Microinvasive Ductal Carcinoma In Situ Research Articles

Ductal Carcinoma In Situ (DCIS) and Microinvasive DCIS: Role of Surgery in Early Diagnosis of Breast Cancer.

Advances in treatments, screening, and awareness have led to continually decreasing breast cancer-related mortality rates in the past decades. This achievement is coupled with early breast cancer diagnosis. Ductal carcinoma in situ (DCIS) and microinvasive breast cancer have increasingly been diagnosed in the context of mammographic screening. Clinical management of DCIS is heterogenous, and the clinical significance of microinvasion in DCIS remains elusive, although microinvasive DCIS (DCIS-Mi) is distinct from "pure" DCIS. Upfront surgery has a fundamental role in the overall treatment of these breast diseases. The growing number of screen-detected DCIS diagnoses with clinicopathological features of low risk for local recurrence (LR) allows more conservative surgical options, followed by personalised adjuvant radiotherapy plans. Furthermore, studies are underway to evaluate the validity of surgery omission in selected low-risk categories. Nevertheless, the management, the priority of axillary surgical staging, and the prognosis of DCIS-Mi remain the subject of debate, demonstrating how the paucity of data still necessitates adequate studies to provide conclusive guidelines. The current scientific scenario for DCIS and DCIS-Mi surgical approach consists of highly controversial and diversified sources, which this narrative review will delineate and clarify.

Additional Excision Biopsy in Patients With Atypical Ductal Hyperplasia at Ultrasound-guided Vacuum-assisted Breast Biopsy.

We conducted this single-center, retrospective study to identify predictors of upgrading to malignancy and to discuss the necessity of additional excision biopsy in patients who were diagnosed with atypical ductal hyperplasia (ADH) at ultrasound (US)-guided vacuum-assisted breast biopsy (VABB) based on our 18-year, single-center experience. The current study was conducted in a total of 12,160 patients who were evaluated at our medical institution during an 18-year period between January of 2003 and December of 2020. We included the patients who were diagnosed with ADH at US-guided VABB using the Mammotome® (Devicor Medical Products, Inc., Cincinnati, OH, USA). We therefore included a total of 114 patients (n=114) with ADH in the current study. Of 114 eligible patients, 36 underwent additional excision biopsy and the remaining 78 did not. Of these 36 patients, 15 were found to have an upgrading to malignancy at a rate of upgrading of 41.7%. These include 7 cases (46.6%) of low-grade ductal carcinoma in situ (DCIS), 3 cases (20.0%) of intermediate grade DCIS, 1 case (6.7%) of microinvasive DCIS, 3 cases (20.0%) of multifocal lobular carcinoma in situ, and 1 case (6.7%) of mucinous carcinoma. Finally, only suspicious microcalcification on mammography was a significant predictor of upgrading to malignancy (p=0.023). An additional excision biopsy is recommended to reduce the rate of upgrading to malignancy in patients who were diagnosed with ADH through a US-guided VABB.

Our sentinel lymph node experience in patients diagnosed with DCIS and microinvasive breast carcinoma

Aim: Along with the increased availability of radiologic imaging methods, early identification of tumor tissue, and patient surveillance programs; ductal carcinoma in situ (DCIS) and microinvasive DCIS became more commonly identified in the tru-cut biopsy specimens and resected samples of patients. Pathological examinations of the excision materials from these patients reveal invasive tumors, microinvasions or DCIS alone. Recently, it has become debatable whether to perform a sentinel lymph node biopsy (SLNB) in patients diagnosed with DCIS or microinvasive DCIS. In this present study, we evaluated the diagnosis made by examining the excision material, any presence of lymph node metastases, and the relationship of hormone profile to the presence of metastases in the patients diagnosed with DCIS or microinvasive DCIS by the examination of tru-cut biopsy specimens. Based on our study results, we discussed the requirement for SLNB in patients with a tru-cut diagnosis of DCIS or microinvasive DCIS.Materials and Methods: The study included 172 patients, who underwent surgical excision and SLNB after receiving a tru-cut biopsy diagnosis of DCIS and microinvasive DCIS in our hospital from the year 2010 to 2018.Results: Tru-cut biopsy diagnoses were DCIS and microinvasive DCIS in 69.8% (120 patients) and 30.2% (52 patients) respectively. SLNB metastases were identified in 35.8% (n=43) of the DCIS positive patients and 44.2% (n=23) in the microinvasive DCIS positive patients. The diagnosis of invasive ductal carcinoma after mastectomy was made at a rate of 90.0% (n=108) among the DCIS positive patients and 92.3% (n=48) among the microinvasive DCIS positive patients. Conclusion: SLNB metastases were found in 35.8% (n=43) and 44.2% (n=23) of the DCIS positive patients and microinvasive DCIS positive patients, respectively. We conclude that SLNB should be favorably proper to perform in the patients with tru-cut diagnoses of DCIS and microinvasive DCIS because a high rate of SLNB metastases was detected in our DCIS and microinvasive DCIS patients and a high rate of invasive ductal carcinoma diagnosis was made after examining the excision material of these patients.

