Ductal Carcinoma In Situ With Microinvasion Research Articles

Clinical comparison between ductal carcinoma in situ and ductal carcinoma in situ with microinvasion

Objective To analyze the differences in the treatment patterns, clinical characteristics, treatment outcomes and prognostic factors between breast cancer patients with ductal carcinoma in situ (DCIS) and ductal carcinoma in situ with microinvasion (DCIS-MI). Methods Clinical data of 866 female patients including 631 DCIS cases and 235 DCIS-MI cases treated in our institution between 1999 and 2013 were retrospectively analyzed. The local control (LC), disease-free survival (DFS) and overall survival (OS) rates were calculated by Kaplan-Meier survival analysis. The prognostic factors were identified by Log-rank test. Results Similar LC, DFS and OS rates were obtained between two groups (all P>0.05). The univariate analysis demonstrated that Her-2-positive patients had worse OS and DFS than Her-2-negative counterparts. Patients undergoing breast-conserving surgery without radiotherapy had lower LC and DFS rates compared with those receiving radical mastectomy. Conclusions DCIS and DCIS-MI patients have similar clinical prognosis in terms of OS, LC and DFS. Her-2 positive is an unfavorable prognostic factor for DFS and OS. The LC and DFS rates in the breast-conserving surgery alone group are worse than those in the mastectomy group. Key words: Breast ductal carcinoma in situ; Breast ductal carcinoma in situ with microinvasion; Breast neoplasm/radiotherapy; Breast neoplasm/surgery; Prognosis

Clinic-Pathological Features of Breast Ductal Carcinoma in Situ with Micro-Invasion

Background: To investigate the differences of clinic-pathological features among ductal carcinoma in situ (DCIS), ductal carcinoma in situ with micro-invasion (DCIS-MI) and early invasive carcinoma (IDC) in stage T1.Methods: From January 2014 to December 2018, 308 cases DCIS, DCIS-MI 92 cases and 111 cases of T1a, 343 cases of T1b, and 1032 cases of T1c were investigated in a retrospective analysis. The population and clinic-pathological characteristics including age, menstrual status, surgical mode, lymph node status and molecular markers were compared in each group. Survival rate of all patients were followed-up for 5 years.Results: Compared with DCIS-MI group, the higher breast-conserving rate and lower lymph node metastasis rate in the DCIS group were shown in the DCIS-MI group (p < .05). There were no significant differences in tumor diameter, number of tumors, ER, PR, HER2 and Ki67 expression, molecular typing, (p > .05). The expression of Ki67 in T1a, T1b and T1c groups increased gradually with elevated grades (p < .05). The proportion of HER2-positive patients in DCIS-MI group was significantly higher than that in T1a-b-c (p < .05). There were no significant differences in DFS and OS between the 3 groups (p > .05).Conclusions: The clinic-pathological features of DCIS-MI are similar to those of DCIS and T1a, but significantly different from T1c.

Values of Minimal Apparent Diffusion Coefficient,Difference between Ratios of Apparent Diffusion Coefficients,and Dynamic Contrast-enhanced Magnetic Resonance Imaging Features in Diagnosing Breast Ductal Carcinoma In Situ with Microinvasion

Objective To explore the values of minimal apparent diffusion coefficient(ADCMin),difference between ratios of apparent diffusion coefficients(ADCDR),and dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)in the treatment of breast ductal carcinoma in situ with microinvasion(DCIS-Mi).Methods Totally 27 patients with DCIS-Mi and 31 patients with breast ductal carcinoma in situ(DCIS)were collected in our hospital from October,2016 to June,2018.Philips Ingenia 3.0T superconducting magnetic resonance scanner and dedicated phase-controlled array surface coil were used for breast examinations.ADCMin and maximum apparent diffusion coefficient(ADCMax)were selected from multiple regions of interest(ROI)in the apparent diffusion coefficients(ADC)figure,and ADCDR was calculated.In addition,DCE-MRI characteristics were analyzed.Results The ADCMin of DCIS-Mi was significantly lower than that of DCIS[(1.15±0.03)×10 3 mm 2/s vs.(1.34±0.04)×10 -3 mm 2/s,t=-7.192,P=0.002],the ADCDR was significantly higher than that of DCIS[(0.32±0.03)×10 -3 mm 2/s vs.(0.18±0.08)×10 -3 mm 2/s,t=-10.228,P<0.001],and the early enhancement rate of DCIS-Mi was higher than that of DCIS[159.71(157.82,162.49)% vs.147.29(143.59,160.22)%,Z=-3.578,P=0.007].The background parenchymal enhancement of DCIS-Mi was moderate,severe,and non-lump-like,mainly segmental,and the internal enhancement was heterogeneous or clustered circular.Multivariate Logistic regression analysis showed that non-internal characteristics of the mass,the edge of the mass,internal enhancement characteristics of the mass,time-intensity curve,early enhancement rate,ADCMin and ADCDR were the optimal variables for the diagnosis of DCIS-Mi,and the optimal variables were shown by receiver operating characteristic(ROC)curve analysis:the area under curve,sensitivity and specificity of ADCMin,ADCDR,non-tumor internal enhancement,and tumor internal enhancement were higher,with the critical values being 1.12×10 -3 mm 2/s,0.31×10 -3 mm 2/s,1.50,and 1.50,respectively.Conclusion DCE-MRI combined with ADC value(especially ADCMin,ADCDR,non-mass internal enhancement,and mass internal enhancement)is helpful in differentiating breast DCIS-Mi and DCIS.

