Primary Ductal Carcinoma In Situ Research Articles

Is breast magnetic resonance imaging (MRI) useful for diagnosis of additional sites of disease in patients recently diagnosed with pure ductal carcinoma in situ (DCIS)?

PurposeTo determine if breast MRI is useful for detecting additional or invasive sites of disease in patients initially diagnosed with pure DCIS. Materials and methodsA retrospective review of women diagnosed with pure DCIS who underwent a breast MRI for evaluation of extent of disease was performed at a single institution from January 2013 to April 2015. Data analysis included imaging (mammography, ultrasound and MRI) and pathology characteristics (histology and biomarker status) of the primary DCIS as well as descriptors for the additional sites of disease incidentally found by breast MRI. ResultsA total of 108 patients were diagnosed with pure DCIS during this time period. A breast MRI for staging was recommended for all patients. 76 patients had an MRI performed, ages ranging from 38 to 79 years old (median, 53 years); sizes ranging from 0.3 to 10cm (mean, 2.2cm). A total of 52 patients (68%) either had suspicious new finding(s) (n=27, 36%) or bigger tumor size than originally visualized on mammography (n=43, 57%). A total of twenty-seven patients (36%) had other MRI findings suspicious for additional sites of disease in either breast (four in the ipsilateral breast and twenty-three in the contralateral breast). From this group of patients, twenty-three (85%) patients underwent MRI-guided biopsy as recommended. The four patients who did not have the recommended MRI guided-biopsy either underwent total mastectomies or refused the biopsy. Six out of the twenty-three patients (26%) were diagnosed with an additional site of cancer (5 DCIS and 1 IDC) (7.9%, CI=3.7%, 16.2%). All of the six patients had contralateral disease (100%) and none had a second site of disease in the ipsilateral breast. The size of the additional sites of disease ranged from 0.4 to 8cm (mean, 3.1cm) and the size of the primary lesion in this selected group ranged from 0.1 to 10.9cm (mean, 5.6cm). Ages ranged from 44 to 63 years old (median, 52.5 years). Five out 6 patients (83%) presented with the first site of disease as pure DCIS with estrogen (ER) and progesterone (PR) receptors positive and one case (17%) was pure DCIS ER/PR- negative. The second incidental lesion found on MRI demonstrated 5 cases of contralateral pure DCIS and 1 case of contralateral invasive disease. From this group, we did not have the data for biomarker analysis for the second site of disease in 2 cases and 3 cases showed concordant biomarker status between the first and second sites of disease. The 1 case that presented with an invasive component in the contralateral side of the initially biopsy-proven pure DCIS had discordant biomarkers compared to the first site of disease: the first site of pure DCIS was ER/PR-negative and the second site of invasive ductal carcinoma (IDC) presented with ER/PR-positive status. ConclusionFrom a total of 76 patients with recent diagnosis of pure DCIS who underwent staging breast MRI examination for diagnosis of additional sites of disease, approximately 8% (95% confidence interval=3.7%, 16.2%) was diagnosed with an additional site of cancer and 1.3% (95% confidence interval=0.2%, 7%) of the total cases had invasive disease in the additional sites with different biomarker status; changing their management and prognosis.

Abstract 4738: Risk of ipsilateral invasive breast cancer after DCIS: a comparison of primary DCIS and subsequent invasive disease by morphological and immunohistochemical analysis

Abstract INTRODUCTION. The wide spread adoption of population-based breast cancer screening has led to a substantial increase in diagnosis of ductal carcinoma in situ (DCIS). When detected, almost all DCIS is treated to prevent progression to invasive disease, even though the majority of DCIS will never progress. Yet, we are unable to discriminate harmless from potentially hazardous DCIS. Hence, there is an urgent need to find characteristics of DCIS and biomarkers that predict subsequent invasive tumor development. In this study, we compared primary DCIS lesions with their subsequent ipsilateral invasive breast cancer (iIBC), to explore how the initial DCIS lesion and its subsequent iIBC are related. PATIENTS AND METHODS. We used a population-based, nation-wide cohort consisting of 2,654 women who were treated for primary DCIS by breast conserving surgery (BCS) only. Within a median follow-up time of 10.7 years, 316 women developed a subsequent iIBC (12%). FFPE tissue blocks of both DCIS and subsequent iIBC could be collected for 158 of these 316 women. We assessed histology characteristics, tumor location, estrogen and progesterone receptor status, p16 expression, and HER2 and p53 overexpression. Additionally, DNA and RNA were simultaneously isolated from 100 DCIS and 100 matched subsequent iIBC specimens for extensive molecular profiling. RESULTS. More than 95% of the invasive recurrences were located at or near the site of the primary DCIS. Concordant histological grade was found in 94% of the matched pairs and identical immunohistochemical (IHC) marker expression in 58%. Of the 44 patients with HER2 positive DCIS, 36% developed HER2 negative iIBC. Furthermore, this change in HER2 status was also a main cause of a change in surrogate intrinsic subtype (based on ER, PR, HER2) between DCIS and iIBC, which was observed in 16% of the patients. These dissimilarities were not found when we compared invasive disease with synchronous DCIS (present in 83 of 158 patients). Molecular analyses is still ongoing. CONCLUSION. This is the first time that an unbiased comparison could be made between primary DCIS and its subsequent iIBC within such a large patient group, integrating clinical, histological and IHC data. Our results suggest that the majority of invasive breast cancers in our cohort reflect outgrowth of residual disease based on tumor location and histological grade. DCIS and iIBC are very similar when comparing histological grade, but frequently show differences on the IHC level. Remarkably, the dissimilarities in HER2 status and surrogate intrinsic subtype as seen in primary DCIS vs. iIBC are missing when comparing IBC with synchronous DCIS. As a next step, we will analyse the lesions on the molecular level, to verify these findings and to look for molecular characteristics of DCIS that could be associated with progression to invasive disease. Citation Format: Lindy L. Visser, Lotte L. Elshof, Koen van de Vijver, Emma J. Groen, Mathilde Almekinders, Marjanka K. Schmidt, Flora van Leeuwen, Emiel J. Rutgers, Michael Schaapveld, Esther H. Lips, Jelle Wesseling. Risk of ipsilateral invasive breast cancer after DCIS: a comparison of primary DCIS and subsequent invasive disease by morphological and immunohistochemical analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4738. doi:10.1158/1538-7445.AM2017-4738