Sentinel lymph node biopsy in microinvasive ductal carcinomain situ

Microinvasive breast cancer is an uncommon pathological entity. Owing to the rarity of this condition, its surgical axillary management and overall prognosis remain controversial. A database was analysed to identify patients with microinvasive ductal carcinoma in situ (DCIS) who had surgery for invasive breast cancer at the European Institute of Oncology, Milan, between 1998 and 2010. Women who had undergone axillary staging by sentinel lymph node biopsy were included in the study. Of 257 women with microinvasive breast cancer who underwent sentinel lymph node biopsy (SLNB), 226 (87·9 per cent) had negative sentinel lymph nodes (SLNs) and 31 had metastatic SLNs. Twelve patients had isolated tumour cells (ITCs), 14 had micrometastases and five had macrometastases in sentinel nodes. Axillary lymph node dissection was performed in 16 of the 31 patients with positive SLNs. After a median follow-up of 11 years, only one regional first event was observed in the 15 patients with positive SLNs who did not undergo axillary lymph node dissection. There were no regional first events in the 16 patients with positive SLNs who had axillary dissection. Good disease-free and overall survival were found in women with positive SLNs and microinvasive DCIS. This study is in line with studies showing that SLNB in microinvasive DCIS may not be useful, and supports the evidence that less surgery can provide the same level of overall survival with better quality of life.

Abstract 1465: Analysis of tumor-infiltrating lymphocytes (TILs) reveals biologically different subgroups of breast ductal carcinoma in situ

Abstract Background: Treatment of breast ductal carcinoma in situ (DCIS) aims to prevent invasive recurrence. Recent studies have shown an important impact of TILs on the outcome of invasive breast cancer, however their influence on breast DCIS prognosis has not been fully explored. In this study we investigated whether the amount and/or phenotype of TILs can help recognizing DCIS subgroups of different biology and recurrence risk. Methods: The study included 134 patients, diagnosed and treated for a DCIS from 2001 to 2005 in our institution. Formalin-fixed and paraffin-embedded (FFPE) cancer tissue samples, taken before any treatment, were retrospectively collected. H&E whole tissue sections served for assessment of the cancer size, grade, histotype, architecture, mitotic index and amount of stromal lymphocytic (Ly) infiltrate. The latter was semi-quantitatively graded into 4 grades (0 - absent, 1 - mild, 2 - moderate, 3 - intense). Ly-phenotype was assessed by immunohistochemistry (IHC) on tissue microarrays (TMAs), constructed by sampling each case at the area of the densest Ly-infiltration (3 cores of 0.6 mm diameter per case). The number/mm2 of the CD8+, CD4+, FOXP3+, CD20+ and CD38+ mononuclear cells was determined. TMAs served also for estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki67 IHC staining, as well as for HER2 amplification status. Results: There were 97 DCIS and 37 microinvasive DCIS (micDCIS). The micDCIS displayed significantly more diffuse architecture, frequent HER2 amplification (HER2amp), higher grade, lower ER expression (0.029<p<0.044 for each) and more peritumoral Ly-infiltrate (grades 2+3, micDCIS vs DCIS, 51.5% vs. 39.0%, p = 0.036). All but CD20+ cells were more numerous in micDCIS than in DCIS (0.0016<p<0.05). Within the entire cohort, the cases having the (CD8+/CD4+):(CD20+/CD38+) ratio higher than 1 had a significantly greater risk of containing a microinvasive component (OR 3.47 (1.26-9.57), p = 0.029). Interestingly, that ratio was significantly higher (p = 0.012) in micDCIS than in the DCIS with grade 2 or 3 Ly-infiltrate (Ly-DCIS, n = 38). On the other side, there was no difference between micDCIS and Ly-DCIS in architecture, histograde, HER2amp rate and ER expression. Cluster analysis further confirmed significant similarities between micDCIS and Ly-DCIS, putting them both apart from non-Ly-DCIS (p = 0.0034). The overall 10-year recurrence rate was 13% (18/134 pts). No parameter significantly correlated with recurrence risk, however the micDCIS have received significantly more treatment than DCIS (axillary lymphadenectomy (p<10-7), chemotherapy (p = 0.031) or hormonal therapy (p = 5.4×10-6)). Conclusion: These results indicate that Ly-DCIS might be biologically and immunologically similar to micDCIS. TILs in DCIS are worth investigating in larger studies, as they could be a marker of microinvasion and help tailoring the initial treatment of the disease. Citation Format: Marie Beguinot-Cornillon, Marie-Melanie Dauplat, Fabrice Kwiatkowski, Guillaume Lebouedec, Lucie Tixier, Christophe Pomel, Frederique Penault-Llorca, Nina Radosevic-Robin. Analysis of tumor-infiltrating lymphocytes (TILs) reveals biologically different subgroups of breast ductal carcinoma in situ. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1465.

