乳管内视镜下导管内肿瘤的诊断和处理

目的 :探讨乳管内视镜对导管内乳头状瘤和导管内癌的诊断价值和处理的指导意义。方法 :对1998年 11月～ 2 0 0 0年 8月 6 8例乳管内隆起性病变中乳头状瘤及导管内癌的乳管内视镜下特征及处理进行分析和总结。结果 :6 8例乳管内隆起性病变中诊断导管内乳头状瘤 6 1例 ,术后证实乳头状瘤 55例 ,准确性为 90 .2 % ;诊断导管内癌 7例 ,术后均被证实 ,准确性为 10 0 %。乳管内视镜下导管内乳头状瘤及导管内癌各有其形态特征。全部患者经乳管内视镜定位后进行了手术。结论 :乳管内视镜对导管内乳头状瘤和导管内癌的诊断准确性高 ,其病变定位功能可指导手术范围。     

Grade of Ductal Carcinoma In Situ Accompanying Infiltrating Ductal Carcinoma As an Independent Prognostic Factor

BackgroundSeveral studies about the relationship between IDC and DCIS have been reported, but no consensus has been reached regarding clinical characteristics and prognostic value.Patients and MethodsWe reviewed the medical records of patients who underwent surgery for IDC between 2006 and 2008. DCIS adjacent to IDC was pathologically classified as either high-grade DCIS or non–high-grade DCIS.ResultsAmong 1751 IDC patients within the study period, 1384 patients (79.0%) had concomitant DCIS. There was no survival difference between patients with pure IDC and those with IDC and concomitant DCIS. However, patients with high-grade DCIS had worse survival than did patients with non–high-grade DCIS or pure IDC (5-year recurrence-free survival rates for IDC with non–high-grade DCIS, pure IDC without DCIS, and IDC with high-grade DCIS were 97%, 93%, and 86%, respectively; P = .001). This tendency was maintained regardless of estrogen receptor status or histologic grade of IDC. In a Cox regression model, patients with IDC and accompanying high-grade DCIS had a 2.5-fold higher probability of local or distant relapse than did those with IDC and low-grade DCIS (hazard ratio, 2.51; 95% confidence interval, 1.12–5.64).ConclusionsThe prognosis of patients with invasive breast cancer differed according to the grade of concomitant adjacent DCIS. Accordingly, the grade of adjacent DCIS should be considered as a prognostic factor in the clinical management of patients with breast cancer. However, in our study, the follow-up periods were short to confirm prognostic effect. Further studies are needed.     

Prospective Analysis Using a Novel CNN Algorithm to Distinguish Atypical Ductal Hyperplasia From Ductal Carcinoma in Situ in Breast

IntroductionWe previously developed a convolutional neural networks (CNN)-based algorithm to distinguish atypical ductal hyperplasia (ADH) from ductal carcinoma in situ (DCIS) using a mammographic dataset. The purpose of this study is to further validate our CNN algorithm by prospectively analyzing an unseen new dataset to evaluate the diagnostic performance of our algorithm.Materials and MethodsIn this institutional review board-approved study, a new dataset composed of 280 unique mammographic images from 140 patients was used to test our CNN algorithm. All patients underwent stereotactic-guided biopsy of calcifications and underwent surgical excision with available final pathology. The ADH group consisted of 122 images from 61 patients with the highest pathology diagnosis of ADH. The DCIS group consisted of 158 images from 79 patients with the highest pathology diagnosis of DCIS. Two standard mammographic magnification views (craniocaudal and mediolateral/lateromedial) of the calcifications were used for analysis. Calcifications were segmented using an open source software platform 3D slicer and resized to fit a 128 × 128 pixel bounding box. Our previously developed CNN algorithm was used. Briefly, a 15 hidden layer topology was used. The network architecture contained 5 residual layers and dropout of 0.25 after each convolution. Diagnostic performance metrics were analyzed including sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve. The “positive class” was defined as the pure ADH group in this study and thus specificity represents minimizing the amount of falsely labeled pure ADH cases.ResultsArea under the receiver operating characteristic curve was 0.90 (95% confidence interval, ± 0.04). Diagnostic accuracy, sensitivity, and specificity was 80.7%, 63.9%, and 93.7%, respectively.ConclusionProspectively tested on new unseen data, our CNN algorithm distinguished pure ADH from DCIS using mammographic images with high specificity.     

