Extent Of Ductal Carcinoma In Situ Research Articles

More microinvasive foci in larger tumours of breast ductal carcinoma in situ.

Microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. This study aimed to investigate the potential influence of Mi on survival and assess its correlations with clinicopathological parameters, prognosis and molecular markers. The number of Mi foci in a cohort of 66 DCIS-Mi cases was assessed from haematoxylin and eosin-stained sections. Disease-free survival, clinicopathological parameters and biomarker expression were correlated with the number of Mi foci. Higher numbers of Mi foci were found in larger tumours (P = 0.031). Greater extent of DCIS is associated with multifocal Mi.

Abstract LB165: Preclinical evaluation of carnosic acid (CA) and rosemary extract standardized to 40% carnosic acid (RE40CA) for the prevention of invasive breast cancer

Abstract Background: There is an unmet need for the development of safer and more effective therapies for the prevention of human invasive breast cancer, for which ductal carcinoma in situ (DCIS) is a precursor. Currently, anti-hormonal therapies are the only option in individuals previously diagnosed with hormone receptor positive breast cancer. However, these agents are associated with many side effects. Furthermore, there are currently no preventive options for hormone receptor negative breast cancers. To study DCIS progression, we developed a model referred to as MIND (Mouse-INtraDuctal) in which patient-derived DCIS cells and cell lines are injected intraductally and studied as they progress to invasive ductal carcinoma (IDC). Previously we provided strong evidence for the role of B Cell Lymphoma-9 (BCL9) as a potential driver of DCIS malignancy. We chose to target BCL9 using RE40CA and its active ingredient CA previously identified in a screen for inhibitors of β-catenin binding to BCL9. Experimental Strategy: CA and RE40CA were administered to DCIS.COM MIND animal models for four weeks by oral gavage or mixed in a powder diet formulation. Drug plasma levels were evaluated by LC-MS. Four weeks following drug administration, mammary glands were excised and evaluated for efficacy and expression of biomarkers of aggressive DCIS, nuclear β-catenin and BCL9. For efficacy studies, mammary glands containing DCIS like lesions were processed and subjected to immunofluorescence staining using anti-human CK-5, anti-SMA, Dapi, β-catenin and BCL9. Extent of DCIS in vivo growth, number of invasive lesions, tumor number and tumor volume were evaluated for each mammary gland. Results: Efficacy studies showed a significant reduction in the number of invasive lesions by administration of CA by oral gavage (CA OG:10mg/kg), CA at 200mg/kg diet (CA200), CA400 and RE40CA 500. A significant reduction in extent of DCIS in vivo growth was achieved by CA OG and RE40CA 500. A significant reduction in the number of tumors was achieved by CA OG, RE40CA OG (25mg/kg equivalent to CA 10mg/kg), RE40CA 100, RE40CA 500 and RE40CA 1000. A significant reduction in tumor volume was achieved by CA OG, RE40CA OG, RE40CA 100, RE40CA 500 and RE40CA 1000. Linear regression modelling was used to compare statistical differences among the groups and differences that reached p-value <0.05 were considered significant. Administration of CA or RE40CA by oral gavage was also associated with a significant loss of nuclear BCL9/β-catenin expression in DCIS epithelial cells. Dietary administration of CA and RE40CA as OG or mixed in powder diet showed an increasing trend in plasma concentrations as the dose was increased. Evaluation of HE stained sections of animal organs by histopathology showed no evidence in any tissue of necrosis, degeneration, inflammation or neoplasia. Additionally, no consistent lesions attributable to treatment were observed in any of the animals or groups. Conclusion: Administration of CA and RE40CA are safe and effective in prevention of DCIS malignancy. Future studies are aimed at testing the efficacy of CA/RE40CA using DCIS cell lines representing other DCIS subtypes (ER+/PR+ and HER2 overexpressing) as well as patient derived DCIS MIND animal models. Supported by NCI PREVENT Cancer Preclinical Drug Development Program, 75N91019D00016/75N91020F00001. Citation Format: Yan Hong, Aditi Rastogi, Aryamitra Banerjee, Brandon L. Plattner, Matthew Lindeblad, Alexander V. Lyubimov, Timothy Fields, Seema A. Khan, Altaf Mohammed, Jeremy J. Johnson, Fariba Behbod. Preclinical evaluation of carnosic acid (CA) and rosemary extract standardized to 40% carnosic acid (RE40CA) for the prevention of invasive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB165.

