Study On The Relationships Between The Expression Of FGFR1 And AIB1 And Luminal Breast Cancer And Its Prognosis

Objectives: Ranking No.1 among the malignant tumors occurring to women,Breast cancer is fatally threatening women's health with its incidence rate continuing to rise and patients becoming younger in age.According to the statistics,about 1400,000 patients are diagnosed with breast cancer each year around the world.Thanks to diversified therapies,breast cancer has become one of the malignant tumors that have the best prognosis.In china,the estrogen receptor(ER)and progesterone receptor(PR)of about 60% to 70%breast cancer patients show positive expression.Endocrine therapy(ET)is effective in about 30% of the cases where whether the hormone receptors of the patients express or not cannot be determined,and in 70% of the cases where both ER and PR are positive.Therefore,ET is a necessary therapy for the patients whose hormone receptors show positive expression.According to different molecular subtyping and proliferation capacity of tumor cells,the breast cancer in which the hormone receptors show positive expression falls into two categories---Luminal A and B.For those patients,Tamoxifen(TAM)and aromatase inhibitors(AIs)are the commonly used medicine for endocrine therapy,reducing the death rate by 30% and substantially improving the survival prognosis.Clinical data,however,shows that primary and secondary endocrine resistance is still found on approximately 25% of the breast cancer patients.To improve the prognosis,increase the overall life span,and reveal the endocrine resistance mechanism,it is vital to study new therapeutic targets based on molecules.Fibroblast growth factor receptor 1(FGFR1)is connected with breast tumor cell proliferation,endocrine resistance and poor prognosis;particularly,for those whose ER shows positive expression and/or whose cancer is poorly differentiated,the augmentation of FGFR1 is one of the main factors that cause early tumor recurrence andendocrine resistance.Amplified in breast cancer 1(AIB1)is a proto-oncogene,the augmentation or over-expression of which is related to the emergence and development of many kinds of tumors,including breast tumor.Studies have shown that high levels of AIB1 and HER2 in breast cancer patients indicate poor clinical prognosis and endocrine resistance,and that whether TAM or AIs is applied in endocrine therapy,AIB1 might be an important marker of efficacy prediction.It is reported that AIB1 is an independent marker that can predict the effect and prognosis of hormonal therapy in breast cancer treatment.This study tests the FGFR1 and AIB1 in 80 Luminal breast cancer patients,look into their relationship with various Luminal subtype breast cancers,and analyzes whether there is difference among different pathological features.Through research data,the positive expressions of FGFR1 and AIB1 in patients with drug resistance and in those with effective treatment are known,whether FGFR1 and AIB1 with negative expressions means better prognosis than FGFR1 and AIB1 with positive expressions is revealed,the relationship between FGFR1,AIB1 and endocrine resistance is defined,and whether the breast cancer prognosis can be predicted is determined.It further discusses whether FGFR1 and AIB1 express differently when the ER and PR of Luminal breast cancer have different expressions,as well as their correlation,thus revealing whether FGFR1 and AIB1 can predict the prognosis of different subtypes of Luminal breast cancer,and providing evidence for Luminal breast cancer prognosis and the search for new endocrine therapy targets.Methods:1 Cases With S-P immunohistochemical techniques,this study tested the samples of 80 breast cancer patients admitted to Hengshui People's Hospital from November30,2008 to September 1,2010.The samples,whose S-P indicate that the hormone receptors show positive expressions,were clearly diagnosed by the physicians in the pathology department and had detailed and accurate medical records.The patients can be visited successfully in the follow-up process.2 FGFR1 and AIB1 testsThe expressions of FGFR1 and AIB1 in each of the 80 samples are tested,based on which to find out whether there is certain correlation,and to analyze the different expressions of the two in various features of Luminal breast cancer in the medical records,as well as their relationship with the hormone receptors of breast cancer.3 Follow-up visits Through the reserved contact means in medical records,such as phone numbers or WeChat and so on,the study traced the clinic reexamination and return-to-hospital treatment for the 80 patients,from the operation day to April30,2015 or the last follow-up contact.According to the conditions of the patients on record,the correlation between FGFR1,AIB1 and the prognosis of Luminal cancer,every subtype of the Luminal cancer and their prognosis are analyzed,so as to reveal whether their positive expressions have some bearing on the deterioration after the endocrine resistance in Luminal cancer.4 Statistical analysis SPSS21.0 is used for data statistics.Enumeration data is tested by ?2or Fisher's Exact Test.And the correlation between variables was analyzed by Spearman rank correlation analysis.Kaplan-Meier is applied to evaluate the recurrence rate of endocrine resistance.Log rank is used to test the differences of the recurrence rate,and the differences are taken as having statistical significance when P<0.05.Inspection level ?