Ductal Carcinoma in Situ: A French National Survey. Analysis of 2125 Patients

BackgroundDuctal carcinoma in situ (DCIS) represents 15% of all breast cancers in France. The first national survey was conducted in 2003. The present multi-center real-life practice survey aimed at assessing possible changes in demographic, clinical, pathologic, and treatment features.Material and MethodsFrom March 2014 to September 2015, patients diagnosed with DCIS from 71 centers with complete information about age, diagnostic features, and treatment modalities were prospectively included.ResultsA total of 2125 patients with a median age of 58.6 years from 71 centers were studied. DCIS was diagnosed by mammography in 87.5% of cases. Preoperative biopsy was performed in 96% of cases. The median tumor size was 15 mm. Nuclear grade was low, intermediate, and high in 12%, 36%, and 47% of cases, respectively. Margins were considered to be negative in 83% of cases. Overall mastectomy and lumpectomy rates were 25% and 75%, respectively. The immediate breast reconstruction rate was 50%. Sentinel node biopsy and axillary dissection rates were 41% and 2.6%, respectively. After lumpectomy, 97% of patients underwent radiotherapy, and 32% received a boost dose. Only 1% of patients received endocrine therapy. Compared with our previous survey, the median tumor size remained the same, and the proportion of high-grade lesions increased by 9%. The mastectomy rate decreased by 4%.ConclusionsThe clinical practice identified in this survey complies with French DCIS guidelines. About 10% of patients with low-grade DCIS may be eligible to participate in treatment de-escalation trials.     

Role of FDG-PET/CT in Prediction of Underestimation of Invasive Breast Cancer in Cases of Ductal Carcinoma In Situ Diagnosed at Needle Biopsy

BackgroundThe aim of this study was to evaluate the significance of FDG-PET/CT for predicting the underestimation of invasive breast cancer in cases of DCIS at needle biopsy.Patients and MethodsOf 83 consecutive cases with diagnoses of DCIS at primary needle biopsy who underwent curative surgery between 2010 and 2013, the association between the SUV_max on FDG-PET/CT before excision and the underestimation of invasive breast cancer was examined.ResultsThere were 29 (34.9%) cases diagnosed to have invasive breast cancer at excision. Receiver operating characteristics curve analysis showed the cutoff value of the SUV_max to predict underestimation of invasive breast cancer was 1.6. The rates of underestimation were 61.5% for patients with a tumor of SUV_max > 1.6 and 11.4% for patients with a tumor of SUV_max ≤ 1.6 (P < .001). A high value of SUV_max was significantly associated with symptomatic presentation (P < .001), palpability (P < .001), mass formation (P = .013), high Breast Imaging Reporting and Data System category (P = .011), and core needle biopsy (P = .007). In multivariate analysis, high SUV_max was only a significant predictive factor of underestimation of invasive breast cancer (hazard ratio, 11.7; 95% confidence interval, 3.70-37.0; P < .001).ConclusionSUV_max on FDG-PET/CT is useful for predicting the underestimation of invasive breast cancer in cases of DCIS at needle biopsy.     

CXCR4 is Expressed in Ductal Carcinoma in situ of the Breast and in Atypical Ductal Hyperplasia

Recent evidence attributed important influence of chemokines and their receptors on motility, homing, and proliferation of cancer cells at specific metastatic sites. Here we report that the CXCL12 (SDF-1alpha) chemokine receptor CXCR4 is expressed in human ductal carcinoma in situ (DCIS) as well as in atypical ductal hyperplasia. CXCR4 was expressed in pure DCIS and DCIS with concurrent invasive disease. In 66% of the samples, atypical ductal hyperplasia was present, and > 92% exhibited positive CXCR4-staining. Expression of CXCR4 at this very early step of tumor development indicates a role of this receptor in providing a selective advantage to such cells on their way to metastasizing carcinomas. These results strengthen the ideas to target chemokine networks involved in tumor progression and metastatis as a therapeutic approach in malignant disease or as a chemoprevention strategy, blocking the transition from premalignancy to malignancy.     

Validation of a Nomogram in the Prediction of Local Recurrence Risks after Conserving Surgery for Asian Women with Ductal Carcinoma in Situ of the Breast