Predictive value of ductal carcinoma in situ with invasive breast cancer in core needle biopsies for final pathologic size of intraductal elements

Preoperative evaluations of the size of ductal carcinoma in situ (DCIS) extension in invasive breast cancer (IBC) are problematic and markers of the actual size of DCIS remain elusive. This study aimed to quantify DCIS on core needle biopsy (CNB) and investigated its association with degree of DCIS extension on paired resection specimens, instead of with presence or absence of an extensive intraductal component or margin status as in earlier studies. This series examined 150 IBCs diagnosed from paired CNB and resection specimens. The DCIS/invasion ratio was calculated using the sum of each element size from CNB. In resection specimens, cases in which the greatest dimension of DCIS extension was longer than the greatest dimension of invasive size were defined as extended DCIS (Ext-DCIS). DCIS/invasion ratio level correlated positively with the degree of Ext-DCIS (P = 0.003). Using receiver operating characteristic curve analysis, setting cases with the subgroup of DCIS extension with greatest dimension > 2.5 times that of the invasive size in the resection specimen (Ext-DCIS > 2.5) as the positive class provided the best discrimination ability for DCIS/invasion ratio (0.375). In multivariate analysis, DCIS/invasion ratio > 0.375 was significantly associated with Ext-DCIS > 2.5 (P = 0.033). In conclusion, DCIS/invasion ratio > 0.375 in CNB was identified as a predictor of Ext-DCIS > 2.5 in resection specimens, suggesting that an approach combining DCIS/invasion ratio from CNB with preoperative staging may better predict the extent of DCIS and facilitate better surgical planning.

Imaging of Noncalcified Ductal Carcinoma In Situ.

Ductal carcinoma in situ (DCIS) is a commonly encountered malignancy, accounting for approximately 20% of new breast cancer diagnoses in the United States. DCIS is characterized by a proliferation of tumor cells within the terminal duct lobular unit with preservation of the basement membrane. Typically nonpalpable and asymptomatic, DCIS is most often detected as calcifications on screening mammography. However, DCIS may also be noncalcified. When compared to calcified DCIS, noncalcified DCIS is more likely to be symptomatic, with patients most often presenting with nipple discharge or a palpable mass. Diagnosing noncalcified DCIS is challenging since it may be occult or subtle on mammography, and ultrasound findings can be nonspecific and may be interpreted as benign fibrocystic changes. In cases with a calcified component of DCIS, the extent of DCIS may be underestimated by mammography because not all involved areas may calcify. Breast magnetic resonance imaging (MRI), although less readily available than mammography and ultrasound, is advantageous in detecting noncalcified DCIS, especially high grade DCIS, which may not develop microcalcifications. MRI relies on abnormal contrast uptake due to tumor vascularity and changes in vessel density and permeability. This pictoral review presents the spectrum of imaging findings of noncalcified DCIS to assist radiologists in accurately detecting and describing its key imaging findings. Utilizing different modalities, we review the differential diagnoses for noncalcified DCIS, show illustrative cases of noncalcified DCIS, and discuss the importance of this entity.

Comparative analysis of margin status in breast conservation surgery and its correlation with subsequent re-excision findings.

SummaryPurposeBreast-conservation surgery (BCS) has become a standard treatment option for invasive breast carcinoma (IBC) and ductal carcinoma in situ (DCIS). The strongest predictor of local recurrence remains the surgical margin status. We evaluated the margin positivity by quantifying the tumor on positive margins and analyzing the histologic factors including type and extent in determining the likelihood of residual disease upon re-excision.MethodRetrospective analysis of 210 BCS performed at Mount Sinai Medical Center from the period of January 2011 - December 2017 revealed that 58 had IBC, DCIS, or both, with positive margins that were followed by re-excision.ResultThe margins had IBC in 18 (31%), DCIS in 32 (55.2%) and both in 8 (13%) cases. Thirty-eight cases (65.5%) were free of carcinoma on re-excision. Of 40 cases with margins positive for DCIS, 16 (40%) had residual DCIS. Of 26 cases with IBC at the margins, and 5 had residual disease (19%). This difference was statistically significant (p = 0.002). Of 21 cases with extensive DCIS, 12 had residual disease (p = 0.02) as compared to only 4 out of 19 without extensive DCIS. None of the cases with clinging/micro-papillary DCIS had residual disease, while 51% of the other types (solid, cribriform, come-do) had residual disease (p = 0.02). The area of DCIS as measured on the involved margin correlated with the amount of residual disease on re-excision (p = 0.03).ConclusionMargins positive for DCIS are more likely to have residual disease on re-excision in comparison to margins positive for only IBC. The type and extent of DCIS appears to influence the likelihood of residual disease.