Abstract CT137: Standard therapy versus active surveillance for low grade DCIS: the LORD trial

Abstract The introduction of population-based breast cancer screening and implementation of digital mammography have led to an increased incidence of ductal carcinoma in situ (DCIS) without a decrease in the incidence of advanced breast cancer. This suggests DCIS overdiagnosis exists. We hypothesize that asymptomatic, low-grade DCIS can safely be managed by active surveillance. If progression to invasive breast cancer would still occur, this will be low-grade and hormone receptor positive with excellent survival rates. Also, breast-conserving treatment will still be an option, if no prior radiotherapy has been applied. It also may save many low-grade DCIS patients from intensive treatment. We will compare active surveillance with conventional treatment, being either wide local excision (WLE) only, WLE plus radiotherapy or mastectomy, possibly followed by hormonal therapy for primary low-grade DCIS, detected by calcifications only, in a phase III, open-label, non-inferiority, multi-center, randomized clinical trial legally supported by the Breast Cancer Group of the European Organisation for the Research and Treatment of Cancer (EORTC-1401-BCG). The Dutch Centers are coordinated by the BOOG Study Center (BOOG 2014-04). Randomization will be 1:1 in to one of the following arms: active surveillance or standard treatment per local policy. In total, 1240 women (≥ 45 years) with asymptomatic, pure, low-grade DCIS, based on vacuum-assisted biopsies of calcifications as detected by population-based or opportunistic screening, without prior breast cancer, will be included. Assuming 25% of randomized women qualified to enroll in the study will drop out or will be excluded from per protocol population, at least 1,240 women need to be randomized to obtain the 930 patients required for the evaluation of the primary endpoint. The same follow-up scheme will be applied in both study arms, i.e. annual mammography for a period of 10 years. The primary end-point is ipsilateral invasive breast tumor-free rate at 10 years. Secondary end-points are among others: overall survival, breast cancer-specific survival, mastectomy rate and patient reported outcomes. Accrual has started in January 2017. Acknowledgements: This trial is funded by Pink Ribbon Netherlands, the Dutch Cancer Society and Dutch Cancer Society/Alpe d’HuZes. Citation Format: Jelle Wesseling, Frederieke van Duijnhoven, Konstantinos Tryfonidis, Aleksandra Peric, Elise van Leeuwen-Stok, Nina Bijker, Lotte Elshof, Emiel Rutgers. Standard therapy versus active surveillance for low grade DCIS: the LORD trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT137. doi:10.1158/1538-7445.AM2017-CT137

Cause-specific Mortality in a Population-based Cohort of 9799 Women Treated for Ductal Carcinoma In Situ.

To assess cause-specific mortality in women treated for ductal carcinoma in situ (DCIS). From screening and treatment perspective, it is relevant to weigh the low breast cancer mortality after DCIS against mortality from other causes and expected mortality in the general population. We conducted a population-based cohort study comprising 9799 Dutch women treated for primary DCIS between 1989 and 2004 and estimated standardized mortality ratios (SMRs). After a median follow up of 9.8 years, 1429 patients had died of whom 284 caused by breast cancer (2.9% of total cohort). DCIS patients <50 years experienced higher mortality compared with women in the general population (SMR 1.7; 95% confidence interval, CI: 1.4-2.0), whereas patients >50 had significantly lower mortality (SMR 0.9; 95% CI: 0.8-0.9). Overall, the risk of dying from general diseases and cancer other than breast cancer was lower than in the general population, whereas breast cancer mortality was increased. The SMR for breast cancer decreased from 7.5 (95% CI: 5.9-9.3) to 2.8 (95% CI: 2.4-3.2) for women aged <50 and >50 years, respectively. The cumulative breast cancer mortality 10 years after DCIS was 2.3% for women <50 years and 1.4% for women >50 years treated for DCIS between 1999 and 2004. DCIS patients >50 years had lower risk of dying from all causes combined compared with the general female population, which may reflect differences in health behavior. Women with DCIS had higher risk of dying from breast cancer than the general population, but absolute 10-year risks were low.

The method of detection of ductal carcinoma in situ has no therapeutic implications: results of a population-based cohort study

BackgroundPopulation screening with mammography has resulted in increased detection of ductal carcinoma in situ (DCIS). The aim of this population-based cohort study was to assess whether the method of detection should be considered when determining prognosis and treatment in women with DCIS.MethodsThis study includes 7042 women aged 49–75 years, who were surgically treated for primary DCIS between 1989 and 2004 in the Netherlands. We calculated cumulative incidences of ipsilateral and contralateral invasive breast cancer and all-cause mortality among women with screen-detected, interval, or non-screening-related DCIS, and assessed the association between method of detection and these outcomes, using multivariable Cox regression analyses.ResultsCompared with non-screening-related DCIS, women with screen-detected DCIS had a lower risk of developing ipsilateral invasive breast cancer (hazard ratio (HR) = 0.75, 95% CI = 0.59–0.96), but a similar risk of contralateral invasive breast cancer (HR = 0.86, 95% CI = 0.67–1.10). The absolute difference in risk of ipsilateral invasive breast cancer was 1% at 15 years. Screen detection was associated with lower all-cause mortality (HR = 0.85, 95% CI = 0.73–0.98); when we additionally accounted for the occurrence of invasive breast cancer the magnitude of this effect remained similar (HR = 0.86, 95% CI = 0.75–1.00).ConclusionsScreen detection was associated with lower risk of ipsilateral invasive breast cancer and all-cause mortality. However, the absolute difference in risk of ipsilateral invasive breast cancer was very low and the lower all-cause mortality associated with screen-detected and interval DCIS might be explained by a healthy-user effect. Therefore, our findings do not justify different treatment strategies for women with screen-detected, interval, or non-screening-related DCIS.

