Diagnosis Of Ductal Carcinoma In Situ Research Articles

Abstract P6-10-20: Ductal carcinoma in situ (DCIS) of the breast: miRNA deregulation correlates with the Oncotype DX risk score

Abstract Background: Ductal carcinoma in situ (DCIS) is considered a non-obligate precursor of invasive breast cancer (IBC). It is estimated that 5-14% of women diagnosed with DCIS experience an ipsilateral IBC. Current clinical criteria do not discriminate well between women with DCIS who will and those who will not develop ipsilateral IBC or a DCIS recurrence. The Oncotype DX DCIS assay (12 genes) was derived from a multigene expression array (Oncotype DX, 21 genes), and includes 5 proliferation genes, PGR, GSTM1, and 5 reference genes. This assay has been shown to predict risk of subsequent ipsilateral IBC and DCIS, and is used by clinicians to evaluate both the risk of local recurrence and need for radiation therapy. Since abnormal expression of microRNAs (miRNAs) is thought to contribute to the development of IBC, and that very few studies have evaluated miRNA expression deregulation in DCIS lesions, we sought to determine if specific miRNA expression changes may help identify DCIS lesions with different Oncotype DX DCIS scores. Methods: For this study, we selected archived specimens from 52 women diagnosed with DCIS between 2012 and 2018, whose DCIS lesions were tested with the Oncotype DX DCIS assay (low (n=35), intermediate (n=11), high (n=6) risk scores). Total RNA was extracted by macrodissection of the DCIS lesions. MiRNA expression differences between DCIS lesions were evaluated using small-RNA next-generation sequencing. Quantitative PCR validations were performed using Taqman miRNA assays on the top 15 differentially expressed miRNAs Results: Small-RNA expression data obtained by next-generation sequencing of 43 DCIS RNA specimens identified miRNAs differentially expressed between the risk score groups. Fifteen differentially expressed miRNAs were selected for their association based on Oncotype DX DCIS score differences (miR-142-3p, miR-142-5p, miR-744, miR-155, miR-30c, miR-150, miR-146a, miR-190b, miR-135b, miR-193b) or on age of the patients (miR-19b, miR-19a, miR-135a, miR-132). QPCR validation of these 15 miRNAs, using RNA from 30 DCIS lesions with known Oncotypes DX DCIS scores, of which 21 were samples that had been sequenced (low (n=8), intermediate (n=9), and high (n=4)), and 9 were not sequenced (low (n=7), intermediate (n=1), high (n=1)) and identified 5 miRNAs (miR-135a (p=<0.05), miR-190b (p=0.043), miR-205 (p=<0.001), miR-30c (p=<0.01), miR-744 (p=<0.038)) that emerged for their association with the score groups. These 5 miRNAs provided a good discrimination tool between low and intermediate-high score samples. A composite score including these 5 miRNAs showed a highly significant association with the Oncotype DX DCIS Score (p=<0.001). Conclusions: Our analyses identified a subset of 5 miRNAs that is significantly associated with the Oncotype DX DCIS score of DCIS lesions. Interestingly, three of these miRNAs (miR-205, miR-744 and miR-135b) have been reported to regulate proliferation pathways, while the other two (miR-30c, and miR-190b) have been associated with estrogen expression pathways in breast cancer cells. Importantly, increased expression of miR-30c in IBC has been associated with benefit from endocrine therapy while increased expression of miR-205 has been associated with benefit from tyrosine kinase inhibitors in IBC, as well. Mir-205 has also been reported as a radiosensitizer in breast cancer cells. Altogether, our data suggest that evaluation of miRNA expression levels may add predictive and prognostic value to the diagnosis of DCIS. Citation Format: Olivier Loudig, Iddo Ben-Dov, Christina Liu, Miglena Komforti, Susan Fineberg. Ductal carcinoma in situ (DCIS) of the breast: miRNA deregulation correlates with the Oncotype DX risk score [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-10-20.

Sentinel lymph node positivity in patients undergoing mastectomies for ductal carcinoma in situ (DCIS).