Abstract PD8-07: Does resection of cavity shave margins result in lower positive margin and re-excision rates in patients with stage 0-III breast cancer? Results from a prospective multicenter randomized controlled trial

Abstract INTRODUCTION: Routine resection of cavity shave margins has been shown in single center studies to result in a significant reduction in positive margin and re-excision rates. In this prospective multicenter randomized controlled trial, we sought to validate these findings across practice settings. METHODS: Nine centers across the United States, varying in practice setting and patient population, participated in this clinical trial of 398 stage 0-III breast cancer patients undergoing partial mastectomy (with or without resection of selective cavity margins). Participants were stratified by clinical stage and randomized 1:1 to either have routine cavity shave margins resected (“shave”) or not (“no shave”). Randomization group was revealed to the surgeon intraoperatively, after they had completed their standard partial mastectomy and were ready to close. Positive margins were defined as “tumor at ink” for invasive cancer or within 2 mm for ductal carcinoma in situ (DCIS). Adverse events were defined as seromas requiring percutaneous drainage, and/or hematomas or abscesses requiring operative intervention. RESULTS: Median patient age was 65 (range; 29-94). 116 patients had invasive disease, 74 had DCIS, 179 had both, and 29 had no residual cancer at the time of partial mastectomy. The median invasive cancer size was 1.2 cm (range; 0.05-8.00 cm); the median extent of DCIS was 0.9 cm (range; 0.05-6.40 cm). The “shave” and “no shave” groups were well matched at baseline for clinicopathologic and demographic factors. FactorShave (n=197)No Shave (n=201)p-valueAge (years); median (range)67 (36-94)64 (29-89)0.585Race 0.062-- White173 (87.8%)164 (81.6%) -- Black20 (10.2%)33 (16.4%) -- Asian2 (1.0%)2 (1.0%) -- Native American0 (0%)2 (1.0%) -- Unknown/Declined2 (1.0%)0 (0%) Hispanic ethnicity28 (14.2%)32 (15.9%)0.806Invasive tumor size (cm); median (range)1.30 (0.09-8.00)1.20 (0.05-7.50)0.282DCIS extent (cm); median (range)0.80 (0.10-6.40)1.00 (0.05-5.50)0.906Invasive histology 0.556-- Ductal177 (89.8%)186 (92.5%) -- Lobular16 (8.1%)13 (6.5%) -- Mucinous3 (1.5%)2 (1.0%) -- Other1 (0.5%)0 (0%) Neoadjuvant therapy15 (7.6%)19 (9.5%)0.592Palpable tumor57 (28.9%)56 (27.9%)0.825Node positive*24 (16.3%)16 (10.6%)0.175*Of the 298 patients who had lymph nodes evaluated Prior to randomization, positive margin rates were similar in the “shave” and “no shave” groups (38.1% vs. 37.3%, respectively, p=0.918). After randomization, however, those in the “shave” group were significantly less likely than those in the “no shave” group to have positive margins (8.6% vs. 37.3%, respectively, p<0.001). They were also less likely to require re-excision or mastectomy for margin clearance (8.6% vs. 23.9%, p<0.001). There were no significant differences between the two groups in terms of adverse events (p=0.280). Rates of seroma (1.5% vs. 0.5%, p=0.368), hematoma (0.5% vs. 0.5%, p=1.000) and abscess (0.3% vs. 0%, p=0.495) were similar between the “shave” and “no shave” groups, respectively. CONCLUSION: Resection of cavity shave margins significantly reduces positive margin and re-excision rates in patients with stage 0-III breast cancer undergoing partial mastectomy. Citation Format: Chagpar AB, Tsangaris T, Garcia-Cantu C, Howard-McNatt M, Chiba A, Berger AC, Levine E, Gass JS, Gallagher K, Lum SS, Martinez RD, Willis AI, Pandya SV, Brown EA, Fenton A, Mendiola A, Murray M, Haddad V, Solomon NL, Senthil M, Bansil H, Ollila D, Snyder SK, Edmonson D, Lazar M, Namm JP, Li F, Butler M, McGowan NE, Herrera ME, Avitan YP, Yoder B, Dupont E. Does resection of cavity shave margins result in lower positive margin and re-excision rates in patients with stage 0-III breast cancer? Results from a prospective multicenter randomized controlled trial [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 PD8-07.