Abstract P3-17-03: DCIS and the risk of breast cancer death - A case control study

Abstract Introduction The risk of breast cancer death after a primary ductal carcinoma in situ (DCIS) is less than 2 % after 10 years. Whereas in situ recurrences do not influence survival, a 17-fold elevated risk of breast cancer specific mortality has been shown for invasive recurrences. Adjuvant radiotherapy (RT) effectively reduces recurrences after breast conserving surgery (BCS) for DCIS, but no studies have been able to demonstrate a survival benefit from adjuvant RT treatment or from choosing mastectomy instead of BCS. Here patient and tumour related risk factors for breast cancer death in women with a pure primary DCIS were studied. Patients and methods Women registered with a primary DCIS, between 1992-2012 in three of Sweden´s health care regions with a population of approximately 5.2 million, were enrolled in a nested case-control study. Out of 6,964 women with DCIS, 96 patients who later died from breast cancer were identified. Four controls per case (n=318) were randomly selected by incidence density sampling. We retrieved medical records and pathology reports and calculated OR with 95% CIs for various variables using conditional logistic regression. Results Of the 96 cases, 10 patients developed distant metastasis without a known local recurrence. In 56 patients death was preceded by an invasive ipsilateral recurrence and in 3 patients by a recurrent ipsilateral DCIS. Seven patients had invasive breast events in both the ipsilateral and the contralateral breast. Seventeen patients had contralateral invasive breast cancer and 3 patients contralateral DCIS. Multifocality and tumour size over 25mm (OR 2.6 (1.6 to 4.2)), positive or uncertain margin status (OR 2.8 (1.6 to 4.9)) and detection outside screening (OR 2.1 (1.2 to 3.9)) increased the risk of breast cancer death in univariate analysis, when adjusted for age and year of diagnosis. Suspicion of micro-invasion and nuclear grade 3 was associated with a nonsignificant increased risk, OR 1.8 (0.6 to 5.0) and 2.6 (0.9-6.5), respectively. The risk was not affected by age or treatment. Tumour size and margin status remained significant in the multivariable analysis, when adjusted for treatment and for contralateral breast cancer (OR 2.0 (1.2 to 3.7)). Conclusion In the present study, large tumours and positive or uncertain margin status were significant risk factors for later breast cancer death after a primary DCIS. More extensive treatment was not related to a lower risk. The significance of tumour biology and nuclear grade will be further examined and evaluated. Citation Format: Wadsten C, Garmo H, Fredriksson I, Sund M, Wärnberg F. DCIS and the risk of breast cancer death - A case control study [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 P3-17-03.

Abstract P3-02-04: Is breast magnetic resonance imaging (MRI) useful for diagnosis of additional sites of disease in patients recently diagnosed with ductal carcinoma in situ (DCIS)?

Abstract Purpose: To determine if breast MRI is useful for detecting additional sites of disease in patients initially diagnosed with pure DCIS. Materials and Methods: A retrospective review of women diagnosed with pure DCIS who underwent a breast MRI for evaluation of extent of disease was performed at a single institution from January 2013 to April 2015. Data analysis included imaging (mammography, ultrasound and MRI) and pathology characteristics (histology and biomarker status) of the primary DCIS as well as descriptors for the additional sites of disease incidentally found by breast MRI. Results: A total of 94 patients were diagnosed with pure DCIS during this time period, ages ranging from 38 to 79 years old (median, 58.5 years); sizes ranging from 0.6 to 16 cm (mean, 4.5 cm). A total of 28 patients (30%) had other MRI findings suspicious for additional sites of disease in either breast. From this group of patients, 23 (82%) patients underwent MRI-guided biopsy. The 5 patients who did not have the MRI guided-biopsy either underwent total mastectomies or declined biopsy. Five out of the twenty-three patients (22%) were diagnosed with an additional site of cancer. Three of these patients were Hispanic, one was Asian/Pacific and one was Caucasian. Of the five patients, five had contralateral disease (100%) and none had a second site of disease in the ipsilateral breast. The size of the additional sites of disease ranged from 0.4 to 7.2 cm (mean, 2.1 cm) and the size of the primary lesion in this selected group ranged from 0.4 to 9 cm (mean, 3.4 cm). Ages ranged from 47 to 63 years old (median, 55 years). Four out of five patients (80%) presented with the first site of disease as pure DCIS with estrogen (ER) and progesterone (PR) receptors positive and one case (20%) was pure DCIS ER/PR- negative. The second incidental lesion found on MRI demonstrated 3 cases of contralateral pure DCIS. From this group, all the biomarkers status for the first and second site were concordant. From the 5 cases of second disease, 2 (40%) presented with invasive component in the contralateral side of the initially biopsy-proven pure DCIS and, one of these cases had discordant biomarkers compared with the first site of disease, the first site of pure DCIS was ER/PR-negative and the second site of invasive ductal carcinoma (IDC) presented with ER/PR-positive status. Conclusion: From a total of 94 patients with recent diagnosis of pure DCIS who underwent breast MRI examination for diagnosis of additional sites of disease, approximately 5% were diagnosed with an additional site of cancer and 2% of the total cases had invasive disease in the additional sites with different biomarker status; changing their management and prognosis. Breast MRI plays a role in the setting of staging patients initially diagnosed with pure DCIS. Citation Format: Ortiz-Perez T, Benveniste AP, Ebuoma LO, Sepulveda KA, Severs FJ, Kapoor M, Sedgwick EL. Is breast magnetic resonance imaging (MRI) useful for diagnosis of additional sites of disease in patients recently diagnosed with ductal carcinoma in situ (DCIS)? [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 P3-02-04.

The Relationships between HER2 Overexpression and DCIS Characteristics.

