Treatment Of Ductal Carcinoma In Situ Research Articles

Invasive recurrence after breast conserving treatment of ductal carcinoma in situ of the breast in the Netherlands: time trends and the association with tumour grade.

The first aim of this study was to examine trends in the risk of ipsilateral invasive breast cancer (iIBC) after breast-conserving surgery (BCS) of ductal carcinoma in situ (DCIS). A second aim was to analyse the association between DCIS grade and the risk of iIBC following BCS. In this population-based, retrospective cohort study, the Netherlands Cancer Registry collected information on 25,719 women with DCIS diagnosed in the period 1989-2021 who underwent BCS. Of these 19,034 received adjuvant radiotherapy (RT). Kaplan-Meier analyses and Cox regression models were used. A total of 1135 patients experienced iIBC. Ten-year cumulative incidence rates of iIBC for patients diagnosed in the periods 1989-1998, 1999-2008 and 2009-2021 undergoing BCS without RT, were 12.6%, 9.0% and 5.0% (P < 0.001), respectively. For those undergoing BCS with RT these figures were 5.7%, 3.7% and 2.2%, respectively (P < 0.001). In the multivariable analyses, DCIS grade was not associated with the risk of iIBC. Since 1989 the risk of iIBC has decreased substantially and has become even lower than the risk of invasive contralateral breast cancer. No significant association of DCIS grade with iIBC was found, stressing the need for more powerful prognostic factors to guide the treatment of DCIS.

Abstract PO5-03-02: Ductal carcinoma in situ: An excess regard of the axilla?

Abstract Abstract: Ductal Carcinoma in Situ (DCIS) is a malignant proliferation of the epithelial inside the breast duct, which does not invade the myoepithelial layer and, therefore, does not have the capacity to generate metastases. [1]. However, an upstaging after surgery is possible, since there may be a concomitant invasive lesion that was not diagnosed in the pathological examination from biopsy, being discovered only after the surgical procedure [1]. In the pre-screening mammography era, DCIS was diagnosed. more commonly in symptomatic women presenting with a palpable nodule, papillary flow, or through an incidental finding on a breast biopsy [2], accounting for 1-2% of cancer cases. [3]. After the advent of mammographic screening, the incidence has considerably increased among asymptomatic women with mammographic changes such as calcifications. [4]. Nowadays the diagnosis of DCIS corresponds to 20-25% of biopsies secondary to screening mammographic changes. [1]. As we do know that the chance of axillary metastasis is potentially null, old series where axillary dissection (AD) was performed ipsilareral to the index tumor, axillary involvement was observed in less than 1% of cases [9]. Objectives: Our objective in this study was to describe in a single breast cancer reference center the surgical treatment of patients diagnosed with DCIS (mastectomy or breast conservative surgery – BCS). Methods: A retrospective analysis was made using the Pérola Byington Hospital’s database, from January 2011 to December 2019. During this period, 11,373 cases of breast cancer were treated int the institution and 812 (7.4%) were DCIS. Data was available and we could analyze 494 patients who underwent vacuum-guided biopsy guided by mammography or ultrasound and were diagnosed with DCIS and underwent surgical treatment at the Hospital. We grouped the patients into 3 age groups: under 40, 40-49, and 50 and over. In all groups, we had patients who underwent SNB using the patent blue technique or AD and were evaluated using the H&amp;E method. It is not part of the Institutional protocol to perform IHC in axillary lymph nodes. We had also evaluated the type of surgery (BCS or mastectomy) in each age group. Results: DCIS was diagnosed through mammographic alterations in 62% of all cases and nuclear grade 2 was the most common, with 47%, followed by grade 3 and 1, 46% and 4%, respectively. In 2% of cases the data was missing. Comedoconecrosis was present in 78% of our specimens. BCS was the most frequently surgery performed (73% of cases), with the axillary approach being performed in 35% of these patients (32% for SNB and 3% for AD). While 27% of patients underwent radical surgery and in this group 92% were submitted to axillary approach (70% SNB and 22% AD). In the group of patients younger than 40 years, 74% of patients (17 out of 23 in total) underwent an axillary approach regardless of the type of surgery. When evaluating the predetermined age groups, we saw that most of our patients were 50 years or more (69%), followed by patients between 40-49 years (26%) and 5% in patients under 40 years. In 3% of cases (16 in 494) we reclassified the lesion as invasive carcinoma. None of them had a lymph node involved by malignant cells after surgery and that’s include the cases reclassified as invasive carcinoma. Conclusion: The results obtained in this analysis showing no axillary involvement will make us rethink the indications for the concomitant surgical approach of the breast and the axilla in cases with a diagnosis of DCIS as a way to reduce the axillary surgical overtreatment. It was not our goal to compare the costs and complications of each method of diagnosis and the prognostic factors after the treatment of DCIS. Citation Format: Andressa Amorim, Andre Mattar, Marcellus Ramos, Reginaldo Coelho Lopes, Luciana Damous, Luiz Henrique Gebrim. Ductal carcinoma in situ: An excess regard of the axilla? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-03-02.

Abstract PS01-10: Surgical margins in breast conserving surgery (BCS) for ductal carcinoma in-situ (DCIS) and clinical outcomes: significant associations with increased recurrence and overall survival