Values of 5mC, 5hmC, and TET2 for identifying the presence and progression of breast precancerous lesion.

BackgroundThis study aimed to evaluate the correlations of 5‐methylcytosine (5mC), 5‐hydroxymethylcytosine (5hmC), and ten‐eleven translocation enzyme 2 (TET2) expressions in lesion tissue with histological classification of breast precancerous lesion.MethodsEighty‐three patients with breast ductal intraepithelial neoplasia (DIN), 20 patients with breast ductal carcinoma in situ with microinvasion (DCIS‐MI), and 10 patients with invasive breast cancer were included. Histological classification of the DIN patients was classified as DIN1A, DIN1B, DIN1C, DIN2, and DIN3. 5mC, 5hmC, and TET2 expressions in lesion tissues from biopsy were assessed by immunohistochemistry (IHC) assay.Results5hmC and TET2 were negatively associated with histological classification as validated by both IHC score and IHC semi‐quantification expression grades in total patients (all P < .05); however, no correlation of 5mC with histological classification was found (all P > .05). 5mC (P = .004) was negatively but 5hmC (P < .001) was positively correlated with TET2, while no association of 5mC with 5hmC was discovered in total patients (P = .078). In addition, 5mC was positively associated with ER expression in total patients (P = .040). In subgroups, 5mC was negatively correlated with 5hmC in DIN1C patients (P = .023) and invasive cancer patients (P = .044), and 5mC was negatively associated with TET2 in DIN1B patients (P = .004) as well as DCIS‐MI patients (P = .003).Conclusion5hmC and TET2 have the potentials to serve as biomarkers that could assist in the identification of presence and progression of breast precancerous lesion.

Axillary evaluation is not warranted in patients preoperatively diagnosed with ductal carcinoma in situ by core needle biopsy.

BackgroundPatients diagnosed with ductal carcinoma in situ (DCIS) by core needle biopsy (CNB) have a great chance of upstaging to invasive cancer. Positive axillary status can be found in these patients. This study sought to identify clinicopathological factors associated with upstaging and axillary metastasis in patients preoperatively diagnosed with DCIS by CNB.Materials and MethodsThis study identified 604 patients (cT1‐3N0M0) with preoperative diagnosis of pure DCIS by CNB who had undergone axillary evaluation from August 2006 to December 2015 at Fudan University Shanghai Cancer Center (FUSCC). Predictors of upstaging and axillary lymph nodes metastasis were analyzed, respectively.ResultsOf all 604 patients, 121 (20.03%) and 193 (31.95%) patients were upstaged to DCIS with microinvasion (DCISM) and invasive breast cancer (IBC). Positive axillary lymph nodes were identified in 41 (6.79%) patients. Predictors of upstaging included tumor size on ultrasonography (>2 cm) (OR 1.786, P = .002) and ER+HER2+ status (OR 1.874, P = .022) in multivariate analysis. Factors associated with axillary lymph nodes metastasis included tumor size on pathology (OR 2.336, P = .038) and number of lesions (OR 3.354, P = .039) in multivariate analysis. In addition, upstaging on final pathology had a significant influence on axillary lymph nodes status (P < .001).ConclusionAxillary evaluation was recommended in patients with larger tumor size (>2 cm), multifocal lesions or ER+HER2+ status. Despite of a 51.98% upstaging rate, the rate of axillary metastasis in these patients was relatively low, supporting the omission of axillary evaluation in selected patients with low risk of upstaging or axillary metastasis.