=0.05.Results:1 The positive expressions of FGFR1 and AIB1 in every subtype of Luminal breast cancer Among the 80 Luminal breast cancer samples tested,the positive expression rate of FGFR1 is 36.25%(29/80),and that of AIB1 is 43.75%(35/80).The positive expression rate of FGFR1 is 18.18%(4/22)in Luminal A compared with 43.10%(25/58)in Luminal B,and the differences between the results have statistical significance(P<0.05).The positive expression rate of AIB1 is22.72%(5/22)in Luminal A compared with 51.72%(30/58)in Luminal B,and the differences between the results have statistical significance(P<0.05).2 The correlation between the expressions of FGFR1,AIB1 and the different clinical and pathological features of Luminal breast cancer In Luminal breast cancer cases,the positive expression rate of FGFR1 in tumors larger than 2 cm in diameter is remarkably higher than in those less than or equal to 2 cm in diameter(P<0.05);the rate in positive lymphatic metastasis group is also substantially higher than in the negative lymphatic metastasis group(P<0.05);the higher the histological grade is,the higher the positive expression rate,and the differences have statistical significance(P<0.05),but the expression has no relations with other factors(P>0.05).The expression rate of AIB1 in the group that has lymphatic metastasis is apparently higher than in the group that has no lymphatic metastasis,and the differences have statistical significance(P<0.05);the rate in histological grade III is higher than in histological grade I~II(P<0.05),and it has no relations with other factors such as the primary tumor size,clinical stages,and the age and menstruation state of the patients(P>0.05).3 The correlation between FGFR1 and AIB1 expressionsIn the 80 Luminal breast cancer cases,the expressions of FGFR1 and AIB1 are positively associated with each other(r=0.698,P=0.000).4 The correlation between positive expressions of FGFR1 and AIB1 and endocrine resistance and prognosisAmong the 80 cases,there are 45 cases where deterioration occurred after orally taking endocrine drugs and the treatment failure caused the deterioration;the total resistance rate is 56.25%(45/80).There are 24 resistance cases in the 29 patients whose FGFR1 showed positive,with the resistance rate being 82.75 %(24/29),while 21 resistance cases in patients whose FGFR1 showed negative,with the resistance rate being 41.17%(21/51).There are 17 resistance cases in 45 patients whose AIB1 showed negative,with the resistance rate being 37.77 %(17/45),while 28 resistance cases in 35 patients whose AIB1 showed positive,with the resistance rate being 80.00 %(28/35).According to Log rank test,the positive expressions of both FGFR1 and AIB1 have statistical differences with endocrine resistance(P<0.05).5 The correlation between different subtypes of Luminal breast cancer and endocrine resistance and the prognosis In the 22 Luminal A breast cancer cases,there are 7 patients that experienced deterioration after orally taking endocrine drugs,the resistance rate being31.81%(7/22);in the 58 Luminal B breast cancer cases,there are 38 patients that underwent deterioration,the resistance rate being 65.51%(38/58).According to Log rank test,patients with different subtypes of Luminal cancer reacted differently to hormone therapy and there is statistical significance(P<0.05).6 The correlation between the expressions of FGFR1 and AIB1 in Luminal breast cancer and hormone receptors In the collected data,there are 21 cases that show the expressions of both FGFR1 and ER,and 7 cases that show the expressions of both FGFR1 and PR.According to Spearman rank correlation analysis,the expressions of FGFR1 and ER are positively associated with each other(r=0.614,P=0.000),and the expressions of FGFR1 and PR are negatively associated with each other(r=-0.621,P=0.000).The analyses of the co-expression of AIB1 with ER and with PR indicate that the expressions of AIB1 and ER are not remarkably associated with each other(r=0.126,P=0.265),and the expression of AIB1 and PR are negatively associated with each other(r=-0.648,P=0.000).Conclusion:1 The expression rates of both FGFR1 and AIB1 in Luminal B breast cancer cases are higher than those in Luminal A cases.In Luminal breast cancer cases,the expression of FGFR1 is related with the primary tumor size,the existence of lymphatic metastasis,and the histological grade.In cases that have larger primary tumor size,lymphatic metastasis and higher histological grade,the positive expression rate of FGFR1 is relatively higher.The expression rate of AIB1 is remarkably higher in cases that have positive lymphatic metastasis and higher histological grade than in negative cases,while it has no relations with the patients' age,menstruation state,tumor size and clinical stages,and all the differences have no statistical significance.2 In Luminal breast cancer cases,the expression of FGFR1 and AIB1 are positively associated with each other;the protein expression of FGFR1 are positively associated with ER,but negatively associated with PR.The protein expression of AIB1 has no statistical differences at different ER expression level,and is negatively associated with the expression of PR,and the differences have statistical significance.3 After the treatment of endocrinetherapy,the recurrence rate of patients with positive FGFR1?AIB1 is higher than those with negative expression,and the differences have statistical significance,which indicates that the positive expression of FGFR1 and AIB1 is related with endocrine resistance;Luminal B breast cancer patients are more likely to have endocrine resistance than Luminal A patients.