Current guidelines recommend sentinel lymph node biopsy (SLNB) for patients undergoing mastectomy for a preoperative diagnosis of ductal carcinoma in situ (DCIS). We examined the factors associated with sentinel lymph node positivity for patients undergoing mastectomy for a diagnosis of DCIS on preoperative core biopsy (PCB). The Institutional Breast Cancer Database was queried for patients with PCB demonstrating pure DCIS followed by mastectomy and SLNB from 2010 to 2018. Patients were divided according to final pathology (DCIS or invasive cancer). Clinico-pathologic variables were analyzed using Pearson's chi-squared, Wilcoxon Rank-Sum and logistic regression. Of 3145 patients, 168(5%) had pure DCIS on PCB and underwent mastectomy with SLNB. On final mastectomy pathology, 120(71%) patients had DCIS with 0 positive sentinel lymph nodes (PSLNs) and 48(29%) patients had invasive carcinoma with 5(10%) cases of ≥1 PSLNs. Factors positively associated with upstaging to invasive cancer in univariate analysis included age (P=.0289), palpability (P<.0001), extent of disease on imaging (P=.0121), mass on preoperative imaging (P=.0003), multifocality (P=.0231) and multicentricity (P=.0395). In multivariate analysis, palpability (P=.0080), extent of disease on imaging (P=.0074) and mass on preoperative imaging (P=.0245) remained significant (Table 2). In a subset of patients undergoing mastectomy for DCIS with limited disease on preoperative evaluation, SLNB may be omitted as the risk of upstaging is low. However, patients who present with clinical findings of palpability, large extent of disease on imaging and mass on preoperative imaging have a meaningful risk of upstaging to invasive cancer, and SLNB remains important for management.

Multicentre study of the risk of invasive cancer and use of sentinel node biopsy in women with a preoperative diagnosis of ductal carcinoma in situ.

Ductal carcinoma in situ (DCIS) in the breast that is diagnosed by biopsy implies a risk of upstaging to invasive carcinoma (IC) on final pathology. These patients require a sentinel lymph node biopsy (SLNB) for axillary staging. A two-stage procedure is not always feasible and precise selection of patients who should be offered SLNB is crucial. The aims were: to determine the rate of upstaging, and use of redundant and required SLNB in women with a preoperative diagnosis of DCIS; and to identify patient and tumour characteristics that increase the risk of upstaging. Patients with DCIS treated between 2008 and 2016 were identified using Orbit operation planning system software, and those suitable for the study were selected based on review of the medical records. Upstaging rates and proportions of redundant and required SLNBs were calculated. Associations between clinicopathological characteristics and upstaging were analysed using univariable and multivariable logistic regression analyses. Of 1368 patients initially identified, 975 women with a preoperative diagnosis of DCIS were included in the study. Tumours in 246 of these patients (25·2 per cent) were upstaged to IC. Redundant SLNB was performed in 392 of 975 women (40·2 per cent). Forty-four patients (4·5 per cent) with a final diagnosis of IC were not offered SLNB and thus potentially undertreated. In adjusted analysis, DCIS size, palpability and mass formation identified by breast imaging were associated with increased risk of upstaging. The Van Nuys classification was not associated with upstaging. Most patients with IC on final pathology underwent SLNB, but a considerable number of patients with DCIS had a redundant SLNB. Lesion size, palpability and mass formation, but not Van Nuys classification group, are suggested risk factors for upstaging.

Predictive factors for the presence of invasive components in patients diagnosed with ductal carcinoma in situ based on preoperative biopsy

BackgroundIn patients diagnosed with ductal carcinoma in situ (DCIS) with needle biopsy before surgery, invasive component (IC) is often found in the postoperative tissue, which results in altered post-surgical care. However, there are no clinically available factors to predict IC, and few MRI studies are available for the detection of IC in DCIS patients. The purpose of this study was to evaluate which risk factors can predict IC preoperatively.MethodsPatients with a DCIS diagnosis based on preoperative biopsy, who underwent breast surgery Kangbuk Samsung Hospital between Jan 2005 and June 2018, were retrospectively evaluated. Clinico-pathological and breast MRI factors were compared between DCIS and DCIS with IC in postsurgical specimens.ResultsOf the 431 patients with a preoperative diagnosis of DCIS, 34 (7.9%) showed IC during the postoperative pathological investigations, and 217 (50.3%) underwent breast MRI. Among MRI-related factors, Mass-like enhancement on MRI was the sole but significant predictor of IC (HR = 0.26, C.I. = 0.07–0.93, p = 0.038), while nipple-areolar complex invasion, enhancement peak and pattern were not statistically significant. Nuclear grade was the only significant predictor of IC in the analysis of other clinico-pathological factors (HR = 2.39, C.I. = 1.05–5.42, p = 0.038 in univariate analysis, HR = 2.86, C.I. = 1.14–7.14, p = 0.025 in multivariate analysis).ConclusionsMass-like enhancement on MRI and high nuclear grade were associated with IC in patients with preoperative diagnosis of DCIS. Considering the high sensitivity of breast MRI for IC, further evaluation of the predictive value of MRI in preoperative DCIS patients is desirable.

