Breast-conserving Surgery For Ductal Carcinoma In Situ Research Articles

Abstract PS01-08: Management of ipsilateral breast tumor recurrence following breast conservation surgery for ductal carcinoma in situ – a data-free zone

Abstract Background: Breast-conserving surgery (BCS) is well established for the management of ductal carcinoma in situ (DCIS). Although a growing body of data support re-conservation therapy (RBCS) for ipsilateral breast tumor recurrence (IBTR) following BCS in invasive cancer, neither randomized trials nor guidelines address management of IBTR following BCS for DCIS. Here we aim to compare the outcomes of mastectomy vs RBCS for a large series of DCIS patients with IBTR. Methods: We identified women treated with BCS for DCIS at MSKCC who developed IBTR as a first event. Between those treated with mastectomy vs RBCS, we compared the clinicopathologic characteristics for the initial and recurrent tumors, the use of adjuvant RT (both upfront (“primary RT”) and post IBTR (“secondary RT”)) and/or tamoxifen, the rate of third events (local, regional, distant), breast cancer specific (BCSS) and overall survival (OS). Results: From our service databases among 3001 women treated with BCS for DCIS (1978-2010), we found 383 who developed an IBTR as a first event and were treated at our institution between 1983-2023, 186 (49%) with RBCS and 197 (51%) with mastectomy. RBCS was more frequent over time and comprised 56% of patients treated between 2014 and 2023. Among those treated with mastectomy, the initial tumors were significantly more likely to have necrosis (74% vs 59%), high grade (47% vs 28%), comedo histology (38% vs 20%), and to have received primary RT at the time of BCS (61% vs 21%). Between those who underwent mastectomy vs RBCS, there were no significant differences in disease-free interval, in the pathologic characteristics of their IBTR, or in the proportion of invasive vs in situ disease. For patients treated with RBCS, 11 (5.9%) received both primary and secondary RT and 77 (41.3%) received neither (Table 1a). For patients treated with a mastectomy only 8.5% had secondary RT (Table 1b). At a median follow-up of 5.1 years post-IBTR, third local events in total were more frequent for RBCS vs mastectomy (16.1% vs 3.0%, 0.001), but there were no differences in BCSS or OS. Among RBCS patients, third local events (breast re-recurrence) were least frequent among those who received primary and secondary RT, and comparable between with who did vs did not receive secondary RT (16% (13/82) vs 16% (117/104), Table 2). Conclusions: Our data show that for women with isolated IBTR following BCS for DCIS and treated by mastectomy vs RBCS, 1) treatment with mastectomy was associated with less favorable initial pathology and more frequent use of primary RT, 2) re-recurrence was more frequent with RBCS, and 3) BCSS and OS were comparable. In an era of increasing surgical de-escalation, our data suggest a wider role for RBCS and – as for patients having RBCS for IBTR following invasive cancer – further study of the relationship between secondary RT and the rate of third breast events. Citation Format: Brian Diskin, Varadan Sevilimedu, Kimberly Van Zee, Monica Morrow, Hiram Cody. Management of ipsilateral breast tumor recurrence following breast conservation surgery for ductal carcinoma in situ – a data-free zone [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 PS01-08.

Tailored radiation dose according to margin width for patients with ductal carcinoma in situ after breast-conserving surgery

A 2 mm resection margin is considered adequate for ductal carcinoma in situ (DCIS). We assessed the effectiveness of a tailored radiation dose for margins < 2 mm and the appropriate margin width for high-risk DCIS. We retrospectively evaluated 137 patients who received adjuvant radiotherapy after breast-conserving surgery for DCIS between 2013 and 2019. The patients were divided into three– positive, close (< 2 mm), and negative (≥ 2 mm) margin groups. Radiation dose to the tumor bed in equivalent dose in 2 Gy fractions were a median of 66.25 Gy, 61.81 Gy, and 59.75 Gy for positive, close, and negative margin groups, respectively. During a median follow-up of 58 months, the crude rates of local recurrence were 15.0%, 6.7%, and 4.6% in the positive, close, and negative margin groups, respectively. The positive margin group had a significantly lower 5-year local recurrence-free survival (LRFS) rate compared to the close and negative margin groups in propensity-weighted log-rank analysis (84.82%, 93.27%, and 93.20%, respectively; p = 0.008). The difference in 5-year LRFS between patients with the high- and non-high-grade tumors decreased as the margin width increased (80.4% vs. 100.0% for margin ≥ 2 mm, p < 0.001; 92.3% vs. 100.0% for margin ≥ 6 mm, p = 0.123). With the radiation dose tailored for margin widths, positive margins were associated with poorer local control than negative margins, whereas close margins were not. Widely clear margins (≥ 2 mm) were related to favorable local control for high-grade DCIS.

