Surgery For Ductal Carcinoma In Situ Research Articles

Abstract P1-22-06: A longitudinal cohort study of outcomes in 311 women with unresected ductal carcinoma in situ detected through the English breast screening programme

Abstract Background The variable natural history of ductal carcinoma in situ (DCIS) is poorly understood. The aim of this retrospective cohort study was to determine the outcomes of women who were diagnosed through the English National Health Service Breast Screening Programme (NHS BSP) and had no surgery for screen-detected DCIS. Method English NHS BSP databases were searched for women diagnosed with DCIS without invasive cancer on needle biopsy between 1 April 2001 and 31 March 2018 inclusive, who had no record of surgery within 6 months of diagnosis. These were cross-referenced with cancer registry data for further treatment, event information and mortality records. Details of potentially eligible women were sent to the relevant breast screening units for verification and for completion of data forms detailing clinical, radiological and pathological findings, non-surgical treatment, subsequent clinical course and outcomes. Results Data for 311 eligible women (median age 62 years) were included, with median follow-up (primary DCIS diagnosis to either surgery, development of invasive disease, death or last known to be alive) of 4.1 years (range 0.5 to 17.4 years). The median age at diagnosis was 64 years (range 47 to 90 years). Sixty (19%) women developed invasive breast cancer, 56 ipsilateral and 4 contralateral. Twenty-two women (7%) underwent surgery for DCIS (>6 months after diagnosis) and 86 (28%) died of other causes. Women with high or intermediate grade DCIS were significantly more likely to develop ipsilateral invasive breast cancer (iIBC) than those with low grade DCIS. 28/123 (23%) with high grade DCIS, 21/105 (20%) with intermediate grade DCIS, 5/76 (7%) with low grade DCIS and 2/7 (29%) with an unknown grade of DCIS developed iIBC. Ipsilateral invasion risk increased approximately linearly with time for at least 10 years. Women who developed iIBC were significantly younger than those who did not. This was driven primarily by a strong association among those with high grade DCIS. There was no significant difference in age between those with intermediate and low grade DCIS respectively who did or did not develop iIBC. The median baseline size of DCIS in women who developed iIBC was higher than in women who did not develop iIBC, both overall and in each of the three grade categories (median sizes - high grade 38 mm vs 29 mm, p=0.19; intermediate grade 35 mm vs 18 mm, p=0.31; low grade 18 mm vs 15 mm, p=0.38). This reached statistical significance for all grades combined: 37 mm (range 3-95) v 20 mm (range 3-200), p=0.02. Of the 262 women with a known microinvasion status, 8/25 (32%) with definite or possible microinvasion were subsequently diagnosed with ipsilateral invasive cancer compared to 38/237 (16%) without microinvasion (p=0.027). There was no significant association on univariable analysis between risk of iIBC and microcalcification as the predominant radiological feature (iIBC and microcalcification 47/258 vs iIBC and other radiological feature 7/46; p=0.83), the presence of histological necrosis (iIBC and necrosis, 14/89 vs iIBC and no necrosis, 31/157; p=0.49) or the use of ET (iIBC and ET 11/67 vs iIBC and no ET 45/244; p=0.86). Of the 51 invasive cancers that developed with a known grade, 46 (90%) were grade 2 or 3. Conclusion The findings suggest that women diagnosed with high or intermediate grade DCIS and those with microinvasion should continue to be offered surgery. For those with low grade DCIS there is a need for shared decision-making in the choice of surgery or active surveillance based on a discussion of the risks and benefits of the options as currently understood, and in the light of the low reproducibility of DCIS grading. Citation Format: Karen Clements, Anthony Maxwell, Bridget Hilton, Matthew Wallis, Cliona Kirwan, Hilary Stobart, Elena Provenzano, Nisha Sharma, Janet Litherland, Abeer Shaaban, David Dodwell, Joanne Dulson-Cox, Elinor Sawyer, Senthurun Mylvaganam, Olive Kearins, Samantha Brace-McDonnell, Sarah Pinder, Alastair Thompson. A longitudinal cohort study of outcomes in 311 women with unresected ductal carcinoma in situ detected through the English breast screening programme [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-22-06.

Abstract P3-18-11: Meeting the challenge of successful one-stage lumpectomy for DCIS