Repression of miR-135b-5p promotes metastasis of early-stage breast cancer by regulating downstream target SDCBP

Metastasis is an essential event for breast cancer (BC) progression even after initial surgery. The identification of patients with a high probability of metastasis at an early stage is particularly important in clinical practice and requires individualized treatment or early prevention. A retrospective study of 242 cases of ductal carcinoma in situ with microinvasion (DCIS-Mi), the first stage of invasive BC, was performed in this follow-up analysis. Of all patients, 8 developed metastases, and they were all included for further mechanistic studies with control group of 24 DCIS-Mi by matched-pair designing. By screening DCIS-Mi with different prognoses, we found that the DCIS-Mi that metastasized had significantly lower miR-135b-5p expression than the DCIS-Mi that did not. The function of miR-135b-5p was studied in vitro and in vivo invasion and metastasis assays. We also validated a novel target gene for miR-135b-5p, syndecan binding protein (SDCBP), and assessed the functional consequences of SDCBP by invasion assays. By checking different BC cell lines, a strong inverse correlation between miR-135b-5p and SDCBP expression was recorded. For the functional study, the inhibition of miR-135b-5p was accompanied by increased BC cell growth, epithelial–mesenchymal transition (EMT), migration and invasion in vitro. Interestingly, silencing SDCBP can reverse miR-135b-5p-dependent EMT and proliferation. In vivo studies demonstrated that the newly revealed miR-135b-5p/SDCBP axis increased cell proliferation, invasion and malignant transformation, as well as promoted metastasis in a xenograft tumor mouse model. Thus, our clinical patient cohort and functional data suggest that miR-135b-5p/SDCBP is a crucial determinant of BC metastasis at a very early stage. Our results may shed light on the importance of miR-135b-5p molecular diagnosis and prognosis, as well as the early prevention of BC for metastasis.

DCIS with Microinvasion: Is It In Situ or Invasive Disease?

Ductal carcinoma in situ (DCIS) with microinvasion (DCISM) can be challenging in balancing the risks of overtreatment versus undertreatment. We compared DCISM, pure DCIS, and small volume (T1a) invasive ductal carcinoma (IDC) as related to histopathology, treatment patterns, and survival outcomes. Women ages 18-90years who underwent breast surgery for DCIS, DCISM, or T1a IDC were selected from the SEER Database (2004-2015). Multivariate logistic regression and Cox proportional hazards models were used to estimate the association of diagnosis with treatment and survival, respectively. A total of 134,569 women were identified: 3.2% DCISM, 70.9% DCIS, and 25.9% with T1a IDC. Compared with invasive disease, DCISM was less likely to be ER+ or PR+ and more likely to be HER2+. After adjustment, DCIS and invasive patients were less likely to undergo mastectomy than DCISM patients (DCIS: OR 0.53, 95% CI 0.49-0.56; invasive: OR 0.86, CI 0.81-0.92). For those undergoing lumpectomy, the likelihood of receiving radiation was similar for DCISM and invasive patients but lower for DCIS patients (OR 0.57, CI 0.52-0.63). After adjustment, breast-cancer-specific survival was significantly different between DCISM and the other two groups (DCIS: HR 0.59, CI 0.43-0.8; invasive: HR 1.43, CI 1.04-1.96). However, overall survival was not significantly different between DCISM and invasive disease, whereas patients with DCIS had improved OS (HR 0.83, CI 0.75-0.93). Although DCISM is a distinct entity, current treatment patterns and prognosis are comparable to those with small volume IDC. These findings may help providers counsel patients and determine appropriate treatment plans.

Ductal Carcinoma In Situ with Microinvasion on Core Biopsy: Evaluating Tumor Upstaging Rate, Lymph Node Metastasis Rate, and Associated Predictive Variables.

The role of sentinel lymph node biopsy (SLNB) when ductal carcinoma in situ with microinvasion (DCISM) is identified on core biopsy is unclear. Our aim was to assess the upstage rate to invasive cancer and axillary lymph node metastasis in patients diagnosed with DCISM, and whether predictive variables could be identified that may help inform who would most likely benefit from a surgical axillary evaluation. We performed a retrospective review of 70 patients diagnosed with DCISM on core biopsy. Patients with concomitant or prior invasive cancer were excluded. Demographic, clinical, radiographic, histologic, and treatment data were collected. Fisher's exact test and univariable and multivariable logistic regression were performed to identify variables that may be associated with tumor upstaging and nodal metastasis. Time-to-event distributions were summarized using the Kaplan-Meier method. On final surgical pathology, 49 patients (70%) had a final diagnosis of DCISM or T1mi cancer, whereas 21 patients (30%) were upstaged to measurable invasive cancer (> 1mm). One of 49 patients (2%) with DCISM on final pathology and 4 of 21 patients (19%) with measurable invasive cancer showed sentinel lymph node metastases. Although the upstage rate to measurable invasive cancer in our cohort of patients with DCISM on core biopsy was 30%, findings of a positive SLNB remain low at 7%. No predictive variables were identified to inform whether the routine practice of SLNB may be omitted in some patients with DCISM.