Extent of ductal carcinoma in situ according to breast cancer subtypes: a population-based cohort study

Ductal carcinoma in situ (DCIS) is a precursor of invasive breast carcinoma (IBC). The DCIS component is often more extensive than the invasive component, which affects local control. The aim of our study was to analyze features of DCIS within different IBC subtypes, which may contribute to the optimization of personalized approaches for patients with IBC. Patients with IBC reported according to the synoptic reporting module in the Netherlands between 2009 and 2015 were included. Data extraction included characteristics of the invasive component and, if present, several features of the DCIS component. Resection margin status analyses were restricted to patients undergoing breast-conserving surgery (BCS). Differences between subtypes were tested by a Chi-square test, spearman’s Rho test or a one-way ANOVA test. Overall, 36.937 cases of IBC were included. About half of the IBCs (n = 16.014; 43.4 %) were associated with DCIS. Her2+ IBC (irrespective of ER status) was associated with a higher prevalence of adjacent DCIS, a larger extent of DCIS and a higher rate of irradicality of the DCIS component as compared to ER+/Her2− and triple-negative subtypes (P < 0.0001 for all variables). The prevalence of DCIS in triple-negative IBC on the other hand was lowest. In this large population-based cohort study, we showed significant differences between the prevalence and extent of DCIS according to IBC subtypes, which is also reflected in the resection margin status in patients treated with BCS. Our data provide important information regarding the optimization of local therapy according to IBC subtypes.

DCIS of the breast: The value of preoperative MRI.

Ductal carcinoma in situ (DCIS) of the breast is commonly treated surgically. The intent of this study was to evaluate whether preoperative MRI could add to mammography in predicting the extent of the disease. A series of patients with DCIS attending our surgical clinic for preoperative assessment were offered MRI as part of a prospective study. The extent of the disease indicated by mammography and MRI was compared with histopathology after definitive treatment. The null hypothesis was that MRI does not add to mammography in accurately predicting disease extent. Fifty patients make up the basis of this report. Mammography was concordant with the pathology in 31/50. MRI and mammography combined were concordant in 43/50. This is a statistically significant difference (P = 0.01, Fisher's exact test). Upstaging to mastectomy by MRI was correct in 7/8 patients, but downstaging was correct in only 2/4. The null hypothesis is rejected. MRI does add to mammography in accurately predicting the extent of DCIS. Upstaging by MRI is usually reliable.

Reporting the greatest linear extent of ductal carcinoma in situ on needle core biopsy

Ductal carcinoma in situ (DCIS) of the breast is staged as pTis regardless of size; however, extent of DCIS correlates with local recurrence rates and likelihood of close or positive margins. As a result, DCIS extent influences patient management and is an important element in the College of American Pathologists tumor summary checklist for excision specimens. There are no recommendations regarding routine reporting of DCIS extent on needle core biopsy material, and to our knowledge, no systematic studies have evaluated the impact of reporting this in biopsy material. Consecutive cases of DCIS performed or reviewed at our institution were identified by pathology report search over a 7-year period. The greatest linear extent of DCIS on core biopsy was compared with the estimated extent in the excision. Of 241 total cases, there were 157 (65%) cases in which the DCIS extent on biopsy was smaller, 13 (5%) cases in which the sizes were equal, and 70 (29%) cases in which the biopsy size was greater, including 30 (12%) with no residual tumor on excision. Mean extent was greater on excision than on core biopsy (16.0 versus 5.7 mm; P < .0001); however, the opposite was seen when only small tumors (≤ 10 mm final size) were considered (4.5 versus. 3.6 mm; P = .0161). There was strong linear correlation (r = 0.9761; P < .0001) between the size change (excision size minus biopsy size) and final pathologic size. For accurate tumor summary checklist completion, DCIS extent should be reported for needle biopsy material, particularly in the setting of small tumors.

