Pathologic findings from the national surgical adjuvant breast project. Correlations with concordant and discordant estrogen and progesterone receptors

Abstract

Pathologic materials were available for review from 1597 women with Stage II (positive regional node metastases) invasive breast cancer in whom estrogen receptor (ER) and progesterone receptor (PR) assays of the primary tumor were performed. These women were enrolled in a clinical trial comparing the effect of postmastectomy adjuvant L‐phenylalanine mustard (L‐PAM) and 5‐fluorouracil (5‐FU) with and without tamoxifen (NSABP Protocol No. 9). Significant pathologic and clinical associations with receptor status were similar for both ER and PR except that the latter, unlike ER, was not related to patient age. Regression analyses revealed that the most significant pathologic features related to a concordant positive ERPR receptor status was low (well differentiated) nuclear and histologic grades, slight or absent tumor lymphoid infiltrate, slight or absent necrosis and moderate or marked elastica in decreasing order of importance. All of the factors enumerated are directly or indirectly related to tumor differentiation. Recognition of four or five conforming pathologic features allows for the prediction of either ER or PR status in 70% to 80% of instances respectively, and the presence of three features in 69%. This latter figure is similar to that of estimation of nuclear grade alone. Thirty percent of ERPR estimates were discordant i.e., either ER‐PR+ or ER+PR‐. Pathologic features associated with discordant assays were not similar to those found when the ERPR estimates were concordant. Life table analyses revealed patients with discordant receptors to exhibit disease‐free survival intermediate to that of those with ER+PR+ and ER‐PR‐ values. This information suggests that a discordant receptor status is more reflective of an aberration of ER metabolism than a methodologic error. Histograms correlating frequency of nuclear grades with levels of ER and PR were comparable and revealed patterns indicating the propriety of relating values less than 10 fm/mg as being receptor negative. The frequency of well‐differentiated nuclei increased with ascending levels of ER and PR.