Abstract Introduction: Positive lumpectomy margins are associated with an increased risk for ipsilateral tumor recurrence, and necessitate additional procedures to achieve acceptable margins. Re-excision rates are higher in patients with ductal carcinoma in situ (DCIS) versus those with invasive carcinoma. The purpose of this study was to investigate the clinicopathologic characteristics, surgical techniques, and other outcomes associated with re-excision over time following primary breast conserving surgery for DCIS. Methods: Our institutional Breast Cancer Database was queried for patients treated with lumpectomy as the primary procedure for pure DCIS from 2010-2021. Cases of microinvasive disease were excluded. The primary endpoint was the rate of re-excision following lumpectomy. Variables of interest included patient demographics and clinicopathologic characteristics. As a secondary analysis, adjusted odds ratios for the association of MarginProbe® with re-excisions were calculated using a multivariable logistic regression model controlling for age, tumor size, breast density and DCIS subtype. Individual comparisons of continuous variables were based on t-tests, group proportions compared with one-way ANOVA, and categorical variables compared using Chi Square tests. Results: Out of a total of 695 patients in our cohort, 221 (32%) had re-excisions. There was a statistically significant 2% decline per year in the number of re-excisions (p=0.005). Patients who underwent re-excision had larger size of DCIS (2.37 cm vs 1.37 cm, p<0.001). Papillary-type DCIS was associated with an increased rate of re-excision surgery (Table 1). Prior to the introduction of the MarginProbe® for intraoperative margin assessment in 2014, approximately 42% of patients with DCIS underwent re-excisions. This decreased to 24.9% in the post-2013 time frame (p=0.02). In an unadjusted estimate for the odds ratio for association, patients who underwent lumpectomy with MarginProbe® were 81% less likely to require re-excision (OR = 0.19, 95% CI = 0.12, 0.31, p<0.0001). In a logistic regression model controlling for potential confounders with re-excision as the dependent variable and MarginProbe® as the primary explanatory variable, patients for whom the MarginProbe® was used were 66% less likely to require re-excision when controlling for age, tumor size, menopausal status, breast density, and pathology (OR = 0.34, 95% CI 0.16, 0.69). Of patients who required re-excision, 20% went on to mastectomies as their second procedure. After each unsuccessful re-excision, a larger proportion of patients converted to mastectomy. In total, 26% of patients who had unsuccessful primary surgery went on to mastectomies. Of patients who proceeded to mastectomy as their second procedures, 13% were found to carry BRCA1 or 2 mutations. Conclusions: In our study of patients diagnosed with pure DCIS and treated with primary breast conserving surgery, larger size of DCIS and papillary subtype were associated with an increased rate of re-excision procedures. A proportion of patients with unsuccessful primary lumpectomies required multiple procedures to complete their surgical treatment and 26% went on to mastectomy. Patients whose primary procedures included intraoperative margin assessment with the MarginProbe® were significantly less likely to require re-excision. Intraoperative margin assessment is an important tool that can support breast conserving surgery in the challenging population of patients with DCIS. Table 1.Clinicopathologic CharacteristicsVariableNo Re-excision (n=313)Re-Excision (n=100)P-ValueAge; mean (SD)61.48 (12.01)58.04 (13.39)0.016Age of Menopause; mean (SD)50.22 (5.18)48.13 (5.45)0.004Size of DCIS; mean (SD)1.37 (1.25)2.37 (2.00)<0.001Breast Density (%)0.149N/A6 (1.9)2 (2.0)Entirely Fatty10 (3.2)3 (3.0)Extremely Dense19 (6.1)13 (13.0)Heterogeneously Dense165 (52.7)42 (42.0)Scattered Fibroglandular113 (36.1)40 (4.0)DCIS SubtypePapillary93 (29.7)48 (48.0)0.001Cribiform206 (65.8)69 (69.0)0.641Solid190 (60.7)60 (60.0)0.994Comedo54 (17.3)25 (25.0)0.117Surgical Margins (%)<0.001Close (>0 and <1mm)3 (1.0)60 (60.0)Negative (≥1 mm)310 (99.0)13 (13.0)Positive (≤0 mm)0 (0.0)27 (27.0) Citation Format: Joshua A Feinberg, Charles DiMaggio, Nakisa Pourkey, Jennifer Chun Kim, Jenny Goodgal, Amber Guth, Deborah Axelrod, Freya Schnabel. Meeting the challenge of successful one-stage lumpectomy for DCIS [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-11.

Abstract P1-22-04: Decision aids and risk prediction models to support decision making about DCIS treatment: A systematic literature review

Abstract Background: Although most low-risk ductal carcinoma in situ (DCIS) lesions will not progress to invasive breast cancer if left untreated, clinical guidelines advise surgery with/without radiotherapy for all women diagnosed with DCIS. There is therefore increasing concern about the possible overtreatment of DCIS. Currently, clinical trials are being conducted to investigate the safety of active surveillance in low-risk DCIS patients. It is hypothesized that, in future, both surgery and active surveillance will be accepted treatment strategies. Active surveillance is offered to women in the ongoing trials and is expected to become a standard DCIS management option in the future. Choosing whether to undergo surgery for DCIS or to opt for active surveillance can be a difficult decision fraught with uncertainty for both patients and oncologists. Good quality decision support tools such as prediction models and patient decision aids to guide decision making about DCIS management, including the option of active surveillance, are therefore urgently needed. The aim of this study is to identify and evaluate the quality of published decision aids and prediction models aiming to support decision making about DCIS treatment. Methods: A systematic literature review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement criteria. The databases Medline(ovid), Embase (ovid), Scopus, and TRIP were searched to identify published manuscripts describing the development and/or evaluation of DCIS decision aids and prediction models. The protocol was published in the PROSPERO database (ID CRD42020212297). The CHARMS (Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies) checklist was used to evaluate the methodological quality of prediction models and the IPDAS (International Patient Decision Aid Standards) checklist was used to evaluate the quality of decision aids. Data extraction was performed by two researchers with discrepancies resolved through consensus. Results: The review identified 10,636 publications, 33 describing the development and/or validation of four decision aids and seven clinical prediction models were selected (Table 1). The decision aids identified met at least 50% of the IPDAS quality criteria. However, most decision aids lacked tools to help patients reflect on the information received and to facilitate discussion of the information with their family and healthcare providers. Most prediction models were designed to predict the risk of a subsequent ipsilateral breast event after a primary DCIS. No models included the option of active surveillance. Sufficient, good quality, external validation was lacking for all prediction models identified. Conclusions: There are only a few decision aids available that can be used to support patients diagnosed with DCIS. These decision aids could be improved to facilitate the processing of information by patients and enhance communication between patients and their support system and healthcare providers. There is no prediction model that considers active surveillance as a management option for DCIS, and based on the available evidence, there is no prediction model that can be recommended for use in clinical practice. More and qualitatively better validations are required in the future. Table 1.Overview of DCIS decision aids and prediction models identifiedDCIS DECISION AIDSDecision aid by Berger-Hoger et al.(2014)Communication aid by De Morgan et al.(2009)onlineDeCISion.org by Ozanne et al.(2016)DCISoptions.org by COMET trial team(SABCS 2020)Target audience:Women with DCISCliniciansClinicians and women with DCISWomen with DCISLanguage:GermanEnglishEnglishEnglishEvaluation study conducted:YesYesNot reportedNot reportedDesign evaluation study:RCTInterviewNot applicableNot applicableSample size evaluation study:6425Not applicableNot applicableMain finding evaluation study:More active patient involvementCommunication tool assists shared decision makingNot applicableNot applicableImplementation study conducted:None retrievedNone retrievedNone retrievedNone retrieved% IPDAS criteria met regarding:Content87%57%65%78%Development process71%59%67%42%Effectiveness100%50%75%75%DCIS PREDICTION MODELSOncotype DCIS(Solin et al. (2013))DCISionRT/PreludeDX(Bremer et al. (2018))Van Nuysprognostic index(Silverstein et al. (1995))MSKCC DCIS nomogram(Rudlof et al. (2010))Patient prognostic score(Sagara et al. (2016))PredictCBC(Giardello et al. (2019))CBC Risk model(Chowdhury et al. (2017))Predicted outcome:Ipsilateral breast eventIpsilateral breast eventIpsilateral breast eventIpsilateral breast eventIpsilateral breast eventContralateral breast cancerContralateral breast cancerTool based on:Multigene assayBiomarkers + clinico-pathological factorsClinicopatho-logical factors onlyClinicopatho-logical factors onlyClinicopatho-logical factors onlyClinicopatho-logical factors onlyClinicopatho-logical factors onlyIntended to support decision making about:Need for adjuvant radiotherapyNeed for adjuvant radiotherapyType of surgery and need for radiotherapyNeed for adjuvant radiotherapyNeed for adjuvant radiotherapyScreening or prophylactic mastectomyScreening or prophylactic mastectomyRisk of bias based on CHARMS:ModerateModerateModerate/HighModerateLowLowLowNumber (external) validations:3193001Reported C-index/AUC0.68None reportedNone reported0.61-0.68None reported0.52None reportedThis work was supported by Cancer Research UK and by KWF Dutch Cancer Society (ref.C38317/A24043) Citation Format: Renée SJM Schmitz, Erica Wilthagen, Frederieke van Duijnhoven, Marja van Oirsouw, Ellen Verschuur, Thomas Lynch, Rinaa S Punglia, Shelley Hwang, Jelle Wesseling, Marjanka K Schmidt, Eveline Bleiker, Ellen G Engelhardt, Grand Challenge PRECISION consortium. Decision aids and risk prediction models to support decision making about DCIS treatment: A systematic literature review [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-22-04.

