| Background: Ductal carcinoma in situ with micro-invasion(DCIS-Mi)is defined as invasive focus no more than 1 mm in greatest dimension in a background of ductal carcinoma in situ(DCIS)of breast.DCIS and DCIS-Mi has increased significantly with the wide spread of mammography screening.Generally DCIS-Mi exhibits favorable prognosis,but the specific imaging features,biological behavior and long-term outcomes of DCIS-Mi has not yet been elucidated.The prognostic and predictive value of multigene expression profiling has been widely accepted in invasive breast cancer,but there has no such study on DCIS-Mi patients.The aim of this study was to explore the clinicopathological and prognostic features of DCIS-Mi and conduct a preliminary research of multigene assay on DCIS-Mi.Methods: One hundred and thirty five female breast cancer patients who underwent radical breast surgery were retrospectively analyzed between June 2009 and November2016 in Ruijin Hospital,Shanghai Jiaotong University,School of Medicine and all of the paraffin sections were diagnoised as DCIS-Mi.The reports and images of breast ultrasound(US),mammography(MMG)and magnetic resonance imaging(MRI)were carefully reviewed.Pearson’s Chi-square test or Fisher’s exact test was used to compare the clinicopathological features between US,MMG and MRI.Six hundred and two female breast cancer patients who were treated in our center between September 2002 and December 2014 were retrospectively reviewed,including 359 pure DCIS,84 DCIS-Mi and 159 DCIS-T1 a.Clinicopathological features were collected and compared between different types of breast cancer.Kaplan-Meier curves were applied to estimate disease-free survival(DFS)and overall survival(OS).Cox regression was used to identify independent prognostic factors.Sixty three female DCIS-Mi breast cancer patients who were treated in our center from September 2009 to Novemember 2015 were recruited for multigene assay.RT-PCR assay of 12 genes were conducted in paraffin-embedded tumor tissue of DCIS component to calculate the DCIS Score.Corelations of DCIS Score and routine clinico-pathologic factors were evaluated.Logistic regression were applied to determine independent predictive factors for DCIS Score.Results: Among the 135 DCIS-Mi patients,the median age at diagnosis was 53 years(range,30–82),patients who received breast US,MMG or MRI before surgery were 131,121 and 125 respectively.For breast ultrasound,there were 92.4% patients expressed as mass,for MMG,67.8% patients presented with calcification,and for MRI,about 60%patients detected as non-mass enhancement.The sensitivity for US,MMG,and MRI were93.9%,83.5% and 97.6% respectively.After a median follow-up of 31 months,the 3-year estimated disease free survival(DFS)rate of DCIS-Mi patients was significantly lower than that of pure DCIS patients(89.5% vs97.1%,P=0.009).Patients with DCIS-Mi or DCIS-T1 a tumors had comparable 3-year estimated DFS rates(89.5% vs 94.3%,P=0.13).No significant difference in overall survival(OS)was found among different groups(99.6%,100% and 99.1% for DCIS,DCIS-Mi and DCIS-T1 a,P=0.797).In chemotherapy and trastuzumab-naive DCIS-Mi patients,human epidermal growth factor receptor2(HER2)positivity(HR=21.8,95%CI,1.7-286.8,P=0.019)were independent predictor of worse DFS on multivariate analysis.Among the 63 patients who were conducted a 12 genes RT-PCR,the median age was 54years(range,31–82).Patients who were categoried as low,intermediate and high risk were30(47.6%),10(15.9%)and 23(36.5%).DCIS Score distribution was significantly different between different tumor size,tumor differentiaton,ER status,PR status,HER2 status and molecular subtypes(all P value less than 0.05).The results of prognostic analysis make no sense in different category risk group.Conclusions:This study compared the features between US,MMG and MRI for DCISMi patients.The specific expression of DCIS-Mi on US,MMG,and MRI was mass,calcification and non-mass enhancement respectively.US and MRI had a higher sensitivity for DCIS-Mi while MMG had the lowest sensitivity.DCIS-Mi displayed a comparable survival to that of DCIS-T1 a and a more aggressive biological behavior than pure DCIS.Patients with HER2-positive DCIS-Mi had a worse survival and adjuvant chemotherapy plus target therapy needs to be further optimized in those patients.The present study performed a preliminary research of 12-gene assay among DCIS-Mi breast cancer patients.DCIS Score correlated significantly with tumor size,grade,ER status,PR status,HER2 status and molecular subtypes.Further studies with larger cohort and longer follow-up are needed to explore the prediction value of prognosis for DCIS Score. |
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