Pregnancy-associated plasma protein A. A clinically significant predictor of early recurrence in stage I breast carcinoma is independent of estrogen receptor status.

Pregnancy-associated plasma protein-A (PAPP-A) immunopositivity and extensive tumor necrosis have been shown to correlate significantly with early (less than 24 months) recurrence in patients with Stage I breast carcinoma negative for estrogen receptor (ER). In this study we have extended our analysis of Stage I disease to include 30 ER-positive cases. Twenty-five traditional clinical and pathologic features were reviewed in addition to the immunoperoxidase staining characteristics of PAPP-A for examination of the independent relationship of immunopositivity both to early recurrence and to ER and progesterone receptor (PR) status. Clinical recurrence developed in 6 of 30 (20%) patients, 4 of the 30 (13%) patients experiencing early recurrence. Pearson chi-square tests revealed significant correlations between early recurrence and PAPP-A tumor positivity (P less than 0.002), younger age (P less than 0.009), and premenopausal status (P less than 0.03). Stepwise regression analysis showed that PAPP-A-positive staining correlated independently with early recurrence. Of the 10 PAPP-A-positive tumors, 4 (40%) recurred within 2 years, compared with no early recurrences in the 20 PAPP-A-negative cases. With a comparison of frequency of PAPP-A positivity of ER-positive (30%) tumors and ER-negative tumors (40%), there was no correlation with ER or PR status. PAPP-A tumor positivity is independent of ER status and is a clinically significant independent predictor of early recurrence in both ER-positive and ER-negative Stage I patients.