Mastectomy or Margin Re-excision? A Nomogram for Close/Positive Margins After Lumpectomy for DCIS.

Anatomic extent of ductal carcinoma in situ (DCIS) may be uncertain in spite of clinical, pathologic, and imaging data.Consequently close/positive margins are common with lumpectomy for DCIS and often lead to a challenge in deciding whether to perform a re-excision or mastectomy. From a single health system, we identified cases of lumpectomy for DCIS with close/positive margins who underwent re-excision for the purpose of constructing a nomogram. In total, 289 patients were available for analysis. The patients were randomly divided into two sets allocating 70% to the modeling and 30% to the validation set.A multivariable logistic regression model was used to estimate the probability of overall positive margin status using multiple clinicopathologic predictors.Nomogram validation included internal tenfold cross-validation, internal bootstrap validation, and external validation for which a concordance index was calculated to assess the external validity. Significant predictors of persistent positive margins from regression modeling included necrosis at diagnosis (non-comedo or comedo); DCIS not associated with calcifications on core biopsy; high-grade DCIS; progesterone receptor positivity; and number of positive margins at initial surgery.When subjected to internal validation, the nomogram achieved an uncorrected concordance index of 0.7332, a tenfold cross-validation concordance index of 0.6795, and a bootstrap-corrected concordance index of 0.6881. External validation yielded an estimated concordance index of 0.7095. Using clinical and pathologic variables from initial diagnosis and surgery for DCIS, this nomogram predicts persistent positive margins with margin re-excision, and may be a valuable tool in surgical decision-making.

Abstract PS1-03: Active surveillance for DCIS: Clinical outcomes at 5.6 years mean follow-up