Ductal Carcinoma In Situ (DCIS) at Breast MRI: Predictors of Upgrade to Invasive Carcinoma

To determine the upgrade rate of magnetic resonance imaging (MRI)-detected ductal carcinoma in situ (DCIS) and to identify patient, imaging, and pathologic features that may predict the risk of upgrade. Medical chart review from January 2007 to December 2016 identified 60 patients with 61 cases of MRI-detected DCIS and negative mammographic evaluations within 1 year prior to the MRI. Imaging and pathology reports were reviewed. Standard statistical tests, including Student's t-tests and chi-square tests, were used to compare patient, imaging, and pathologic features between the cases of DCIS that did and did not upgrade to invasive carcinoma at surgery. Over a 10-year period, 60 patients (mean age 52 years, range 30-76 years) were diagnosed with 61 cases of MRI-detected DCIS. Two-thirds of DCIS cases were detected on MRI examinations that were performed for purposes of high-risk screening (67.2%, 41/61). MRI features that led to the DCIS diagnosis were nonmass enhancement in 78.7% (48/61), enhancing mass in 16.4% (10/61), nonmass enhancement and enhancing mass in 3.3% (2/61), and enhancing focus in 1.6% (1/61). Thirteen cases (21.3%, 13/61) were upgraded to invasive ductal carcinoma at surgery. DCIS cases that upgraded were larger on MRI (40 mm vs 17 mm, p < 0.01) and more likely to be associated with comedonecrosis at biopsy (38.5% [5/13] vs 6.3% [3/48], p < 0.01). The upgrade rate of MRI-detected DCIS to invasive ductal carcinoma at surgery is 21.3%. Features that are associated with upgrade include large size on MRI and the presence of comedonecrosis at biopsy.

Estimating the magnitude of clinical benefit of systemic therapy in patients with DCIS or pre-invasive disease of the breast

The challenge of effective management of ductal carcinoma in situ (DCIS) and other pre-malignant disorders of the breast is to select patients who will not progress to invasive carcinoma from those at the highest risk who require radiotherapy and/or endocrine therapy to minimize the risk of a subsequent invasive recurrence. Although IBIS-II and NSABP-B35 DCIS phase III trials proved that tamoxifen 20 mg/day and anastrozole reduce the risk of ipsilateral and contralateral events, the toxicities of both drugs have hampered the drug uptake by high-risk women. We recently reported results of a 3-year placebo-controlled trial of low-dose (5 mg/d) tamoxifen in 500 women with intraepithelial neoplasia (70% DCIS). At a median follow-up of 5 years, women randomly assigned to low-dose tamoxifen had half the number of subsequent diagnoses of DCIS or invasive cancer compared with those randomly assigned to placebo but no increase in thromboembolic events or endometrial cancers. The 5-year number needed to treat was 22 (95% CI, 20–27). Our attention is now focused on prognostic and predictive markers to identify patients who can derive the greatest benefits from low dose tamoxifen, such as for instance the expression of 23 genes involved in cell cycle progression (CCP). In conclusion, we endorse an active treatment of DCIS as the standard of care.

Evidence map of ductal carcinoma in situ management options.

Ductal carcinoma in situ (DCIS) has the potential to progress to invasive carcinoma. The optimal management of DCIS and methods for individualizing treatment of DCIS are still being determined. This evidence map depicts the robustness and topical span of research on DCIS management choice on patient-centered and clinical outcomes. We searched PubMed, EMBASE, PsycINFO, PubMed Health, PROSPERO, and clinical practice guideline sites to identify systematic reviews of DCIS management options and consulted with topic experts. A bubble plot visualizes the literature volume and research content for patient-centered outcomes. An online decision tree facilitates discussions with patients and guides through the available evidence. In total, 40 systematic reviews met inclusion criteria. The research syntheses addressed DCIS management options, including the role of magnetic resonance imaging, axillary surgery/sentinel lymph node biopsy, and excisional biopsy. The map shows existing evidence for mutually exclusive treatment options including active surveillance, breast-conserving surgery, nipple sparing mastectomy, and simple mastectomy. Research findings for intraoperative radiation, adjuvant radiation therapy, adjuvant hormone therapy, hypofractionation radiotherapy, accelerated partial breast irradiation, radiation therapy plus boost, and combined radiation and hormone therapy, as well as for breast reconstruction after mastectomy and surveillance mammography postsurgery are also displayed. The evidence map highlights a scarcity of robust evidence on patient-centered outcomes. The evidence map provides an overview of DCIS research showing the range of management options and remaining decisional dilemmas that follow a diagnosis of DCIS. It maps the evidence in accessible tools to guide practice and future research. : Video Summary:http://links.lww.com/MENO/A448.

