Tumor histology and stage but not p53, Her2-neu or cathepsin-D expression are independent prognostic factors in breast cancer patients.
BACKGROUND
Several factors are currently employed for prognosis assessment and treatment determination in breast cancer. An array of molecular parameters, such as p53, Her2-neu (c-erbB 2) and Cathepsin-D, are also examined to improve clinical patient management. We have conducted a statistically powerful study of the prognostic value of conventional factors and of the investigational factors p53, Her2-neu and Cathepsin-D in patients with invasive breast carcinoma, in order to compare their significance. Our analysis was extended to determine the associations of p53 and Her2-neu with risk of death and relapse among patients with and without lymph node metastases.


METHODS
In a set of 125 primary breast tumors, p53 and Her2-neu expression were immunohistochemically evaluated. Cathepsin-D, estrogen and progesterone receptor concentrations were determined in cytosols by a standard immunoradiometric assay.


RESULTS
Over a mean of 62 months, 49 patients (39%) had a relapse and 29 patients (23%) died. Overexpression of p53, Her2-neu and Cathepsin-D was observed in 31%, 46% and 88% of cases, respectively. Overall survival was associated with histology (hazard ratio 0.04, 95% confidence interval: 0.01, 0.49 for lobular tumors) and stage (hazard ratio 5.94, 95% confidence interval: 1.30, 27.15 for stage III samples). Disease-free survival was also related to histology (hazard ratio 0.23, 95% confidence interval: 0.08, 0.73 for lobular tumors) and stage (hazard ratio 4.27, 95% confidence interval: 1.36, 13.36 for stage III tumors). Patients with both negative nodal status and Her2-neu overexpression tended to display an elevated risk of death.


CONCLUSIONS
Our results support the prognostic power of tumor histology and stage and emphasize the need for further studies on the prognostic impact of p53. Her2-neu and Cathepsin-D in breast cancer. Additionally, our analysis indicates that deregulation of Her2-neu might characterize a subgroup of node-negative patients with poor prognosis who could benefit from an aggressive adjuvant therapy.
Department of Surgery, St Savvas Hospital, Athens, Greece.
D P
DP
Korkolis
E
E
Tsoli
D
D
Fouskakis
J
J
Yiotis
G J
GJ
Koullias
D
D
Giannopoulos
E
E
Papalambros
N I
NI
Nikiteas
C A
CA
Spiliopoulou
E
E
Patsouris
P
P
Asimacopoulos
V G
VG
Gorgoulis
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D002402:Cathepsin D / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D002402:Cathepsin D; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53