Abstract Introduction: Standard treatment for ductal carcinoma in situ (DCIS) involves surgical excision with radiation and often endocrine therapy. However, not all DCIS progresses to invasive ductal carcinoma (IDC); thus, surgical intervention may constitute overtreatment for DCIS that has low risk for progressing to IDC. A period of active surveillance (AS) with magnetic resonance imaging (MRI) monitoring may offer the opportunity to stratify lesions with high and low risk for invasion and to avoid overtreatment of DCIS. The purpose of this study was to characterize the outcomes of a cohort of women who elected to go on AS to avoid surgical intervention and to identify whether clinical and imaging features would identify patients who should convert to operative management. Methods: The clinicopathologic variables and outcomes of patients with DCIS who prospectively enrolled in MRI monitoring studies between 2002 and 2019 were retrospectively analyzed with IRB approval. We included 64 cases among 63 women who declined standard operative management for DCIS and had at least two breast MRIs. Clinicopathologic data and physician recommendations regarding continuing surveillance versus converting to operative management were recorded from the medical record. Those who had surgical excision showing IDC were considered to have progressed; those with only DCIS at excision or no operative intervention were considered to have stable disease. Results: Women in the cohort were an average of 53.6 years (29.8 - 78.9) old, and nearly all cases of DCIS with estrogen receptor (ER) status were ER+ (98.3%). Of the 64 cases in the cohort, 57 received endocrine therapy (89.1%). Average length of time on AS was 2.7 years (.2 – 11.9) with a median of 3 (2 – 18) MRIs performed and mean follow-up time 5.6 years (0.9 – 15.3). A total of 31 cases (48.4%) eventually had surgical excision while 33 (51.6%) remained on AS. There were 17 cases with IDC at surgery (26.6%). The IDC was an average of 1.5 cm (0.1 – 9.0) and most commonly ER + (88.2%), HER2 + (53.3%), grade 2 (58.9%), and node negative (82.4%). Only 7 women did not take endocrine therapy, but 3 of those women had IDC (42.9%). In 15 of the 17 cases with IDC (88.2%), the physician noted concern for progression in their clinic note and recommended surgical excision. This occurred a mean of 1.9 years (0.2 – 6.5) from the start of AS, with 47%, 67%, and 87% of cases identified within 1, 2 and 3 years from the start of AS. Suspicion of progression was based on an increase in lesion size or prominence on MRI and/or increase in calcifications on mammography. Of those that were identified as good candidates to continue AS with no concern for progression (n = 49), 16 chose to undergo surgical excision (32.7%) and 2 had IDC (4.1%). Conclusion: After over a decade of following women who seek alternatives to surgery for DCIS, we have identified clinicopathologic and imaging features that discriminate good candidates for AS and endocrine risk reducing therapy from those best treated with surgical excision. In our cohort of mostly ER+ patients receiving endocrine therapy on AS, over half of the cohort (51.6%) avoided surgical intervention. Her2 status, Oncotype DCIS, and Mammaprint scores of IDC is in process and will be presented. Our data support the study of AS as a method to stratify the risk of IDC and avoid overtreatment. We will present a personalized AS algorithm (based on biology and imaging) that we intend to prospectively test in the ATHENA network and NCI funded MCL consortium. Table 1: Cohort CharacteristicsFull Cohort (n=64)No evidence of IDC (n=47)IDC at surgery (n=17)Age at Diagnosis (years)53.6 (29.8 - 78.9)52.9 (29.8 - 74.5)55.5 (41.9 - 78.9)Time on AS (years)2.7 (.2 - 11.9)2.8 (.2 - 11.9)2.2 (.3 -5.9)Follow-Up (years)5.6 (0.9 - 15.3)Menopausal StatusPremenopausal26 (40.6%)22 (46.8%)4 (23.5%)Postmenopausal35 (54.7%)24 (51.1%)11 (64.7%)Unknown3 (4.7%)1 (2.1%)2 (11.8%)Breast CompositionFatty4 (6.3%)3 (6.4%)1 (5.9%)Scattered14 (21.9%)9 (19.1%)5 (29.4%)Heterogeneous27 (42.2%)19 (40.4%)8 (47.1%)Extreme17 (26.5%)14 (29.8%)3 (17.6%)Unknown2 (3.1%)2 (4.3%)0 (0.0%)ER StatusPositive57 (89.1%)41 (87.2%)16 (94.1%)Negative1 (1.6%)0 (0.0%)1 (5.9%)Unknown6 (9.3%)6 (12.8%)0 (0.0%)PR StatusPositive50 (78.1%)36 (76.6%)14 (82.3%)Negative5 (7.8%)3 (6.4%)2 (11.8%)Unknown9 (14.1%)8 (17.0%)1 (5.9%)GradeHigh20 (31.3%)15 (31.8%)5 (29.4%)Intermediate32 (50.0%)21 (44.6%)11 (64.7%)Low10 (15.6%)9 (19.1%)1 (5.9%)Unknown2 (3.1%)2 (28.5%)0 (0.0%Hormone TherapyYes57 (89.1%)43 (91.5%)14 (82.4%)No7 (10.9%)4 (8.5%)3 (17.6%) Citation Format: Case Brabham, Rita Mukhtar, April Liang, Paul Kim, Gillian Hirst, Amrita Basu, Heather Greenwood, Rita Freimanis, Alexander Borowsky, Shelley Hwang, Rick Baehner, Gregor Krings, Nola Hylton, Laura Esserman. Active surveillance for DCIS: Clinical outcomes at 5.6 years mean follow-up [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-03.

Abstract ES2-1: Guiding decisions to omit radiotherapy after breast-conserving surgery for DCIS. Can genomic biomarkers help?

Abstract Most women diagnosed with ductal carcinoma in situ (DCIS) will be treated with breast-conserving surgery followed by whole breast radiation. We will review the evolving role of genomic biomarkers to personalize radiotherapy treatment recommendations after breast-conserving surgery for DCIS. Citation Format: E Rakovitch. Guiding decisions to omit radiotherapy after breast-conserving surgery for DCIS. Can genomic biomarkers help? [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 ES2-1.

Abstract P3-03-34: Sentinel lymph node biopsy is unnecessary in ductal carcinoma in situ patients diagnosed by biopsy

Abstract Background: Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer 2018 state that sentinel lymph node (SN) biopsy is unnecessary for patients treated with breast-conserving therapy (BCT) and with an expected final pathological diagnosis of ductal carcinoma in situ (DCIS). Regardless of whether they were diagnosed with DCIS by biopsy before surgery, 78% of patients currently undergo axial procedures in Japan because invasive lesions may be detected in surgical specimens. This study examined whether SN biopsy can be omitted in DCIS patients diagnosed by biopsy and which factors are associated with invasion. Methods: Patients who underwent definitive surgery for DCIS diagnosed by preoperative biopsy at our institution from May 2004 to January 2018 were investigated retrospectively. The factors associated with upstaging to invasive cancer from DCIS were examined with Fisher's exact test and the t-test. (Age, Tumor size, Operation (Mastectomy or BCT), Biopsy method (Core Needle Biopsy or Vaccume-Assisted Biopsy), Mammography (ditected or not-detected), Ultrasound (ditected or not-detected, mass or non-mass), Comedo, ER, PgR, HER2) Results: A total of 311 patients were enrolled in this study, of whom 277 (89.1%) underwent SN; six of these (2.2%) had SN metastasis. All six cases were upstaging to invasive cancer: five (1.8%) had micrometastasis and one had macrometastasis (0.4%). From a surgical viewpoint, SN metastasis were detected in 3/161 (1.9%) cases treated with mastectomy and 3/150 (2.4%) cases treated with BCT. Although all three cases treated with BCT had micrometastasis, one case treated with mastectomy had macrometastasis (the other two cases had micrometatastasis). A total of 80/311 cases (25.7%) upstaged to invasive cancer and the only predictor of invasion was tumor size on images (p=0.0002). We could not determine the effective cut-off for tumor size because the area under the receiver operating characteristic curve was 0.63<0.70. Tabule 1.Tumor size on images was the only predictor of invasion. Upstaging (N=80)DCIS (N=231)P valueTumor size: mm (95% Confidence Interval)47.5 (41.9-53.2)33.9 (30.5-37.3)0.0002 Conclusion: Tumor size was found to be the only predictor of invasion. Only 2.2% of DCIS patients had SN metastasis despite the fact that 25.7% patients were upstaged to invasive cancer. We conclude that SN biopsy is not necessary for DCIS patients diagnosed by biopsy. Citation Format: Uemoto Y, Kondo N, Wanifuchi-Endo Y, Hisada T, Nishikawa S, Katagiri Y, Kato H, Takahashi S, Toyama T. Sentinel lymph node biopsy is unnecessary in ductal carcinoma in situ patients diagnosed by biopsy [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 P3-03-34.