Abstract Background: Optimal surgical margin in breast conserving surgery (BCS) for DCIS are not established, largely due to an absence of accurate margin data. A margin width of 2mm was adopted by the American College of Surgeons (ACS). The UK Association of Breast Surgery (ABS) recommended a 1mm margin. Conducting a randomized controlled trial to answer this question is unfeasible; therefore we used retrospective histological margin data from available datasets to assess whether there is an association between margin width and time to recurrence (TTR). Methods: Patients were included if aged &amp;gt;18 years with a new diagnosis of DCIS alone, between 2003-2014, within UK NHS Breast Screening Programme (BSP). Primary treatment included BCS and a minimum histological excision margin width recorded. Exclusion criteria included: i) prior history of DCIS; ii) prior history of invasive cancer or its diagnosis within 3 months of initial surgical treatment for DCIS. Data was extracted from English Cancer Registries (CR), ABS and Sloane audits. TTR was defined as time from diagnosis to local or distant recurrence. Cox regression was used to compare TTR by surgical margin width utilising a range of thresholds, with focus on &amp;lt; 1mm vs ≥1mm; &amp;lt; 2mm vs ≥2mm and ≥1- &amp;lt; 2mm vs ≥2mm. Patients with 0mm margin or where categorized as “clear/not stated” were excluded from these analyses. Models were adjusted for age group, DCIS grade and size, ER status, number of BCSs, radiotherapy (RT) received, diagnosis year and CR centre. Overall survival (OS) was a secondary endpoint. Results: 17,260 patients diagnosed with DCIS having BCS as definitive surgery were identified between 2003-2014; 679 (5%), 2105 (15%), 1339 (10%) and 9744 (70%) with recorded margins of &amp;gt;0- &amp;lt; 1mm, ≥1- &amp;lt; 2mm, ≥2- &amp;lt; 3mm and ≥3mm, respectively. 10,253 (59%) patients received RT and in 7,007 (41%) RT receipt was unknown. Overall, 14,004 (81%), 3,052 (18%) and 201 (1%) patients had one, two and ≥3 BCSs respectively; there was no significant change in these percentages over time (p=0.2 Cuzick test). Median follow-up time for the cohort was 8.2 years (IQR: 6.1-11.2). 2221 (13%) patients had a subsequent event: 1741/2221 (78%) invasive recurrence and 480/2221 (22%) DCIS alone. The annual event rate over 15 years of follow-up was relatively consistent at 1.2% per annum (pa) for margins ≥2mm versus 1.8% pa for margins &amp;lt; 2mm. A shorter TTR was observed for patients with surgical margins &amp;lt; 1mm vs ≥1mm (adjusted HR=1.30; 95%CI: 1.05-1.62; p=0.02); &amp;lt; 2mm vs ≥2mm (adjusted HR=1.20; 95%CI: 1.06-1.36; p=0.004) and ≥1- &amp;lt; 2mm vs ≥2mm (adjusted HR=1.20; 95%CI: 1.04-1.40; p=0.02). Margins &amp;gt;2mm did not appear to significantly improve TTR (adjusted HR=0.96; 95%CI: 0.85-1.08; p=0.50 for ≥5mm vs ≥2- &amp;lt; 5mm). Models also showed that risk of recurrence increased as the number of BCSs increased (adjusted HR=1.25; 95%CI: 1.10-1.43: p&amp;lt; 0.001 for 2 vs 1 and adjusted HR=2.03; 95%CI: 1.36-3.03: p&amp;lt; 0.001 for 3+ vs 1). In total, 1552 (9%) patients had died. OS appeared reduced for patients with surgical margins &amp;lt; 2mm vs ≥2mm (adjusted HR=1.25 (1.07-1.45); p=0.005) and for ≥1- &amp;lt; 2mm vs ≥2mm (adjusted HR=1.28 (1.07-1.54); p=0.008). Margins &amp;lt;2mm did not appear to significantly improve OS further (adjusted HR=1.06; 95%CI: 0.92-1.21; p=0.43 for ≥5mm vs ≥2- &amp;lt; 5mm). Conclusion: Patients with DCIS with histological margins of &amp;lt; 2mm, adjusted for other clinical factors, have significantly worse TTR and OS rates compared to margins ≥2mm; the increased annual event rate is consistent out to 15 years. More than 1 BCS is also associated with an increased risk of recurrence. These findings are important for the treatment of patients with DCIS. Citation Format: John Robertson, D Mark Sibbering, Sikhuphukile Ndebele-Mahati, Olive Kearins, Sarah Pinder, Ashu Gandhi, Judith Bliss, Lucy Kilburn. Surgical margins in breast conserving surgery (BCS) for ductal carcinoma in-situ (DCIS) and clinical outcomes: significant associations with increased recurrence and overall survival [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS01-10.

Abstract PO4-22-05: Changes in Treatment Recommendation for Patients with Ductal Carcinoma In Situ Using a 7-Gene Predictive Biosignature: Analysis of the PREDICT Australia Study

Abstract Background: The role of adjuvant radiotherapy (RT) following breast-conserving surgery (BCS) for women with ductal carcinoma in situ (DCIS) remains controversial. Although there is Level 1 evidence supporting the use of RT to reduce the risk of local recurrence, prognostic and predictive tools are needed to better stratify the individual risks and benefits of RT. The 7-gene predictive DCIS biosignature provides a validated score (DS) for women receiving BCS that assesses 10-year risk of DCIS recurrence and development of invasive breast cancer with and without adjuvant RT. We established a registry to evaluate the decision impact of the 7-gene predictive biosignature on DCIS treatment recommendations in an Australian setting. Methods: The PREDICT study is a prospective, multi-institutional registry for patients who received DCISionRT testing as part of their routine care. The registry includes females 26 and older who are diagnosed with DCIS and are candidates for BCS and eligible for RT. Treating physicians completed treatment recommendation forms before and after receiving test reports to capture surgical, radiation and hormonal treatment (HT) recommendations and patient preferences. Results: This planned interim analysis was performed in 483 patients with complete data treated at 43 clinical sites in Australia. The median age of patients was 61 years, 19% were 50 or younger, nuclear grade was high in 51%, and tumor size was 2.5 cm or greater in 15%. Overall, RT recommendation (yes/no) was changed for 41% of women and HT recommendation was changed for 9% after testing with a net reduction in recommended RT of 14% (66% pre-assay to 52% post-assay p&amp;lt; 0.001). Of patients recommended to receive RT pre-test, 42% were recommended to not receive RT post-test and of the patients recommended to not receive RT pre-test, 40% were recommended to receive RT post-test. The post-test RT recommendation rate increased with increasing DS score (&amp;lt; 2, 2-4, &amp;gt;4), with 9% of patients recommended RT for DS&amp;lt; 2, 62% for DS 2-4, and 100% for DS 4-10. The use of the test resulted in different RT recommendations than with clinicopathology alone, where RT recommendations were changed for 49%, 37%, and 34% for women of age&amp;lt; 50 yrs, with Grade 3 DCIS, or with DCIS &amp;gt; 2.5 cm, respectively. Collectively, this suggests that physicians had a high confidence in the test results when making their final treatment recommendations with the test results. Conclusions: This analysis demonstrates that the use of the 7-gene predictive biosignature resulted in significant changes in recommendations to add or omit RT in this study of 483 women. The integration of DCISionRT into the clinical decision-making processes has a substantial impact on recommendations to personalize care and prevent over- or under-treatment. Table 1: Impact of DCISionRT on Adjuvant Radiation Recommendations by Clinicopathologic Features Citation Format: Yvonne Zissiadis, Bruce Mann, David Speakman, Christobel Saunders, Marcus Dreosti, Christopher Pyke, Daniel De Viana, Melissa Bochner, James French, Sally Baron-Hay, Karuna Mittal, Steven Shivers, Troy Bremer. Changes in Treatment Recommendation for Patients with Ductal Carcinoma In Situ Using a 7-Gene Predictive Biosignature: Analysis of the PREDICT Australia Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-22-05.