AimsAt our centre, ductal carcinoma in situ (DCIS) was commonly treated with breast-conservation therapy (BCT). Local recurrence after BCT is a major concern. The aims of our study were to review the outcomes of DCIS treatment in our patients and to evaluate a nomogram from Memorial Sloan Kettering Cancer Centre (MSKCC) for predicting ipsilateral breast tumour recurrence (IBTR) in our Asian population.Materials and methodsChart reviews of 716 patients with pure DCIS treated from 1992 to 2011 were carried out. Univariable Cox regression analyses were used to evaluate the effects of the 10 prognostic factors of the MSKCC nomogram on IBTR. We constructed a separate National Cancer Centre Singapore (NCCS) nomogram based on multivariable Cox regression via reduced model selection by applying the stopping rule of Akaike's information criterion to predict IBTR-free survival. The abilities of the NCCS nomogram and the MSKCC nomogram to predict IBTR of individual patients were evaluated with bootstrapping of 200 sets of resamples and the NCCS dataset, respectively. Harrell's c-index was calculated for each nomogram to evaluate the concordance between predicted and observed responses of individual subjects.ResultsStudy patients were followed up for a median of 70 months. Over 95% of patients received adjuvant radiotherapy. The 5 and 10 year actuarial IBTR-free survival rates for the cohort were 95.5 and 92.6%, respectively. In the multivariate analysis, independent prognostic factors for IBTR included use of adjuvant endocrine therapy, presence of comedonecrosis and younger age at diagnosis. These factors formed the basis of the NCCS nomogram, which had a similar c-index (NCCS: 0.696; MSKCC: 0.673) compared with the MSKCC nomogram.ConclusionThe MSKCC nomogram was validated in an Asian population. A simpler NCCS nomogram using a different combination of fewer prognostic factors may be sufficient for the prediction of IBTR in Asians, but requires external validation to compare for relative performance.     

A N0 Predicting Model for Sentinel Lymph Node Biopsy Omission in Early Breast Cancer Upstaged From Ductal Carcinoma in Situ

BackgroundA prediction model with high sensitivity for the detection of negative axillary involvement can reduce additional axillary surgery in patients with ductal carcinoma in situ (DCIS) upstaged to invasive cancer while saving patients with pure DCIS from unnecessary axillary surgeries. Using a nationwide database, we developed and validated a scoring system for guidance in selective sentinel lymph node biopsy omission.Patients and MethodsA total of 41,895 patients with clinically node-negative breast cancer from the Korean Breast Cancer Registry were included. The study cohort was randomly divided for the development and validation of the prediction model. Missing data were filled in using multiple imputation. Factors that were significantly associated with axillary lymph node (ALN) metastasis in > 50% of datasets were included in the final prediction model.ResultsThe frequency of ALN metastasis in the total cohort was 24.5%. After multivariable logistic regression analysis, variables that were associated with ALN metastasis were palpability, multifocality, location, size, histologic type, grade, lymphovascular invasion, hormone receptor expression, and Ki-67 level. A scoring system was developed using these factors. The areas under the receiver operating characteristic curve for the scoring system was 0.750 in both training and validating sets. The cutoff value for performing sentinel lymph node biopsy was determined as a score of 4 to obtain prediction sensitivity higher than 95%.ConclusionsA scoring system to predict the probability of ALN metastasis was developed and validated. The application of this system in the clinic may reduce unnecessary axillary surgeries in patients with DCIS and minimize additional axillary surgery for upstaged patients with invasive cancer.     

乳腺轻、重度乳头状瘤病和导管内癌中p16蛋白表达的比较观察

目的:探讨p16基因蛋白表达与乳腺乳头状瘤病及导管内癌的相关性。方法:应用免疫组化法检测40例导管内癌、40例重度乳头状瘤病、40例轻度乳头状瘤病、25例正常乳腺组织中p16蛋白的表达情况。结果:p16基因蛋白在导管内癌组表达阳性率为40.0%,重度乳头状瘤病组为52.5%,轻度乳头状瘤病组为72.5%,正常乳腺组织为92.0%,四组比较有显著性差异,χ2=21.018,P<0.05;导管内癌组与重度乳头状瘤病组比较无显著性差异,χ2=1.257,P>0.05;导管内癌组与重度乳头状瘤病组合并与轻度乳头状瘤病组比较有显著性差异,χ2=7.424,P<0.05;p16基因蛋白表达强度在四组间比较有显著性差异,χ2=23.474,P<0.05。结论:p16基因蛋白表达异常在乳腺乳头状瘤病及导管内癌的发生中起重要作用,可为乳头状瘤病变的临床治疗提供较有价值的依据。     

Tubular Carcinoma of the Breast: Clinicopathologic Features and Survival Outcome Compared with Ductal Carcinoma In Situ

Purpose

Tubular carcinoma (TC) of the breast is an uncommon histological subtype of invasive breast cancer with an excellent prognosis compared with standard invasive ductal carcinoma. Recent studies suggested a possible precursor role for low grade ductal carcinoma in situ (DCIS) in the development of TC. The goal of this analysis was to understand the clinicopathologic features and outcomes of TC by comparing TC with DCIS.

