Clinical Analysis And Prognosis Of 115 Cases Of Breast Cancer Accompanied With Primary Cancers Of Other Organs

Objective:To explore the clinicopathological parameters and prognostic values of breast cancer(BC)accompanied with multiple primary cancer(MPC),aiming at improving the prognosis of patients.Methods:The clinical data of 115 BC patients with MPC in Guangxi Medical University Tumor Hospital from January 2003 to August 2018 were retrospect analyzed.Resected samples were identified by two pathologists independently.According to the order of incidence of breast cancer or other cancer successively,the 115 BC accompanied with MPC patients were divided into first cancer is breast cancer(F-BC)and first cancer is not breast cancer(F-NBC).The clinical and clinicopathological parameters and prognosis of the two groups were analyzed and compared.According to the interval time(IT),the patients were divided into synchronous MPC(s-MPC)and metachronous MPC(m-MPC),the clinicopathological parameters were analyzed and compared,and to explore the prognosis of MPC patients.Categorical variables were assessed for significance using the chi-squared test and Fisher exact probability test,as appropriate.Survival curves were estimated using the Kaplan-Meier method and compared using the Log-rank test.Analysis of risk factors by Cox Proportional Hazard Regression Model.Results: 1.The study evaluated a total of 115 patients,114 female and 1 male.There were 102(88.7%)patients with two primary cancers and other 13(11.3%)patients with three or more.The median age at diagnosis of first cancer was 50 years(range,20-83 years),and second cancer was 55 years(range,25-88 years).2.The median interval time between the initial primary cancer and second primary cancer was 38.2 months(range,0.1-244.2 months).47.8%(55 cases)suffered second primary cancer in 3 years after the first primary cancer diagnosed,and 68.7%(79 cases)in 5 years.Breast cancer(9 cases),lung cancer(6 cases)and thyroid cancer(3 cases)were the most prevalent secondary primary tumors in the s-MPC group.And the m-MPC group’s(interval time>6 months)second primary cancers most commonly occurred in thyroid gland(18 cases),gynecologic system(19 cases)and lung(10 cases).3.There were 83 patients in the F-BC group(first primary cancer is breast),and its secondary primary cancers most commonly occurred in thyroid gland(21 cases),gynecologic system(20 cases)and lung(16 cases).However,The F-NBC group(first primary cancer is not breast)included 32 patients,among which 31 cases were breast cancer as the second primary cancer and 1 case was breast cancer as the third primary cancer.And gynecological tumor(7 cases),lung cancer(6 cases)and colorectal cancer(5 cases)were the most prevalent first primary tumors in F-BC group patients.4.With respect to TNM staging,27 patients(23.5%)had stage I,69(60%)had stage II and 19(16.5%)had stage III disease.21 patients(25.3%)had TNM stage I,50(60.2%)had stage II and 12(14.5%)had stage III in the F-BC group.However,the F-NBC group included 32 patients,and 6 patients(18.8%)had stage I,19(59.4%)had stage II and 7(21.9%)had stage III disease.But there was no significant difference in TNM staging between the two groups(P=0.55).5.There were 70 cases of ER/PR(+)patients,30 cases of HER(+)patients and 15 cases of triple-negative breast cancer(TNBC)patients.The F-BC group included 83 patients,and the molecular classification as following: 46 cases(55.4%)of ER/PR(+)patients,23 cases(27.7%)of HER-2(+)patients,and 14 cases(16.9%)of TNBC patients.While,there were 21 patients in F-NBC group,and ER/PR(+)in 24 patients(75%),HER-2(+)in 7 patients(21.9%),and triple-negative breast cancer in 1 patient(3.1%).But there was no significant difference in molecular classification between the two groups(P=0.078).6.For the treatment of breast cancer,105 patients(91.3%)received surgical treatment.The first primary cancer was treated with chemotherapy in 87 patients(75.7%),radiotherapy in 23 patients(20%)and endocrine therapy in 37 patients(32.2%).The number of patients receiving surgical treatment,chemotherapy,radiotherapy and endocrine therapy for the second primary cancer was 78(67.8%),53(48.2%),15(13%)and 10(8.7%),respectively.7.The 5 years progression-free survival(PFS)rate for 115 cases breast cancer accompanied with MPC was 57% and median PFS was 84.1 months(range,1-301 months).K-M analysis showed that N1-3 staging,BMI≥24,history