Age and race/ethnicity differences in decisional conflict in women diagnosed with ductal carcinoma in situ

PurposeWomen diagnosed with ductal carcinoma in situ (DCIS) face confusion and uncertainty about treatment options. The objective of this study was to determine whether there are differences in decisional conflict about treatment by age and race/ethnicity.MethodsA cross-sectional survey was conducted of women (age ≥ 18) diagnosed with DCIS enrolled at Kaiser Permanente of Southern California. The Decisional Conflict Scale (DCS) measured personal perceptions of decision uncertainty, values clarity, and effective decision-making. We used a multivariable regression to study whether age, race, and ethnicity were associated with patient-reported DCS.Results45% (N = 1395) of women who received the online survey, participated. The mean age was 56 (± 9.6) years, the majority were white. Compared to women younger than 50, women aged 60–69 reported lower overall DCS scores (-5.4; 95% CI -1.5 to -9.3). Women > 70 had lower values clarity scores (-9.0; 95% CI -2.8 to -15.2) about their treatment compared to women aged 50–59 and 60–69 (-7.1; 95% CI -2.9 to -11.3 and − 7.2; 95% CI -2.9 to -11.5) and likewise, lower effective decision-making scores (-5.4; 95% CI -1.7 to -9.2 and − 5.2; 95% CI -1.4 to -9.0) compared to women < 50. Compared to whites, blacks reported lower decision conflict (-4.4; 95% CI 0.04 to -8.8) and lower informed decision (-5.2; 95% CI -0.18 to -10.3) about DCIS treatment.ConclusionYounger women reported higher decisional conflict about DCIS treatment, compared to older women (> 70). Age based tailored discussions about treatment options, health education, and supportive decision-making interventions/tools may reduce decision conflict in future DCIS patients.Trade registrationThe IRB number is 10678.

Mode of Detection of Second Breast Cancers in Patients Undergoing Surveillance After Treatment of Ductal Carcinoma in Situ.

For patients undergoing posttreatment surveillance after ductal carcinoma in situ (DCIS), the NCCN Guidelines for Breast Cancer recommend annual breast imaging and physical examination every 6 to 12 months for 5 years, and then annually. The aim of our study was to evaluate the modes of detection (imaging, patient reported, or physical examination) of second cancers in a cohort of patients undergoing surveillance after primary DCIS treatment to better inform surveillance recommendations. We performed a retrospective cohort study of patients with DCIS treated between January 1, 2008, and December 31, 2011, within a large integrated health care system. Information on patient demographics, index DCIS treatment, tumor characteristics, and mode of detection of second breast cancer was obtained from the electronic health record or chart review. Our study cohort consisted of 1,550 women, with a median age of 59 years at diagnosis. Surgical treatment of DCIS included lumpectomy (75.0%; n=1,162), unilateral mastectomy (21.1%; n=327), or bilateral mastectomy (3.9%; n=61), with or without sentinel lymph node biopsy. Additionally, 44.4% (n=688) and 28.3% (n=438) received radiation and endocrine therapies, respectively. Median follow-up was 10 years, during which 179 (11.5%) women were diagnosed with a second breast cancer. Of the second cancers, 43.0% (n=77) were ipsilateral and 54.8% (n=98) contralateral, and 2.2% (n=4) presented with distant metastases; 61.5% (n=110) were invasive, 36.3% (n=65) were DCIS, and 2.2% (n=4) were Paget's disease. Second breast cancers were imaging-detected in 74.3% (n=133) of cases, patient-detected in 20.1% (n=36), physician-detected in 2.2% (n=4), and detected incidentally on imaging or pathology from procedures unrelated to oncologic care in 3.4% (n=6). In our cohort of patients undergoing surveillance following diagnosis and treatment of DCIS, 2% of second breast cancers were detected by a clinical breast examination. This suggests that survivorship care should prioritize mammography and patient education regarding breast self-examination and symptoms that warrant evaluation to detect second breast cancers.

The effects of contemporary treatment of DCIS on the risk of developing an ipsilateral invasive Breast cancer (iIBC) in the Dutch population

PurposeTo assess the effects of contemporary treatment of ductal carcinoma in situ (DCIS) on the risk of developing an ipsilateral invasive breast cancer (iIBC) in the Dutch female population.MethodsClinical data was obtained from the Netherlands Cancer Registry (NCR), a nationwide registry of all primary malignancies in the Netherlands integrated with the data from PALGA, the Dutch nationwide network and registry of histo- and cytopathology in the Netherlands, on all women in the Netherlands treated for primary DCIS from 2005 to 2015, resulting in a population-based cohort of 14.419 women. Cumulative iIBC incidence was assessed and associations of DCIS treatment type with subsequent iIBC risk were evaluated by multivariable Cox regression analyses.ResultsTen years after DCIS diagnosis, the cumulative incidence of iIBC was 3.1% (95% CI: 2.6–3.5%) in patients treated by breast conserving surgery (BCS) plus radiotherapy (RT), 7.1% (95% CI: 5.5–9.1) in patients treated by BCS alone, and 1.6% (95% CI: 1.3–2.1) in patients treated by mastectomy. BCS was associated with a significantly higher risk for iIBC compared to BCS + RT during the first 5 years after treatment (HR 2.80, 95% CI: 1.91–4.10%). After 5 years of follow-up, the iIBC risk declined in the BCS alone group but remained higher than the iIBC risk in the BCS + RT group (HR 1.73, 95% CI: 1.15–2.61).ConclusionsAlthough absolute risks of iIBC were low in patients treated for DCIS with either BCS or BCS + RT, risks remained higher in the BCS alone group compared to patients treated with BCS + RT for at least 10 years after DCIS diagnosis.

Treatments and Prognosis of the Breast Ductal Carcinoma In Situ

IntroductionWith progress in treatments, breast ductal carcinoma in situ (DCIS) outcomes have substantially improved. However, as various treatment methods are used in different countries and institutions, consensus on the optimal treatment method is lacking. This study aimed to analyze the prognostic factors and provide a reference for optimizing the clinical treatment of DCIS. Patients and MethodsThis retrospective clinical study collected data from DCIS patients at the Sun Yat-sen University Cancer Center from 2010 to 2017. The Kaplan–Meier method and Cox regression model were used to assess disease-free survival (DFS), overall survival (OS), and local control (LC) rates. ResultsAmong the 483 included patients, 83.6% (404) underwent mastectomies. The median follow-up time was 101 months. The number of patients undergoing breast-conserving surgery (BCS) with radiotherapy has gradually increased. Axillary lymph node dissection was the main surgery performed from 2010 to 2015, and the proportion of sentinel lymph node biopsies (SLNBs) has increased. LC and DFS rates with BCS without radiotherapy were significantly lower than those with mastectomy (P = .002; P < .001). Additionally, the patients who did not undergo axillary surgery had worse LC and OS rates than those who underwent SLNB (P = .028 and P = .038). Endocrine therapy (ET) or its duration had no significant effect on prognosis. ConclusionIn conclusion, BCS without radiotherapy and lack of axillary surgery were independent prognostic factors. We recommend performing BCS with radiotherapy and SLNB more in clinical practice, as well as shortening the ET duration.

