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S-Phase Fraction and Urokinase Plasminogen Activator Are Better Markers for Distant Recurrences Than Nottingham Prognostic Index and Histologic Grade in a Prospective Study of Premenopausal Lymph Node–Negative Breast Cancer

From the Jubileum Institute, Department of Oncology, and Department of Pathology and Cytology, Lund University Hospital, Lund; Department of Pathology, Helsingborg Hospital, Helsingborg, Sweden; and Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.

Address reprint requests to Per Malmström, MD, Department of Oncology, Lund University Hospital, SE-221 85 Lund, Sweden; email: Per.Malmstrom{at}onk.lu.se

PURPOSE: Histologic grade, Nottingham Prognostic Index (NPI), estrogen receptor (ER) and progesterone receptor (PgR) status, and tumor size have previously been shown to be important prognostic indicators for distant recurrence of breast cancer. The purpose of this study was to compare the prognostic value of these factors with flow cytometric S-phase fraction (SPF), urokinase plasminogen activator (uPA), and plasminogen activator inhibitor type 1 (PAI-1) in premenopausal patients with lymph node–negative breast cancer.

PATIENTS AND METHODS: In 237 consecutive premenopausal patients with lymph node–negative breast cancer and freshly frozen tumor material available, SPF, ER and PgR status, uPA and its inhibitor PAI-1, histologic grade, and NPI were evaluated.

RESULTS: SPF was univariately the most powerful prognostic factor for distant recurrence, followed by uPA, histologic grade, PgR, age, ER, NPI, and PAI-1, the latter being nonsignificant. Multivariate analysis revealed that neither NPI nor histologic grade was significant after adjustment for SPF, a fact that may be explained by the strong association between these factors. uPA was, however, an independent prognostic factor in addition to SPF, NPI, or histologic grade.

CONCLUSION: In this prospective study, SPF and uPA were found to be independent prognostic factors in premenopausal women with lymph node–negative breast cancer. We suggest that SPF, if performed under standardized conditions, can replace histologic grade as a selection instrument for adjuvant medical treatment. The value of the combination of SPF and uPA needs to be confirmed in an independent prospective trial.

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