The aim of this study was to demonstrate the correlation between human epidermal growth factor receptor 2 (HER2) overexpression and some poor prognosis factors in patients affected by ductal carcinoma in situ (DCIS). We evaluated 48 cases of DCIS, divided into two groups according to HER2 amplification status. Nuclear grade and "cancerization of lobules" were determined within primary DCIS and Ki67, estrogen receptor (ER), PR, and HER2 expression was established using immunohistochemistry. The histopathological variables in HER2-positive and in HER2-negative patients were compared to determine the recurrence risk. We also considered the median age at the time of surgery according to HER2 status. There were 11 recurrences (23%), 6 DCIS (55%), and 5 invasive cancer (45%). In an 8-year-long median follow-up, we hypothesized high risk of recurrence in HER2-positive DCIS. Patients with HER2-positive DCIS were younger than HER2-negative ones (p = 0.002). HER2-positive DCIS was also related to histopathological predictors of recurrence such as high nuclear grade (p < 0.001), high Ki67 expression (p = 0.003), low ER and PgR levels (p < 0.001), and the presence of "cancerization of lobules" (p < 0.049). Our trial suggests that HER2 amplification in primary DCIS is identified more frequently in younger patients and hypothesizes high risk of recurrence in HER2-positive DCIS related to histopathological predictors of overall relapse as high nuclear grade, high Ki67 expression, low ER and PgR levels, and the presence of "cancerization of lobules." In HER2-positive DCIS, other variables of recurrence risk are compared to HER2-negative lesions, without statistical significance. Our results show that HER2 testing might suggest clinicians the optimal treatment of patients with DCIS.

Large variation between hospitals in immediate breast reconstruction rates after mastectomy for breast cancer in the Netherlands

The present study aimed to describe the use of immediate breast reconstruction (IBR) after mastectomy for invasive breast cancer and ductal carcinoma in situ (DCIS) in hospitals in the Netherlands and determine whether patient and tumor factors account for the variation. Patients undergoing mastectomy for primary invasive breast cancer or DCIS diagnosed between January 1, 2011 and December 31, 2013 were selected from the NABON Breast Cancer Audit. All the 92 hospitals in the Netherlands were included. The use of IBR in all hospitals was compared using unadjusted and adjusted analyses. Patient and tumor factors were evaluated by univariate and multivariate analyses. In total, 16,953 patients underwent mastectomy: 15,072 for invasive breast cancer and 1881 for DCIS. Unadjusted analyses revealed considerable variation between hospitals in postmastectomy IBR rates for invasive breast cancer (mean 17%; range 0-64%) and DCIS (mean 42%; range 0-83%). For DCIS, younger age and multifocal disease were factors that significantly increased IBR rates. For patients diagnosed with invasive breast cancer, IBR was more often used in younger patients, multifocal tumors, smaller tumors, tumors with a lower grade, absence of lymph node involvement, ductal carcinomas, or hormone-receptor positive/HER2-positive tumors. After case-mix adjustments for these factors, the variation in the use of IBR between hospitals remained large (0-43% for invasive breast cancer and 0-74% for DCIS). A large variation between hospitals was found in postmastectomy IBR rates in the Netherlands for both invasive breast cancer and DCIS even after adjustment for patient and tumor factors.

Abstract 2576: Radiation therapy delay and risk of ipsilateral breast tumors in women with ductal carcinoma in situ

Abstract Objectives: To examine the relationship between radiation therapy delay and risk of subsequent breast events in the ipsilateral breast and to identify factors that are associated with delay in women with ductal carcinoma in situ (DCIS). Methods: From the Missouri Cancer Registry, we identified the women who were diagnosed with first primary DCIS between 1996 and 2011 and treated with breast conserving surgery (BCS). Radiation therapy delay was defined as the first radiation therapy that was delivered greater than eight weeks after BCS. Propensity scores were calculated for radiation therapy delay and no radiation therapy during the first course of treatment. A propensity score-adjusted Cox proportional hazards regression analysis was conducted to estimate the hazard ratio (HR) of ipsilateral breast tumors. Logistic regression analysis was conducted to identify factors associated with delay. Results: Among 5,916 patients, 1,053 (17.8%) received radiation therapy greater than eight weeks after BCS and 1,702 (28.8%) did not receive radiation therapy during the first course of treatment. During the 72- month follow-up, 182 (3.1%) developed ipsilateral breast tumors. After adjustment for propensity scores, the HR of ipsilateral breast tumors was 1.26 (95% CI, 1.00-1.59; p = 0.049) for radiation therapy delay and 1.35 (95% CI, 1.03-1.76; p = 0.03) for no radiation therapy compared with timely radiation therapy. Radiation therapy delay was associated with black race, being non-married and on Medicaid, later years of diagnosis, larger tumor size micropapillary architecture, and positive surgical margin. Conclusions: Receipt of radiation therapy greater than eight weeks after BCS was associated with a significantly increased risk of ipsilateral breast tumors in women with DCIS. Timeliness of radiation therapy should be improved, particularly for black and Medicaid patients. Citation Format: Ying Liu, Shumei Yun, Min Lian, Graham Colditz. Radiation therapy delay and risk of ipsilateral breast tumors in women with 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 2576.