Role of contrast-enhanced mammography in the preoperative detection of ductal carcinoma in situ of the breasts: a comparison with low-energy image and magnetic resonance imaging.

To compare contrast-enhanced mammography (CEM) with low-energy image (LEI) alone and with magnetic resonance imaging (MRI) in the preoperative diagnosis of ductal carcinoma in situ (DCIS). In this single-center retrospective study, we reviewed 98 pure DCIS lesions in 96 patients who underwent CEM and MRI within 2weeks preoperatively. The diagnostic performances of each imaging modality, lesion morphology, and extent were evaluated. The sensitivity of CEM to DCIS was similar to that of MRI (92.9% vs. 93.9%, p = 0.77) and was significantly higher than that of LEI alone (76.5%, p = 0.002). The sensitivity of CEM to calcified DCIS (92.4%) was not significantly different from LEI alone (92.4%) and from MRI (93.9%, p = 1.00). However, CEM contributed to the simultaneous comparison of calcifications with enhancements. CEM had considerably higher sensitivity compared with LEI alone (93.8% vs. 43.8%, p < 0.001) and performed similarly to MRI (93.8%, p = 1.00) for noncalcified DCIS. All DCIS lesions were enhanced in MRI, whereas 94.9% (93/98) were enhanced in CEM. Non-mass enhancement was the most common presentation (CEM 63.4% and MRI 66.3%). The difference between the lesion size on each imaging modality and the histopathological size was smallest in MRI, followed by CEM, and largest in LEI. CEM was more sensitive than LEI alone and comparable to MRI in DCIS diagnosis. The enhanced morphology of DCIS in CEM was consistent with that in MRI. CEM was superior to LEI alone in size measurement of DCIS. This study investigated the value of CEM in the diagnosis and evaluation of DCIS, aiming to offer a reference for the selection of examination methods for DCIS and contribute to the early diagnosis and precise treatment of DCIS. • DCIS is an important indication for breast surgery. Early and accurate diagnosis is crucial for DCIS treatment and prognosis. • CEM overcomes the deficiency of mammography in noncalcified DCIS diagnosis, exhibiting similar sensitivity to MRI; and CEM contributes to the comparison of calcification and enhancement of calcified DCIS, thereby outperforming MRI. • CEM is superior to LEI alone and slightly inferior to MRI in the size evaluation of DCIS.

Prediction of coexisting invasive carcinoma on ductal carcinoma in situ (DCIS) lesions by mass spectrometry imaging.

Due to limited biopsy samples, ~20% of DCIS lesions confirmed by biopsy are upgraded to invasive ductal carcinoma (IDC) upon surgical resection. Avoiding underestimation of IDC when diagnosing DCIS has become an urgent challenge in an era discouraging overtreatment of DCIS. In this study, the metabolic profiles of 284 fresh frozen breast samples, including tumor tissues and adjacent benign tissues (ABTs) and distant surrounding tissues (DSTs), were analyzed using desorption electrospray ionization-mass spectrometry (DESI-MS) imaging. Metabolomics analysis using DESI-MS data revealed significant differences in metabolite levels, including small-molecule antioxidants, long-chain polyunsaturated fatty acids (PUFAs) and phospholipids between pure DCIS and IDC. However, the metabolic profile in DCIS with invasive carcinoma components clearly shifts to be closer to adjacent IDC components. For instance, DCIS with invasive carcinoma components showed lower levels of antioxidants and higher levels of free fatty acids compared to pure DCIS. Furthermore, the accumulation of long-chain PUFAs and the phosphatidylinositols (PIs) containing PUFA residues may also be associated with the progression of DCIS. These distinctive metabolic characteristics may offer valuable indications for investigating the malignant potential of DCIS. By combining DESI-MS data with machine learning (ML) methods, various breast lesions were discriminated. Importantly, the pure DCIS components were successfully distinguished from the DCIS components in samples with invasion in postoperative specimens by a Lasso prediction model, achieving an AUC value of 0.851. In addition, pixel-level prediction based on DESI-MS data enabled automatic visualization of tissue properties across whole tissue sections. Summarily, DESI-MS imaging on histopathological sections can provide abundant metabolic information about breast lesions. By analyzing the spatial metabolic characteristics in tissue sections, this technology has the potential to facilitate accurate diagnosis and individualized treatment of DCIS by inferring the presence of IDC components surrounding DCIS lesions. © 2023 The Pathological Society of Great Britain and Ireland.

Association of quantitative MRI features of DCIS with surgical upstaging and recurrence after treatment.

e12540 Background: Ductal carcinoma in situ (DCIS) is a common preinvasive breast cancer typically identified on screening mammography. Pure DCIS is nonlethal, but 20-25% of DCIS cases identified on core biopsy upstage to invasive cancer at surgery and about half progress to invasive disease if not treated. As a result, most DCIS patients undergo excision and radiation therapy. DCIS score is a multigene assay that can aid in radiation treatment decision-making and serve as a surrogate marker of ipsilateral breast recurrence (IBR) risk. Breast MRI can accurately depict DCIS span and has potential to assess biology and IBR risk. We sought to assess the associations of advanced quantitative MRI features with upstaging and DCIS score. Methods: In this IRB-approved single institution prospective clinical trial, patients recommended for biopsy of calcifications or those who had residual calcifications after a biopsy yielding pure DCIS consented to receive a multiparametric breast MRI (dynamic contrast-enhanced and diffusion-weighted) prior to surgery. The following quantitative MRI features were obtained: functional tumor volume (FTV), volume transfer constant (Ktrans), extracellular extravascular volume fraction (ve), background parenchymal enhancement (BPE), and apparent diffusion coefficient (ADC). Patients with biopsy-proven DCIS were followed through completion of surgery to determine upstaging. DCIS score was performed in those with sufficient excision-proven pure DCIS. Associations of MRI features with invasive upstaging and DCIS score and were evaluated by Spearman’s correlation and the Wilcoxon rank-sum test. Results: Of the 120 patients enrolled in the study, 57 (48%) were diagnosed with pure DCIS on core biopsy. Fifty-five patients underwent surgery, 13 of whom (24%) upstaged to invasive disease. Thirty-eight pure DCIS lesions had sufficient tissue to generate a DCIS Score. Several MRI features were associated with upstaging and DCIS Score: Ktrans (p &lt; 0.01) was significantly higher in lesions that upstaged to invasive disease. Higher DCIS scores were associated with lower Ktrans (p = 0.04) and ve (p = 0.05) values. No statistically significant associations were observed between FTV, BPE, or ADC and invasive upstaging or DCIS Score. Conclusions: This trial suggests advanced quantitative MRI features may help identify DCIS lesions at risk for upstaging to invasive disease and IBR. Specifically, an imaging feature of vascular permeability (Ktrans) showed an expected positive association with upstaging. Imaging features of vascular permeability (Ktrans and ve) showed counterintuitive inverse associations with DCIS Scores. Future research in larger cohorts is needed to validate these findings, better determine the biological reasons for these associations, and determine whether MRI features can be used clinically to optimize DCIS treatment. Clinical trial information: NCT03495011 .