Updates and Debate Concerning Margin Adequacy and Management following Breast-Conserving Surgery

Objective: Breast-conserving surgery (BCS) experienced a significant surge during the last decades due to the increase of early breast cancer detection. Central to the discussion is margin adequacy which represents one of the most significant predictive factors for local relapse. This paper aims to shed light on the problem of margins in breast surgery. Mechanism: We performed a systematic narrative review of the literature by conducting a search using Medline/PubMed, Scopus, and Embase. The following keywords were considered: “breast-conserving surgery” AND “margins”/“margin”. Findings in Brief: In the case of invasive breast cancer, “no ink on tumor” can be considered an adequate margin, while for ductal carcinoma in situ (DCIS), a distance of 2 mm from tumor should be obtained. Many novel tools have been developed based both on the latest radiological imaging techniques and on the tissue expression of certain markers, with the aim of precise navigation of tumor excision and intraoperative evaluation of cavity excision margins. Oncoplastic surgery can be considered oncologically safe while improving the cosmetic outcome and patients’ quality of life. The appropriate use of adjuvant treatments in the context of a multidisciplinary and personalized management of breast cancer is the only means to omit a second intervention in some carefully selected cases. Conclusions: Debate still exists concerning the definition of adequate clear margin following BCS for DCIS. Further studies are required to better assess multimodal treatment approaches in this condition.

The clinical significance of HER2 expression in DCIS.

HER2 is an established prognostic and predictive marker for patients with invasive breast cancer. The clinical and biological significance of HER2 overexpression in patients with ductal carcinoma in situ (DCIS) remains poorly defined. DCIS is a heterogeneous disease and some patients with DCIS will not progress to invasive breast cancer. However, clinically significant recurrence rates have been reported after breast-conserving surgery for DCIS and approximately half of these cases will be life-threatening invasive recurrences. Since the incidence of DCIS is rising due to the widespread use of screening mammography, there is robust interest in selecting high-risk DCIS patients that may benefit from adjuvant therapies. Molecular prognostic and predictive models in early invasive breast cancer help clinicians identify patients that will benefit from chemotherapy. Molecular subtyping and profiling could also be useful in treating DCIS patients. According to current practice guidelines, HER2 testing is not recommended in DCIS patients. Nevertheless, evidence suggests that HER2-positive DCIS cases may be associated with adverse clinicopathological parameters and increased recurrence rates. This review summarizes the existing body of evidence linking HER2 expression and ipsilateral breast cancer recurrence in DCIS. HER2, as well as its correlation with other clinicopathological markers might be a useful prognostic and predictive marker, helping clinical decision-making in DCIS patients.

Trends in adjuvant therapy after breast-conserving surgery for ductal carcinoma in situ of breast: a retrospective cohort study using the National Breast Cancer Registry of Japan.

Radiotherapy (RT) and endocrine therapy (ET) are standard treatment options after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). We investigated the national patterns of adjuvant therapy use after BCS for DCIS in Japan. We obtained relevant data of patients diagnosed with DCIS undergoing surgery and treated with BCS between 2014 and 2016 from the Japanese Breast Cancer Registry database. The relationship between the clinicopathologic, institutional, and regional factors, and adjuvant treatment was examined using multivariable analyses. We identified 9516 patients who underwent BCS for DCIS. Overall, 23% received no adjuvant treatment, 71% received RT, 32% received ET, and 26% received combination therapy. The percentages of patients who received ET and combination therapy in 2016 were significantly lower [odds ratio (OR): 0.71, 0.77, respectively] than in 2014. The proportion of RT was low among young or elderly patients (OR: 0.75, 0.44, respectively) and in non-certified facilities (OR: 0.56). The proportion of ET was high in non-certified facilities (OR: 1.58) and among patients with positive margins (OR: 1.62). Combination therapy was higher among patients with positive margins (OR: 1.53). Our study found a distinct adjuvant treatment pattern after BCS for DCIS depending on clinicopathologic factors, year, age, which indicate that physicians provide individualized treatment according to the background of the patients and the biology of DCIS. The facilities and regions remain significant factors of influencing adjuvant treatment pattern.

