(Background) Activation of growth factor receptor (GFR) signaling is related with ER+/PR- breast cancer (BC). Proportion of ER+/PR- phenotype in ER+ BC in postmenopausal patients is higher than that in premenopausal. However, this phenomenon cannot be explained by only GFR signaling activation. We hypothesized that ER+/PR- phenotype in postmenopausal patients has at least two subtypes, one is related with activation of GFR signaling and the other is related with suppression of PR expression due to low estrogenic stimulation.

(Purpose) The aim of this study is to clarify out hypothesis.

(Patients and methods) We measured serum E2 levels with radioimmuno assay (range of E2 levels: 1.3 to 50 pg/ml) in 154 postmenopausal ER+ BC patients. Cut-off levels of ER and PR were used 10% or more expression in tumor cells. We analyzed the correlation between serum levels of E2 and clinicopathological factors including PR expression. We also examined the relationship between HER2 expression levels and ki67 labeling index in ER+/PR- BC. In addition, we analysed the difference in ki67 LI between in premenopausal patients (n = 65) and in postmenopausal patients.

(Results) Median serum levels of E2 in ER+/PR+ phenotype (6.7 pg/ml) were significantly higher than in ER+/PR- phenotype (4.5 pg/ml)(p = 0.036). Serum levels of E2 was positively associated with body mass index (p = 0.01). However, there was no significant difference between serum E2 levels and other clinicopathological factors including tumor size, nodal status, nuclear grade, levels of ER expression and ki67 LI. In ER+/PR- phenotype, ki67 LI were varied (Median: 7.5%, range: 0.5 to 85%). Ki67 LI in Postmenopausal patients with ER+/PR- phenotype was significantly lower than that in premenopausal patients with ER+/PR- phenotype (p = 0.0022). Expression levels of HER2 was positively associated with ki67 LI(p = 0.002).

(Conclusions) ER+/PR- cancer in postmenopausal patients may have two types of phenotype. One is highly proliferative phenotype that is stimulated with GFR signaling. The other is low proliferative one that PR expression is suppressed by without sufficient estrogen supply. Serum levels of E2 might affect development of ER+ BC in postmenopausal women, especially in case of no activation of GFR signaling.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-05-06.