Clinicopathological Features And Survival Analysis Of Invasive Ductal Carcinoma With Coexisting Ductal Carcinoma In Situ

Objective:Breast cancer is one of the most common malignant tumors in female.Since the late 1970s,breast cancer has been on a global upward trend and has gradually risen to the most commonly diagnosed female cancer.The latest cancer statistics by the American Cancer Society in 2017 reported that breast cancer alone is expected to account for 30%of all new cancer diagnoses in women.Although China used to be a low-incidence area of breast cancer.The incidence of breast cancer has risen rapidly in recent years,which pose a serious threat on the health of women.According to the latest cancer data of China reported by the National Cancer Center in 2017,about 10000 people in China are diagnosed cancer each day,of which breast cancer has leapt to the top of female cancers.In recent years,with the increasing awareness of breast disease,the use of breast imaging and the extensive application of breast biopsy,the incidence of breast carcinoma in situ(DCIS)and early breast cancer has gradually increased.The current clinical treatment of ductal carcinoma in situ is mainly in surgical treatment,with the risk of progressing into invasive ductal carcinoma(IDC)when not handled properly.Invasive ductal carcinoma is the most common type of breast cancer in clinical work,which is different from DCIS in tumor characteristics and clinical treatment programs.At present,the main clinical treatment is combination of surgery,chemotherapy and endocrine therapy.Foreign studies have shown that 30-60%of patients with IDC,coexisting DCIS is diagnosed.For the coexistence of intraductal carcinoma and invasive ductal carcinoma(DCIS-IDC).Other studies argue that there is a difference between coexisting DCIS and pure DCIS.However,the biological behavior of IDC in DCIS-IDC is still unclear.To investigate the clinicopathological features and survival analysis of invasive ductal carcinoma with coexisting ductal carcinoma in situ patients and provide a reference for the diagnosis and treatment of DCIS-IDC,this study compared them to the patients with pure invasive ductal carcinoma.Methods:Review the 418 patients that accept treatment in The Second Hospital of Shandong University from February 2013 to February 2016,all of which were diagnosed as unilateral invasive ductal carcinoma by pathology.Among them,163 cases were DCIS-IDC and 255 cases were pure IDC.All patients were first diagnosis,no metastasis,no serious organ diseases.Make retrospective review on the clinical factors,pathologic data and therapeutic methods by consulting the medical records.Clinical factors include age,height,weight,menstrual status,status of marriage and fertility,lactation history,chief complaint,chief complaint,side and physical examination of first diagnosis.Pathologic data included histological grades,estrogen receptor(ER),progesterone receptor(PR),human growth factor receptor 2(Her-2)and KI67 index.Therapeutic methods include surgery,chemotherapy,endocrine therapy,etc.Recurrence and survival status,recurrence time,death time were acquired through telephone follow-up,medical records of outpatient and inpatient and the follow-up of our central.All the DCIS-IDC patients in the same center in 2017 were reviewed of the immunohistochemical indicators of both DCIS and IDC part,then the IDC of DCIS-IDC were divided into two sources for analysis.SPSS 23.0 were used for statistical analysis.The distribution of the two groups and chief complaint were analyzed by descriptive analysis.Clinicopathological characteristics and therapeutic methods were analyzed through Chi-squared test and independent-sample t test.Factors that have univariate correlation are included to execute in multivariate analysis.The Kaplan-Meier Log-rank test were used for univariate recurrence and survival analysis.All statistical tests were bilateral considering significance levels at P<0.05.Results:Part Ⅰ1.Basic characteristicsA total of 418 patients with IDC were included,among which,255 cases were pure IDC group(61.0%),163 cases were DCIS-IDC group(39.0%).There was no significant statistical difference among chief complaint time(t=0.005,P=0.996)and chief complaint(χ2= 2.886,P = 0.577)between the two groups.The main chief complaint was breast lump found by self-examination,followed by breast discomfort or pain,breast lump found by healthy physical examination,nipple discharge and other reasons.2.Clicinal factorsThere