Breast cancer aromatase expression evaluated by the novel antibody 677: Correlations to intra-tumor estrogen levels and hormone receptor status

Breast cancer tissue estrogen levels on an average exceed plasma as well as benign breast tissue levels. To evaluate the contribution of intra-tumor aromatization to individual tumor estrogen levels (estradiol, E 2; estrone, E 1; estrone sulfate, E 1S), breast cancer tissue sections obtained during mastectomy in 28 postmenopausal breast cancer patients were stained for aromatase protein expression using the aromatase antibody 677. The findings were correlated to intra-tumor estrogen levels determined with a highly sensitive HPLC-RIA. Staining with 677 alone (irrespective of the hormone receptor status) revealed no difference in tumor E 2 levels comparing 677+ versus 677− tumors, although a non-significant trend towards higher tumor E 1 and E 1S levels was observed in 677+ breast cancers. In contrast, tumor levels of E 2 were significantly higher in ER+ tumors compared to ER− tumors ( P < 0.001) and to benign breast tissue from the same breast ( P < 0.001). Analysing the additional effect of positive staining with the aromatase antibody 677 on tumor estrogen levels in the subgroup of ER+ tumors, revealed significantly higher tumor levels of E 2 (mean level of 544.7 versus 197.1 fmol/g tissue) as well as a non-significant trend concerning tumor E 1 (mean level of 296.9 versus 102.1 fmol/g tissue). The mean tumor tissue E 1S level was observed somewhat lower in ER+677+ (103.5 fmol/g) versus ER+677− tumors (190.1 fmol/g). In the subgroup of ER+PgR+ tumors, tissue levels of E 2 were also found to be significantly higher among 677+ compared to 677− tumors: 873.2 fmol/g (95% CI 395.9–1925.6) versus 217.9 fmol/g (95% CI 88.8–534.9) ( P = 0.015). In conclusion, our results indicate a moderate effect of aromatase enzyme expression evaluated by IHC using the antibody 677 on intra-tumor estrogen levels among ER+ breast cancers. A substantial interindividual variation in the ratios between the individual estrogen fractions suggests additional effects, like alterations in other enzymes to be involved in the intra-tumor estrogen homeostasis.