Increased Likelihood of Mastectomy in Human Epidermal Growth Factor Receptor 2-positive Ductal CarcinomaIn Situ

Patients with human epidermal growth factor receptor 2 (HER2neu)-positive breast invasive cancer are known to have larger, more aggressive tumors. Little research exists on the relationship between HER2neu status and extent of ductal carcinoma In Situ (DCIS). A retrospective review of a single-institution database was performed for patients with DCIS between the years 2002 and 2011. A single blinded breast radiologist reviewed preoperative imaging. Pathology was reviewed for extent of DCIS. Primary outcome was mastectomy. Multivariate logistic regression was used to determine adjusted mastectomy risk. There were 166 cases, 34 HER2neu-positive. HER2neu receptor-positive patients had larger lesions on imaging: 4.0 versus 2.7 cm, by 2.9 versus 1.5 cm (P = 0.0499 and 0.0182). HER2neu-positive patients with DCIS were more likely than HER2neu-negative to undergo mastectomy than lumpectomy (53 vs 28%, P = 0.006). Pathology revealed a trend toward larger lesions in HER2neu-positive patients (2.96 vs 2.22 cm, nonsignificant). Patients with HER2neu-positive disease were three times more likely to undergo mastectomy (odds ratio, 2.9; 95% confidence interval, 1.23 to 6.78). Patients with HER2neu-positive DCIS had greater extent of disease by imaging and were more likely to undergo mastectomy than HER2neu-negative. These findings will help surgeons counsel patients on surgical treatment.

Risk of recurrence of ductal carcinoma in situ by oncotype Dx technology: Some concerns

Predicting which patients with ductal carcinoma in situ (DCIS) will develop local disease recurrence: we have been trying to do that for 30 years. But now we can. The Holy Grail has been recovered in the form of Oncotype Dx, or so we have been told.1 A single genetic test capable of identifying the risk of local disease recurrence after breast conservation in patients with mammographically detected DCIS would obviate the need to factor in DCIS grade, size, and margin width, and patient age. The Oncotype Dx DCIS gene signature assay was validated in a registration trial2 that strictly defined a permissible size of ≤25 mm for low-to-intermediate grade tumors and ≤10 mm for high-grade tumors and those with margin widths of ≥3 mm. Unfortunately, most medical oncologists ordering the Oncotype Dx DCIS assay do not appreciate the limitations of the validated results. They order the $4000 test for patients with DCIS of all sizes and all margin widths. The test, if valid, is only valid if the strict protocol required of the Eastern Cooperative Oncology Group (ECOG) E5194 trial is adhered to. A transected DCIS is likely to recur in spite of a low score on the Oncotype Dx assay. A recent example of a 46-year-old woman with a low-risk Oncotype Dx score had 42 mm of disease and 3-mm margins. Her DCIS grade was intermediate with focal necrosis. A Van Nuys Prognostic Index calculation3 results in a total score of 9 (grade score of 2, size score of 3, margin score of 2, and age score of 2). Oncotype Dx provided a 10-year risk of disease recurrence of 15%, whereas the University of Southern California/Van Nuys Prognostic Index projects a local recurrence risk of 40% to 50% without irradiation. The Oncotype Dx assay is in essence a grading system based on gene expression, and is comparable to histologic grading of DCIS. Because it does not factor in a variety of important predictive factors such as age, margin width, extent of DCIS, nuclear grade, and necrosis, it is not likely to be accurate for the majority of patients. No single test, especially one in which other prognostic factors are ignored, can validly estimate the risk of local recurrence among patients with DCIS. The authors made no disclosures. Michael D. Lagios, MD1 Melvin J. Silverstein, MD2 1The Breast Cancer Consultation Service, Tiburon, California 2Department of Breast Surgery, Hoag Memorial Hospital Presbyterian, Newport Beach, California