Abstract P3-17-01: Long-term rates of breast preservation after breast-conserving therapy for ductal carcinoma in situ

Abstract Background: Despite evidence that radiotherapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) halves the risk of recurrence, the benefit of RT in the management of DCIS continues to be a matter of controversy. One argument against the use of RT after BCS is that patients who develop ipsilateral local recurrence (LR) can be salvaged with further breast-conserving surgery such that the omission of RT will lead to high rates of breast preservation while minimizing exposure to RT. Breast preservation is an important determinant of quality of life for women with early stage breast cancer and DCIS. Yet the management of LR and the impact of RT on the resultant long-term risks of bilateral breast preservation in a population of women with DCIS are unclear. We assessed the treatment of LR, the impact of RT on the use of salvage mastectomy and the long-term risks of bilateral breast preservation achieved in a population of women with DCIS treated with BCS alone or BCS+RT. Methods: A population-based analysis of women diagnosed with DCIS from 1994-2003 treated with BCS alone or BCS+RT with pathology review. Treatment and outcomes, including the development of LR and contralateral breast events, were determined by administrative databases with validation by review of operative or pathology reports. Median follow-up was 10.2 years for cases treated by BCS alone, 11.6 years for those treated by BCS+RT. We used a propensity-adjusted Cox proportional hazards model to evaluate factors associated with the use of salvage mastectomy for LR and to evaluate factors associated with any mastectomy. We assessed the risk of long-term breast preservation by calculating the KM 10-year risk of ipsilateral mastectomy and any mastectomy. Results: The population cohort includes 3303 women with pure DCIS;1649 (50%) were treated by BCS alone, 1654 (50%) received BCS+RT. Women treated with RT had more high risk features of DCIS than those treated by BCS alone. LR developed in 343 (21%) women treated by BCS alone and in 257 (15.5%) women treated by BCS+RT (p<0.01). Most women who developed LR received salvage mastectomy, irrespective of age at diagnosis and histology. Salvage mastectomy was used in 57.4% (197/343) of cases that recurred after BCS alone and in 67.6% (173/257) that recurred after BCS+RT. The likelihood of receiving salvage mastectomy for LR was similar in patients initially treated by BCS+RT vs. those initially treated BCS alone. Most (90%) of mastectomies were performed for a LR. Overall, individuals initially treated by BCS+RT had a 29% lower probability of having a mastectomy at 10 years compared to those treated by BCS alone (HR=0.71, 95%CI: 0.60,0.84,p<0.0001). The 10 year mastectomy-free survival rates are 82.7% for women initially treated by BCS alone and 87.3% for those treated by BCS+RT (p=0.0096). Conclusion: Women who received RT after BCS for DCIS experience a greater likelihood of long-term bilateral breast preservation. This is attributable to the lower risks of LR and that most local recurrences after breast-conserving therapy are treated by salvage mastectomy. Long-term breast preservation should be considered in discussions weighing the benefits and risks of RT after conservative surgery for DCIS. Citation Format: Rakovitch E, Nofech-Mozes S, Hanna W, Gu S, Fong C, Tuck A, Sengupta S, Elavathil L, Jani P, Done S, Miller N, Youngson B, Bonin M, Chang M, Paszat L. Long-term rates of breast preservation after breast-conserving therapy for ductal carcinoma in situ [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-17-01.

Boost Radiotherapy for the Treatment of Ductal Carcinoma In Situ Remains Controversial

Over the past 40 years, technological advances and improved screening practices have resulted in a substantial increase in the diagnosis of ductal carcinoma in situ (DCIS). Accounting for approximately 20% to 30% of breast cancer cases, DCIS is associated with low mortality rates, but local relapse is a matter of concern, and death may occur in cases of insufficient local treatment. As demonstrated in previous studies, one predictive factor for local relapse is age, with younger patients having a higher risk of an ipsilateral breast tumor recurrence as DCIS or invasive cancer. Other risk factors include close or positive surgical margins and tumor necrosis. Whole-breast irradiation following breastconserving surgery for DCIS statistically significantly reduces the risk of local relapse compared with breastconserving surgery alone. Accepted as the current standard of care, adjuvant whole-breast radiotherapy has been demonstrated to reduce local invasive and noninvasive recurrence in patients with DCIS undergoing breast-conservation therapy in 4 large prospective randomized controlled trials (National Surgical Adjuvant Breast and Bowel Project B-17, European Organisation for Research and Treatment of Cancer 10853, United Kingdom/Australia and New Zealand, and SweDCIS) and in an Oxford overview. Although a complementary radiotherapy boost to the tumor bed has been shown to considerably improve local disease control in patients with invasive breast cancer, this strategy remains controversial for DCIS, with the majority of studies resulting in no therapeutic or survival advantage. In a study of boost radiotherapy involving one of the largest populations to date, Rakovitch and colleagues focused on a population of individuals with confirmed DCIS who were treated with breast-conservation therapy and boost radiotherapy. The participants were followed for 10 years, which allowed for a high study power and provided data on the 10-year rates of local recurrence and local recurrence-free survival (LRFS). The population of this study included 235 patients who were younger than 45 years of age, although the median age was 56 years. In addition, it included patients who had positive surgical margins before radiotherapy, 39% of whom underwent a hypofractionated scheme of 40-44 Gy in 16 fractions rather than the conventional scheme of 50 Gy in 25 fractions. This study, unique in several patient and treatment characteristics, did not identify a subset of women for whom the administration of boost radiotherapy was associated with a lower rate of

Epidemiology of ductal carcinoma in situ in Western Australia: implications for surgical margins and management.