Imaging features that distinguish pure ductal carcinoma in situ (DCIS) from DCIS with microinvasion.

Patients with ductal carcinoma in situ with microinvasion (DCISM) have worse cancer-specific survival, disease-free survival and overall survival, and a higher mortality rate compared with patients with ductal carcinoma in situ (DCIS). Distinguishing DCISM from DCIS via preoperative imaging could help to predict the prognosis of patients. The present study compared the sonographic and mammographic features of patients with DCIS and DCISM. A total of 147 women (94 patients with DCIS and 53 patients with DCISM) were retrospectively included. The sonographic lesions were classified as either masses or non-mass abnormalities. The lesions observed on mammography were classified as calcifications only, mass, asymmetry or architectural distortion. Statistical comparisons were performed using the Mann-Whitney U test, χ2 test, Fisher's exact test and multiple logistic regression analysis. Univariate and multivariate analyses showed that the presence of calcifications (P=0.038) and vascularity (P=0.025) on sonography were associated with DCISM. Furthermore, a lager distribution of calcifications was associated with a higher likelihood of DCISM (P=0.002). In conclusion, the presence of calcifications and vascularity on sonography or a lager distribution of calcifications on mammography may suggest DCISM.

Factors associated with upstaging in patients preoperatively diagnosed with ductal carcinoma in situ by core needle biopsy.

ObjectivePatients preoperatively diagnosed with ductal carcinoma in situ (DCIS) by core needle biopsy (CNB) exhibit a significant risk for upstaging on final pathology, which leads to major concerns of whether axillary staging is required at the primary operation. The present study aimed to identify clinicopathological factors associated with upstaging in patients preoperatively diagnosed with DCIS by CNB. MethodsThe present study enrolled 604 patients (cN0M0) with a preoperative diagnosis of pure DCIS by CNB, who underwent axillary staging between August 2006 and December 2015, at Fudan University Shanghai Cancer Center (Shanghai, China). Predictive factors of upstaging were analyzed retrospectively.ResultsOf the 604 patients, 20.03% (n = 121) and 31.95% (n = 193) were upstaged to DCIS with microinvasion (DCISM) and invasive breast cancer (IBC) on final pathology, respectively. Larger tumor size on ultrasonography (> 2 cm) was independently associated with upstaging [odds ratio (OR) 1.558,P = 0.014]. Additionally, patients in lower breast imaging reporting and data system (BI-RADS) categories were less likely to be upstaged (4B vs. 5: OR 0.435, P = 0.002; 4C vs. 5: OR 0.502, P = 0.001). Overall, axillary metastasis occurred in 6.79% (n = 41) of patients. Among patients with axillary metastasis, 1.38% (4/290), 3.31% (4/121) and 17.10% (33/193) were in the DCIS, DCISM, and IBC groups, respectively. ConclusionsFor patients initially diagnosed with DCIS by CNB, larger tumor size on ultrasonography (> 2 cm) and higher BI-RADS category were independent predictive factors of upstaging on final pathology. Thus, axillary staging in patients with smaller tumor sizes and lower BI-RADS category may be omitted, with little downstream risk for upstaging.

American Society of Breast Surgeons’ Practice Patterns After Publication of the SSO-ASTRO-ASCO DCIS Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation

The SSO-ASTRO-ASCO consensus guideline on margins for breast-conserving surgery with whole breast irradiation in ductal carcinoma in situ (DCIS) recommended a 2-mm margin. We sought to determine the impact of guideline publication on clinician practice. A total of 3081 members of the American Society of Breast Surgeons (ASBrS) received a survey. Respondents' clinical practice type and duration, guideline familiarity, and margin width preferences before and after publication were assessed. Clinical practice pattern differences before and after publication were investigated using McNemar's test. A total of 767 (24.9%) of those surveyed responded. Most (92.4%) indicated guideline familiarity. Of those familiar, re-excision preference for DCIS and a positive margin remained the same before (94.4%) and after (94.3%) publication (McNemar's test p = 1.0). Following publication, surgeons were more likely to avoid re-excision to achieve margins wider than 2-mm (82.3% pre versus 87.5% post, p = 0.002). More surgeons performed re-excision for a close margin with pure DCIS (25.9% pre versus 36.5% post, p < 0.001) and with DCIS with microinvasion (DCIS-M) (40.7% pre versus 52.3% post, p < 0.001). For patients with invasive disease with extensive intraductal component (EIC) and a close margin, preference to avoid re-excision was similar (51.2% per versus 55.2% post, p = 0.071). Since guideline publication, surgeons are less likely to perform re-excision to obtain a margin greater than 2-mm and more likely to perform re-excision to obtain a 2-mm margin for both pure DCIS and DCIS-M. Preference to avoid re-excision with a close margin and EIC was similar before and after publication.