Abstract P5-17-06: Prognostic value of method of detection in primary pure DCIS

Abstract Background Population-based mammographic screening programs have led to a substantial increase in incidence of ductal carcinoma in situ (DCIS). We assessed whether the method of detection provides prognostic information among women with DCIS detected through the Dutch screening program (screen-detected DCIS) and those with DCIS not detected within the national screening program (non-screen-detected DCIS). This could have impact on the treatment strategy of screen-detected DCIS as compared to symptomatic DCIS. Methods We studied a population-based retrospective cohort comprising 7,106 women aged 49-76 years with primary pure DCIS, who were treated by mastectomy or breast conserving surgery with or without radiotherapy between 1989 and 2004 in the Netherlands. Risk of subsequent ipsilateral and contralateral invasive breast cancer and overall survival among women with screen-detected (n=4,905) and non-screen-detected (n=2,201) DCIS were compared using Cox regression, adjusting for treatment (time-dependent), age (time-scale), diagnosis period and follow-up duration. Because of gradual implementation of the screening program in the Netherlands, we defined two periods based on year of DCIS diagnosis: 1989-1998 (gradual implementation of screening) and 1999-2004 (full coverage of screening). Results With a median follow-up of 10.5 years (interquartile range 7.7-14.0 years) 366 ipsilateral (screen-detected DCIS n=234, non-screen-detected DCIS n=132) and 380 contralateral (screen-detected DCIS n=245, non-screen-detected DCIS n=135) invasive breast cancers were diagnosed, and 1,088 of 7,106 women died (screen-detected DCIS n=603, non-screen-detected DCIS n=485). From 1989 to 2004 the number of non-screen-detected DCIS remained stable (mean 140, range 110-187 per year), whereas the number of screen-detected primary pure DCIS increased from 8 in 1989 to 596 in 2004. Ipsilateral invasive breast cancer risk was lower for screen-detected DCIS compared to DCIS not detected within the national screening program, irrespective of DCIS treatment, period of diagnosis, and follow-up duration (adjusted hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.59-0.92, p &amp;lt; 0.01). The prognostic value of method of detection was similar across categories of treatment, period of diagnosis, and follow-up duration. The risk of contralateral invasive breast cancer did not differ between screen-detected DCIS and non-screen-detected DCIS (adjusted HR 0.89, 95% CI 0.71-1.11, p = 0.3) and neither did all-cause mortality (adjusted HR 0.91, 95% CI 0.79-1.04, p = 0.2). Conclusion Women with primary pure DCIS detected through the Dutch screening program had lower risk of subsequent ipsilateral invasive breast cancer, irrespective of DCIS treatment, compared to women whose DCIS was not detected within the national screening program. However, the magnitude of this risk difference does not warrant a different treatment strategy of screen-detected DCIS as compared to non-screen-detected DCIS. Having a screen-detected DCIS was not associated with risk of subsequent contralateral invasive breast cancer and all-cause mortality. Citation Format: Elshof LE, Schaapveld M, Schmidt MK, van Leeuwen FE, Rutgers EJTh, Wesseling J. Prognostic value of method of detection in primary pure DCIS. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-17-06.

Abstract P5-17-09: Biomarkers to distinguish hazardous from harmless ductal carcinoma in situ (DCIS) of the breast

Abstract Background. The incidence of DCIS has increased since the introduction of population-based screening. This has not resulted in a decrease in invasive breast cancer incidence, implying overdiagnosis exists. All women with DCIS are still intensively treated, by surgery, radiotherapy, and/or hormonal treatment, although only a minority will develop a subsequent invasive breast cancer. As we cannot discriminate such hazardous from harmless DCIS lesions, accurate prognostic biomarkers are urgently needed. In the current study we aim to identify molecular markers for DCIS aggressiveness, using a large population-based cohort. Patients and methods. We used a population-based, nation-wide cohort consisting of 10,090 women treated for primary DCIS between 1989 and 2004 with a median follow-up time of 10.7 years. Within this cohort, a case-control study was set up to analyse which markers are associated with progression to invasive breast cancer. Formalin-fixed paraffin embedded (FFPE) tissue blocks were retrieved from 1580 DCIS patients who were treated by breast conserving surgery without radiotherapy (316 DCIS patients with a subsequent ipsilateral invasive breast cancer (iiBC): i.e. the "cases"; and 1264 DCIS patients without subsequent invasive breast cancer: i.e. the "controls"). A first study using this population-based cohort will involve immunohistochemistry (IHC) on 200 "cases" and 500 "controls" for an 8-marker IHC panel (ER, PR, HER2, Ki67, p16, p53, COX-2, and Annexin A1). Molecular subtypes of the DCIS and invasive breast cancer lesions will be determined and intra-individual heterogeneity will be assessed. IHC marker expression will be both compared between "cases" and " controls" as well as between DCIS lesions and its subsequent invasive breast cancer. In a second study, DNA and RNA will be isolated from these specimens, using laser microdissection, and extensive molecular profiling will be performed. Results. We have collected FFPE tissue blocks of 287 "cases" and 1149 "controls" (86% of requested material) from 56 participating hospitals. At present, the specimens of 223 "cases" (matched DCIS and iiBC specimen) and 103 "controls" have been centrally revised for extensive morphological characteristics. Only a small part (14%) of the specimens had to be excluded from the study population. IHC staining of the tissue specimens, using the 8-marker IHC panel is ongoing. Conclusion. Within a nation-wide cohort of 10,090 patients diagnosed with primary DCIS, we were able to collect tissue material of a representative case-control series of 200 "cases" with subsequent invasive breast cancer and 500 invasive breast cancer-free "controls". This is the first time such a large unique, unbiased DCIS series, with long-term follow-up is analysed integrating clinical, histological, and immunohistochemical data. The results will be presented at SABCS 2015. Citation Format: Visser L, Elshof L, Groen E, van de Vijver K, Lips E, de Maaker M, Nieboer F, Schaapveld M, Rutgers E, Wesseling J. Biomarkers to distinguish hazardous from harmless ductal carcinoma in situ (DCIS) of the breast. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-17-09.

Abstract P6-08-02: Developing in vitro models of ductal carcinoma in situ from primary tissue