In 2010, the Australian Institute of Health and Welfare published a report examining the characteristics of Australian women diagnosed with ductal carcinoma in situ (DCIS). This study identified the characteristics of women who were diagnosed with DCIS in Western Australia (WA) 1996-2005, and built on a national study by determining the rate of second operation and breast cancer events (BCE) in WA. A retrospective analysis of data from the WA Cancer Registry and the Hospital Morbidity Database was undertaken. The main outcome measures were histological characteristics, second operation rate, breast cancer events. A total of 1356 cases of DCIS were diagnosed in WA between 1996 and 2005, with a minimum 5-year follow-up. The age-standardised incidence rate in 2005 was 15.4 per 100,000 women. 72% of patients received breast-conserving therapy for primary treatment, 18% of patients requiring a second operation to obtain adequate margins and 35% of patients received postoperative radiotherapy. 17.3% of cases had a subsequent BCE, with the 5- and 10-year probabilities being 4.36 and 8.27%, respectively. A BCE was significantly associated with age (p<0.001), no second operation (p<0.001) and no radiotherapy (p=0.049 recurrence, p=0.043 invasion). This study supports the need to ensure adequate margins during primary surgery for DCIS is obtained to reduce the need for a second operation or the risk of a subsequent BCE. The consideration of mastectomy versus radiotherapy should be made in conjunction with the identified risk factors, specifically age and whether a second operation was performed.

Abstract P1-01-21: Is it safe to skip intra-operative frozen section examination of sentinel lymph node for core biopsy-diagnosed DCIS?

Abstract Background Our initial experience on sentinel lymph node (SLN) biopsy with on-table frozen section examination has shown to be an accurate alternative to axillary dissection in the staging of invasive breast cancer. Patients with a preoperative diagnosis of ductal carcinoma in-situ (DCIS) by core biopsy follow a similar treatment pathway because the risk of axillary metastasis and histological upstaging in the final excisional specimen is not negligible. Intra-operative frozen section reporting facilitates axillary clearance in a single operation when necessary. However, with the declining role of completion axillary dissection for those with minimal SLN involvement, its significance in DCIS is questioned. Methods A retrospective analysis was performed for patients with core biopsy-diagnosed DCIS undergoing SLN biopsy at the time of definitive surgery. Those with evidence of microinvasion in the core biopsy specimen were excluded. SLN were identified by blue dye, radioactive isotope, or combined mapping technique, and examined by intra-operative frozen section. Full axillary dissection was performed if frozen section was positive for metastasis, whereas patients with failed SLN localization were spared from the procedure. All lymph nodes harvested would undergo further paraffin section with immuno-histochemical staining. The results of SLN biopsy in relation to the final pathology of the primary tumour and the axillary disease status were analysed. Results From March 2002 to March 2013, 297 patients who had a core biopsy diagnosis of DCIS underwent simultaneous SLN biopsy with their definitive excisional operation. SLN localization was successful in 283 patients (95.3%). Metastases in SLN were found in 19 (6.4%) of them. Axillary dissection, either in the same or second operative setting, was completed in 12 (4%) patients. Only four (1.3%) showed additional positive lymph nodes in the rest of axilla. All of these four patients had invasive disease revealed in their primary lesions upon final pathological assessment. Overall, 83 patients (27.9%) had histological upstaging from DCIS to microinvasive or invasive carcinoma. It was more commonly associated with the presence of a palpable (48.5% versus 21.6%, p = 0.0067) or radiological (46.3% versus 19.7%, p = 0.0047) mass lesion. Out of the 214 patients who remained in the category of “pure DCIS”, six (2.8%) had SLN metastases. Three proceeded to axillary dissection and their SLN were confirmed to be the only positive ones in the axilla. Conclusion Although SLN metastases were rare in patients with “pure DCIS”, underestimation of invasive disease was frequent on core biopsy. Performing SLN biopsy during definitive surgery for DCIS allowed correct nodal staging in a single operation. Nevertheless, in contrast to invasive carcinoma, frozen section examination could safely be foregone since the additional yield of completion axillary dissection was shown to be slim in “pure DCIS” even if SLN shows positive results. However, management of SLN in DCIS with high risk features should follow that of invasive breast cancer in view of the considerable chance of histological upstaging. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-21.

Ductal Carcinoma In Situ: A Rose by Any Other Name

Ductal Carcinoma In Situ: A Rose by Any Other Name

Association of MRI and locoregional recurrence (LRR) rates in ductal carcinoma in situ (DCIS) patients treated with or without radiation therapy (RT).