Abstract 5561: Molecular imaging of calcification and soft tissue defines prognosis of DCIS to invasive breast cancer

Abstract Introduction: Ductal carcinoma in situ (DCIS) is a non-obligatory precursor to invasive breast cancer (IBC). Currently there are no reliable markers to indicate if DCIS will progress IBC after an initial treatment, or if it will remain as DCIS. Because of this uncertainty, standard treatment for DCIS includes surgery with or without radiotherapy. Breast microcalcifications are a common feature in the mammographic detection of DCIS and occur in around 80% of DCIS and 50% of IBC. Despite this, their potential role in the development of DCIS and with progression to IBC remains largely unexplored. The main aim of the study is to identify novel biomarkers for DCIS prognosis, based on chemical and molecular compositional changes of calcifications and their surrounding soft tissue in DCIS. Methods: Consecutive tissue section from 422 patients were analyzed using mid-infrared and Raman hyperspectral imaging and X-ray diffraction (XRD) and included (i) ‘DCIS controls’ (DCIS without recurrence) (n=193), (ii) ‘DCIS cases’ (DCIS which subsequently recurred as an invasive disease) (n=123), (iii) ‘synchronous DCIS with invasive cancer’ (n=44) and ‘benign’ (n=62) groups. Both parametrized and data mining approaches including cluster analysis, unsupervised and supervised multivariate statistical analysis and biomodelling based on leave-one-sample-out cross-validation were used to classify the data and develop DCIS prediction models. Results: Prediction modelling of 314 calcification and soft tissue spectral images from 170 patients (‘DCIS controls’=118 versus ‘DCIS cases’=52) showed an AUROC mean value of 0.85 in distinguishing DCIS that did not recur from DCIS that recurred as IBC. Prediction modelling of XRD data from 124 patients (‘DCIS controls’=67 versus ‘DCIS cases’=57) showed an AUROC mean value of 0.80. The calcification spectral features showed pathology specific changes in phosphate to carbonate ratio as well as changes in magnesium whitlockite content. The epithelial features showed changes in protein secondary structure and content indicating structural remodeling between the two groups. XRD parametrized data analysis corroborated these observations in terms of difference in whitlockite, as well as crystallinity/unit axis of the measured calcifications. The prediction models are currently being tested independently on the remaining sample data. Conclusion: Complementary chemical and molecular analysis of breast calcifications and soft tissue using spectroscopy and XRD imaging predicts the likely progression of DCIS to IBC. Subject to the ongoing validation of biomarkers, these approaches appear as promising DCIS risk assessment tools that can inform diagnosis, prognosis and treatment options. Citation Format: Jayakrupakar Nallala, Doriana Calabrese, Sarah Gosling, Esther Lips, Rachel Factor, Allison Hall, Sarah Pinder, Ihssane Bouybayoune, Elinor Sawyer, Lorraine King, Jeffrey Marks, Thomas Lynch, Donna Pinto, Jelle Wesseling, Shelley Hwang, Keith Rogers, Nick Stone, Grand Challenge PRECISION consortium. Molecular imaging of calcification and soft tissue defines prognosis of DCIS to invasive breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5561.

Abstract P4-02-22: Breast microcalcification chemistry predicts DCIS prognosis

Abstract Introduction: Microcalcifications are a common feature in mammographic detection of ductal carcinoma in situ (DCIS), and occur in &amp;gt;80% of cases. Known to be present as type I (calcium oxalate-CaO) and type II (carbonated calcium hydroxyapatite-CHAP) microcalcifications, their association with DCIS and their role in the progression of DCIS to invasive breast cancer (IBC) remains unexplored. In an effort to understand the factors involved in DCIS prognosis, it is hypothesized that changes in the chemical composition of calcifications, in tandem with molecular changes in the surrounding soft tissue, will define patients with DCIS who will progress to develop IBC from those who remain with a stable DCIS phenotype. To this end, a novel label-free approach of hyperspectral imaging using mid-infrared (mid-IR) and Raman spectroscopy was used to probe calcification chemistry and molecular composition of the surrounding ductal and stromal soft tissue. The main aim of the work is to identify biomarkers for DCIS prognosis, based on chemical and molecular compositional changes of calcifications and the surrounding soft tissue. It is anticipated that the spectral biomarkers will provide patients and clinicians an informed risk assessment whether to undertake treatment for DCIS or to be placed under active surveillance. Methods: Tissue samples from 422 patient have been obtained and include (i) ‘pure DCIS’ (DCIS without recurrence) (n=193), (ii) ‘DCIS with invasive recurrence’ (DCIS from patients who subsequently were known to develop invasive disease) (n=123), (iii) ‘DCIS plus contemporaneous invasive cancer’ (n=44) and ‘benign’ (n=62) samples. Serial tissue sections were measured using mid-IR and Raman hyperspectral imaging approaches targeting the same calcification and soft tissue regions from specific DCIS ducts. Hyperspectral imaging data was initially pre-processed to digitally remove paraffin and unintended spectral interferences. The pre-processed data was subjected to cluster analysis followed by unsupervised and supervised machine learning classification models to identify spectral features associated with DCIS and its progression to IBC. Results: Cluster analysis based segmentation of hyperspectral images revealed histopathological features including calcifications, epithelium, necrotic areas, connective tissue and stroma. Spectra were extracted from each of the histopathological features using image coordinates, and biomodelling analysis was performed. Initial analysis of 314 calcification images from 170 patients with (i) ‘pure DCIS’ (n=118) and (ii) ‘DCIS with invasive recurrence’ (n=52) showed an area under the receiver operating characteristic (AUROC) mean value of 85% in distinguishing pure DCIS from DCIS that later recurred as IBC. The calcification features appeared to indicate pathology specific changes in phosphate and carbonate content as well as changes in magnesium whitlockite content. Similar analysis of the surrounding soft tissue spectral features showed an AUROC mean value of 85% (necrotic regions surrounding calcifications) and 76% (epithelium) respectively. The epithelial features showed changes in protein secondary structure and content, which together with the calcification changes indicate structural remodelling in DCIS that progresses to IBC, from those that do not. Perspectives: In the ongoing analyses of imaging data from 422 patients, it is anticipated that molecular/structural features from calcification and soft tissue imaging data will provide important cues in understanding DCIS prognosis and could be a promising way forward in determining management of DCIS risk and treatment underpinned by the identification of specific discriminatory spectral markers. Acknowledgments: This work was supported by Cancer Research UK and by KWF Kankerbestrijding (ref. C38317/A24043). Citation Format: Jayakrupakar Nallala, Doriana Calabrese, Sarah Gosling, Esther Lips, Rachel Factor, Allison Hall, Sarah E. Pinder, Ihssane Bouybayoune, Lorraine King, Jeffrey Marks, Thomas Lynch, Donna Pinto, Jelle Wesseling, E Shelley Hwang, Keith Rogers, Nick Stone. Breast microcalcification chemistry predicts DCIS prognosis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-22.