Abstract BACKGROUND: Because there are currently no reliable predictors for progression of ductal carcinoma in situ (DCIS) to invasive disease, nearly all patients receive aggressive therapy, leading to over-treatment in many cases. Few in vitro models for studying DCIS progression have been developed. We report here the successful culture and expansion of primary DCIS from surgical specimens using a conditional reprogramming protocol. MATERIALS AND METHODS: From 2/2014 to 4/2015, patients with percutaneous core needle biopsy demonstrating DCIS were enrolled in a tissue banking protocol after informed consent was received. Under supervision of the surgical pathologist, fresh tissue measuring between 5-15 mm in length was taken from lumpectomy or mastectomy specimens. Tissue was divided such that half was mechanically and enzymatically dissociated and then cultured in medium conditioned by irradiated mouse fibroblasts and supplemented with rho-associated protein kinase (ROCK) inhibitor, and the second half, known as the "mirror image" remained as part of the clinical specimen. RESULTS: Of 49 consented patients, mean age was 59 ± 10 years. 7 were excluded due to final pathology not consistent with DCIS: 4 upstaged to invasive ductal cancer, 2 had microinvasion and 1 showed pleomorphic lobular carcinoma in situ. Of the remaining 42, 9 were failures: 5 tissues were not received in lab and 4 cases were received, but no cells grew in culture. Of the remaining 33 cases of DCIS, 70% (n=23) and 27% (n=9) were nuclear grade 2 and 3 respectively. 91% (n=30) were ER-positive, with H-score ranging between 4 and 300. 19 (58%) were expanded in cell culture for up to two months in culture, and 14 were frozen immediately after mechanical dissociation for future growth. The 19 cell cultures could be cryopreserved and expanded. The cultures are almost exclusively composed of cytokeratin 8- and EpCAM-positive luminal cells and cytokeratin 14-, cytokeratin 5-, and p63-positive basal mammary epithelial cells, suggesting maintenance of heterogeneity in vitro. Furthermore, as assessed by luminal and basal marker expression, these cells retain their cellular identities both in the "conditionally reprogrammed" proliferative state and when conditioned media and ROCK inhibitor were withdrawn. When grown to 100% confluency, the cultures appear to organize into luminal and basal layers as well as luminal compartments surrounded by basal cells. CONCLUSION: Primary cultures of DCIS derived directly from patient tissues may serve as in vitro models for the study of DCIS. Citation Format: McAuliffe PF, Brown DD, Oesterreich S, Lee AV, Johnson RR, McGuire KP, Davidson NE, Brufsky AM, Dabbs DJ. Developing in vitro models of ductal carcinoma in situ from primary tissue. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-08-02.

Abstract P1-05-01: The epithelial to mesenchymal transition: Identifying a signature of recurrence in ductal carcinoma in situ

Abstract Background: The epithelial to mesenchymal transition (EMT) plays a critical role in the progression from non-invasive to invasive breast carcinomas (IBC). It is characterized by alterations in gene expression, changes in cellular polarity, the disruption of tight junctions; production of metalloproteinases, transforming growth factor-β (TGFβ) induction, expression of cancer stem cell markers, hypoxia, decrease in e-cadherin expression, along with other molecular biological events. Several transcription factors including ZEB1/2, TWIST1, SNAIL1/2, FOX family, GATA4/6 are involved in the process. There is a need to identify the molecular events driving the progression of ductal carcinoma in situ (DCIS); and to derive a signature that differentiates DCIS lesions that have the potential to recur as a subsequent DCIS, an IBC, or to not recur. To catalog the changes associated with EMT that may reveal a clinically relevant signature of progression from DCIS to DCIS or IBC recurrences using a panel of 200 genes related to EMT. Methodology: RNA was extracted from formalin-fixed paraffin embedded (FFPE) sections of pure primary DCIS lesions representing three categories of outcome: those that did not recur; those that recurred with a subsequent DCIS; and those that recurred with invasive cancer. RNA abundance profiling was performed using Nanostring platform and data processing using an R statistical environment. Levels of mRNA abundance were modelled as a function of recurrence status. Coefficients were fit to terms representing the effect and the standard errors of the coefficient were adjusted with an empirical Bayes moderation. Model-based t-tests were then used to test if the coefficients were significantly different from zero. Results: Using a technical control sample, pairwise comparisons across three replicates showed high correlation (ρ=0.99, Pρ&amp;lt;2.2x10-16 for all 3 comparisons), suggesting the robustness of the assay. In our preliminary survey of 45 patients across the three groups, we have identified a number of genes that showed differential mRNA abundance levels between patients who recurred (either DCIS or invasive recurrence) vs. those who did not recur. Using Random Forest analysis in a leave-one-out cross-validation approach, we were able to obtain a classifier with a sensitivity of 82% and specificity of 58%. Based on these initial findings, an additional 200 samples have been processed to support these initial findings. Conclusion: The current literature provided increasing evidence that transcriptomic patterns reflecting the EMT may reveal novel biomarkers and elucidate molecular mechanisms leading to improved prognosis. Among breast carcinomas, differential expression of the EMT genes has been associated with a worse outcome, among estrogen receptor-negative and basal-like carcinomas. However, the understanding of the role of EMT genes in DCIS is limited; therefore, to elucidate whether the EMT plays a role in the progression of DCIS, we have designed an EMT gene panel that also includes genes that are significant prognosticators for IBC, including ER, PgR, Ki67 and HER2. In an exploratory analysis of cases trained based on clinical outcome, the sensitivity for predicting recurrence (whether DCIS or invasive) was 82%. Citation Format: Felipe Lima J, Yao CQ, Yan F, Dion D, Quintayo MA, Lungu I, Nofech-Mozes S, Pruneri G, Viale G, Boutros PC, Bartlett JMS, Bayani J. The epithelial to mesenchymal transition: Identifying a signature of recurrence in ductal carcinoma in situ. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-05-01.

Abstract P5-17-02: Treatment and prognosis of DCIS during twenty years. A population-based register study from a Swedish cohort