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.

Deep learning analysis of breast MRIs for prediction of occult invasive disease in ductal carcinoma in situ

PurposeTo determine whether deep learning-based algorithms applied to breast MR images can aid in the prediction of occult invasive disease following the diagnosis of ductal carcinoma in situ (DCIS) by core needle biopsy. Materials and methodsOur study is retrospective. The data was collected from 2000 to 2014. In this institutional review board-approved study, we analyzed dynamic contrast-enhanced fat-saturated T1-weighted MRI sequences from 131 patients with a core needle biopsy-confirmed diagnosis of DCIS. We explored two different deep learning approaches to predict whether there was an occult invasive component in the analyzed tumors that was ultimately identified at surgical excision. In the first approach, we adopted the transfer learning strategy. Specifically, we used the pre-trained GoogleNet. In the second approach, we used a pre-trained network to extract deep features, and a support vector machine (SVM) that utilizes these features to predict the upstaging of DCIS. We used nested 10-fold cross validation and the area under the ROC curve (AUC) to estimate the performance of the predictive models. ResultsThe best classification performance was obtained using the deep features approach with GoogleNet model pre-trained on ImageNet as the feature extractor and a polynomial kernel SVM used as the classifier (AUC = 0.70, 95% CI: 0.58–0.79). For the transfer learning based approach, the highest AUC obtained was 0.68 (95% CI: 0.57–0.77). ConclusionsConvolutional neural networks might be used to identify occult invasive disease in patients diagnosed with DCIS by core needle biopsy.

A clinical study on synchronous relation between ductal CA in situ and invasive ductal carcinoma of breast

Introduction: We have lot of studies regarding Ductal Carcinoma in Situ (DCIS) succeeding into Invasive Ductal Carcinoma (IDC) of the breast. Still, there is hardly any study on the coexistence of both and its clinical significance. The aim of this study is to evaluate the clinical and pathological parameters of synchronous DCIS and IDC to estimate the prognostic factors. Materials and Methods: Total 42 patients with a final diagnosis of synchronous DCIS and IDC diagnosed in 20015-18 were included in the study. Statistical analysis was done using SPSS software utilizing the appropriate analytical methods. Results: Majority of the patients in this study group presented with early breast cancer (64.3%).48% were Her2 subtype and 31% were triple negative. Grade 3 lesions were more common (57%). 81% of the IDC associated histology was Not Otherwise Specified (NOS) type. Recurrence was common in node positive disease (59.5%), those with lymphovascular emboli (59.5%) and perinodal spread (76%) on histopathological examination. Conclusion: Synchronous DCIS and IDC disease being appears to have a destructive nature compared to the course of IDC alone being. Prognostic factors linking to IDC appears to associate well with recurrence than that of the prognostic factors of DCIS module in such synchronous setting.

217P - The routine use of sentinel lymph node biopsy in high risk DCIS lesions is not justified

BackgroundThe use of sentinel lymph node biopsy (SLNB) during breast surgery for ductal carcinoma in situ (DCIS) is controversial. It is accepted in high risk lesions (high histological grade, palpable, large >25mm, and multifocal lesions) since it avoids a second operation if the definitive diagnosis reveals infiltrating ductal carcinoma (IDC) and its recommended due to some technical obligations in patients with planned total mastectomy or with tumor localization to the upper outer quadrant.. We aimed to evaluate the use of SLNB in patients with preoperative diagnosis of high risk DCIS lesions. MethodsA monocentric retrospective study was conducted on 467 patients with primary diagnosed DCIS operated for partial or total mastectomy with or without SLNB. The frequency of each risk factor, and the incidence of IDC were calculated in the overall series. The predictive value of each risk factor is calculated by comparing these factors in the groups depending to the definitive pathology (IDC vs DCIS) using the chi square test. A value of p<0.05 was considered significant. ResultsBreast surgery was done within a median of 42 ± 23 days of DCIS diagnosis. Median age was 57± 10 years. High risk DCIS lesions accounted for 73.1% of all cases (342/468). Grade III lesion, multifocal, palpable and larger than 25mm lesions were present in 263 (56.3%), 61 (13.1%), 86 (18.4%) and 99 (21.2%) respectively. IDC was diagnosed in 95/468 patients (20.3%) in the global series and in 75patients/342 (22%) in the patients with high risk lesions. A palpable lesions and a tumor diameter >25mm were associated with higher risk of invasive carcinoma (p=0.007 and p=0.017 respectively).Overall SLNB was done in 383 patients (82%), of which 318 patients (83%) had high risk lesions. A Positive SLN was detected in overall 5 patients (1.3%), all of which had high risk lesions (5/318: 1.6%). ConclusionsIn our study, the preoperative classification of high risk lesion showed a 79% sensitivity (75/95) and a 22% specificity (75/342) of detecting IDC. A positive SLN was found in only 1.6% of patients with high risk CDIS lesions operated for SLNB. The use of SLNB in patients with high risk DCIS avoids reoperation in 22% of cases. Nevertheless the low risk of positive SLN finding in this setting cannot justify its routine use. Legal entity responsible for the studyJean Marie Nogaret. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Preoperative Delays in the Treatment of DCIS and the Associated Incidence of Invasive Breast Cancer