Dynamic Contrast-Enhanced MRI Reveals the Extent and the Microvascular Pattern of Breast Ductal Carcinoma In Situ

To report the role of magnetic resonance imaging (MRI) in assessing the extent of breast ductal carcinoma in situ (DCIS). To assess whether the microvascularity pattern in DCIS correlates with magnetic resonance enhancement. Eighty-five histologically proven DCIS (77 pure DCIS, eight microinvasive DCIS) were prospectively studied with MRI. The morphology of magnetic resonance enhancement and the kinetic curve was recorded. Histopathologically, intraductal lesions were classified according to Van Nuys score. Tumor microvascularity was immunohistochemically assessed in a subset of 24 DCIS evaluating the number of microvessels, microvascularity area, and microvascularity pattern (diffuse or periductal). On the mammogram, 74% of DCIS appeared as microcalcifications. On MRI, 70% of DCIS showed enhancement. Non-mass-like uptake was observed in 78% of cases. The mean size of nonenhancing carcinomas was significantly lower than that of enhancing carcinomas (p = 0.033). The diffuse pattern was more frequent than the periductal pattern. A significant relationship between the morphology of MR enhancement and the microvascularity pattern was observed (p = 0.036); thus, 90% of DCIS showing segmental enhancement on MRI displayed a diffuse pattern while all DCIS with ductal enhancement showed a periductal pattern. There was a significant relationship between the maximum area of microvascularity and the vascular pattern (p = 0.015); periductal patterns showed larger areas than diffuse patterns. The lesion size was significantly larger as the Van Nuys score increased (p < 0.001) and was also related to the number of microvessels (p = 0.012). The mean area of microvascularity of DCIS was significantly larger as the Van Nuys score increased (p = 0.02). Breast MRI helps depict the extent of DCIS and reveals its microvascular pattern.

Recognizing breast ductal carcinoma in situ on fine‐needle aspiration: A diagnostic dilemma