Abstract P3-01-06: Can axillary evaluation be omitted in patients preoperatively diagnosed with ductal carcinoma in situ by core needle biopsy?

Abstract Background Patients diagnosed with ductal carcinoma in situ (DCIS) by core needle biopsy (CNB) have a great chance of upgrading invasive cancer on the final pathology. Positive axillary lymph nodes can be found in these patients. The present study sought to identify clinicopathological factors associated with upgrading and axillary lymph nodes metastasis in patients preoperatively diagnosed with DCIS by CNB. Materials and Methods This study identified 604 patients (cT1-3N0M0) with preoperative diagnosis of pure DCIS by CNB who had undergone axillary evaluation from August 2006 to December 2015 at Fudan University Shanghai Cancer Center (FUSCC). Predictors of upgrading and axillary lymph nodes metastasis were analyzed, respectively. Results Of all 604 patients, 513 (84.93%) and 91 (15.07%) patients had undergone sentinel lymph nodes biopsy (SLNB) and axillary lymph nodes dissection (ALND), respectively. Overall, 121 (20.03%) and 193 (31.95%) patients were upgraded to DCIS with microinvasion (DCISM) and IDC on final pathology, respectively. Positive axillary lymph nodes were identified in 41 (6.79%) patients, of which 35 (5.80%) patients had 1-2 positive axillary lymph nodes, 6 (0.99%) patients had 3 or more positive axillary lymph nodes. Among patients with axillary lymph nodes metastasis, 4 (9.76%), 4 (9.76%) and 33 (80.48%) patients were in DCIS, DCISM and IDC group, respectively. Predictors of upgrading included tumor size on ultrasonography (P=0.001), Ki-67 (P=0.046) and molecular subtype (P=0.007) in univariate analysis. In multivariate analysis, patients with larger tumor size on ultrasonography (&amp;gt;2cm) (OR 1.767, P=0.001) were more likely to be upgraded on final pathology. Also, ER+ HER2+ patients were more likely to be upgraded than ER+ HER2- patients (OR 1.659, P=0.047). Factors associated with axillary lymph nodes metastasis included nipple discharge (P&amp;lt;0.001), tumor size on pathology (P=0.037), number of lesions (P=0.039), axillary evaluation methods (P=0.029) and molecular subtype (P=0.049) in univariate analysis. Whereas, only nipple discharge and larger tumor size on pathology (&amp;gt;2cm) reached statistical significance in multivariate analysis (OR 5.959, P&amp;lt;0.001; OR 2.361, P=0.042). In addition, further analysis showed upgrading on final pathology had a significant influence on axillary lymph nodes status (P&amp;lt;0.001). However, this correlation was not shown between patients with DCIS and DCISM in pairwise comparison. Conclusion The data of upgrading and axillary lymph nodes metastasis in patients with an initial diagnosis of DCIS by CNB was comparable in this cohort with published data. Despite of a 51.98% upgrading rate, the rate of axillary lymph nodes metastasis in these patients is low, which supports the omission of axillary evaluation in selected patients. Citation Format: Si J, Yang B, Guo R, Huang N, Quan C, Chen J, Wu J. Can axillary evaluation be omitted in patients preoperatively diagnosed with ductal carcinoma in situ by core needle biopsy? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-06.

Ductal carcinoma in situ and ductal carcinoma in situ with microinvasion: correlation of FDG uptake with histological and biological prognostic factors.

Several studies investigated the correlation between the intensity of fluorodeoxyglucose (FDG) uptake and some histological and biological characteristics in breast cancer. Ductal carcinoma in situ (DCIS) is generally thought to be a precursor lesion of invasive breast cancer. The aim of this study was to assess the correlation between FDG uptake values on positron emission tomography/computed tomography (PET/CT) with histological and biological prognostic factors in DCIS and ductal carcinoma in situ with microinvasion (DCIS-Mi). PET/CT images for initial staging of confirmed DCIS and DCIS-Mi patients, taken between July 2004 and December 2009, were reviewed retrospectively. Maximum standardized uptake values (SUVmax) and tumor background count density ratio on PET/CT were compared with tumor characteristics. Histological and biological prognostic factors included tumor size, nuclear grade, Van Nuys Prognostic Index, estrogen receptor, progesterone receptor, HER2, and Ki-67 index. In total, 87 lesions from 83 patients (all females; mean age 51±9years) were studied. The Van Nuys Prognostic Index group was 1 in 25 lesions, 2 in 36, and 3 in 26. On statistical analysis, significant differences in SUVmax and tumor background count density ratio were seen between the Van Nuys Prognostic Index groups and according to tumor size and HER2. The correlation between SUVmax and Ki-67 was significant. However, the correlation between tumor background count density ratio and Ki-67 was not statistically significant. In DCIS and DCIS-Mi cases, significant correlations were found between increased FDG uptake and several histological and biological factors for poor prognosis (tumor size, Van Nuys Prognostic Index, and HER2).