BackgroundAlthough treatment delays have been associated with survival impairment for invasive breast cancer, this has not been thoroughly investigated for ductal carcinoma in situ (DCIS). With trials underway to assess whether DCIS can remain unresected, this study was performed to determine whether longer times to surgery are associated with survival impairment or increased invasion.MethodsA population-based study of prospectively collected national data derived from women with a clinical diagnosis of DCIS between 2004 and 2014 was conducted using the National Cancer Database. Overall survival (OS) and presence of invasion were assessed as functions of time by evaluating five intervals (≤ 30, 31–60, 61–90, 91–120, 121–365 days) between diagnosis and surgery. Subset analyses assessed those having pathologic DCIS versus invasive cancer on final pathology.ResultsAmong 140,615 clinical DCIS patients, 123,947 had pathologic diagnosis of DCIS and 16,668 had invasive ductal carcinoma. For all patients, 5-year OS was 95.8% and unadjusted median delay from diagnosis to surgery was 38 days. With each delay interval increase, added relative risk of death was 7.4% (HR 1.07; 95% CI 1.05–1.10; P < 0.001). On final pathology, 5-year OS for noninvasive patients was 96.0% (95% CI 95.9–96.1%) versus 94.9% (95% CI 94.6–95.3%) for invasive patients. Increasing delay to surgery was an independent predictor of invasion (OR 1.13; 95% CI 1.11–1.15; P < 0.001).ConclusionsDespite excellent OS for invasive and noninvasive cohorts, invasion was seen more frequently as delay increased. This suggests that DCIS trials evaluating nonoperative management, which represents infinite delay, require long term follow up to ensure outcomes are not compromised.

Fractionation in adjuvant radiotherapy for invasive breast cancer and ductal carcinoma in situ in Ontario, Canada from 2009 to 2015.

The use of hypofractionated radiotherapy (HFRT) in patients with breast cancer and ductal carcinoma in situ (DCIS) in Ontario, Canada, from 2009 to 2015 was reported. A retrospective cohort study was conducted using data from the Institute for Clinical Evaluative Sciences (ICES). Patients with a breast cancer or DCIS diagnosis between 2009 and 2015 who received adjuvant breast or chest wall radiation were included. Trends in HFRT use (≤16 fractions) and factors associated with HFRT use in a multivariable logistic regression model with physician-level random effect were reported. The approximate number of hours that could be saved if all patients were to receive HFRT was calculated. A total of 42072 patients were included. All included characteristics were significantly associated with HFRT use. Hypofractionated radiotherapy use in patients with breast cancer and DCIS increased to around 75% in 2015. In stage I/II patients with mastectomy and chest wall radiation, HFRT use increased to 40% in 2015. Hypofractionated radiotherapy use in patients with regional nodal radiation or reconstruction has increased but remains under 20%. For breast cancer patients with breast-conserving surgery (BCS) and breast radiation, 56265 visits corresponding to 7200hours of treatment or 3500 additional HFRT courses could have been saved. In conclusion, HFRT use in Ontario has increased in all patient populations but is nonuniform among physicians and institutions. Use of HFRT in chest wall and regional nodal radiation remains relatively lower than in breast cancer and DCIS patients with BCS.