Abstract PD5-05: Including a 21-gene assay recurrence score in multivariable predictive model generation improves prediction of local recurrence after breast conserving surgery for ductal carcinoma-in-situ

Abstract Introduction Accurate prediction of local recurrence (LR) after breast conserving surgery (BCS) for ductal carcinoma-in-situ (DCIS) is crucial to personalize recommendations for adjuvant radiotherapy (RT). The 21-gene recurrence score (RS) predicts for distant metastases for woman with invasive breast cancer. We hypothesised that the RS could improve prediction of LR after BCS for DCIS. Methods We performed a population-based analysis of 1226 woman aged ≤74 treated with BCS ± RT for pure DCIS. Expert pathology review was obtained for all cases, as was the RS. Treatment and outcomes were obtained by deterministic linkage to administrative databases and chart review. Clinico-pathologic features obtained included: age, tumor size, nuclear grade, presence of comedonecrosis, multifocality, margins, and adjuvant radiation. The outcome assessed was local recurrence by 10 years from diagnosis of DCIS. The LR prediction model was developed using multivariable Cox regression, where a non-parametric approach was implemented to estimate the baseline hazard function. The proportional hazards assumption was assessed and time-interaction terms were included with each covariate in the model. Models were ranked based on c-statistic, log-likelihood estimate, and Akaike information criterion (AIC). Backward selection was used to obtain the final reduced model with time-interaction terms. Calibration for the best model was examined by grouping predicted 10-year risk of LR into deciles and plotting against observed 10-year risk of LR based on mean Kaplan-Meier estimates. Internal validation was performed by bootstrapping. Results Of the 1226 woman included, 514 were treated with BCS alone and 712 received adjuvant RT. Median follow up from time of treatment was 16 years (interquartile range (IQR): 14-18). The median age was 56 years (IQR: 49-64). Margins were negative in 90.5% of cases. Tumor size was ≤1cm in 430 (35.1%), 1-2.5cm in 633 (51.6%), and &amp;gt;2.5cm in 163 (13.3%). The median RS was 15 (IQR: 8-30) and the mean RS was 21.37 (SD 18.93). The best predictive model included the RS and had a c-statistic of 0.68 as well as the lowest AIC. This model included the following variables: RS, age, tumor size, nuclear grade, margin status, comedonecrosis (≤30% vs higher), multifocality, and treatment (BCS vs BCS+RT); it also included the following interaction terms: treatment and time, RS and time, comedonecrosis and time, and treatment and tumor size. Due to the non-linear relationship between certain characteristics and the risk of LR, quadratic terms for RS and age were also included. This model was well calibrated overall, especially in the lower risk range around the 10% risk threshold. It was also well calibrated in this risk range in the subset of woman who were treated with BCS alone. Conclusion The best performing model generated to predict LR after BCS for DCIS includes the RS. Work is ongoing to compare RS and the 12-gene DCIS score in terms of prediction of LR, as well as prediction of invasive LR specifically. This work can help guide future clinical de-escalation trials by better identifying woman with truly low risk of LR after BCS for DCIS. Citation Format: Ezra Hahn, Rinku Sutradhar, Sumei Gu, Lawrence Paszat, Danielle Rodin, Sharon Nofech-Mozes, Cindy Fong, Eileen Rakovitch. Including a 21-gene assay recurrence score in multivariable predictive model generation improves prediction of local recurrence after breast conserving surgery for ductal carcinoma-in-situ [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD5-05.