Methods

A retrospective review identified 70 patients with TC and 1,106 patients with DCIS between 1995 and 2011. Student t-test and Fisher exact test were used to compare the clinicopathologic characteristics of TC patients with those of DCIS patients. The Kaplan-Meier method and Cox regression analysis were used to determine disease-free survival (DFS) rates.

Results

Compared to DCIS, TC exhibited favorable clinicopathologic characteristics such as a lower nuclear grade (92.3%), higher expression of hormonal receptors (estrogen receptor-positive, 92.9%; progesterone receptor-positive, 87.0%), and less frequent overexpression of human epidermal growth receptor 2 (12.9%). DFS did not differ significantly between the TC and DCIS groups (5-year DFS, 100% vs. 96.7%; 10-year DFS, 92.3% vs. 93.3%; p=0.324), and cancer-specific deaths were not noted in either group. However, axillary lymph node involvement was observed in six (8.6%) of the 70 patients with TC. Three of these patients had small tumors (≤1 cm).

Conclusion

In our study cohort, TC was associated with an excellent prognosis and a low rate of lymph node metastasis. However, lymph nodes metastases were found even in patients with small tumors (≤1 cm). Axillary staging must be considered for all patients with TC of the breast.     

Possible Prognostic Role of HER2/Neu in Ductal Carcinoma In Situ and Atypical Ductal Proliferative Lesions of the Breast

HER2/neu is a well-established prognostic and predictive factor for invasive breast cancer. However, the role of HER2/neu in ductal breast carcinoma in situ (DCIS) is debated and recent data have suggested that it is mainly linked to in situ local recurrence. Although molecular data suggest that atypical ductal hyperplasia (ADH) and duct carcinoma in situ (DCIS) are related lesions, albeit with vastly different clinical implications, the role of HER2/neu expression in atypical ductal hyperplasia is not well de ned either. The aim of this study was to evaluate over expression of HER2/neu in DCIS and cases of ADH in comparison with invasive breast carcinoma. Archival primary breast carcinoma paraf n blocks (n15), DCIS only (n10) and ductal epithelial hyperplasia and other breast benign lesions (n25) were analyzed for HER2/neu immunoexpression. Follow up was available for 40% of the patients. HER2/neu was positive in 80%of both DCIS and invasive carcinoma, and 67% of atypical ductal hyperplasia (ADH) cases. Thus at least a subset of patients with preinvasive breast lesions were positive, which strongly suggests a role for Her2/neu in identifying high-risk patients for malignant transformation. Although these are preliminary data, which need further studies of gene ampli cation within these patients as well as a larger patient cohort with longer periods of follow up, they support the implementation of routine Her2/neu testing in patients diagnosed as pure DCIS and in orid ADH.     

Patterns of Fractionation and Boost Usage in Adjuvant External Beam Radiotherapy for Ductal Carcinoma in Situ in the United States

Background

While the roles of hypofractionated (HFxn) radiotherapy and lumpectomy boost in the adjuvant management of invasive breast cancer are supported by the results of clinical trials, randomized data supporting their use for ductal carcinoma in situ (DCIS) are forthcoming. We sought to evaluate current national trends and identify factors associated with HFxn and boost usage using the National Cancer Database.

钼靶、彩超及磁共振在乳腺导管原位癌中的诊断价值

目的 探讨如何合理选用钼靶(mammography, MG)、彩超(color Doppler ultrasonography, CDUS)、磁共振(magnetic resonance imaging,MRI)对乳腺导管原位癌（ductal carcinoma in situ,DCIS）进行诊断。方法 收集2009年7月-2014年9月贵阳医学院临床医学院收治的DCIS患者资料,对26例资料完整的患者术前影像学资料进行总结分析,并用Kruskal-Wallis方法进行检验。结果 DCIS在钼靶X线上的表现有钙化（73%, 19/26）、结构紊乱（36%, 8/26）、结节（30%, 7/26）,其中特征性的表现为密集细小钙化（70%, 18/26）;在彩超上的表现有结节（85%, 22/26）、导管扩张（11.5%,3/26）,其中典型的表现为无包膜、低回声结节（59%, 13/22）;在MRI增强上的特征表现为非肿块样强化病灶（73%, 19/26）,病灶时间-信号强度（TIC）曲线多呈Ⅱ、Ⅲ型（73%, 19/26）。钼靶、彩超、磁共振对DCIS诊断率分别为77%、50%、85%,钼靶联合彩超为85%,三者联合为96%,差异有统计学意义（P＜0.05)。结论 钼靶、彩超、磁共振均可发现DCIS,各具优势,不同影像学检查相应结合,可有效提高DCIS诊断率。     

Expression of Leptin,Leptin Receptor,Adiponectin, and Adiponectin Receptor in Ductal Carcinoma In Situ and Invasive Breast Cancer

Purpose

Adipocytokines, such as leptin, resistin, and adiponectin, are associated with obesity and breast cancer. Several studies have indicated that adipocytokines may influence tumor growth or differentiation. The aims of this study were to determine the expression of leptin, leptin receptor (ObR), adiponectin and adiponectin receptor (AdipoR) in human breast cancer, to evaluate their prognostic significance in the breast cancer.