Evaluation of high molecular weight cytokeratin (HMWCK), p27, C-X-C chemokine receptor type 4 (CXCR-4) and stromal cell-derived factor 1 (SDF-1) expressions related to tumor progression in breast cancer

Objectives: Breast cancer is the most common cancer and the most common reason for cancer death in women population. The immunohistochemical markers which could have prognostic information are always needed. Methods: This study included 365 cases of invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS) and ductal epithelial hyperplasia. The cases divided into the following two groups according to the presence of cancer: 1) cancer group (298 cases; cases with IDC and DCIS), 2) non-cancer group (67 cases without cancer; cases with usual ductal epithelial hyperplasia [UDH] and atypical ductal epithelial hyperplasia [ADH]). All histological slides stained with high molecular weight cytokeratin (HMWCK), p27, C-X-C chemokine receptor type 4 (CXCR-4), stromal cell-derived factor 1 (SDF-1) immunohistochemically. Results: IDC was present in 277 cases, of which 213 had pure IDC, and 64 had DCIS component adjacent to the invasive tumor. Twenty-one cases had only DCIS. Of 67 cases with epithelial hyperplasia, 31 had ADH, and 36 had UDH. Among cases with IDC, 143 had lymph node excision, of which 73 had metastasis in one or more lymph nodes, and 70 did not have metastatic disease. The expression of p27 was found to be significantly lower in the cancer group as compared to that in the non-cancer group (p &amp;lt; 0.0001). CXCR-4 expression in IDC was found to be higher than that of DCIS group. SDF-1 expression was observed to be significantly higher in cancer cases than that of non-cancer cases (p = 0.03). Conclusions: The higher CXCR-4 and SDF-1 expressions are associated with tumor progression, tumor size, and lymph node status. In benign proliferative lesions, both HMWK and p27 expressions were helpful in differential diagnosis of borderline atypical ductal hyperplasia and DCIS.

Diagnostic value of MRI and mammography in ductal carcinoma in situ of the breast

Objective To investigate the diagnostic value of MRI and molybdenum target in ductal carcinoma in situ (DCIS). Methods From June 2014 to June 2018, 58 patients diagnosed as DCIS in Heji Hospital Affiliated to Changzhi Medical College were chosen.MRI and mammography were performed, and the diagnostic potency of the two methods was observed. Results The coincidence degree of molybdenum target X-ray and MRI diagnosis: the coincidence coefficient kappa=0.452 of molybdenum target X ray and MRI showed that the two diagnostic methods were in general anastomosis.The diagnostic consistency of different examination methods: the diagnostic consistency of molybdenum target combined with MRI (96.6%) was significantly higher than that of molybdenum target X(82.8%), the difference was statistically significant (χ2=5.95, P 0.05). Conclusion Molybdenum target and MRI in diagnosis of DCIS have their own characteristics.Combined application can improve the diagnostic effect. Key words: Breast neoplasms; Carcinoma, ductal, breast; Magnetic resonance imaging; Mammography

Low-grade screen-detected ductal carcinoma in situ progresses more slowly than high-grade lesions: evidence from an international multi-centre study.

Nuclear grade is an important indicator of the biological behaviour of ductal carcinoma in situ (DCIS). De-escalation of treatment has been suggested for low-grade DCIS. Our aim is to estimate the relative rate of progression of DCIS by nuclear grade by analysing the distribution of nuclear grade by detection at initial or subsequent screening. We asked International Cancer Screening Network sites to complete, based on their screening and clinical databases, an aggregated data file on DCIS detection, diagnosis and treatment. Eleven screening programs reported 5068 screen-detected pure DCIS in nearly 7 million screening tests in women 50-69years of age. For all programs combined, low-grade DCIS were 20.1% (range 11.4-31.8%) of graded DCIS, intermediate grade 31.0% and high grade 48.9%. Detection rates decreased more steeply from initial to subsequent screening in low compared to high-grade DCIS: the ratios of subsequent to initial detection rates were 0.39 for low grade, 0.51 for intermediate grade, and 0.75 for high grade (p < 0.001). These results suggest that the duration of the preclinical detectable phase is longer for low than for high-grade DCIS. The findings from this large multi-centre, international study emphasize that the management of low-grade DCIS should be carefully scrutinized in order to minimize overtreatment of screen-detected slow-growing or indolent lesions. The high variation by site in the proportion of low grade suggests that further pathology standardization and training would be beneficial.

Combined application of pharamcokinetic DCE-MRI and IVIM-DWI could improve detection efficiency in early diagnosis of ductal carcinoma in situ.

