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Prediction of Relapse and Survival in Breast Cancer Patients by pS2 Protein Status

Division of Endocrine Oncology [J. A. F., J. G. M. K.] and Department of Statistics [W. L. J. v. P.] The Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands; Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique [M-C. R., P. C.], Faculté de Médecine, Strasbourg, France; CIS Bioindustries [P. S., J. F.], Laboratorie des Produits pour Analyse Médicale, Bagnols/Cèze Cédex, France; and Laboratory for Public Health [M. N.], Department of Pathology, Leeuwarden, The Netherlands

Application of systemic adjuvant therapy for primary breast cancer patients requires a more accurate identification of patients at high risk for recurrence. We have quantitatively assessed the cytosolic levels of estrogen-regulated pS2 protein in tumors of 205 breast cancer patients (median follow-up, 47 mo). There were no significant associations between the level of pS2 protein and tumor size, lymph node status, and differentiation grade. Using length of relapse-free survival (RFS) and overall survival (OS) as end points, 11 ng of pS2 protein/mg of cytosol protein were found as the best cutoff level to discriminate between positive (pS2⁺) and negative (pS2^-). Patients with pS2^- tumors showed significantly shorter RFS and OS (P < 0.0001) than patients with pS2⁺ tumors. Also after adjustment for tumor size, lymph node status, and estrogen receptor (ER) status, pS2 negativity was associated with earlier recurrence and death. Tumors positive for pS2 (55 of 205, 27%) were almost exclusively confined to the subclass of ER⁺ tumors (53 of 55, 96%). The death rate for patients with pS2⁺ tumors was one-tenth of the death rate for patients with pS2^-/ER^- tumors. In the patients with ER⁺ tumors, the prognostic power of the pS2 status was especially present in patients whose tumors were also positive for the progesterone receptor (5-yr RFS and OS, 85% and 97% for ER⁺/PgR⁺/pS2⁺ tumors compared with 50% and 54% for the patients with ER⁺/PgR⁺/pS2^- tumors). In patients with axillary lymph node involvement (N⁺), pS2 status could discriminate strongly between a good and bad prognosis group (5-yr RFS and OS, 65% and 88% for N⁺/pS2⁺ compared with 32% and 34% for N⁺/pS2^-). A similar phenomenon was observed in patients without axillary lymph node involvement (5-yr RFS and OS, 89% and 95% for N⁰/pS2⁺ compared with 58% and 82% for N⁰/pS2^-).

We conclude that the pS2 status of human primary breast tumors is an important variable for the identification of patients at high risk for recurrence and death. Knowledge of the cytosolic pS2 status appeared of particular importance to identify patients at high risk in the ER⁺/PgR⁺ subclass of tumors, and in both the N⁰ and N⁺ subclasses of patients.

¹ To whom requests for reprints should be addressed, at Dr. Daniel den Hoed Cancer Center, P. O. Box 5201, 3008 AE Rotterdam, The Netherlands.

Received 11/28/89. Revised 2/19/90.

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