S-phase fraction and urokinase plasminogen activator are better markers for distant recurrences than Nottingham Prognostic Index and histologic gradein a prospective study of premenopausal lymph node-negative breast cancer

Purpose: Histologic grade, Nottingham Prognostic Index (NPI), estrogen rece ptor (ER) and progesterone receptor (PSR) status, and tumor size have previ ously been shown to be important prognostic indicators for distant recurren ce of breast cancer. The purpose of this study was to compare the prognosti c value of these factors with flow cytometric S-phase fraction (SPF), uroki nase 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, SP F, ER and PgR status, uPA and its inhibitor PAI-1, histologic grade, and NP I were evaluated. Results: SPF was univariately the most powerful prognostic factor for dista nt recurrence, followed by uPA, histologic grade, PgR, age, ER, NPI, and PA I-l,the latter being nonsignificant. Multivariate analysis revealed that ne ither NPI nor histologic grade was significant after adjustment for SPF, ct fact that may be explained by the strong association between these factors . uPA was, however, an independent prognostic factor in addition to SPF, NP I, or histologic grade. Conclusion: In this prospective study, SPF and uPA were found to be indepen dent prognostic factors in premenopausal women with lymph node-negative bre ast cancer. We suggest that SPF, if performed under standardised conditions , can replace histologic grade as a selection instrument for adjuvant medic al treatment. The value of the combination of SPF and uPA needs to be confi rmed in an independent prospective trial. (C) 2001 by American Society of C linical Oncology.