PurposeDuctal carcinoma in situ (DCIS) is a precursor of invasive ductal breast carcinoma (IDC). This study aimed to use pharamcokinetic dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) and intravoxel incoherent motion diffusion‐weighted imaging (IVIM‐DWI) for the early diagnosis of DCIS.MethodsForty‐seven patients, including 25 with DCIS (age: 28–70 yr, mean age: 48.7 yr) and 22 with benign disease (age: 25–67 yr, mean age: 43.1 yr) confirmed by pathology, underwent pharamcokinetic DCE‐MRI and IVIM‐DWI in this study. The quantitative parameters Ktrans, Kep, Ve, Vp, and D, f, D* were obtained by processing of DCE‐MRI and IVIM‐DWI images with Omni‐Kinetics and MITK‐Diffusion softwares, respectively. Parameters were analyzed statistically using GraphPad Prism and MedCalc softwares.ResultsAll low‐grade DCIS lesions demonstrated mass enhancement with clear boundaries, while most middle‐grade and high‐grade DCIS lesions showed non‐mass‐like enhancement (NMLE). DCIS lesions were significantly different from benign lesions in terms of Ktrans, Kep, and D (t = 5.959, P < 0.0001; t = 5.679, P < 0.0001; and t = 5.629, P < 0.0001, respectively). The AUC of Ktrans, Kep, D and the combined indicator of Ktrans, Kep, and D were 0.936, 0.902, 0.860, and 0.976, respectively. There was a significant difference in diagnostic efficacy only between D and the combined indicator (Z = 2.408, P = 0.016).ConclusionDCE‐MRI and IVIM‐DWI could make for the early diagnosis of DCIS, and reduce the misdiagnosis of DCIS and over‐treatment of benign lesions.

Sentinel node mapping and ductal carcinoma in situ.

Pure ductal carcinoma in situ (DCIS) is typically unassociated with a risk of regional lymph node involvement. Retrospective series maintain that larger tumors or high-grade histopathology may harbor a risk of lymph node involvement. Our community hospital retrospectively reviewed a series wherein women with DCIS were subjected to sentinel lymph node biopsy based on large tumor size and/or high-grade histopathology. 232 consecutive women with a diagnosis of pure DCIS were evaluated independently by two breast surgeons, one who typically offers sentinel node mapping to patients with tumors larger than 10mm and the other who offers sentinel node mapping to women with grade3 tumors. 60 women (26%) underwent sentinel node mapping along with appropriate surgery directed to the breast. Women were offered risk-adjusted adjuvant radiotherapy and anti-endocrine therapy. At a median follow-up of 18months (range 6-132months), 9 women (15%) were identified with regional axillary nodal disease. A statistical analysis was conducted between women who did or did not undergo sentinel node mapping because there was overlap in large tumor size and high grade between the two groups. A univariate logistic regression statistic showed a trend toward a significant relationship between grade3 tumors and a risk of occult nodal involvement. This was not confirmed by multivariate analysis. In our moderate-sized surgical experience evaluating women with pure DCIS who underwent a sentinel node mapping due to large tumor size or high grade histology, we were unable to confirm that either is predictive of occult node involvement.

Abstract P5-18-04: HER2 overexpression in ductal carcinoma in situ: A biomarker for risk stratification and therapeutic implication

Abstract Background: After initial treatment for ductal carcinoma in situ (DCIS), a subsequent clinically significant event (SCSE) such as another diagnosis of DCIS, atypia or invasive breast cancer (IBC), will likely lead to further surgical/medical therapy. Pathologically, DCIS is treated on the basis of estrogen (ER) and progesterone receptor (PR) status with hormonal therapy (HT), ie, tamoxifen (TMX) or aromatase inhibitor, regardless of human epidermal growth factor receptor (HER2) overexpression. Although HER2 is a well-established prognostic marker for IBC, the role of HER2 in DCIS is less appreciated. Recent studies have documented the prognostic value of p16, COX-2 and Ki67 as prognostic biomarkers for locoregional invasive recurrences due to abrogated response to cellular stress (ARCS). Notably, a high-risk population of DCIS patients lacking ER expression but over-expressing HER2, p16 and COX-2 has been recently identified. In the present study, we compared expression levels of HER2 and the 3 ARCS markers in a large cohort of DCIS patients treated with contemporary standard of care and with &amp;gt;5-year follow-up to assess their association with cancer progression and predictive value for developing a SCSE. Methods: Formalin-fixed paraffin-embedded tissue sections from 99 patients diagnosed with primary DCIS(1999-2013) were stained forER, PR and HER2 expression by immunohistochemistry (IHC).If equivocal, HER2 amplification was assessed by Silver In Situ Hybridization. An additional slide was stained forp16, Ki67 and COX-2 using a novel multiplex IHC strategy. Quantification of the 3 ARCS markers' expression in both epithelial and stromal compartments was carried out using a software (InformTM)-guided approach. For expression level comparison of the three markers between HER2+ and HER2- DCIS, Wilcoxon-Mann-Whitney test was used. Fisher's exact or Chi-square test was used for other data analysis. Results: Simultaneous increase in epithelial p16, COX-2 and Ki67 expression in DCIS lesions was associated with subsequent IBC progression. HER2+ DCIS was significantly associated with high grade (p=0.0014), comedo-necrosis subtype (p=0.0022) compared to HER2- lesions. Upregulation of stromal COX-2 and p16 was significantly (p=0.008) associated with progression to SCSE in HER2- DCIS. The majority (5/6, 83%) of HER2+ DCIS patients treated with HT developed a SCSE, while only 22% (6/27) of HER2- DCIS patients treated with HT developed a SCSE. COX-2 upregulation was significantly associated with resistance to HT in HER2+ DCIS patients. Conclusion: High expression of p16, COX-2 and Ki67 in DCIS lesions can serve as powerful predictive biomarkers for DCIS progression to IBC. Our preliminary data suggest that overexpression of stromal p16 and COX-2 may help predict SCSEs in HER2- DCIS. Additionally, assessment of HER2 expression in DCIS may allow identification of patients who would not benefit from traditional HT as HER2 overexpression may predict TMX resistance. Since our data suggest that TMX resistance in HER2+ DCIS may be linked to upregulation of COX-2, one may propose that COX-2 inhibitors in conjunction with TMX may minimize TMX resistance in HER2+ DCIS. These preliminary data will need to be reproduced in a larger cohort to solidify their significance. Citation Format: Yin J, Gascard P, Last B, Singh M, Tlsty T, Tjoe JA. HER2 overexpression in ductal carcinoma in situ: A biomarker for risk stratification and therapeutic implication [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-18-04.