Ductal Carcinoma in Situ of the Breasts: Review of MR Imaging Features

The incidence of ductal carcinoma in situ (DCIS) has increased over the past few decades and now accounts for over 20% of newly diagnosed cases of breast cancer. Although the detection of DCIS has increased with the advent of widespread mammography screening, it is essential to have a more accurate assessment of the extent of DCIS for successful breast conservation therapy. Recent studies evaluating the detection of DCIS with magnetic resonance (MR) imaging have used high spatial resolution techniques and have increasingly been performed to screen a high-risk population as well as to evaluate the extent of disease. This work has shown that MR imaging is the most sensitive modality currently available for identifying DCIS and is more accurate than mammography in evaluating the extent of DCIS. MR imaging is particularly sensitive for identifying high-grade and intermediate-grade DCIS. DCIS may have variable morphologic features on MR images, with non-mass enhancement morphology being the most common manifestation. Less commonly, DCIS may also manifest as a mass on MR images, in which case it is most likely to be irregular. The kinetics of DCIS are also variable, with fast uptake and a plateau curve reported as the most common kinetic pattern. Additional MR imaging tools such as diffusion-weighted imaging and quantitative kinetic analysis combined with the benefit of high field strength, such as 3 T, may increase the sensitivity and specificity of breast MR imaging in the detection of DCIS.

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.

Abstract P3-14-06: The Utility of Margin Index to Predict Residual DCIS Following Breast Conserving Surgery

Abstract Background: Although breast conserving surgery (BCS) is commonly performed for ductal carcinoma in situ (DCIS), patients may require re-excision for close or positive margins to rule out residual disease. The concept of margin index (defined as margin distance/tumor size) has been found to predict residual disease in patients with invasive breast cancer, but this concept has yet to be evaluated for patients with DCIS. We sought to determine if DCIS margin index (defined as the closest margin of DCIS/extent of DCIS) was predictive of residual disease. Methods: We performed a chart review of all in situ breast cancers treated with BCS at an academic breast center in 2009. DCIS margin index was calculated as closest margin distance of DCIS (mm)/extent of DCIS (mm). Non-parametric statistical analyses were performed to evaluate the relationship between margin index and residual DCIS. Results: 177 patients with DCIS were treated with BCS in 2009. Of these, 87 (49.1%) underwent resection of additional tissue for close margins or as routine practice, and had recorded quantitative margin distances and tumor sizes such that margin index could be calculated. Of these, 18 (20.7%) had residual DCIS in the additional tissue excised. Median patient age was 60.4 years (range; 31.9–91.4). Of the 50 patients with available immunohistochemistry analysis, 42 (84%) were ER-positive and 36 (72%) were PR-positive respectively. 12 (13.8%) had low grade DCIS, 53 (60.9%) intermediate grade DCIS, and 22 (25.3%) high grade DCIS. Median tumor size was 16mm (range; 1–80 mm); and median margin distance was 2 mm (range; 0–18 mm). Median margin index was 0.125 (range; 0 to 18). Factors correlating with residual DCIS on univariate analysis were high tumor grade (33.3% vs. 23.2%, p = 0.044), PR-negativity (66.7% vs. 22.7%, p = 0.044), increasing tumor size (median 27.5 mm vs. 15.0 mm, p = 0.003), decreasing margin distance (median 1.0 mm vs. 2.1 mm, p = 0.004), and lower margin index (median 0.032 vs. 0.200, p &amp;lt; 0.001). Patient age and ER status were not correlated with residual DCIS. In a multivariate model controlling for grade and PR-status, margin index was no longer a significant predictor of residual disease, although a trend was noted (p = 0.076). To determine the relative strength of margin index (vs. extent of DCIS and margin distance) in predicting residual DCIS, a second multivariate model including PR-status, grade, extent of DCIS and margin distance was created. In this second model, extent of DCIS (p = 0.634) and margin distance (p = 0.152) were less predictive of residual disease than margin index was in the first model. PR-negativity remained the only predictor of residual disease in both. Conclusions: Margin index is a stronger predictor of residual DCIS than either margin distance or extent of DCIS, but loses significance when taking PR status into account. That PR-negativity is strongly associated with residual DCIS (independent of tumor size, grade and margin status) is intriguing and warrants further research. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-14-06.