Predictors of Reexcision following Breast-Conserving Surgery for Ductal Carcinoma In Situ

Reexcision following breast-conserving surgery (BCS) in women with ductal carcinoma in situ (DCIS) results in adjuvant treatment delays, higher health care costs, and undesirable cosmetic outcomes. The purpose of this study is to determine patient, imaging, pathological, and surgical predictors of reexcision following BCS for DCIS. A retrospective review of women with DCIS who had BCS from 2007 to 2016 was conducted. Patient, imaging, pathological, and surgical features, in addition to surgical outcomes, were collected from medical records. Standard statistical tests were used to compare features between patients who did and did not undergo at least one reexcision. A multivariable logistic regression model was fit to assess features associated with reexcision. A total of 547 women (mean age 59years; range 30-88years) diagnosed with DCIS at core needle biopsy underwent BCS. Of all women, 31.6% (173/547) had at least one reexcision. With multivariable analysis, features associated with reexcision included younger patient age (adjusted odds ratio [aOR] 0.98, 95% confidence interval [CI] 0.97-1.0, p = 0.049), African-American race (aOR 2.66, 95% CI 1.13-6.26, p = 0.03), biopsy modality of ultrasound (aOR 2.35, 95% CI 1.22-4.53, p = 0.01), and earlier year of surgery (aOR 0.92, 95% CI 0.86-0.98, p = 0.01). No pathological features of DCIS were associated with reexcision risk. In our cohort of nearly 550 women with DCIS who underwent BCS, 31.6% had at least one reexcision. Features associated with reexcision include younger patient age, African-American race, biopsy modality of ultrasound, and earlier year of surgery.

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

Abstract Most women diagnosed with ductal carcinoma in situ (DCIS) will be treated with breast-conserving surgery followed by whole breast radiation. We will review the evolving role of genomic biomarkers to personalize radiotherapy treatment recommendations after breast-conserving surgery for DCIS. Citation Format: E Rakovitch. Guiding decisions to omit radiotherapy after breast-conserving surgery for DCIS. Can genomic biomarkers help? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES2-1.

International comparison of cosmetic outcomes of breast conserving surgery and radiation therapy for women with ductal carcinoma in situ of the breast

PurposeTo assess the cosmetic impact of breast conserving surgery (BCS), whole breast irradiation (WBI) fractionation and tumour bed boost (TBB) use in a phase III trial for women with ductal carcinoma in situ (DCIS) of the breast. Materials and methodsBaseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/− TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres. Cosmetic failure was a global score of fair or poor. Cosmetic deterioration was a score change from excellent or good at baseline to fair or poor at three years. Odds ratios for cosmetic deterioration by WBI dose-fractionation and TBB use were calculated for both scoring systems. Results1608 women were enrolled from 11 countries between 2007 and 2014. 85–90% had excellent or good baseline cosmesis independent of geography or assessment method. TBB (16 Gy in 8 fractions) was associated with a >2-fold risk of cosmetic deterioration (p < 0.001). Hypofractionated WBI (42.5 Gy in 16 fractions) achieved statistically similar 3-year cosmesis compared to conventional WBI (50 Gy in 25 fractions) (p ≥ 0.18). The adverse impact of a TBB was not significantly associated with WBI fractionation (interaction p ≥ 0.30). ConclusionsCosmetic failure from BCS was similar across international jurisdictions. A TBB of 16 Gy increased the rate of cosmetic deterioration. Hypofractionated WBI achieved similar 3-year cosmesis as conventional WBI in women treated with BCS for DCIS.

Abstract P5-18-03: A predictive model for local recurrence in patients treated for ductal carcinoma in situ of the breast (DCIS)

