RISING LEVELS OF ESTROGEN-RECEPTOR IN BREAST-CANCER OVER 2 DECADES

Background. The incidence of estrogen receptor (ER)positive breast can cer apparently is increasing. It remains unclear whether this increase is due to an improvement in receptor assay sensitivity, a change in p atient characteristics, or a change in tumor biology. Methods. The dis tribution of ER, tumor size, and patient age for 11,195 tumor specimen s gathered from patients nationwide from 1973 to 1992 were analyzed. A ll assays were performed in a single laboratory. A single-label, dextr an-coated charcoal (DCC) method was used from 1973 to 1984, and a dual -label, DCC method, which allows the determination of both ER and prog esterone receptor levels in the same assay, was used from 1985 to 1992 . Results. The median level of ER has increased steadily from 14 fmol per milligram of protein in 1973 to 58 fmol per milligram of protein i n 1992 (P < 0.0001). The percentage of ER-positive tumors also rose fr om 73-78% during the same period (P = 0.008). When the assay method wa s modified from single to dual label, no abrupt or stepwise increase o ccurred. Tumor size decreased over the same period (P < 0.0001). From 1973 to 1977, 48% of tumors were larger than 2 cm, and 15% were larger than 5 cm, compared to 60% and 9%, respectively, from 1988 to 1992. T he percentage of women older than 50 years of age remained relatively constant over time. After adjusting for tumor size, age, number of pos itive lymph nodes, and change in assay method, a sustained rise in ER level remained. In a multivariate analysis that included age, age grou p, year of biopsy, tumor size, and number of positive nodes, the year of biopsy still was independently predictive of ER level (P < 0.0001). Conclusion. The measured level of ER in primary breast cancers has in creased during the last 2 decades. It is unlikely that technical impro vements or changes in tumor size, age, or nodal status fully explain t his increase. The rising level of ER may reflect a change in breast ca ncer biology and in hormonal events that influence breast cancer genes is and growth.