Abstract P3-14-05: Recurrence in Patients Diagnosed with Ductal Carcinoma in Situ: Predictors and Prognostic Significance

Abstract Background: While patients diagnosed with ductal carcinoma in situ (DCIS) enjoy a favorable prognosis, recurrence after definitive management does occur in a subset of these patients. Factors influencing the development of recurrence, and the ultimate impact of this event on overall survival, remain poorly understood. We sought to determine clinicopathologic factors affecting recurrence and the prognostic role this plays in patients with DCIS. Methods: A retrospective chart review of 205 consecutive patients who presented to an academic breast center with DCIS from 2000 to 2003 was conducted under an IRB-approved protocol. Non-parametric statistical analyses comparing patients who recurred to those who did not were then performed using SPSS Statistical Software. Results: With a median follow-up of 8.5 years, 14 (6.8%) of the 205 patients who presented with DCIS between 2000–2003 had an invasive or in situ recurrence. The median age of all patients at the time of diagnosis of their initial DCIS was 55.5 years (range; 35.8–88.9). 51 (24.9%) had possible (albeit not definitive) microinvasion on their initial specimen. The majority were grade 2 (91; 44.4%), and 99 (48.3%) had comedo histology. The median size of DCIS on the initial excision was 10 mm (range; 0.1–80). All patients underwent definitive surgery to negative margins. The mean time to recurrence was 4.7 years (range; 1.1–10.6). On bivariate analysis, histologic grade of DCIS was the only factor that was significantly correlated with the risk of recurrence. Patients with grade 3 DCIS were more likely to develop a recurrence compared to those with grade 2 or grade 1 DCIS (12.3% vs. 3.3% vs. 0%, respectively, p = 0.032). Patient age, race, extent of DCIS, and histologic subtype were not associated with recurrence (see table below). 5-year actuarial overall survival was no different between those who developed a recurrence and those who did not (92.9 vs. 95.7%, p = 0.171). Conclusions: Approximately 7% of patients diagnosed with DCIS will recur within 10 years. Patients with high grade DCIS are more likely to recur, and this seems to be more predictive of recurrence than other clinicopathologic markers. Irrespective of whether or not patients with DCIS recur, overall survival is not significantly different between these two groups, and patients with DCIS enjoy an outstanding prognosis regardless. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-14-05.

Management of ductal carcinoma in situ according to Van Nuys Prognostic Index in Australia and New Zealand

Clinicians often use the Van Nuys Prognostic Index (VNPI) to determine management of ductal carcinoma in situ (DCIS). The VNPI uses age, extent of DCIS, pathological grade and resection margins to stratify patients into three groups pertaining to risk of local recurrence: low-risk (where breast-conserving surgery - BCS - alone appears adequate), intermediate-risk (where BCS plus radiotherapy is recommended) and high-risk (where mastectomy may be the safest option). The purpose of this study was to determine patterns of management of DCIS in Australia and New Zealand according to the VNPI. Using the National Breast Cancer Audit for the period 2004-2009, 4578 cases of DCIS were identified where complete data were available. Patterns of management according to the VNPI were determined. The chi-squared test was used for statistical analysis. In VNPI group 1, 77% of patients were treated with BCS compared with 63% in group 2 and 32% in group 3. Of patients in group 1 who underwent BCS, 58% also received adjuvant radiotherapy, compared with 80% in group 2. In group 3, 68% were treated with mastectomy, and of those who underwent BCS, 86% received radiotherapy. Overall, 23% of DCIS cases did not conform to best practice according to individual VNPI prognostic groupings. Significant differences in the management of DCIS according to VNPI groups were observed. The results suggest the possibility that some patients in the low-risk group were over-treated, while a proportion of patients in the intermediate- and high-risk groups were under-treated.

Discordance Between Pathologic and Radiologic Tumor Size on Breast MRI May Contribute to Increased Re-excision Rates

Preoperative breast MRI does not decrease re-excision rates in patients who undergo lumpectomy. We evaluated concordance of tumor size on MRI and pathologic size in patients who underwent re-excision of margins after lumpectomy. A retrospective review of patients at the Cedars-Sinai Breast Center who received breast MRI was performed. We found that MRI was performed before lumpectomy in 136 patients. Mean age was 55.2 years (standard deviation ± 12.6). Re-excision occurred in 34 per cent (n = 46). Of those undergoing re-excision, 35 per cent (16/46) were re-excised for ductal carcinoma in situ (DCIS) at the lumpectomy margin. There was no significant difference between radiologic and pathologic size of the tumor (1.94 vs 2.12 cm; P = 0.159). In those who underwent re-excision, the radiologic size was underestimated compared with the pathologic size (2.01 vs 2.66 cm; P = 0.032). Patients with pure DCIS lesions (n = 9) also had smaller radiologic tumor size compared with pathologic (0.64 vs 2.88 cm; P = 0.039), and this difference trended toward significance in those who underwent re-excision (0.55 vs 3.50 cm; P = 0.059). Discordance between tumor size on MRI and pathologic size may contribute to re-excisions in patients who undergo lumpectomy. The limitations of breast MRI to evaluate the extent of DCIS surrounding many breast cancers, and the impact on re-excision rates, should be further evaluated.

