A Comparison Of Clinico-pathological Characteristics Between ER+/PR+ And ER+/PR- Breast Tumors

ObjectiveWe studied the differences in the clinicopathological and molecular biological factors between ER+/PR+ and ER+/PR- breast cancers,in order to find assistant markers to predict the response to endocrine therapy.We also studied the relationship between the EGF which promotes the proliferation of estrogen dependent cells and the signal pathway of ER.The relationship betweenα₂-adrenergic receptor signal pathway and ER and EGF was also approached.MethodsPartâ… :4000 female breast cancer patients with known ERfPR expression status were enrolled into this retrospective study.Clinicopathological factors and molecular biological factors such as c-erbB-2 and PS2 detected by immunohistochemistry were compared between the two groups.Partâ…¡:Breast cancer cells were treated with fulvestrant,and the effects to the proliferation of MCF-7,T-47-D and MCF-7 RTR(MCF-7 resistant to anthracycline) were detected by WST.The effect of EGF to MCF-7 and its interaction with fulvestrant were detected respectively by WST.Western blot were used to examine the expression of ER in cancer cells which pretreated with fulvestrant or EGF or both. In addition,MCF-7 was treated withα₂-adrenergic receptor antagonist(yohimbine), and cell proliferation and the interaction with EGF were detected by WST.We also examined the expression of ER in MCF-7 which were pretreated with yohimbine and EGF.ResultsPart I:Age distribution of ER+/PR+ and ER+PR- patients was similar and the peak onset age was same(50 years old),however it was significantly higher than that of patients with ER- tumors(48 years old)(P＜0.05).Univariate analysis showed that ER+/PR- tumors more likely had larger tumor size,more positive lymph nodes, higher histological grade,lower level of ER,higher level of HER-2 than ER+/PR+ tumors(P＜0.05),however the expression of P53 and PS2 was lower in ER+/PR-tumors than that in ER+/PR+ tumors(P＜0.05).Multivariate analysis indicated that positive PR expression was associated with the level of ER(OR=2.598,95%CI= 1.702～3.966,P=0.001),PS2(OR=1.417,95%CI=1.020～1.970,P=0.038) and HER-2(OR=0.575,95%CI=0.398～0.829,P=0.003 ).Besides,age was an important factor to PR expression.The number of patients who were older than 50 with PR positive tumor was as half as that of patients younger than 50(OR=0.607,95%CI =0.452-0.817,P=0.001).Partâ…¡:Fulvestrant could significantly inhibit the proliferation of MCF-7 and T-47D,but no effect to MCF-7 RTR.Fulvestrant could down regulate the expression of ER in breast cancer cells.EGF could significantly enhance the proliferation of MCF-7 and slightly down regulate the expression of ER.But this EGF-mediated motility could be partly inhibited by fulvestrant pretreatment.Yohimbine could inhibit the proliferation of MCF-7 ceils and intercept the EGF-mediated motility.Yohimbine could enhance the expression of ER in MCF-7 cells and inhibit the down regulate of ER expression by EGF.ConclusionER+/PR+ and ER+/PR- tumors may have linking in etiology.The mechanism of whether PR expression or not in ER+ breast cancer may be involved in many different aspects.PS2 may be a good assisted marker to predict the response to endocrine therapy.According to these differences, new target of therapy may provide the possibility of improving the response and prognosis for patients with ER+/PR- tumors.This study demonstrates that EGF enhances the proliferation of MCF-7 breast cancer cells and that fulvestrant pretreatment inhibits EGF-mediated motility.The selectiveα₂-adrenergic receptor antagonist(Yohimbine) inhibited MCF-7 proliferation via EGF and enhanced the expression of ER.α₂-adrenergic receptor is proposed as a possible novel medical therapy target for hormone dependent breast cancer.