In this study, we evaluated cytomorphologic features of different subgroups of ductal carcinoma in situ (DCIS); we compared seven cytologic features between DCIS and invasive ductal carcinoma (IDC) aspirates to determine whether diagnosis of stromal invasion can be made based on fine-needle aspiration (FNA) findings. There were 142 cases of DCIS and 1,978 cases of IDC enrolled in our study. FNA analysis revealed 80.3% sensitivity for DCIS and 94.7% sensitivity for IDC. High and intermediate grade DCIS exhibited marked nuclear abnormality (92.1% vs. 35.7%, 30.0%; P1 < 0.001, P2 < 0.001) and necrosis (69.7% vs. 0%, 10.0%; P1 < 0.001, P2 = 0.001) in a higher percentage of cases compared to low grade DCIS and intraductal/intracystic papillary carcinoma. The rates of background macrophages (71.3% for DCIS and 21.9% for IDC, P < 0.001) and extensive necrosis (54.0% for DCIS and 16.7% for IDC, P < 0.001) were significantly higher in DCIS compared to IDC. Lymphocytes were observed in conjunction with tumor cells more frequently in IDC (81.3%) compared to DCIS (36.8%, P < 0.001). Stromal fragments associated with tumor cells were only observed in invasive lesions (11.9% micro-invasive DCIS and 52.1% IDC). Tubular structures were found exclusively in IDC (11.5%). Cytologic criteria for diagnosis of high and low grade DCIS are different. The suspicion of DCIS is raised when background macrophages and extensive necrosis are observed. Stromal invasion is suggested by FNA if lymphocytes are entwined around tumor cells or if stromal fragments associated with tumor cells or tubular structures are observed.

The usefulness of ultrasonography in a ductal carcinoma in situ screening program for Japanese woman.

24 Background: Although varying among areas, the mammogram (MMG) screening rate is very low in Japan as compared to the U.S. at approximately 20% versus nearly 80% in the U.S. On the other hand, rates of ductal carcinoma in situ (DCIS) detection among diagnosed breast cancers differ minimally: 20% in the U.S., and 15% in Japan. This is a small difference considering the difference MMG screening rates. Racial differences have been suggested to be attributable to the organization of screening programs in Japan, which also use ultrasonography (US) breast cancer screening, as well as breast size in Japanese women. Methods: We retrospectively evaluated MMG and US images of 91 DCIS cases, all 91 Japanese women who under underwent surgery between May 2010 and February 2012. US (TOSHIBA Aplio, probe 9MHz) was performed with knowledge of MMG findings. The 91 cases were divided into group with tumor detected by MMG and US (M&amp;U), MMG detection only (M), and US detection only (U). The following parameters were analyzed: US shape (Tumor-forming lesion: TFL, Non-tumor-forming lesion: NTFL, Cystic-forming lesion: CFL), Skin-Muscle distance: SMD. We excluded asynchronous bilateral breast cancers and micro-invasive DCIS. Results: Sixty-eight lesions (73.0%) were identified by US, which revealed a NTLF in 52 cases, TLF in 9 cases and CFL in 7 cases. All cases with false-negative findings on US (Group M, n = 23) showed micro-calcifications on MMG (n=22) and with the tumor (n=1). In the U group, SMD was only 23 mm versus 43.4mm in the M group. No difference was observed in body mass index or pathological tumor diameter between the U and M. Conclusions: We found US to reveal DCIS in 73% of our cases upon reevaluation. Although US examination would not likely increase the screening detection rate for DCIS in Japanese women, US may reveal more DCIS in Japanese women, in which the breasts are comparatively small, than in western women. Further comparison of possible racial difference is warranted.

Outcome of Patients with Ductal Carcinoma In Situ and Sentinel Node Biopsy

In sentinel node biopsy (SNB), tumor-positive findings, mainly micrometastases and isolated tumor cells (ITC) have been found in up to 8%-16% of patients with pure ductal carcinoma in situ (DCIS) or microinvasive DCIS (DCISM). The prognostic significance of such findings is largely unknown. The aim of this study is to examine the outcome of DCIS and DCISM patients with SNB. A total of 280 breast cancer patients with pure or microinvasive DCIS underwent SNB between April 2001 and December 2010 at the Breast Surgery Unit of Helsinki University Central Hospital. Patient, tumor, SNB procedure, and follow-up data were gathered. The median follow-up was 50months (range 7-123months). Altogether, 21 patients had tumor-positive sentinel node findings. Of these, 14 were in pure DCIS patients (1 macrometastasis, 1 micrometastasis, 12 ITC) and 7 in DCISM patients (1 macrometastasis, 2 micrometastases, 4 ITC). Also, 16 patients, 10 with pure DCIS and 6 with DCISM, underwent completion axillary lymph node dissection (ALND). Only 1 of them, a patient with DCISM, had additional tumor positive finding in the ALND. During a median follow-up of 50months (range 7-123months) there were 5 local recurrences. One patient with pure DCIS and tumor-negative SNB developed overt axillary metastases and later also distant metastases. DCIS and DCISM patients do have tumor positive findings, but a majority of these are ITC or micrometastases. In light of this study, these findings do not affect the outcome of DCIS or DCISM patients.