Sentinel lymph node biopsy in patients with breast ductal carcinoma in situ: Chinese experiences.

The axillary treatment of patients with ductal carcinoma in situ (DCIS) remains controversial. The aim of the present study was to evaluate the roles of sentinel lymph node biopsy (SLNB) in patients with breast DCIS. A database containing the data from 262 patients diagnosed with breast DCIS and 100 patients diagnosed with DCIS with microinvasion (DCISM) who received SLNB between January 2002 and July 2014 was retrospectively analyzed. Of the 262 patients with DCIS, 9 presented with SLN metastases (3 macrometastases and 6 micrometastases). Patients with large tumors diagnosed by ultrasound or with tumors of high histological grade had a higher positive rate of SLNs than those without (P=0.037 and P<0.0001, respectively). Of the 100 patients with DCISM, 11 presented with metastases. Younger patients had a higher positive rate of SLNs (P=0.028). According to the results of this study and the systematic review of recent studies, the indications of SLNB for patients with DCIS are as follows: SLNB should be performed in all DCISM patients and in those DCIS patients who received mastectomy, and could be avoided in those who received breast-conserving surgery. However, SLNB should be recommended to patients who have high risks of harboring invasive components. The risk factors include a large, palpable tumor, a mammographic mass or a high histological grade.

Intratumoral metabolic heterogeneity predicts invasive components in breast ductal carcinoma in situ.

This study investigated whether texture-based imaging parameters could identify invasive components of ductal carcinoma in situ (DCIS). We enrolled 65 biopsy-confirmed DCIS patients (62 unilateral, 3 bilateral) who underwent (18) F-FDG PET, diffusion-weighted imaging (DWI), or breast-specific gamma imaging (BSGI). We measured SUV max and intratumoral metabolic heterogeneity by the area under the curve (AUC) of cumulative SUV histograms (CSH) on PET, tumour-to-normal ratio (TNR) and coefficient of variation (COV) as an index of heterogeneity on BSGI, minimum ADC (ADC min ) and ADC difference (ADC diff ) as an index of heterogeneity on DWI. After surgery, final pathology was categorized as pure-DCIS (DCIS-P), DCIS with microinvasion (DCIS-MI), or invasive ductal carcinoma (IDC). Clinicopathologic features of DCIS were correlated with final classification. Final pathology confirmed 44 DCIS-P, 14 DCIS-MI, and 10 IDC. The invasive component of DCIS was significantly correlated with higher SUV max (p = 0.017) and lower AUC-CSH (p < 0.001) on PET, higher TNR (p = 0.008) and COV (p = 0.035) on BSGI, lower ADC min (p = 0.016) and higher ADC diff (p = 0.009) on DWI, and larger pathologic size (p = 0.018). On multiple regression analysis, AUC-CSH was the only significant predictor of invasive components (p = 0.044). The intratumoral metabolic heterogeneity of (18) F-FDG PET was the most important predictor of invasive components of DCIS. • Preoperative identification of invasion in DCIS is important for axillary nodal management • Higher SUV max and lower AUC-CSH from FDG PET may indicate invasive components of DCIS • Higher TNR and COV from BSGI may indicate invasive components of DCIS • Lower ADC min and higher ADC diff from DWI may indicate invasive components of DCIS • AUC-CSH, an index of metabolic heterogeneity, is an independent predictor for invasive components.

