Distant metastasis after radical treatment of breast cancer: risk factors and their prognostic relevance in 378 consecutive patients.
OBJECTIVE
To evaluate the prognostic significance of 16 clinical, pathomorphological and immunohistochemical features for predicting distant metastasis (DM) and 5-year overall survival (OS) in breast cancer (BC) patients.


METHODS
A retrospective study of 378 patients with invasive BC (T1-3N0-3M0), who were operated between 2000 and 2003 at our Institution, was carried out. Almost 80% had undergone modified radical mastectomy (MRM). Tumor size (T), axillary lymph nodes status (N), age, menstrual status, histological type, grade (G), lymphovascular invasion (LVI), in situ component, estrogen receptor (ER), progesterone receptor (PgR) content, HER-2, Ki-67, p53, bcl-2, cathepsin D and E-cadherin were evaluated. Mean follow- up time was 56 months (range 1-88).


RESULTS
During the follow-up period 66 (17.4%) patients developed DM and 76 (20.1%) patients died. Univariate analysis showed that T (p=0.0001), N (p=0.0001), presence of comedo type in situ component (p=0.0001), LVI (p=0.016), Ki-67 (+) (p=0.007) and cathepsin D (+) (p=0.013) were independent prognostic indicators for increased risk for DM. After multivariate analysis only N (+) status (odds ratio/OR 8.8; 95% confidence interval/ CI 3.5- 21.77; p=0.0001) and presence of comedo type in situ component (OR 2.4; 95% CI 1.19-4.74; p=0.015) retained their significant association with DM development. The same 2 factors also influenced 5-year OS: N(+), OR 3.8; 95% CI: 1.36-10.56; p=0.011; and comedo type in situ component, OR 3.3; 95% CI: 1.61-6.56; p=0.001.


CONCLUSIONS
N (+) status and presence of comedo type in situ component are the most reliable predictors of unfavorable events in BC patients. Our study is among the first ones to find a relationship between the presence of in situ component and risk for DM in patients after MRM. The results also show that comedo type intraductal component, no matter how extensive it is, bears high risk for DM equal to N1 axillary status and patients with presence of such intraductal component should be treated as N(+). The evaluation of optimal number of risk markers is substantial for making an individualized decision regarding adjuvant therapy, especially in N0 group.
Daskalova
I
I
University Centre of Oncology, Department of Surgical Oncology, Medical University, and University Hospital Dr. G. Stranski, Department of Clinical Pathology, Pleven, Bulgaria. iskradaskalova@yahoo.com
Popovska
S
S
Betova
T
T
Velkova
A
A
Ivanova
N
N
Baitchev
G
G
Delijski
T
T
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000556:secondary* / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012307:Risk Factors; D016896:Treatment Outcome
D014408:Biomarkers, Tumor