Tumour‐positive sentinel node findings in patients with ductal carcinoma in situ

Our aim was to evaluate the prevalence of and risk factors for tumour-positive sentinel node (SN) findings in patients with ductal carcinoma in situ (DCIS). Altogether 1,470 patients underwent sentinel node biopsy (SNB) between April 2001 and March 2005 in our unit. According to a histopathological review, 11 of them had microinvasive and 74 pure DCIS and were included in the study. Five patients (7%) with pure DCIS had SN metastases. Three of them had isolated tumour cells (ITC) only. Axillary clearance without further metastatic findings was performed in three patients. The median histological size of DCIS was larger, 50 (45-60) mm in patients with metastatic SN findings than the median of 18 (2-110) mm in those with tumour-negative SN, P=0.0103. All five patients with metastatic SN findings underwent mastectomy. Metastatic SN findings were detected in one (9%) patient with microinvasive DCIS. Metastatic SN findings in patients with pure DCIS may be a sign of missed invasion.

Contrast Enhanced MRI Findings of Ductal Carcinoma in Situ

Purpose: The purpose of this study is to describe characteristic contrast enhanced MR mammographic findings of ductal carcinoma in situ (DCIS) and also DCIS with microinvasion. Materials and Methods: From January 2000 to July 2005, 32 women with 33 lesions affected by DCIS or DCIS with microinvasion underwent contrast enhanced MRI, and they were then retrospectively evaluated. All the patients had previously undergone mammography and ultrasonography. All the findings of mammography, ultrasonography (US), and MRI were analyzed by using an ACR BI-RADS lexicon. Results: All 33 cases were enhanced on the enhanced MR images. A smooth margined homogeneous enhanced mass was seen in the two (2/33) cases, and nonmass enhancement was seen in 31 (31/33) cases. Among the non-mass enhancement, focal enhancement (7/31), ductal enhancement (5/31), segmental enhancement (9/31), and regional enhancement (10/31) were observed. On the kinetic study, a wash-out pattern (10/33), a plateau pattern (20/33), and a persistent pattern (3/33) were demonstrated. No significant differences were noted between the pure and microinvasive DCIS. Conclusion: There is no significant difference between pure and microinvasive DCIS. However, contrast enhanced MR images can demonstrate occult foci, multifocal lesion and the tumor extent of DCIS on mammogram or ultrasonogram.

Ductal carcinoma in situ (DCIS): USC/Van Nuys Prognostic Index (VNPI) and the impact of micropapillary histotype

662 Background: As our knowledge of DCIS has evolved during the past decade, treatment decision making has become much more complex and controversial. We examined the use of VNPI and the effectiveness of micropapillary histotype as a predictor of local recurrence (LR). Methods: We retrospectively collected 408 patients treated from 1988 to 2002 for DCIS or microinvasive DCIS (mi-DCIS), with conservative surgery or mastectomy according to the VNPI. We added to the classic VNPI the micropapillary histotype: with this novel algorithm, score 1 was given to micropapillary DCIS (M-DCIS) G1 and to other histotypes G1–2, while score 3 was given to M-DCIS G2–3, and to other histotypes G3 and/or to mi-DCIS. Finally, we compared sensitivity and specificity of the two prognostic indexes. Results: DCIS was diagnosed in 337 patients and mi-DCIS in 71 women. 267 patients underwent conservative surgery, while 141 underwent mastectomy (96 after a conservative surgery). Adjuvant radiotherapy was given in 58% of conservative-treated patients, and Tamoxifene was prescribed in 25% of cases. Median follow-up was 55 months. Micropapillary histotype was observed in 90 cases. According to the VNPI, LR was significantly related to tumor grade (LR was 0.9% vs 5.3% in grade 1 vs grade 2–3) and size (1.9% vs 6.4% in lesions <15mm vs >15mm), and to the involvement of tumor margins (2.7% vs 7.6% with clear margin >10mm vs <1mm). LR was found in 11.5% of G2–3 M-DCIS vs 4% of other histotypes G3 (p<0.006): it was observed in 3.3% of DCIS vs 8.5% of mi-DCIS (p=0.056). Patients with VNPI score 3–6 showed LR in 1.2% (4/246) vs 8% (13/162) of women with VNPI score 7–9 (p=0.003): with the novel score, only 126 women had score 7–9, with LR in 9.5%, vs 1.75% in the 282 women with score 3–6 (p=0.002). Specificity and sensitivity were 77% and 72% (vs 72% and 76% of VNPI), respectively. Conclusions: Our data showed that micropapillary histotype is of prognostic value of LR in DCIS patients. It could be therefore included in the VNPI in order to identify a low risk group of patients, avoiding overtreatment. Further studies are warranted to confirm our preliminary results. No significant financial relationships to disclose.