Abstract Background: Ductal carcinoma in situ (DCIS) is a heterogeneous precursor, non-invasive breast lesion. There is a lack of specific DCIS molecular predictors of in breast tumour recurrence (IBTR) or progression to invasive breast cancer (IBC) after breast conserving surgery (BCS) +/- radiotherapy (RT). The aim of this was to identify novel biomarkers and combine these with clinical parameters to develop a new model to predict IBTR in patients treated by BCS for DCIS. Methods: A single institution DCIS biomarker discovery study included a case-control matched series of 180 patients (median age 61, range 35-94) treated at the Edinburgh Breast Unit between 2000 and 2010: · 88 patients with low/intermediate grade DCIS treated with BCS alone; 18 recurred within 10 years. · 92 patients with high grade DCIS treated by BCS and RT; 22 recurred within 10 years. Median follow-up was 7.4 years. RNA was extracted from DCIS lesions and whole-genome transcriptomics analysis was performed using Lexogen QuantSeq. Predictive models were generated based upon the most informative genes. Independent validation cohorts are also available and are currently being used for validation. Results: The models developed predict risk of IBTR in patients with low or intermediate grade DCIS treated with BCS alone and high grade DCIS treated with DCIS plus RT. The models were found to be independent of grade and stratify patients into binary groups of high and low risk of recurrence. A promising model was developed based on the expression of 5 genes combined with tumour diameter ≤15mm or &amp;gt;15mm. • In low/intermediate grade DCIS expression levels of a solute carrier family gene, kinetochore associated gene and an immunomodulatory gene are predictive of recurrence. • In high grade DCIS an additional solute carrier and a glutathione S-transferase related gene are predictive of recurrence. • In the training sets the models have 96% (high-grade) and 92% (low/intermediate grade) accuracy of prediction of subsequent recurrence and estimates of IBTR-free survival were highly significant in both groups (&amp;lt;0.0001). Validation of the model by RT-PCR and immunohistochemistry is underway in both the training cohort and an independent validation cohort. Conclusions: · Promising models to predict risk of IBTR in patients treated for DCIS have been developed. · Novel biomarkers that predict recurrence have been identified using new technologies that may have clinical potential. · Independent validation is currently underway. Citation Format: Martinez-Perez C, Turnbull AK, Fernando A, Ekatah GE, Arthur LM, Cartlidge CW, Johns N, Sims AH, Thomas JS, Dixon JM. A predictive model for local recurrence in patients treated for ductal carcinoma in situ of the breast (DCIS) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-18-03.

Clinical risk score to predict likelihood of recurrence after ductal carcinoma in situ treated with breast-conserving surgery

A majority of women with ductal carcinoma in situ (DCIS) receive breast-conserving surgery (BCS) but then face a risk of ipsilateral breast tumor recurrence (IBTR) which can be either recurrence of DCIS or invasive breast cancer. We developed a score to provide individualized information about IBTR risk to guide treatment decisions. Data from 2762 patients treated with BCS for DCIS at centers within the National Comprehensive Cancer Network (NCCN) were used to identify statistically significant non-treatment-related predictors for 5-year IBTR. Factors most associated with IBTR were estrogen-receptor status of the DCIS, presence of comedo necrosis, and patient age at diagnosis. These three parameters were used to create a point-based risk score. Discrimination of this score was assessed in a separate DCIS population of 301 women (100 with IBTR and 200 without) from Kaiser Permanente Northern California (KPNC). Using NCCN data, the 5-year likelihood of IBTR without adjuvant therapy was 9% (95% CI 5-12%), 23% (95% CI 13-32%), and 51% (95% CI 26-75%) in the low, intermediate, and high-risk groups, respectively. Addition of the risk score to a model including only treatment improved the C-statistic from 0.69 to 0.74 (improvement of 0.05). Cross-validation of the score resulted in a C-statistic of 0.76. The score had a c-statistic of 0.67 using the KPNC data, revealing that it discriminated well. This simple, no-cost risk score may be used by patients and physicians to facilitate preference-based decision-making about DCIS management informed by a more accurate understanding of risks.

Paradigm Shift toward Reducing Overtreatment of Ductal Carcinoma In Situ of Breast.

The prevalence of ductal carcinoma in situ (DCIS) of the breast has increased substantially after the introduction of breast cancer screening programs, although the clinical effects of early DCIS detection and treatment remain unclear. The standard treatment for DCIS has involved local breast-conserving surgery (BCS) followed by radiotherapy (RT) or total mastectomy with/without endocrine therapy, and the choice of local treatment is not usually based on clinicopathologic or biological factors. However, we have investigated the effectiveness of local treatment using breast surgery and RT using Surveillance, Epidemiology, and End Results data, and found that the effectiveness of breast surgery was modified by the nuclear grade. Furthermore, breast cancer-specific survival was identical between patients with low-grade DCIS who did and did not undergo surgery. Moreover, we found that RT after BCS for DCIS was only associated with a survival benefit among patients with risk factors for local recurrence, such as nuclear grade, age, and tumor size. Ongoing clinical trials and translational research have attempted to develop a treatment strategy that prevents the overdiagnosis and overtreatment of low-risk DCIS, as well as a biology-based treatment strategy for using targeted therapy. Therefore, to develop a tailored treatment strategy for DCIS, we need to identify molecular and biological classifications based on the results from translational research, national databases, and clinical trials.