A Look into the Ductoscope: Its Role in Pathologic Nipple Discharge

Mammary ductoscopy allows direct visualization of the ductal system and a method for directed excision and pathologic diagnosis. We reviewed our experience with mammary ductoscopy in the evaluation of pathologic nipple discharge. We reviewed all patients who underwent ductoscopy for pathologic nipple discharge at our institution from 2006-2010. All procedures were performed by a single surgeon. Data included patient and imaging characteristics, indications, operative findings, and pathologic outcomes. Descriptive statistics were used for data summary. During the study period, 121 patients underwent ductoscopy and directed duct excision for pathologic nipple discharge, including 66 (55%) with bloody discharge. Breast imaging [mammography, ultrasound, and/or magnetic resonance imaging (MRI)] revealed BIRADS category I/II/III findings in 112 (93%), BIRADS category IV findings in 6 (5%), and was unknown in 3 (2%) patients. Final pathology revealed papillomas in 64 (53%) patients, duct ectasia and associated benign findings in 48 (40%) patients, ductal carcinoma in situ (DCIS) in 7 (6%) patients, and atypical ductal hyperplasia in 2 (1%) patients. None of the patients with DCIS underwent preductoscopy MRI, but all had BIRADS category I/II/III breast imaging. The extent of DCIS identified by ductoscopy and subsequent surgical excision ranged from <1 cm to 10 cm (median 3 cm). The majority of patients with pathologic nipple discharge have benign nonproliferative findings or benign papillomas. Although atypia and malignancy were diagnosed in only 7% of patients who underwent ductoscopy for pathologic nipple discharge, there were no routine imaging findings indicative of these diagnoses preoperatively.

Predictors of Invasion and Axillary Lymph Node Metastasis in Patients with a Core Biopsy Diagnosis of Ductal Carcinoma In Situ: An Analysis of 255 Cases

The diagnosis of ductal carcinoma in situ (DCIS) using core biopsy does not ensure the absence of invasion on final excision. We performed a retrospective analysis of 255 patients with DCIS who had subsequent excision. Clinical, radiologic, and pathologic findings were correlated with risk of invasion and sentinel lymph node (SLN) metastasis. Of 255 patients with DCIS, 199 had definitive surgery and 52 (26%) had invasive ductal carcinoma (IDC) on final excision. Extent of abnormal microcalcification on mammography, and presence of a radiologic/palpable mass and solid type of DCIS were significantly associated with invasion on final excision. Sentinel lymph node biopsy was performed in 131 (65.8%) patients of whom 18 (13.4%) had metastasis. Size of IDC and extent of DCIS on final pathology were significantly associated with positive SLN. Micrometastasis and isolated tumor cells comprised majority (71.4%) of the metastases in DCIS. SLN biopsy should be considered in those with high risk DCIS.

Risk Reduction Strategies for Ductal Carcinoma In Situ

Ductal carcinoma in situ (DCIS) is a premalignant condition that, if left untreated, may progress to invasive breast cancer. After lumpectomy, DCIS can recur, and about half of recurrences are invasive. In 4 randomized trials, radiation has been shown to decrease the local recurrence rate by about half, though it does not change survival. Based on the results of 3 randomized trials, tamoxifen probably decreases cancer recurrence by about 30%, particularly in young women. Low fat diets, weight loss, and physical activity decrease invasive breast cancer recurrence and may be recommended to certain women with DCIS. Prognostic factors include age, extent of DCIS, margin status, grade, and presence of necrosis, although how these affect adjuvant therapy is unclear. Research evaluating other drugs to reduce recurrence risk and on different ways of delivering radiation continues.