Pregnancy-associated plasma protein A and extensive necrosis. Clinically significant predictors of early recurrence in stage I estrogen receptor-negative breast carcinoma

: Despite advances in the detection of early breast cancer, 25 to 35% of patients with stage I disease die from metastatic breast carcinoma. To identify those patients at risk for early recurrence, we reviewed 33 clinical and pathologic features as well as immunoperoxidase-staining characteristics for carcinoembryonic antigen, human chorionic gonadotrophin, pregnancy specific beta-1 glycoprotein, and pregnancy-associated plasma protein A (PAPP-A), in 40 patients with stage I estrogen receptor-negative breast carcinoma. Sixteen of the 40 patients (40%) developed tumor recurrence within 2 years. Pairwise correlations between recurrence and clinicopathologic features, including tumor marker immunostaining, revealed significant correlations between extensive necrosis, nuclear atypia, mitoses, and PAPP-A staining. In multivariant linear discriminant analysis, only PAPP-A staining and extensive necrosis entered as significant independent predictors. In the recurrent group, nine of 16 (56%) were PAPP-A positive compared with one of 24 (4%) in the nonrecurrent group (p less than 0.001), whereas nine of 16 (56%) contained extensive necrosis compared with three of 24 (11%) in the nonrecurrent group (p less than 0.005). When the independent risk factor of PAPP-A positivity and extensive necrosis were combined, 13 of 16 (81%) of the recurrent tumors were either PAPP-A positive or extensively necrotic compared with four of 24 (16%) of the nonrecurrent group. Thus, positive immunostaining for PAPP-A and the presence of extensive necrosis are clinically significant independent predictors of early recurrence in patients with stage I, estrogen receptor-negative breast carcinoma. These risk factors for early recurrence may be helpful in prospectively selecting patients most eligible to receive adjuvant chemotherapy.