Abstract P1-08-07: Risk factors for high-grade and low-grade DCIS in the cancer prevention study-II nutrition cohort

Abstract Background: Nuclear grade, believed to be established early in carcinogenesis, is an indicator of ductal carcinoma in situ (DCIS) prognosis. Women with high-grade DCIS have a higher risk of local recurrence compared to women with low-grade DCIS. Risk factors for DCIS overall are well-characterized but risk factors by grade are not. Given the prognostic capabilities of grade for DCIS, it is of interest to identify whether risk factors by DCIS grade differ. Methods: Among 75,630 women enrolled in the Cancer Prevention Study-II Nutrition Cohort in 1992-1993, we identified 422 who were diagnosed with low-moderate grade DCIS (i.e. grades 1 or 2) and 355 who were diagnosed with high-grade DCIS (i.e. grade 3) during follow-up through 2013. Beginning in 1997, biennial questionnaires were administered to update exposure status, including screening mammography in the previous two years. For this analysis, these questionnaires were used to partition follow-up time into approximately two-year intervals. Because screening is strongly linked to diagnosis of DCIS, contribution of person-time within a specific interval was conditional on reporting a screening mammogram in the interval prior. Multivariate joint Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the associations of known breast cancer risk factors with DCIS overall, and with high-grade and low-grade DCIS individually. Results: Parity (HR=0.70; 95% CI: 0.63-0.78, parous vs. nulliparous), smoking status (HR=0.69; 95% CI: 0.58-0.82, current vs. never smoking) and menopausal status (HR=0.79; 95% CI: 0.73-0.87, natural menopause &amp;lt;50 years vs. natural menopause ≥ 50 years) were inversely associated with risk of DCIS overall. Whereas, positive family history of breast cancer (HR=1.46; 95% CI: 1.36-1.57), personal history of benign breast disease (BBD) (HR=1.73; 95% CI: 1.62-1.85), and current use of combination estrogen and progestin hormone replacement therapy (HR=1.15; 95% CI: 1.04-1.28) were associated with higher risk of DCIS. In analyses stratified on DCIS grade, history of BBD was more strongly associated with higher risk of low-grade (HR=2.21; 95% CI: 1.81-2.70) than with high-grade DCIS (HR=1.29; 95% CI:1.04-1.60) (p for heterogeneity=0.001). Current combination estrogen and progestin hormone replacement therapy use was associated with a higher risk of high-grade DCIS (HR=1.40; 95% CI:1.03-1.90) but not low-grade DCIS (HR=1.02; 95% CI: 0.75-1.40), but the difference by grade was not statistically significant (p=0.5). Conclusions: In this study, which is the first to comprehensively assess risk factors by DCIS grade, the association between personal history of BBD and risk of DCIS appeared to differ by grade. Due to limited power for some risk factor analyses, future studies using larger prospective cohorts or pooled data should be conducted to better identify these associations. Citation Format: Puvanesarajah S, Gapstur SM, Gansler T, Patel AV, Gaudet MM. Risk factors for high-grade and low-grade DCIS in the cancer prevention study-II nutrition cohort [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-07.