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      Association of the 12-Gene Breast DCIS Score ® Assay With Local Recurrence in Patients With Ductal Carcinoma In Situ Treated on Accelerated Partial Breast Radiotherapy Protocols

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          Abstract

          Background

          The following analysis explores clinicopathologic factors and the 12-gene Breast DCIS Score test result in order to better define an appropriate DCIS (ductal carcinoma in situ) population eligible for APBI (accelerated partial breast radiotherapy).

          Methods

          This exploratory analysis aimed to retrospectively measure the association between the 12-gene Oncotype DX Breast DCIS Score ® assay (Redwood City, CA) and relevant clinicopathologic factors with locoregional recurrence in a pooled cohort of women treated with local excision and APBI on prospective phase II (NCT01185145) and phase III (NCT01185132) clinical trials. Univariable Cox proportional hazards regression was used to determine whether there was an association between local recurrence and DCIS Score result risk group (≥ 39 vs < 39) and clinicopathologic factors.

          Results

          This analysis included 104 evaluable patients (n = 18 from NCT01185145 and n = 86 from NCT01185132). The median age was 60 years (range: 40-79). Seventy-nine percent of patients were postmenopausal. The median span of DCIS was 10 mm (range 2-45 mm). Two-thirds of the cohort presented with necrosis (71%). The distribution of DCIS Score ® results ranged from 0 to 82, with 69% of patients having a DCIS Score result < 39. The median follow-up time was 8.2 years in NCT01185145 versus 3.0 years in NCT01185132. There were 6 local ipsilateral breast recurrences. DCIS Score result was significantly associated with local recurrence in univariable modeling, hazard ratio = 10.3 (95% CI 1.7, 198.4); p = 0.010. None of the clinicopathologic characteristics resulted in any significant association with locoregional recurrence.

          Conclusion

          The Breast DCIS Score assay demonstrated risk stratification in this cohort of patients treated with local excision and APBI pooled from two clinical trials. These results are consistent with those recently published utilizing whole breast radiotherapy. Due to the small number of local recurrence events and limited follow-up time, further investigations are needed to confirm findings.

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          Most cited references26

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          Accelerated Partial Breast Irradiation: Executive summary for the update of an ASTRO Evidence-Based Consensus Statement.

          To update the accelerated partial breast irradiation Consensus Statement published in 2009 and provide guidance on use of intraoperative radiation therapy (IORT) for partial breast irradiation in early-stage breast cancer, based on published evidence complemented by expert opinion.
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            • Abstract: found
            • Article: not found

            Radiation therapy for the whole breast: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline

            The purpose of this guideline is to offer recommendations on fractionation for whole breast irradiation (WBI) with or without a tumor bed boost and guidance on treatment planning and delivery.
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              Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast.

              Individual patient data were available for all four of the randomized trials that began before 1995, and that compared adjuvant radiotherapy vs no radiotherapy following breast-conserving surgery for ductal carcinoma in situ (DCIS). A total of 3729 women were eligible for analysis. Radiotherapy reduced the absolute 10-year risk of any ipsilateral breast event (ie, either recurrent DCIS or invasive cancer) by 15.2% (SE 1.6%, 12.9% vs 28.1% 2 P <.00001), and it was effective regardless of the age at diagnosis, extent of breast-conserving surgery, use of tamoxifen, method of DCIS detection, margin status, focality, grade, comedonecrosis, architecture, or tumor size. The proportional reduction in ipsilateral breast events was greater in older than in younger women (2P < .0004 for difference between proportional reductions; 10-year absolute risks: 18.5% vs 29.1% at ages <50 years, 10.8% vs 27.8% at ages ≥ 50 years) but did not differ significantly according to any other available factor. Even for women with negative margins and small low-grade tumors, the absolute reduction in the 10-year risk of ipsilateral breast events was 18.0% (SE 5.5, 12.1% vs 30.1%, 2P = .002). After 10 years of follow-up, there was, however, no significant effect on breast cancer mortality, mortality from causes other than breast cancer, or all-cause mortality.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                17 June 2021
                2021
                : 11
                : 671047
                Affiliations
                [1] 1 Radiation Oncology, Rocky Mountain Cancer Centers , Littleton, CO, United States
                [2] 2 Biostatistics, Exact Sciences Corporation , Redwood City, CA, United States
                [3] 3 Radiation Oncology, Rocky Mountain Cancer Centers , Aurora, CO, United States
                Author notes

                Edited by: Drexell Hunter Boggs, University of Alabama at Birmingham, United States

                Reviewed by: Valentina Lancellotta, Catholic University of the Sacred Heart, Italy; Corrado Spatola, University of Catania, Italy; Kylie Louise Gorringe, Peter MacCallum Cancer Centre, Australia

                *Correspondence: Charles E. Leonard, drcharlesleonard@ 123456mac.com

                This article was submitted to Radiation Oncology, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2021.671047
                8247917
                34221987
                df8475ec-5e90-4430-8fe5-ac5ae6aa8616
                Copyright © 2021 Leonard, Tole, Turner, Bennett, Howell and Carter

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 22 February 2021
                : 28 May 2021
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 27, Pages: 6, Words: 2513
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                breast cancer,radiotherapy,local recurrence,breast ductal carcinoma in situ,partial breast external beam radiotherapy

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