of diabetes,CA153≥30 U/ml,lack of operation of breast cancer,interval time<6 months and breast cancer as secondary tumor were poor prognostic factors affecting PFS(all P<0.05).The multivariate analysis showed that N staging,BMI,CA153,operation mode and initial cancer of MPC are independent factors affecting the prognosis of breast cancer accompanied with MPC patients(all P<0.05).The 3-year and 5-year rates of PFS in F-BC group patients were 87.1% and 66.1%,respectively.And the median PFS was 54.4 months(range,1-301 months).The 3-year and 5-year PFS rates of patients in the F-NBC group were 44.1% and 25.7%,respectively,with a median PFS of 21.4 months(range:2-103 months).Patients in the F-BC group had a significantly longer median PFS than those in the F-NBC group,and the difference was statistically significant(P<0.001).Compared with MPC patients in the F-BC group,diabetes was more common in the F-NBC patients(P=0.002).However,there were no significantly associated with age at diagnosis,TNM staging,molecular classification,etc.between F-BC and F-NBC(all P>0.05).In the F-BC group,K-M analysis showed that CEA≥5ng/ml,lack of operation of breast cancer were poor prognostic factors affecting PFS(all P<0.05).Similarly,in the F-NBC group,patients with high serum CEA level(CEA≥5ng/ml)showed significantly shorter PFS than those with low serum CEA level(CEA<5ng/ml)(P=0.03).The 3-year and 5-year rates of PFS in m-MPC group patients were 78.1% and 59.1%,respectively.And the median PFS was 52.3 months(range,2-301 months).The 3-year and 5-year PFS rates of patients in the s-MPC group were 55.8% and 34.9%,respectively,with a median PFS of 21.4 months(range:1-104 months).Patients in the m-MPC group had a significantly longer median PFS than those in the s-MPC group,and the difference was statistically significant(P=0.048).Compared with patients with m-MPC,patients without surgery were more common in patients with s-MPC(P=0.003).No significant relationships were found between s-MPC and m-MPC,including patients’ age at diagnosis,TNM staging and molecular classification and so on(all P>0.05).In m-MPC patients,patients with high serum CEA(CEA≥5ng/ml)expression showed significantly shorter PFS(P=0.002)than those with low serum CEA(CEA<5ng/ml)expression.Similarly,in s-MPC patients,patients with low serum CEA/CA153(that is CEA<5ng/ml or CA153<30U/ml)expression have better prognosis than high expression(P<0.05).Meanwhile,median PFS for s-MPC patients without surgery was 4.7 months,poorer than 37.7 months,21 months and 26.5 months for patients under radical mastectomy,simple mastectomy and breast conserving surgery,respectively(P=0.002).In the subgroups of T stages,N stages and the expression of ER,PR and HER-2,the prognosis of BC with MPC patients in the F-BC group was better than that in the F-NBC group(all P<0.05).Nonetheless,besides the m-MPC patients have better prognosis than the s-MPC patients in T2-T4(P=0.025),there were no significance on subgroups of others between the s-MPC patients and the m-MPC patients(all P>0.05).8.K-M analysis also revealed that breast cancer accompanied with MPC patients’ initial cancer was lung cancer or thyroid cancer or gynecologic system,had shorter PFS than those as secondary cancer(P= 0.032,0.002 and 0.057,respectively).9.In BC associated with MPC patients whose initial cancer was breast cancer,there were no significance among patients whose secondary cancer were thyroid cancer,gynecological tumor and lung cancer on PFS(P>0.05).Conclusion:(1)Duplex primary cancer is the most prevalent in BC associated with MPC.And Thyroid cancer,gynecological tumor and lung cancer are the most prevalent cancer abide breast cancer in BC associated with MPC.(2)The clinicopathological parameters of ER,PR,her-2 and TNM of breast cancer were not significantly different between F-BC’ and F-NBC’ MPC patients,meanwhile,the same was true in the comparison between s-MPC and m-MPC.(3)N staging,BMI,serum CA153 level,operation mode and initial cancer of MPC are independent factors affecting the prognosis of BC associated with MPC patients.(4)BC associated with MPC patients in the F-BC group is better than that in the F-NBC group,and m-MPC patients have better prognosis than s-MPC patients as well.(5)There is no significance among patients whose secondary cancer is thyroid cancer,gynecological tumor or lung cancer on PFS in patients whose initial cancer was breast cancer.