Abstract P6-05-11: Active surveillance versus conventional treatment in low-risk DCIS; women’s preferences in the LORD trial

Abstract Background: Ductal carcinoma in situ (DCIS) is a potential precursor to breast cancer. Its incidence has increased multifold with the introduction of breast cancer screening and makes for 20% of all malignant breast lesions in women. DCIS has the potential to progress into invasive breast cancer. However, the majority of DCIS lesions are indolent and will never progress during the patient’s lifetime. Consequently, there is a growing concern of overdiagnosis and overtreatment for women with DCIS. The LORD trial is a non-randomized, patient preference trial comparing active surveillance to conventional treatment (i.e., breast conserving surgery with or without radiotherapy or mastectomy). The primary outcome of this trial is the percentage of women without an occurrence of ipsilateral invasive breast cancer after 10 years of follow up. Within the patient preference design, women are free to opt for either treatment arm. In addition to active surveillance of the DCIS, quality of life (QOL) of women included in the LORD trial is also actively monitored. The aims of this study were to: a) describe the distribution of participants within the treatment arms, b) identify women’s motives to opt for their preferred treatment arm, and c) assess factors associated with a preference for either treatment arm. Methods: Data from the baseline patient QOL questionnaire was collected. This questionnaire was completed after the women’s diagnosis and first consultation with their physician. Descriptive statistics were used to assess the distribution in both treatment arms. Thematic analyses were used to describe self-reported reasons for treatment selection derived from the open-ended question about treatment preference. Multivariable logistic regression analyses were used to assess associations between the patient characteristics and their preferred treatment arm. Results: In total 384 women completed the baseline questionnaire, of which 376 entered their final treatment decision. Of these women, 287 (76%) opted for active surveillance and 89 (24%) for conventional treatment. Most frequently cited reason for opting for active surveillance was that treatment was not yet necessary (55%). Also, patients’ reasons for preferring active surveillance alluded to a high level of trust in the active surveillance plan (24%) and that disease progression could be picked up and treated in a timely manner (14%). Furthermore, 11% of patients cited the advice of their healthcare professional as a reason for opting for active surveillance and 8% cited reasons relating to altruism. Most reported reasons for opting for the conventional treatment arm were avoiding unnecessary risks (26%), avoiding cancer worry (18%), the notion that what doesn’t belong, should be removed from the body (18%) and a need for closure (13%). In multivariable logistic regression analyses, high level of education (OR 2.17; 95%CI 1.09-4.38) and higher knowledge score (OR 1.8; 95%CI 1.07-3.02) were associated with a preference for conventional treatment. Furthermore, women opting for active surveillance more often reported the decision to be a shared decision between them and their healthcare professional (OR 2.30; 95%CI 1.18-4.47) compared to women who chose conventional treatment, who more often reported decision-making to be patient-driven. Age and tolerance of uncertainty were not significantly associated with treatment preference. Conclusion: The LORD trial is the first to actively offer women with low-risk DCIS a choice between conventional treatment and active surveillance. Within this trial, most women opt for active surveillance, even though clinical guidelines still recommend treatment for all women with DCIS. Women with low-risk DCIS report high levels of trust in their physicians and the safety of active surveillance. Their preferences also highlight the necessity to proof that de-escalating treatment of low-risk DCIS is safe. Citation Format: Renée S. Schmitz, Ellen G. Engelhardt, Miranda A. Gerritsma, Carine M. Sondermeijer, Sena Alaeikhanehshir, Ellen Verschuur, Marja van Oirsouw, Julia Houtzager, Rosalie Griffioen, Nina Bijker, Ritse M. Mann, Frederieke van Duijnhoven, Jelle Wesseling, Eveline Bleiker. Active surveillance versus conventional treatment in low-risk DCIS; women’s preferences in the LORD trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-11.

Abstract P4-02-02: Changes in treatment recommendation for patients with Ductal Carcinoma In Situ using a 7-gene predictive biosignature: Analysis of the PREDICT Study

