Breast-conserving therapy: proteases as risk factors in relation to survival after local relapse.
OBJECTIVE
To evaluate whether cathepsin D, urokinase-type plasminogen activator (uPA), its inhibitor, plasminogen activator inhibitor-1 (PAI-1), or clinical factors can predict which patients are at risk for developing distant metastases after local recurrence (LR).


METHODS
Of 1,630 patients treated with breast-conserving surgery and radiotherapy of the breast between 1980 and 1992, LR developed in 171 as a first event. From the available primary tumor tissues, we determined the cytosolic levels of cathepsin D, uPA and PAI-1.


RESULTS
In patients with LR, a short (< or = 2 years) disease-free interval (DFI) and skin involvement of LR were associated with poor postrelapse distant metastasis-free survival (PR-DMFS, P = .001, both) and postrelapse overall survival (PR-OS; P < .0001 and P < .0002, respectively). The primary tumor levels of uPA and PAI-1 were elevated for patients with a short DFI (P < .01), but such a relation was not observed for patients with skin involvement. In univariate analyses, high levels of uPA and PAI-1 in the primary tumor were associated with poor PR-OS (P = .038 and P = .040, respectively) but not PR-DMFS. In Cox multivariate analyses for PR-DMFS and PR-OS, only a short DFI and skin involvement of the LR were independently associated with a poor clinical outcome.


CONCLUSIONS
In patients treated with breast-conserving therapy who had LR as a first event, a short DFI and skin involvement were strong indicators for poor PR-DMFS and PR-OS. The proteases studied did not contribute significantly to the final multivariate model.
Meijer-van Gelder
M E
ME
Department of Medical Oncology, Rotterdam Cancer Institute, Dr. Daniel den Hoed Kliniek/Academic Hospital Rotterdam, The Netherlands.
Look
M P
MP
Bolt-de Vries
J
J
Peters
H A
HA
Klijn
J G
JG
Foekens
J A
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D002402:Cathepsin D / Q000032:analysis*; D003600:Cytosol / Q000737:chemistry; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009364:Neoplasm Recurrence, Local; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012307:Risk Factors; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
D009363:Neoplasm Proteins; D017395:Plasminogen Activator Inhibitor 1; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014568:Urokinase-Type Plasminogen Activator; D002402:Cathepsin D