7; p = 0.007) and high SPF (RR = 23.1; p = 0.004) revealed significant correlations with worse DFS. Among patients with diploid (n = 76) and low/intermediate SPF (n = 85) tumors, only one had recurrence of the disease. No association between telomerase activity and clinical outcome was observed.


CONCLUSIONS
In pT1-2/N0/G2 breast cancer patients, DNA ploidy and SPF are relevant prognostic biomarkers that should be considered as additional tools in the therapeutic planning.
Pinto
António E
AE
Serviço de Anatomia Patológica do Instituto Português de Oncologia de Lisboa, E.P.E., Portugal. aepinto@ipolisboa.min-saude.pt
André
Saudade
S
Pereira
Teresa
T
Silva
Giovani
G
Soares
Jorge
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D011003:Ploidies; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D016196:S Phase; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D019098:Telomerase