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

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

Factors influencing local control in patients undergoing breast conservation surgery for ductal carcinoma in situ

BackgroundThe aim of our study was to assess various predictors for local recurrence (LR) in patients undergoing breast conservation surgery (BCS) for ductal carcinoma in situ (DCIS). Materials and methodsAn audit was performed of 582 consecutive patients with DCIS between Jan 1975 to June 2008. In patients undergoing BCS, local guidelines reported a margin of ≥10 mm during the above period. Guideline with regard to margin of excision changes soon after this period.We retrospectively analysed clinical and pathological risk factors for local recurrence in patients undergoing BCS. Statistical analysis was carried out using SPSS version 19, and a cox regression model for multivariate analysis of local recurrence was used. ResultsOverall 239 women had BCS for DCIS during the above period. The actuarial 5-year recurrence rate was 9.6%. The overall LR rate was 17% (40/239. LR was more common in patients ≤50 years: (10/31 patients, 32%) compared to patients > 50 years (30/208, 14%, P = 0.02). Forty three per cent of patients (6/14) with <5 mm margin developed LR which was significantly higher compared to patients with 5–9 mm margin (12%, 3/25) and with ≥10 mm margin (14%, 27/188, P = 0.01). On multivariate analysis age ≤50 years, <5 mm pathological margin were independent prognostic factors for local recurrence. ConclusionOur study shows that younger age (≤50 years) and a margin < 5 mm are poor prognostic factors for LR in patients undergoing breast conservation surgery for DCIS.

Abstract P3-12-02: Patient prognostic score and survival benefit offered by radiotherapy for ductal carcinoma in situ

Abstract Background: In general, radiotherapy (RT) follows breast-conserving surgery (BCS) and remains the standard of care for the surgical management of both invasive carcinoma and ductal carcinoma in situ (DCIS). Although it is associated with better local control, the magnitude of survival benefit conferred by RT for DCIS has not yet been established. We sought to evaluate whether a survival benefit exists with the addition of RT for patients with DCIS and to validate a patient prognostic score to predict survival benefit. Methods: We performed a retrospective longitudinal cohort study by using the Surveillance Epidemiology and End Results database (SEER 17). Between 1988-2007, we identified 32,144 eligible patients who underwent BCS for DCIS. Using age, year of diagnosis, race, tumor size, hormone receptor status, tumor grade, marital status and SEER region, we calculated propensity score weights to balance clinicopathologic factors between patients receiving only surgery and those receiving surgery and RT. This cohort was divided into seven groups according to the previously validated patient prognostic score proposed by Smith et al. Breast cancer mortality (BCM) was assessed using a log-rank test and a multivariable Cox proportional hazards model. Results: Of 32,144 cases of DCIS, 20,329 cases (63%) were treated with RT (+RT group) and 11,815 cases (37%) were treated with surgery alone (-RT group). There were 304 breast cancer-specific deaths observed over the follow-up period (median 96 months). The weighted cumulative incidence of BCM at ten-years was 1.8% for the +RT group compared to 2.1% for the -RT group (p= 0.003). The effect of RT on survival differed by nuclear grade (p= 0.007), age (p= 0.004), and tumor size (p=0.02). We found that the survival benefit for the +RT group was significantly greater than for the –RT group in subgroups of patients with higher nuclear grade, younger age, and larger tumor size, whereas a statistical reduction of BCM with RT was not observed among patients without these prognostic factors. Moreover, the magnitude of survival benefit was significantly correlated with the patient prognostic score [p&amp;lt;0.0001, Table]. Conclusion: In this population-based cohort study, the patient prognostic score for DCIS accurately estimated the magnitude of survival benefit offered by radiotherapy after BCS, suggesting that decisions for RT could be tailored based on prognostic score and patient preference. Limitations of this study include unmeasured confounders such as a lack of information about patients' comorbidities, margin status and endocrine therapy, and further external validation is needed to confirm our results. Patient Prognostic Score and Hazard Ratio (HR) Comparing Mortality between Radiotherapy Group and non-Radiotherapy GroupPatient Prognostic ScoreNumber of patients in -RT groupNumber of patients in +RT groupWeighted HR of BCM95% CIWeighted HR of OM95% CI078213881.20.67 - 2.10.910.76 - 1.11267744801.00.70 - 1.50.880.78 - 0.992410570800.690.51 - 0.940.710.63 - 0.793304854170.730.48 - 1.10.680.58 - 0.81496517010.310.16 - 0.580.420.30 - 0.5852232480.290.09 - 0.910.430.21 - 0.9161515N.A. N.A. Abbreviation: RT, Radiotherapy; BCM, Breast Cancer Mortality; OM, Overall Mortality: N.A., not available Citation Format: Sagara Y, Freedman RA, Vaz-Luis I, Mallory MA, Wong S, Aydogan F, DeSantis S, Barry WT, Golshan M. Patient prognostic score and survival benefit offered by radiotherapy for 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 P3-12-02.