In situ and minimally invasive breast cancer: morphologic and kinetic features on contrast-enhanced MR imaging.

This retrospective study was undertaken to investigate the morphologic and dynamic features of in situ and minimally invasive breast cancer on contrast-enhanced (c.-e.) MR imaging and to examine possible associations to pathology features. A total of 71 patients underwent MR imaging. T1-weighted FLASH-3D images were obtained before and after intravenous administration of Gd-DTPA. Histopathologic analysis of 78 lesions revealed ductal carcinoma in situ (DCIS) n = 50 and DCIS with microinvasion n = 28. MR features were correlated with histopathologic findings. Enhancement in DCIS was focal (73%), diffuse (10%) or ductal (17%). No enhancement occurred in two cases (4%). In 65% enhancement speed was classified as delayed. There was a tendency toward a more ill-defined (83 vs. 43%) enhancement pattern in high grade DCIS and a more ductal (29 vs. 12%) and faster (50 vs. 29%) enhancement in comedo type DCIS. However, significant differences in the enhancement behaviour could neither be demonstrated between high grade and non high grade DCIS nor between comedo and non comedo type DCIS. No significant differences were noted between pure and microinvasive DCIS. In this retrospective analysis the majority (96%) of DCIS lesions show contrast enhancement. However, in only about 50% of DCIS the criteria of a so-called 'typical' enhancement behaviour was fulfilled, that means strong, early, focal ill-circumscribed or ductal. Enhancement that follows a duct is often associated with malignancy, however this feature was only present in 17% of the cases. c.-e. MR imaging allowed the detection of 25 additional foci of DCIS. Therefore malignant in situ lesions can be present with atypical enhancement, and should be taken into consideration in high-risk patients in particular.

Intraductal carcinoma. Analysis of presentation, pathologic findings, and outcome of disease.

A retrospective analysis of 52 patients with intraductal carcinoma or ductal carcinoma in situ (DCIS) and 30 patients with microinvasive DCIS was performed. All patients but one were treated by mastectomy. The average follow-up was 5 1/2 years. The clinical presentation of the patients having DCIS only included the presence of a mass in 33% (17/52), nipple discharge in 34% (18/52), or suspicious mammographic finding in 33% (17/52), whereas in those patients having DCIS with microinvasion, the initial presenting symptom was a mass in 63% (19/30) of the patients, nipple discharge in 13% (4/30), and mammographic finding in 23% (7/30). The presence of axillary lymph node metastasis was identified in one of the 52 patients with DCIS and six (20%) of the 30 patients with DCIS and microinvasion. Associated carcinomas in the mastectomy specimens of patients with DCIS were as follows: DCIS, 18% (9/51); lobular carcinoma in situ, 13% (7/51); Paget's disease, 8% (4/51); and invasive carcinoma, 2% (1/51). In the 30 patients with microinvasion, DCIS was found in other quadrants in 23% (7/51) of the patients; lobular carcinoma in situ, 7% (2/51); Paget's disease, 13% (4/51); and invasive carcinoma, 7% (2/51). There was one death due to cancer in the patients with DCIS only. Of the patients diagnosed as having DCIS with microinvasion, seven patients have developed metastasis and four have died of the disease.