Abstract Background: The role of adjuvant radiotherapy (RT) following breast conserving surgery (BCS) for women with ductal carcinoma in situ (DCIS) remains controversial. Although there is Level 1 evidence supporting the use of RT in reducing the risk of local recurrence, prognostic and predictive tools are needed to better stratify individual risks and benefits of RT. The DCISionRT® Test (PreludeDx, Laguna Hills, CA) is a 7-gene predictive biosignature that uses tumor biology in conjunction with clinicopathologic factors. The test provides a validated score (DS) for women receiving BCS that assesses 10-year risk of DCIS recurrence and development of invasive breast cancer with and without adjuvant RT. We established a registry to evaluate the decision impact of the 7-gene predictive biosignature on DCIS treatment recommendations. Methods: The PREDICT study is a prospective, multi-institutional registry for patients who received DCISionRT testing as part of their routine care. The registry includes females 26 and older who are diagnosed with DCIS and are candidates for BCS and eligible for RT or systemic therapy. Treating physicians completed treatment recommendation forms before and after receiving test reports to capture surgical, radiation and hormonal treatment (HT) recommendations and patient preferences. The primary endpoint is to identify the proportion of patients where testing led to a change in RT recommendation. Additional analyses include changes in recommendations in patient subgroups based on clinicopathologic factors or clinician specialty. Results: Analysis was performed in 2,308 patients treated at 63 clinical sites. The median age of patients was 62 years, 18% were 50 or younger, nuclear grade was high in 33%, and tumor size was 2.5 cm or greater in 11%. Test results were DS Low Risk (DS ≤ 3) for 63% of women and 37% were DS Elevated Risk (DS &amp;gt; 3). Overall, RT recommendation (yes/no) was changed for 38% of women after the 7-gene biosignature testing and HT recommendation was changed for 11%. There was a net decrease in RT recommendation from 71% pre-assay to 53% post-assay (p&amp;lt; 0.001), where RT recommendations decreased 53% in DS Low Risk patients but increased 25% in DS Elevated Risk patients. Surgeons were more likely to change their RT recommendation (47%) than radiation oncologists (35%). When test results indicated DS Elevated Risk, both surgeons (79%) and radiation oncologists (88%) were likely to recommended RT, but when the results were DS Low risk, surgeons were more likely than radiation oncologists to recommend omitting RT (82% vs. 60%, respectively). Compared to traditional clinicopathologic features, the factor most strongly associated with RT recommendation was the biosignature result with other factors of importance being patient preference, tumor size and grade. Conclusions: This analysis demonstrates significant changes in recommendations to add or omit RT based on the 7-gene predictive biosignature in 2,308 patients. The integration of DCISionRT into clinical decision processes has substantial impact on recommendations aimed at optimal management to prevent over- or under-treatment. Table 1. Impact of the 7-gene predictive biosignature on adjuvant radiation recommended by clinicopathologic features. Citation Format: Pat Whitworth, Steven C. Shivers, Chirag Shah, Rakesh Patel, Karuna Mittal, Troy Bremer, Charles Cox. Changes in treatment recommendation for patients with Ductal Carcinoma In Situ using a 7-gene predictive biosignature: Analysis of the PREDICT Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-02.

Clinical Outcomes of Conservative Treatment for Low-Risk Ductal Carcinoma in Situ: A Systematic Review and Pooled Analysis

AimsThe current gold standard of treatment for ductal carcinoma in situ (DCIS) is surgical resection with or without adjuvant radiotherapy. However, the increased detection and radical treatment of DCIS did not result in a declined incidence of invasive breast cancers, leading to the debate if DCIS has been overtreated. While ongoing randomised controlled trials on active surveillance of DCIS are still in progress, this systematic review aims to evaluate the best evidence on conservative treatment for DCIS from the literature. Materials and methodsThis systematic review was conducted in line with the PRISMA statement. We included all relevant studies published up to June 2022 for analysis. The primary outcomes were overall survival and breast cancer-specific survival (BCSS) of conservative treatment for DCIS. ResultsThree studies, with a total of 34 007 women with low-risk DCIS, were included in the analysis. Active and conservative treatments both resulted in excellent 10-year BCSS, with no statistically insignificant difference (98.6% versus 96.0%, 31 478 women). One study comparing 5-year BCSS of active and conservative treatments only in subjects aged over 80 years also reported [AQ1]an insignificant difference (98.2% versus 96.0%, 2529 women). One study measuring 5- and 10-year overall survival between the treatment groups also reported [AQ1]an insignificant difference (5-year: 96.2% versus 92.4%; 10-year: 85.6% versus 86.7%, 31 106 women). ConclusionBCSS between active and conservative treatment for women with low-risk DCIS is both excellent and comparable, suggesting that conservative treatment is a possible alternative without compromising survival.

Surveillance Imaging after Primary Diagnosis of Ductal Carcinoma in Situ.

Background Guidelines recommend annual surveillance imaging after diagnosis of ductal carcinoma in situ (DCIS). Guideline adherence has not been characterized in a contemporary cohort. Purpose To identify uptake and determinants of surveillance imaging in women who underwent treatment for DCIS. Materials and Methods A stratified random sample of women who underwent breast-conserving surgery for primary DCIS between 2008 and 2014 was retrospectively selected from 1330 facilities in the United States. Imaging examinations were recorded from date of diagnosis until first distant recurrence, death, loss to follow-up, or end of study (November 2018). Imaging after treatment was categorized into 10 12-month periods starting 6 months after diagnosis. Primary outcome was per-period receipt of asymptomatic surveillance imaging (mammography, MRI, or US). Secondary outcome was diagnosis of ipsilateral invasive breast cancer. Multivariable logistic regression with repeated measures and generalized estimating equations was used to model receipt of imaging. Rates of diagnosis with ipsilateral invasive breast cancer were compared between women who did and those who did not undergo imaging in the 6-18-month period after diagnosis using inverse probability-weighted Kaplan-Meier estimators. Results A total of 12 559 women (median age, 60 years; IQR, 52-69 years) were evaluated. Uptake of surveillance imaging was 75% in the first period and decreased over time (P < .001). Across the first 5 years after treatment, 52% of women participated in consistent annual surveillance. Surveillance was lower in Black (adjusted odds ratio [OR], 0.80; 95% CI: 0.74, 0.88; P < .001) and Hispanic (OR, 0.82; 95% CI: 0.72, 0.94; P = .004) women than in White women. Women who underwent surveillance in the first period had a higher 6-year rate of diagnosis of invasive cancer (1.6%; 95% CI: 1.3, 1.9) than those who did not (1.1%; 95% CI: 0.7, 1.4; difference: 0.5%; 95% CI: 0.1, 1.0; P = .03). Conclusion Half of women did not consistently adhere to imaging surveillance guidelines across the first 5 years after treatment, with racial disparities in adherence rates. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rahbar and Dontchos in this issue.

Changing trends in the management of ductal carcinoma in situ in Republic of Korea: a comprehensive analysis using Health Insurance Review and Assessment data [2009-2020

Increasing rates of diagnosis of ductal carcinoma in situ (DCIS), given the widespread use of mammography, is a global trend. Various attempts have been made in the selection of surgical methods and application of radiation therapy (RT), and the prevalence of infectious diseases has also affected these attempts. This study aimed to investigate evolving treatment patterns and trends in the management of DCIS in South Korea. We conducted a comprehensive search of the Korean Health Insurance Review and Assessment Service-National Patient Sample (HIRA-NPS) database and selected patients who underwent breast surgery following a DCIS diagnosis between 2009 and 2020. Based on this sample, the analyses were weighted according to the Korean population. We examined annual variations in mastectomy types, reconstructive procedures, and RT utilization from a multidisciplinary perspective. In our weighted sample, 43,780 patients with DCIS underwent surgery, with a consistent annual increase of 10%. The proportion of lumpectomy procedures increased from 56.7% to 65.4%, showing a greater growth rate than that of total mastectomies (TMs). Following the availability of reconstruction data in 2015, shifts have emerged toward a preference for implant-based autologous tissue reconstruction. As we transitioned to the latter part of our study, the trend was marked by the increasing adoption of hypofractionated RT and omission of RT. Of the patients who underwent lumpectomy in 2020, 25.6% adopted hypofractionated RT and 53.8% omitted RT. This transformation was particularly evident among older patients, individuals treated in metropolitan areas, and those treated in small-sized healthcare facilities. Our study sheds light on the changing landscape of DCIS treatment in South Korea incorporating perspectives from surgeons, plastic surgeons, and radiation oncologists. We observed an increase in the rates of lumpectomy and implant-based reconstruction. Adoption of hypofractionated RT and omission of RT showed increasing trends.