57 Background: Perioperative MRI is frequently obtained in women with breast cancer; however, studies have not shown decreased rates of re-excision, and some report unnecessary increases in mastectomy rates. We examined LRR rates among women with DCIS who underwent perioperative MRI as compared to those who did not. Methods: All women who underwent breast-conserving surgery for DCIS in 1997-2010 were included from a prospectively maintained database. Patient characteristics and rates of LRR were compared in women with and without an MRI. Univariate and multivariate analyses were performed. Analysis was repeated in the subset of women who did not receive RT. Results: 2,321 cases were identified; 596 had MRI and 1,725 did not. Women who had MRI were younger, more likely to be premenopausal, have a family history of breast cancer, have a clinical presentation, receive RT and endocrine therapy, be treated in later years, and had fewer close/positive margins. At median follow-up of 57 months there were 184 IBTRs; 5-year LRR rates were 8.5% (MRI) and 7.2% (no MRI) (p = 0.52), and 8-year rates were 14.6% and 10.2%, respectively. MRI was not associated with lower LRR rates after adjustment for age, menopausal status, family history, presentation, adjuvant therapy, margin status, number of excisions, and year of surgery in both the entire cohort and in the subgroup who did not receive RT. Select factors from multivariate analysis for patients with all covariates available are shown in the Table. Conclusions: We observed no association between perioperative MRI and LRR rates for patients with DCIS, even when RT was not given. The benefit of perioperative MRI for DCIS remains uncertain. [Table: see text]

Propensity-score matched pair comparison of accelerated partial breast irradiation (APBI) and whole breast irradiation (WBI) for ductal carcinoma in situ (DCIS).

1123 Background: DCIS remains a cautionary criterion for APBI by the ASTRO APBI consensus statement. We performed a matched analysis to compare the efficacy of WBI and APBI for patients with DCIS. Methods: Women with DCIS treated with APBI or WBI were reviewed. APBI (n=102) patients with ≥2 y follow-up were matched 1:3 to WBI (n=546) patients with ≥5 y follow-up by age, tumor size, nuclear grade, ER status, margin status, and laterality. Ipsilateral breast tumor recurrence (IBTR), distant metastasis (DM), contralateral breast cancer (CLBC) and cause-specific survival (CSS) were compared by cumulative incidence (Gray’s) and competing risks regression (Fine and Gray’s), and overall survival (OS) and disease-free survival (DFS) by Kaplan-Meier (log-rank test). Results: Median follow-up was 4.6 y (2.0-14.7) for APBI and 9.0 y (5.4-27.0) for WBI. Median (range) or percentages are shown (Table). Patients did not differ by match criteria. There were 17 LR, 1 DM, 19 CLBC, 2 CSS, 22 OS, and 19 DFS events during follow-up. The patient groups had similar rates of cancer-related events including ipsilateral and contralateral breast recurrences at both five and eight years. Treatment type, age, tumor size, nuclear grade, ER status, and hormone therapy (HT) were not prognostic of LR or CLBC on uni- and multi-variate analyses. Conclusions: APBI provides equivalent and exemplary outcomes compared to WBI following breast-conserving surgery for DCIS. These findings support previous reports on the efficacy of APBI in the treatment of noninvasive breast carcinoma. Prospective randomized comparison of APBI to WBI for DCIS is needed. [Table: see text]

P5-15-01: Words Matter: Influence of DCIS Diagnosis Terminology on Patient Treatment Decisions.

Abstract Background: Treatment of ductal carcinoma in-situ (DCIS) poses significant challenges. Although retrospective studies suggest that most cases of low grade DCIS will never progress to invasive disease, it remains difficult to accurately identify those patients at greatest risk. In this situation where many diagnosed tumors could follow an indolent course for the patient's lifetime, both systemic therapy and watchful waiting could be reasonable options, similar to those currently offered to patients with early prostate cancer. One strategy that has been suggested to reduce overtreatment is to use terms other than “ductal carcinoma in situ” when explaining a diagnosis of DCIS to a patient. In the current study, we have investigated the effect of terminology on women's stated treatment preference for DCIS. Methods: Women 40–65 years of age were recruited from a database of volunteers at an academic hospital. Subjects with a personal history of breast cancer were excluded. Endpoints were gathered from a web-based survey. Each subject was presented with three different scenarios, each of which used a different terminology for DCIS: non-invasive breast cancer, breast lesion, and abnormal cells. The scenarios included a detailed explanation of the risks and benefits of three treatment options: surgery, systemic treatment only and active surveillance. After reading each scenario, the subject was asked to choose among the treatment options and to explain her choice. Results: 187 subjects completed the survey. More women chose active surveillance when DCIS was described using the terms “abnormal cells” or “breast lesion” than using the term “non-invasive cancer” (Table 1). The majority of women (97/187, 52%) changed their treatment preference when a different term was used to describe DCIS. Of the 97 women who changed their treatment preference, 47 (48%) chose surgery when the term “non-invasive cancer” was used to describe DCIS, but chose a less invasive treatment when “cancer” was not used in the diagnosis. Of 90 people who did not change their treatment preference, 39 (43%) chose active surveillance. Among the three treatments, the percent of women who chose surgery was the highest (84/187; 46%) when the term “non-invasive cancer” was used. 47/84 (56%) of the women who chose surgery when using the term “non-invasive breast cancer” changed their treatment preference when a different term was used. 36/84 (43%) switched to active surveillance while 11/84 (13%) switched to medication. Conclusion: These results support that the specific terminology used to explain a diagnosis of DCIS influences patients’ treatment preference. Moreover, we found that women may entertain treatment preferences other than surgery for DCIS when the tradeoffs of each choice are clearly explained. Avoiding the word “cancer” in the diagnosis may offer a strategy that reduces fear-based treatment decisions and may reduce the burden of overtreatment for DCIS. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-15-01.

P5-08-06: Comparison of Mammographic Density between Ductal Carcinoma In Situ and Benign Breast Disease.