Decreasing Recurrence Rates for Ductal Carcinoma In Situ: Analysis of 2996 Women Treated with Breast-Conserving Surgery Over 30 Years.

Randomized trials of radiation after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) found substantial rates of recurrence, with half of the recurrences being invasive. Decreasing local recurrence rates for invasive breast carcinoma have been observed and are largely attributed to improvements in systemic therapy. In this study, we examine recurrence rates after BCS for DCIS over 3 decades at one institution. We retrospectively reviewed a prospectively maintained database of DCIS patients undergoing BCS from 1978 to 2010. Cox proportional hazard models were used to investigate the association between the treatment period and recurrence, controlling for other variables. Overall, 363 (12%) recurrences among 2996 cases were observed. Median follow-up for patients without recurrence was 75 months (range 0-30 years); 732 patients were followed for ≥10 years. The 5-year recurrence rate for the period 1978-1998 was 13.6 versus 6.6% for the period 1999-2010 [hazard ratio (HR) 0.62, p < 0.0001]. Controlling for age, family history, presentation, nuclear grade, necrosis, number of excisions, margin status, radiation, and endocrine therapy, treatment period remained significantly associated with recurrence, with later years associated with a lower HR (0.74, p = 0.02) compared to earlier. After stratification by radiation use, association of recurrence with treatment period persisted in those treated without radiation (HR 0.62, p = 0.003). Recurrence rates for DCIS have fallen over time, with increases in screen detection, negative margins, and use of adjuvant therapies only partially explaining this decrease. The unexplained decline persists in women not receiving radiation, suggesting it is not due to changes in radiation efficacy but may be due to improvements in radiologic detection and pathologic assessment.

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

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

Long-term Outcomes of Hypofractionation Versus Conventional Radiation Therapy After Breast-Conserving Surgery for Ductal Carcinoma In Situ of the Breast

Whole-breast radiation therapy (XRT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) may decrease the risk of local recurrence, but the optimal dose regimen remains unclear. Past studies administered 50 Gy in 25 fractions (conventional); however, treatment pattern studies report that hypofractionated (HF) regimens (42.4 Gy in 16 fractions) are frequently used. We report the impact of HF (vs conventional) on the risk of local recurrence after BCS for DCIS. All women with DCIS treated with BCS and XRT in Ontario, Canada from 1994 to 2003 were identified. Treatment and outcomes were assessed through administrative databases and validated by chart review. Survival analyses were performed. To account for systematic differences between women treated with alternate regimens, we used a propensity score adjustment approach. We identified 1609 women, of whom 971 (60%) received conventional regimens and 638 (40%) received HF. A total of 489 patients (30%) received a boost dose, of whom 143 (15%) received conventional radiation therapy and 346 (54%) received HF. The median follow-up time was 9.2 years. The median age at diagnosis was 56 years (interquartile range [IQR], 49-65 years). On univariate analyses, the 10-year actuarial local recurrence-free survival was 86% for conventional radiation therapy and 89% for HF (P=.03). On multivariable analyses, age <45 years (hazard ratio [HR] = 2.4; 95% CI: 1.6-3.4; P<.0001), high (HR=2.9; 95% CI: 1.2-7.3; P=.02) or intermediate nuclear grade (HR=2.7; 95% CI: 1.1-6.6; P=.04), and positive resection margins (HR=1.4; 95% CI: 1.0-2.1; P=.05) were associated with an increased risk of local recurrence. HF was not significantly associated with an increased risk of local recurrence compared with conventional radiation therapy on multivariate analysis (HR=0.8; 95% CI: 0.5-1.2; P=.34). The risk of local recurrence among individuals treated with HF regimens after BCS for DCIS was similar to that among individuals treated with conventional radiation therapy.