Abstract The increasing incidence of ductal carcinoma in situ (DCIS) of the breast has been attributed to the wide adoption of mammography screening programmes. The aim of the present study was to analyse trends in incidence, treatment and outcome of DCIS over a 20-year time period in a Swedish health care region, with a source population of two million, based on systemically collected data in a regional Breast Cancer Quality Registry started in 1992. All patients registered with a diagnosis of primary DCIS in the Breast Cancer Quality Registry in the Uppsala-Örebro healthcare region between 1992 and 2012 were included. The study period was divided into four time periods. The registry contains information on tumour characteristics, treatment and follow-up data and is linked to the Swedish cancer registry, to which reporting of all newly diagnosed malignant tumours in Sweden is mandated. To verify the validity of the Breast Cancer Quality Registry, 300 women recorded with a diagnosis of DCIS were randomly selected and their medical records were collected to compare clinical data, treatment data and subsequent breast cancer events compared to registry data. The completeness and reliability of the registration of most key variables were overall good, 91-99%. A total of 2,952 patients with DCIS were registered, of which eight were men. The proportion of DCIS to all diagnosed breast cancers was 9.5%, with no clear increase over time. The majority of the DCIS cases were detected by screening (68%). Tumour size increased over time; in 1992-1997 36.4% were larger than 15mm compared to 64.8% in 2008-2012. The frequency of mastectomy increased from 23.0% to 39.0% and the proportion of patients receiving adjuvant radiotherapy after breast-conserving surgery increased from 30.1% to 67.6%. Axillary lymph node clearance declined over time while the proportion of patients who underwent sentinel node biopsy increased from 1.4% in 1998-2002 to 33.9% in 2003-2007 and 54.9% in 2008-2012. 1992-19971998-20022003-20072008-2012P valueCases693628835796 DCIS size &amp;gt; 15mm252(36.4%)257(40.9%)339(53.8%)511(64.2%)&amp;lt;0.0001Mastectomy161(23.2%)150(23.9%)323(38.7%)313(39.3%)&amp;lt;0.0001BCS519(74.9%)468(74.5%)506(60.6%)476(59.8%)&amp;lt;0.0001BCS+RT156/519(30.0%)178/468(38.0%)347/506(68.6%)322/476(67.6%)&amp;lt;0.0001BCS= Breast conserving surgery, RT= radiotherapy There was no statistical difference in the cumulative incidence of recurrent breast events over time or between different treatment modalities. The relative 5- and 10- year survival rates were 99.0% and 97.0% respectively with no clear trend over time. In conclusion, while the proportion of DCIS did not increase over time between 1992 and 2012, there was a trend towards more intensified management to achieve local control. The increased tumor size over time could be secondary to a higher diagnostic activity, which clearly is manifested by the increased use of sentinel node biopsy. Citation Format: Wadsten C, Heyman H, Holmqvist M, Ahlgren J, Lambe M, Sund M, Wärnberg F. Treatment and prognosis of DCIS during twenty years. A population-based register study from a Swedish cohort. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-17-02.

Abstract B01: B cell lymphoma 9 mediates a cross talk between the canonical Wnt and EGFR signaling in breast cancer

Abstract Human ductal carcinoma in situ (DCIS) are the most common type of non-invasive breast cancers. The five-year survival rate for women diagnosed with non-invasive DCIS is 98% while the five-year survival plummets to 83-27% for breast cancers that have become invasive and have spread to distant sites [also referred to as invasive ductal carcinoma (IDC)]. To study DCIS pathobiology and factors that promote their transition to IDC, we have developed a novel in vivo DCIS model, MIND (mouse-intraductal), that involves intraductal injection of epithelial cells derived from primary human DCIS biopsy and surgical samples thus mimicking the entire process of DCIS to IDC transition. As a complementary approach, we have utilized human DCIS/IDC tandem lesions, which are patient DCIS that show a transition to IDC within the same breast. Analysis of RNA and protein at distinct stages of in situ to IDC using both models showed B cell lymphoma-9 (BCL9) up-regulation to be associated with DCIS transition to IDC. BCL9 is a recently identified co-activator of Wnt-stimulated beta-catenin-mediated transcription. Our studies showed that in vivo silencing of BCL9 led to inhibition of DCIS invasion and reversal of EMT. We have also demonstrated a direct binding interaction between BCL9 and beta-catenin and showed suppression of beta-catenin-mediated transcription by BCL9 knockdown. Analysis of patient DCIS samples revealed a significant correlation between high nuclear BCL9 expression and pathologic characteristics associated with DCIS recurrence: Estrogen receptor (ER) negative and Ki67. Furthermore, analysis of the TCGA data showed BCL9 gene to be upregulated in 26% of breast cancers. This is a significant gene alteration when compared to HER2 (ERBB2) gene (19%) and estrogen receptor (ESR1) gene (8%) alterations in breast cancers. Interestingly, a significantly higher proportion of basal like invasive breast cancers compared to luminal breast cancers showed BCL9 amplification suggesting that BCL9 may predispose to the development of basal breast cancers. We have performed an RPPA analysis on our DCIS cell lines KD BCL9 vs. control. This analysis indicated that BCL9 KD showed down-regulation in a number of genes in the EGFR signaling pathway including p-EGFR, p-HER2, p-STAT3, and p-Src. Conclusion: BCL9 is a molecular driver of DCIS invasive progression. The molecular mechanism for BCL9's role in breast cancer progression is through the enhancement in the canonical Wnt and EGFR signaling. Citation Format: Hanan Elsarraj, Hong Yan, Jennifer Knapp, Anna Tsimelzon, Shixia Huang, Andrew Godwin, Sue Hilsenbeck, Dean Edwards, Fariba Behbod. B cell lymphoma 9 mediates a cross talk between the canonical Wnt and EGFR signaling in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr B01.

The correlation between PLC-β2 and miR-146a in breast ductal carcinoma in situ (DCIS) defines its malignant potential

Ductal carcinoma in situ (DCIS), which represents the most frequently diagnosed tumor in women in industrialized countries, may be a crucial step in the progression of breast lesions to invasive ductal carcinoma (IDC) (1). Among the signaling molecules deregulated in breast tumors, the beta2 isoform of the phosphoinositide-dependent phospholipase C (PLC-b2) strongly correlates with malignancy of invasive tumors and breast tumor-derived cells (2, 3). In breast tumor-derived cell lines cultured under hypoxia, PLC-b2 regulates the levels of cancer stem cell and epithelial-to-mesenchymal transition (EMT) markers (4), suggesting its involvement in breast cancer progression. By using archival FFPE breast tumor samples, we demonstrated that PLC-β2 is up-regulated in DCIS, in which it inversely correlates to the levels of miR-146a, known to act as a tumor suppressor in breast cancer (5). By using the MCF10DCIS cell line, a well-established model of DCIS-derived cells, we demonstrated that the de-regulation of miR-146a is sufficient to modulate the expression of PLC-β2, in turn able to affect the epithelial-to-mesenchymal shift as well as the number of cells expressing CD133. These data indicate that miR-146a and PLC-β2 are members of an intracellular network able to ensure the maintenance of the non-invasive phenotype of DCIS and suggest that alterations in their levels can determine the appearance of an invasive phenotype. The potential prognostic relevance of PLC-β2/miR-146a relationship was investigated in primary DCIS from patients who developed an invasive ductal carcinoma in the contralateral breast. The PLC-β2/miR-146a correlation was found negative in primary DCIS from patients who did not recur and strongly positive in DCIS from patients who developed a contralateral IDC. We propose that the assessment of the correlation between the levels of PLC-β2 and miR-146a in primary DCIS at diagnosis could be beneficial to identify patients with either low or high propensity to develop invasive recurrence. Since a major problem in the management of patients with DCIS is the lack of reliable prognostic markers, our results might be of value in selecting the most appropriate therapies for individual women with non-invasive breast neoplasia.