Abstract Background: High breast density is an independent risk factor for breast cancer as well as benign breast diseases. However there are few studies about breast density of ductal carcinoma in situ (DCIS) and benign breast disease(BBD). In this study, we investigated patterns of breast density of DCIS and BBD, and comparatively analyzed breast densities of DCIS and BBD. Material and Methods From 2008 to 2009, 345 patients underwent surgery for DCIS at Asan Medical Center, and 295 patients for BBD at 2010. We retrospectively reviewed each groups and estimated cranio-caudal view of digital mammogram of unaffected breast by computer-assisted thresholding methods, using Cumulus 4, version 4.0. For BBD we included atypical ductal hyperplasia, fibroadenoma, papilloma(atypical/intraductal), phyllodes tumor(benign/borderline), and excluded unavailable mammogram(mostly, because of scanned films from outside hospitals and previously diagnosed breast cancer). Results Mean ages of each group were 46.51 year old in DCIS group and 41.43 year old in BBD group, and the mean percentage density(PD) were 44.89% and 45.27%, respectively. There was no significant difference between two groups in total population(p=0.79). We categorized into two groups according to the age, ≥50 and &amp;lt;50, for each DCIS and BBD group. Mean percentage density of below 50 year old was 52.92% in DCIS gruop and 49.58% in BBD group(p=0.031). Mean percentage density above 50 year old was 33.67% in DCIS group and 33.29% In BBD group(p=0.867). Conclusion The mean values and distribution patterns of PD were similar between BBD group and DCIS group. However, in the subgroup aged under 50, the DCIS group has significantly higher breast density than the BBD group. Although the causal association of breast density with breast cancer has been relatively well documented, this kind of cross-sectional study has an inherent limitation. The absolute difference between the DCIS group and the BBD group under age 50 (3.34% in table2) needs more investigation for its clinical implications. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-08-06.

Local control with conventional and hypofractionated adjuvant radiotherapy for ductal carcinoma in-situ: is there a difference in outcome?.

Abstract Abstract #1162 Purpose&amp;#x2028; Trials of adjuvant whole breast radiotherapy (WBRT) following breast-conserving surgery for invasive breast cancer indicate equivalent efficacy and morbidity for conventional and hypofractionated treatment. WBRT for ductal carcinoma in-situ (DCIS) improves local control, however an optimal dose fractionation remains undefined. Our group policy allowed for the use of both schedules, therefore we compared local control in women with DCIS following breast-conserving surgery.&amp;#x2028; Methods&amp;#x2028; Two hundred and sixty six patients treated between January 1999 and December 2004 with conventional (50 Gy/25 fractions) or hypofractionated (42.4 Gy/16 daily fractions or 40 Gy/16 fractions + 12.5 Gy/5 fraction boost) radiotherapy schedules to the whole breast after breast-conserving surgery for DCIS were identified and retrospectively reviewed. Treatment schedules were evaluated for outcomes in terms of ipsilateral breast recurrence.&amp;#x2028; Results&amp;#x2028; The median age at diagnosis 56.7 years (range 32.2-83.8 years), and 82% (218 patients) presented with mammographic abnormality. Median tumour size was 1.5 cm (range 0.4-10 cm), grade 3 tumours were present in 105 women (39%), and comedonecrosis in 145 (55%). Fifty-one patients (19%) had multifocal disease. Median follow-up was 45.1 months (range 0.7-106.8 months). Prognostic features were well matched in both groups.&amp;#x2028; One-hundred and four patients (39%) were treated with conventional and 162 (61%) with hypofractionated WBRT. There were a total of 14 confirmed local recurrences in the previously radiated breast. Six recurrences occurred in the 104 (5.8%) patients treated with a conventional schedule and 8 of 162 (4.9%) patients treated with a hypofractionated schedule. Actuarial risk of recurrence at 4 years was 7% with hypofractionated WBRT and 5% with a standard schedule (p=0.85).&amp;#x2028; &amp;#x2028; Eight patients recurred with DCIS and 6 with invasive carcinomas, all 14 were treated surgically with adjuvant treatment as indicated clinically, 1 patient with clinical recurrent disease refused biopsy and further conventional treatment. Univariate analysis showed a trend to increased risk of recurrence with grade 3 tumours (10% at 4 years vs. 3% for grade1/2, p=0.053) and presence of comedonecrosis (8% vs. 2%, p=0.096), but not multi-focal disease (7% vs. 5%, p=0.78).&amp;#x2028; Conclusions&amp;#x2028; Hypofractionated adjuvant WBRT schedules following breast-conserving surgery for DCIS have comparable local control rates to a conventional radiation schedule. Hypofractionated WBRT is more convenient for patients, has equivalent morbidity and should be considered in this patient group. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1162.

Impact of Randomized Clinical Trial Results in the National Comprehensive Cancer Network on the Use of Tamoxifen After Breast Surgery for Ductal Carcinoma in Situ

The National Surgical Adjuvant Breast and Bowel Project B-24 trial, published in June 1999, demonstrated that tamoxifen after breast-conserving surgery (BCS) and radiotherapy for ductal carcinoma in situ (DCIS) reduced the absolute occurrence of ipsilateral and contralateral breast cancer. We assessed the impact of B-24 on practice patterns at selected National Comprehensive Cancer Network (NCCN) centers. Tamoxifen use after surgery was examined among 1,622 patients presenting for treatment of unilateral DCIS between July 1997 and December 2003 at eight NCCN centers. Associations of clinicopathologic and treatment factors with tamoxifen use were assessed in univariate and multivariable logistic regression analyses. Overall, 41% of patients (665 of 1,622) received tamoxifen. The proportion increased from 24% before July 1, 1999, to 46% on or after July 1, 1999. Factors significantly associated with receipt of tamoxifen included diagnosis on or after July 1, 1999 (odds ratio [OR], 3.85; P < .0001), BCS in patients younger than 70 years (OR, 3.21; P = .0073), no history of cerebrovascular or peripheral vascular disease (OR, 3.13; P = .0071), receipt of radiotherapy (OR, 1.82; P = .0009), and previous hysterectomy (OR, 1.34; P = .0459). Tamoxifen use varied significantly by center, from 34% to 74% after BCS and 17% to 53% after mastectomy (P < .0001). Tamoxifen use after surgery for DCIS at NCCN centers increased after presentation of the B-24 results. Rates varied substantially by institution, suggesting that physicians differ in how they weigh the modest reduction in breast cancer risk with tamoxifen against its potential adverse effects in this population.