Abstract PR006: A living biobank of patient-derived ductal carcinoma in situ (DCIS) Mouse-INtraDuctal (MIND) xenografts identifies multiple risk factors of invasive progression

Abstract Ductal Carcinoma in Situ (DCIS) is a non-invasive non-obligate precursor of invasive breast cancer (IBC). DCIS is usually treated by surgery combined with radiotherapy, which can have a large impact on the life of patients. However, many of these DCIS lesions would never progress into IBC. To reduce the overtreatment of DCIS, but assure proper treatment for high risk DCIS, it is crucial to understand the biology underlying DCIS. To study the biology of DCIS we established Mouse INtraDuctal (MIND) patient-derived xenograft (PDX) models by intraductally injecting patient DCIS material into the mammary ducts of female immunocompromised mice. We engrafted 130 samples, which have been incubated in vivo for a period of 12 months. We obtain a take rate of 88% with 46% of our models showing invasive progression. Histology and molecular subtyping by PAM50 classification are well preserved in the MIND models compared to the primary counterpart, ensuring that our MIND models represent the patient disease well. For 102 primary samples we obtained RNAseq profiles as well as for 64 matched MIND-PDX models. In addition whole exome-/panel sequencing data is generated from the same primary DCIS samples together with 12 matched MIND-PDX WES profiles as well as 60 matched Copy Number Variation (CNV) MIND-PDX profiles. Together these data revealed multiple biomarkers related to invasive progression, including factors such as high grade, solid growth, a high copy number aberrations burden, HER2, PTK6 &amp; MYC amplifications and a high Ki67. On top of this we used whole mount imaging of the injected mammary glands extracted from our MIND-PDX models, showing two distinct growth patterns correlated with invasion. And as this is all done in the context of the PRECISION consortium this allows us to confirm and validate our findings in larger sequencing and imaging efforts of human samples. We have also successfully passaged 42 MIND-PDX models which showed minimal changes in pheno- and genotype over time indicating invasive behavior is an intrinsic phenotype of DCIS with minimal evolution, supporting a multiclonal evolution model. Moreover, this provided a collection of 19 stable sequentially transplantable DCIS MIND models including Luminal A, Luminal B, ER+/HER2+ and ER-/HER2+ models. Ultimately these models can be used to validate the biomarkers found to be related to invasive progression, as an example we proved the direct role of HER2 overexpression in invasive progression by inhibiting the HER2 receptor or by overexpressing HER2. In conclusion all this data together enabled us to create a well-characterized biobank of DCIS models with the unique opportunity to follow the natural progression, sequentially transplant 42 models, find genomic and transcriptomic profiles related to high risk DCIS and manipulate gene expression to validate the role of genes in DCIS progression. Citation Format: Stefan J. Hutten, Roebi de Bruijn, Catrin Lutz, Madelon Badoux, Timo Eijkman, Xue Chao, Marta Ciwinska, Andrea Herencia-Ropero, Petra Kristel, Lennart Mulder, Joyce Sanders, Mathilde Almekinders, Alba Llop-Gueverra, Helen R. Davies, Fariba Behbod, Serena Nik-Zainal, Violeta Serra, Jacco van Rheenen, Esther H. Lips, Lodewyk F.A. Wessels, Jelle Wesseling, Colinda Scheele, Jos Jonkers. A living biobank of patient-derived ductal carcinoma in situ (DCIS) Mouse-INtraDuctal (MIND) xenografts identifies multiple risk factors of invasive progression [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr PR006.

Abstract PR008: Duration of endocrine treatment for DCIS impacts second events: Insights from a large registry of cases at two academic medical centers

Abstract Background: Ductal carcinoma in situ (DCIS) incidence has risen with increasing use of screening mammography. It is unclear who benefits from both the amount and type of adjuvant treatment (radiation therapy, (RT), endocrine therapy (ET)) versus what constitutes over-treatment. Our goal was to identify the effects of adjuvant RT, or ET+/- RT versus breast conservation surgery (BCS) alone in a large multi-center DCIS registry of retrospective patients with long follow up. Methods: Data was extracted on women with a primary diagnosis of DCIS (N=2979) between 1985 - 2017 treated in 2 University of California (UC) medical centers. ET treatment and duration was confirmed by chart review for 1916 patients for this analysis. Receipt of ET (N=404) was stratified to &amp;gt; 2 years or &amp;lt; 2 years. Association between treatment type and second events was assessed using Cox regression. Competing risks models were used to assess effect of treatment type on different type of second events (ipsilateral DCIS or invasive, or contralateral combined). Time-varying coefficients were used as appropriate. Results: Median follow up time was 8.2 years for the 1916 patients analyzed. The cumulative second event (any type) rate was 25% at 15 years. In univariate and multivariate analysis adjusting for clinical variables, all treatments reduced the risk of second events compared to BCS only. Further stratifying ET receipt by duration demonstrated significant risk reduction (HR=0.12, P=0.04) only in women taking &amp;gt;2 years of ET, but not in women in the &amp;lt;2year ET group (HR=1.3, P=0.55). In the competing risk model, RT significantly reduces the risk of both ipsilateral DCIS and invasive cancer, and ET &amp;gt; 2 years significantly reduces the risk of ipsilateral invasive cancer. Conclusions: In our registry we show that women with DCIS who took less than 2 years of adjuvant endocrine therapy have a similar second event rate as BCS. In contrast, women who took more than 2 years of ET show a significantly reduced second event rate, similar to those who received either RT or combined ET+RT, which was independent of age, tumor size, grade, or period of diagnosis. This highlights the importance of ET duration for risk reduction of second events following surgery for newly diagnosed DCIS. Citation Format: Thomas O'Keefe, Christina Yau, Emma Iaconetti, Eliza Jeong, Case Brabham, Paul Kim, Joseph McGuire, Ann Griffin, Laura Esserman, Olivier Harismendy, Gillian Hirst. Duration of endocrine treatment for DCIS impacts second events: Insights from a large registry of cases at two academic medical centers [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr PR008.