The clinical features and management of women with ductal carcinoma in situ with microinvasion: A retrospective Cohort study

ObjectiveThe purpose of our study is to demonstrate the clinical features and management of patients with Ductal Carcinoma in situ with microinvasion (DCISM) in a single Chinese cancer center. MethodsRetrospectively analysis of cases between 2003 and 2009 was performed in our institution. The type of treatments, pathological results, and axillary lymph nodes status, hormonal receptor statues (estrogen receptor (ER), progesterone receptor (PR) and Her2) were collected. The disease-free survival rate was calculated from the date of initial diagnosis using the Kaplan–Meier method. ResultsFive hundred and sixty-seven cases were enrolled in our study, 474 pure Ductal Carcinoma in situ (DCIS) and 93 DCISM were included. Among these, 168 (35.4%) was diagnosed with the grade I and 26(5.5%) with grade III in pure DCIS group, compared with 3 (3.2%) and 11(11.8%) with grade I and III in DCISM (p < .0001). We also found that DCISM was associated with comadonecrosis histologic subtype (p < .0001) and presence of luminal B type (ER/PR positive and Her-2 positive) (p < .0032). There were more positive axillary lymph nodes involvement in patients with DCISM than those with DCIS after performing ALND(p = .0284). Patients with DCISM underwent more axillary lymph node dissection (ALND) in Chinese cancer center than those did in US centers (1.1% VS 47.8–68% and 86.1% VS 3.6–6.9%, respectively). No significantly difference was found in the overall survival rate between patients with DCIS and DCISM during median 100 months follow-up. ConclusionsIn a Chinese cancer hospital, the majority of cases underwent mastectomy and ALDN after the diagnosis of DCISM.The optimal treatments of patients with DCISM should be further investigated.

Extent of microinvasion in ductal carcinoma in situ is not associated with sentinel lymph node metastases.

Ductal carcinoma in situ with microinvasion (DCISM) is a rare diagnosis with a good prognosis. Although nodal metastases are uncommon, sentinel lymph node biopsy (SLNB) remains standard care. Volume of disease in invasive breast cancer is associated with SLNB positivity, and, thus we hypothesized that in a large cohort of patients with DCISM, multiple foci of microinvasion might be associated with a higher risk of positive SLNB. Records from a prospective institutional database were reviewed to identify patients with DCISM who underwent SLNB between June 1997 and December 2010. Pathology reports were reviewed for number of microinvasive foci and categorized as 1 focus or ≥2 foci. Demographic, pathologic, treatment, and outcome data were obtained and analyzed. Of 414 patients, 235 (57 %) had 1 focus of microinvasion and 179 (43 %) had ≥2 foci. SLNB macrometastases were found in 1.4 %, and micrometastases were found in 6.3 %; neither were significantly different between patients with 1 focus versus ≥2 foci (p = 1.0). Patients with positive SLNB or ≥2 foci of microinvasion were more likely to receive chemotherapy. At median 4.9 years (range 0-16.2 years) follow-up, 18 patients, all in the SLNB negative group, had recurred for an overall 5-year recurrence-free proportion of 95.9 %. Even with large numbers, there was no higher risk of nodal involvement with ≥2 foci of microinvasion compared with 1 focus. Number of microinvasive foci and results of SLNB appear to be used in decision making for systemic therapy. Prognosis is excellent.

Factors Predicting Microinvasion in Ductal Carcinoma in situ

Whether sentinel lymph node biopsy (SLNB) should be performed in patients with pure ductal carcinoma in situ (DCIS) of the breast has been a question of debate over the last decade. The aim of this study was to identify factors associated with microinvasive disease and determine the criteria for performing SLNB in patients with DCIS. 125 patients with DCIS who underwent surgery between January 2000 and December 2008 were reviewed to identify factors associated with DCIS and DCIS with microinvasion (DCISM). 88 patients (70.4%) had pure DCIS and 37 (29.6%) had DCISM. Among 33 DCIS patients who underwent SLNB, one patient (3.3%) was found to have isolated tumor cells in her biopsy, whereas 1 of 14 (37.8%) patients with DCISM had micrometastasis (7.1%). Similarly, of 16 patients (18.2%) with pure DCIS and axillary lymph node dissection (ALND) without SLNB, none had lymph node metastasis. Furthermore, of 20 patients with DCISM and ALND, only one (5%) had metastasis. In multivariate analysis, the presence of comedo necrosis [relative risk (RR)=4.1, 95% confidence interval (CI)=1.6-10.6, P=0.004], and hormone receptor (ER or PR) negativity (RR=4.0, 95%CI=1.5-11, P=0.007), were found to be significantly associated with microinvasion. Our findings suggest patients presenting with a preoperative diagnosis of DCIS associated with comedo necrosis or hormone receptor negativity are more likely to have a microinvasive component in definitive pathology following surgery, and should be considered for SLNB procedure along with patients who will undergo mastectomy due to DCIS.