was no significant statistical difference between the two groups in age(t=1.574,P=0.116),weight(t=1.528,P=0.127),BMI(χ2=1.764,P=0.623)and side(χ2=0.197,P=0.657).Compared with DCIS-IDC group,pure IDC group has higher height(t = 2.245,P = 0.009).In terms of menstrual status,the proportion of postmenopausal patients in pure IDC patients was significantly higher than that of DCIS-IDC patients(χ2 = 6.401,P = 0.011).Menarche age,menstruating years,menopause age,menstrual cycle,status of marriage and fertility,lactation history,family history of breast cancer and other malignant tumor are of no significant statistical difference between DCIS-IDC group and pure IDC group.3.Pathologic dataIn pure IDC,the proportion of histological grade III patients was significantly higher than the DCIS-IDC group,while the histological grade was grade I,Grade II were lower than those in DCIS-IDC group(χ2=15.992,P<0.001).In immunohistochemistry(IHC),the IHC of IDC in two groups was mainly compared.Results showed that PR positive patients in DCIS-IDC were more than pure IDC patients,the difference was statistical significant(χ2=4.460,P=0.035).The value of KI67 proliferation index in pure IDC group was significantly higher than that in DCIS-IDC group(t = 5.268,P<0.001).There was no significant statistical difference between the two groups in ER(χ2 =0.116,P=0.734)and Her-2(χ2 =6.993,P=0.072).In ER-positive patients,the percentage of ER was higher in the DCIS-IDC group than in the pure IDC group(t = 4.503,P<0.001).There was also a statistical significant difference between the two groups in PR-positive patients(t = 2.945,P =0.003).In terms of molecular subtypes,there was no significant difference between the two groups(χ2=3.920,P=0.417).In the TNM stage,the number of stage Ⅰ patients in the DCIS-IDC group was more than that in the pure IDC group,while stage Ⅱ fewer,and stage Ⅲ was approximately equal(x2=7.456,P=0.024).There was no significant positi-ve difference between the two groups in T stage(χ2=4.738,P=0.192)and N stage(χ2=3.269,P=0.195).Compared with DCIS-IDC patients(32.1%),axillary lymph nodes were more likely to be positive in pure IDC patients(57.2%)with statistically significant differences(χ2=4.471,P=0.034).In physical examination,there was no significant difference between the two groups in tumor diameter(t=1.743,P=0.082).However,the difference was statistically significant in breast ultrasound image(t ＝2.430,P= 0.016).4.Therapeutic methodsThere was no significant statistical difference between patients in the DCIS-IDC group and in the pure IDC group in surgery(χ2=2.589,P=0.138),chemotherapy(χ2=1.502,P=0.240)and endocrine therapy in HR-positive patients(χ2=0.924,P=0.336).5.Multivariate analysisMultivariate analysis showed that height(OR=1.086,95%CI:1.034-1.142,P=0.001),menopausal status(OR=1.693,95%CI:1.048-2.735,P=0.031)and KI67 index(OR=1.018,95%CI:1.003-1.034,P=0.021)are different between the two groups.6.Survival analysis418 patients were followed up for prognosis,a total of 33 cases of local recurrence or distant metastasis,14 patients died.Survival analysis revealed a significant statistical difference in 3-year DFS between the DCIS-IDC group and the pure IDC group(χ2=6.418,P=0.011).Patients in DCIS-IDC group were superior to pure IDC group in DFS.There was no significant statistical difference in 3-year OS between the two groups(χ2=1.764,P=0.184).Part ⅡIn DCIS-IDC,there were no significant statistical difference in ER(t=0.803,P=0.245),PR(t=1.508,P=0.136),Her-2(Z=-1.321,P=0.186)between DCIS part and IDC part.However,the KI67 index of IDC was significantly higher than that of DCIS,and the difference was statistically significant(t=6.271,P<0.001).In 79 patients with DCIS-IDC,the expression of ER,PR,Her-2 in DCIS and IDC was inconsistent in 6 cases(7.59%),and 73 cases(92.41%)were consistent.Then dividing the IDC part in DCIS-IDC into DCIS-derived non-DCIS-derived to comparative analyses,we found that ER(89.0%vs 50.0%,χ2=7.051,P=0.033)and PR(91.8%vs 33.3%,χ2=17.131,P=0.002)and KI67 index(χ2=2.545,P=0.036)were significantly statistical different.However,in the Her-2 group,there was no significant difference between the two groups(χ2=3.262,P=0.353).Conclusion:1.DCIS-IDC had a better prognosis than pure IDC.This may be because DCIS-IDC has smaller tumor size,lower histological grade,lower KI67 index,lower TNM stage,higher ER and PR expression.2.In DCIS-IDC,the one whose expression of ER,PR and Her-2 in the IDC and DCIS were inconsistent,has a higher malignancy.