Informed shared decision-making supported by decision coaches for women with ductal carcinoma in situ: study protocol for a cluster randomized controlled trial.

BackgroundWomen with breast cancer want to participate in treatment decision-making. Guidelines have confirmed the right of informed shared decision-making. However, previous research has shown that the implementation of informed shared decision-making is suboptimal for reasons of limited resources of physicians, power imbalances between patients and physicians and missing evidence-based patient information. We developed an informed shared decision-making program for women with primary ductal carcinoma in situ (DCIS). The program provides decision coaching for women by specialized nurses and aims at supporting involvement in decision-making and informed choices.In this trial, the informed shared decision-making program will be evaluated in breast care centers.Methods/DesignA cluster randomized controlled trial will be conducted to compare the informed shared decision-making program with standard care. The program comprises an evidence-based patient decision aid and training of physicians (2 hours) and specialized breast care and oncology nurses (4 days) in informed shared decision-making. Sixteen certified breast care centers will be included, with 192 women with primary DCIS being recruited.Primary outcome is the extent of patients’ involvement in shared decision-making as assessed by the MAPPIN-Odyad (Multifocal approach to the ‘sharing’ in shared decision-making: observer instrument dyad). Secondary endpoints include the sub-measures of the MAPPIN-inventory (MAPPIN-Onurse, MAPPIN-Ophysician, MAPPIN-Opatient, MAPPIN-Qnurse, MAPPIN-Qpatient and MAPPIN-Qphysician), informed choice, decisional conflict and the duration of encounters.It is expected that decision coaching and the provision of evidence-based patient decision aids will increase patients’ involvement in decision-making with informed choices and reduce decisional conflicts and duration of physician encounters. Furthermore, an accompanying process evaluation will be conducted.DiscussionTo our knowledge, this is the first study investigating the implementation of decision coaches in German breast care centers.Trial registrationCurrent Controlled Trials ISRCTN46305518, date of registration: 5 June 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0991-8) contains supplementary material, which is available to authorized users.

Developing in vitro models of human ductal carcinoma in situ from primary tissue explants.

Because there are currently no reliable predictors for progression of ductal carcinoma in situ (DCIS) to invasive disease, nearly all patients receive comprehensive therapy, leading to over-treatment in many cases. Few in vitro models for studying DCIS progression have been developed. We report here the successful culture and expansion of primary DCIS from surgical specimens using a conditional reprogramming protocol. Patients with percutaneous core-needle biopsy demonstrating DCIS were enrolled in a tissue banking protocol after informed consent was received. Fresh tissue was taken from lumpectomy or mastectomy specimens, mechanically and enzymatically dissociated, cultured in medium conditioned by irradiated mouse fibroblasts and supplemented with rho-associated protein kinase (ROCK) inhibitor, and characterized by immunocytochemistry. Out of 33 DCIS cases, 58% (19) were expanded for up to 2 months in culture, and 42% (14) were frozen immediately after mechanical dissociation for future growth. The cultures are almost exclusively composed of cytokeratin 8- and EpCAM-positive luminal and cytokeratin 14-, cytokeratin 5-, and p63-positive basal mammary epithelial cells, suggesting maintenance of heterogeneity in vitro. Furthermore, as assessed by luminal and basal marker expression, these cells retain their cellular identities both in the "conditionally reprogrammed" proliferative state and after conditioned media and ROCK inhibitor withdrawal. When grown to 100 % confluency, the cultures organize into luminal and basal layers as well as luminal compartments surrounded by basal cells. Primary cultures of DCIS derived directly from patient tissues can be generated and may serve as in vitro models for the study of DCIS.

Molecular phenotypes of DCIS predict overall and invasive recurrence

Molecular phenotypes of invasive breast cancer predict early recurrence. Ductal carcinoma in situ (DCIS) exhibits similar phenotypes, but their frequency and significance remain unclear. To determine whether DCIS molecular phenotypes predict recurrence, 314 women (median age 57.7 years) with primary DCIS who were screened or entered DCIS trials in a specialist breast unit from 1990 to 2010 were studied. Expression of Ki67, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) within primary DCIS was established using immunohistochemistry (IHC). Patients were subdivided into molecular phenotypes using IHC surrogates [Luminal A (ER/PR+HER2-), Luminal B (ER/PR+/HER2+), HER2 type (ER and PR-/HER2+) or triple negative (ER/PR/HER2)] and recurrence rates compared. Overall, there were 57 (18.2%) recurrences, 35 (11.2%) DCIS and 22 (7%) invasive cancer. A low rate of recurrence at 5 years was seen in Luminal A DCIS (7.6%), compared with 15.8%-36.1% in other phenotypes. Independent predictors of overall recurrence on multivariate analysis were involved (<1 mm) surgical margins (HR 4.31, P < 0.001), high-grade lesions (HR 2.28, P < 0.024) and molecular phenotype (HR 5.14, P = 0.001 for Luminal B; HR 6.46, P < 0.001 for HER2 type and HR 3.27, P = 0.028 for triple-negative disease compared with Luminal A DCIS). Independent predictors for invasive recurrence were high Ki67 expression (HR 1.04, P = 0.021) and molecular phenotype (HR 13.4, P = 0.014 for Luminal B; HR 11.4, P = 0.027 for HER2 type and HR 10.3, P = 0.031 for triple negative compared with Luminal A DCIS). DCIS molecular phenotype predicts for both overall and invasive recurrence. HER2 testing of DCIS could help clinicians individualise the treatment of patients with DCIS.