Role of sentinel lymph node biopsy in patients with ductal carcinoma in situ and microinvasion

Aim: Ductal carcinoma in situ with microinvasion (DCISMI) is characterized by one or more areas of focal invasion, 1 mm or less in diameter. While pure ductal carcinoma in situ (DCIS) does not have the potential to metastasize to regional nodes, the presence of microinvasion makes lymph node metastasis possible, leading to current guidelines recommending staging of the axilla with sentinel lymph node biopsy (SLNB). However, there are few studies looking at the risk of lymphatic spread in patients with DCISMI, and indications for axillary staging in such cases is controversial. The aim of the present study was to assess the prevalence of nodal metastasis in patients with DCISMI in order to help ascertain whether SLNB can be safely avoided in DCISMI.Patients and Methods: A retrospective analysis was performed of patients undergoing surgery for DCIS over a 2‐year period (April 2006–08). Data were collected from the National Health Service Breast Screening Programme database and patient case notes. Patients having a SLNB had injection of radioisotope and blue dye. All SLNB were evaluated with serial sectioning and haematoxylin–eosin staining.Results: Over the 2‐year period, 399 screen‐detected breast cancers were treated, of which 310 (77 per cent) were invasive, 17 (4 per cent) had DCISMI and 72 (19 per cent) pure DCIS. The group with DCISMI was studied in more detail. Twelve out of the 17 patients had a wide local excision and five had a mastectomy. All 17 patients with DCISMI had a SLNB. No positive lymph nodes were found in this group.Conclusion: Our data suggest that the risk of nodal metastasis in DCISMI might be low, and question the role of SLNB in DCISMI. We highlight the lack of data on DCISMI and risk of nodal metastasis, and the need for further investigation.

P4-18-05: Ductal Carcinoma In Situ with Microinvasion: Clinical and Pathological Characteristics, Treatments and Outcomes.

Abstract Background: Ductal carcinoma in situ with microinvasion (DCISM) is a rising rare entity. Because of that and its controversial pathological definition, there is a lack of clear recommendations for treatment. The purpose of this study was to describe the clinical and pathological characteristics, treatments and outcomes of our single institutional experience. Patients and methods: Individual clinical and pathological data were collected from 63 women, diagnosed and treated for DCISM at the Claudius Regaud Cancer Hospital between January 2000 and April 2010. All available histological material (45 patients) was reviewed by an expert pathologist. Results: The median age was 56 years (range 34–83). Seven patients (11.5%) had a personal history of DCIS, 27 patients (42%) a familial history of breast cancer. Fourteen patients (22%) had a clinical sign at the diagnosis. Fifty one patients were mammographically detected (81%). All the patients underwent surgery, mastectomy for 17 patients (27.4%) and conservative surgery for 45 (72.6%). Secondary surgery of the breast was required for 21 patients (46.6%) after conservative surgery, enlarging surgery (N=13) or mastectomy (N=8). Surgical axillary lymph node evaluation was performed on 52 patients (82,5%), axillary dissection alone for 10 patients, sentinel node biopsy alone for 37 patients and the 2 methods for 5 patients. The median size of the DCIS was 16mm (6-80mm) with 37/60 (61.7%) grade III Van Nuys classification. The most histological subtype was comedo carcinoma (68%). Concerning the 45 reviewed biopsies, the size of the microinvasive component was ≤ 1mm for 38 lesions and between 1 and 2 mm for 7 lesions. Hormonal receptor status was positive for 29 (64.4%), 27 (64.3%) for estrogen receptors and 20 (44.4%) for progesterone receptors. HER 2 status was performed for 34 patients, among 12 (35%) of them were found overexpressed on the microinvasive component. Lymph node invasion was found among 2 of the 52 patients (3.8 %) who underwent axillary lymph node evaluation. Radiation therapy was delivered to all the patients after conservative surgery (n=37)(50 Gy with a 10 Gy boost for 22 of them) and 2 after mastectomy (chest wall irradiation (50 Gy)). Adjuvant hormonotherapy was delivered on 11 patients (18%). With a median follow-up of 36,4 months (95%CI=[27.7- 44.16]), 62 patients are alive at the last follow-up and 58/63 free of disease (2 relapses and 3 second cancers).The 3 year disease free survival rate was 91.1 (95%CI=[78.1;96.6] ). During follow-up, two local relapses occurred on patients treated by mastectomy. One of them had local invasive relapse at 43 months and she is still NED after 90 months. The second patient who had local invasive carcinoma with axillary node invasion at 32 months treated by conservative surgery, axillary dissection, radiotherapy and chemotherapy, had metastasis at 51 months and passed away after 70 months. Conclusion: Mammographic screening programmes increase the rate of small diagnosed tumours, specially DCISM. Despite a priori good prognostic outcome, 2 axillary node involvements and 2 delayed relapses were observed. So, this kind of presentation deserves better evaluation of relapse risk factors to determine adapted adjuvant therapies. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-18-05.