Methods

Specimens from 198 patients with primary breast cancer were enrolled, and representative paraffin tumor blocks were selected for constructing tissue microarrarys (TMA). Immunohistochemical staining for leptin, ObR, adiponectin, and AdipoR was performed using TMA, and the clinicopathologic characteristics were evaluated from the patient''s medical records.

Results

Stage 0 breast cancer accounted for 41 cases, and 157 cases were invasive cancer. Positive rates of leptin and ObR expression in the ductal carcinoma in situ (DCIS) group were significantly higher than those of the invasive cancer group (97.4% vs. 34.0%, p<0.001; 74.4% vs. 29.8%, p<0.001). However, positive rates of adiponectin and AdipoR expression in the invasive cancer group were significantly higher than those in the DCIS group (53.7% vs. 33.3%, p=0.024; 59.9% vs. 26.3%, p<0.001). High leptin expression was significantly associated with high Ki-67 expression (p=0.016). High adiponectin expression was significantly correlated with smaller tumor size (p=0.001).

Conclusion

We suggest that losses of leptin and ObR expression could be associated with invasive cancer, whereas high adiponectin and AdipoR expression may be associated with breast cancer invasiveness.     

Usefulness of 3-Dimensional-Printed Breast Surgical Guides for Undetectable Ductal Carcinoma In Situ on Ultrasonography: A Report of 2 Cases

Tumor localization is challenging in the context of ductal carcinoma in situ (DCIS) treated with breast-conserving surgery. Conventional localization methods are generally performed under the guidance of ultrasonography or mammography and are rarely performed with magnetic resonance imaging (MRI), which is more sensitive than the aforementioned modalities in detecting DCIS. Here, we report the application of MRI-based individualized 3-dimensional (3D)-printed breast surgical guides (BSGs) for patients with breast cancer. We successfully resected indeterminate and suspicious lesions that were only detected using preoperative MRI, and the final histopathologic results confirmed DCIS with clear resection margins. MRI guidance combined with 3D-printed BSGs can be used for DCIS localization, especially for lesions easily detectable using MRI only.     

Oral Contraceptives and the Risk of Ductal Breast Carcinoma in situ

Recent evidence suggests that oral contraceptive use is associated with little to no increased risk of invasive breast carcinoma. No study has examined the relationship between oral contraceptive use and the risk of non-invasive breast carcinoma, that is, breast carcinoma in situ. Objective. To define the role of oral contraceptive use in the development of breast carcinoma in situ. Methods. The data are 875 ductal carcinoma in situ (DCIS) cases diagnosed among residents of the state of Connecticut from September 15, 1994 to March 14, 1998 and between the age of 20 and 79 years as well as 999 control subjects. Controls are female Connecticut residents collected via random-digit-dial and frequency matched to the cases by 5-year age intervals. Telephone interviews were used to collect information on risk factors and cancer screening history. Logistic regression was used to provide maximum likelihood estimates of the odds ratios (OR) with 95% confidence intervals (95% CI). Results. The risk of being diagnosed with DCIS for women who had ever used oral contraceptives was not increased relative to women who had never used them (OR: 1.0, 95% CI: 0.8, 1.2). The risk did not significantly increase with duration of oral contraceptive use, nor with duration of high estrogen use, time since last use, progestin or estrogen type, or age at first use. Furthermore, the association between oral contraceptive use and DCIS risk did not vary by the presence of a family history of breast cancer or by menopausal status. Conclusions. In these data, no evidence was found for an increased risk of ductal carcinoma in situ associated with the use of oral contraceptives.     

乳腺原位癌的手术治疗和预后

目的探讨乳腺原位癌的手术方式和预后.方法对20年间获得随访的97例103个乳腺原位癌进行回顾性分析.结果乳腺原位癌5年生存率99.0%,10年生存率89.8%,15年生存率83.3%,20年生存率80.0%;导管内癌10年生存率偏低(P＜0.05);各种术式对预后的影响不明显(P＞0.05).结论原位癌的预后可能与乳腺癌的多原发灶有关,而与手术方式关系不明显;乳腺单纯切除术是乳腺原位癌的首选术式.