The significance of margin status in patients with DCIS undergoing breast-conserving surgery.

98 Background: Recently, SSO/ASTRO published a consensus statement on margins for stage I and II invasive breast cancer treated with breast conserving surgery (BCS). We examined patients with ductal carcinoma in situ (DCIS) who underwent BCS to determine the effect of clinicopathologic and treatment factors including margin status, on locoregional recurrence (LRR), breast cancer-specific (BCSS) and overall survival (OS). Methods: From 2003-2010, we conducted a retrospective chart review of 253 consecutively diagnosed patients who underwent BCS for DCIS. Clincopathologic and treatment data were extracted. Margin status was defined by pathology reports with a negative margin as ≥ 2mm, close margin &lt; 2mm and positive margin as tumor on ink. Clinicopathologic variables were tested using the Fisher’s exact test, Chi-square test, ANOVA F-test, and Kruskal-Wallis test. A Cox proportional - Hazards model was used to calculate the impact of these factors on LRR, BCSS and OS. Results: The median age of the cohort was 57 (range 21-89) and the majority were white (79%), ER+ (78%) and underwent radiation therapy (67%). Forty six percent took anti-endocrine therapy. Of 252 patients, 29% had close margins, 63% had negative margins and 7% had unknown margins. One patient had a positive margin and was alive without disease at last follow-up. At a median follow-up of 5 years, OS was 96%. Thirteen patients experienced a LRR with a median time to recurrence of 4.9 years (5 with close margins, 7 with negative, 1 unknown). On multivariate analysis, age and PR status were significant predictors of LRR. Patients with age &gt;70 were more likely to recur than those age 50-69 (HR 6.7 95% CI (1.7-25.4) p= 0.005) as were patients with PR negative tumors (HR 5.7 95% CI (1.7-19.5) p= 0.005). Those patients who did not receive radiation therapy had a worse OS than those who did (HR 4.3 95%CI (1.5-12.6) p = 0.007). No variables were significant for BCSS. Conclusions: In this cohort of patients with DCIS treated with BCS, age and PR status were the only predictors of LRR. OS was only impacted by receipt of radiotherapy. Margin status was not predictive of LRR, BCSS or OS. This data suggests that routine re-excision for close margins may not be warranted.

Outcomes of Low-Risk Ductal Carcinoma In Situ in Southeast Asian Women Treated With Breast Conservation Therapy

To examine the outcomes of Southeast Asian (SEA) women with low-risk ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) and adjuvant radiation therapy. Retrospective chart reviews of patients treated with BCS for DCIS from 1995 to 2011 were performed. Patients meeting the selection criteria from Eastern Cooperative Oncology Group 5194 were included. Most patients received adjuvant radiation therapy (RT) consisting of whole-breast RT delivered to 50 Gy followed by a 10-Gy boost to the tumor bed. Of 744 patients with pathologic diagnosis of pure DCIS identified, 273 met the selection criteria: low-intermediate grade (LIG), n=219; high grade (HG), n=54. Median follow-up for these patients was 60 months. There were 8 ipsilateral breast tumor recurrences (IBTRs) in total, 7 of which were DCIS. The estimated actuarial IBTR rates at 5 and 10 years for the entire cohort are 1.8% and 4.3%, respectively. Of the 219 patients with LIG DCIS, 210 received RT and 9 did not. There were 7 IBTRs in LIG DCIS, 2 among the 9 patients who did not receive RT. The IBTR rates in LIG DCIS at 5 and 10 years are 2.3% and 4.2%, respectively. All patients with HG DCIS received RT. There was only 1 IBTR occurring beyond 5 years, giving an estimated IBTR rate of 4.5% at 10 years. SEA women with screen-detected DCIS have exceedingly low rates of IBTR after BCS, comparable to that observed in reports of similar patients with low-risk DCIS treated with adjuvant radiation.