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Muktar S, Kirby A, Locke I, Settatree S, Kothari G, Nimalasena S, Ranger A, Mohammed K, Reid F, Ross G, Roche N. Oncotype DX Breast DCIS Score® Test: Impact on Radiotherapy Recommendations and Patient Decisional Anxiety. Clin Oncol (R Coll Radiol) 2025; 42:103839. [PMID: 40311271 DOI: 10.1016/j.clon.2025.103839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 03/26/2025] [Accepted: 04/01/2025] [Indexed: 05/03/2025]
Abstract
AIMS Treatment for Ductal Carcinoma in Situ (DCIS) includes surgery followed by radiotherapy (RT) to reduce local recurrence (LR) risk, though RT may be overtreatment for some patients. The Oncotype DX Breast DCIS Score® test is a genomic test that provides individualised LR risk estimates. This study evaluates the impact of the Oncotype test on RT recommendations, patient anxiety and decisional conflict. MATERIAL AND METHODS Women aged ≥45 years with DCIS up to 25mm treated with breast-conserving surgery were invited to participate. Initial RT recommendations and 10-year LR risk predictions were made before Oncotype testing. Post Oncotype testing, final RT recommendations were recorded. Patients completed decisional conflict and anxiety questionnaires before and after receiving Oncotype results. RESULTS A total of 71 participants were included with a median age of 59. Ninety percent of DCIS was intermediate/high-grade with a median size of 12mm. Oncologists changed RT recommendations in 28% (20/71) of cases after receiving the Oncotype result; 21% changed from RT to no RT and 7% from no RT to RT. In 79% of cases, the oncologists' LR estimates were higher than Oncotype predictions. Post Oncotype testing, patient decisional conflict and anxiety decreased. CONCLUSION The Oncotype test changed treatment recommendations regarding adjuvant RT in almost a third of patients. Additionally, the assay was associated with reduced treatment-related decisional conflict and anxiety in patients. LR risk predictions by oncologists were higher than the Oncotype predictions highlighting a need for additional tools to aid decision-making.
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MESH Headings
- Humans
- Female
- Breast Neoplasms/genetics
- Breast Neoplasms/radiotherapy
- Breast Neoplasms/psychology
- Breast Neoplasms/pathology
- Breast Neoplasms/surgery
- Middle Aged
- Anxiety/etiology
- Anxiety/psychology
- Carcinoma, Intraductal, Noninfiltrating/genetics
- Carcinoma, Intraductal, Noninfiltrating/radiotherapy
- Carcinoma, Intraductal, Noninfiltrating/psychology
- Carcinoma, Intraductal, Noninfiltrating/pathology
- Carcinoma, Intraductal, Noninfiltrating/surgery
- Aged
- Decision Making
- Mastectomy, Segmental
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Affiliation(s)
- S Muktar
- The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom
| | - A Kirby
- The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom
| | - I Locke
- The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom
| | - S Settatree
- The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom
| | - G Kothari
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia
| | - S Nimalasena
- The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom
| | - A Ranger
- The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom
| | - K Mohammed
- The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom
| | - F Reid
- The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom
| | - G Ross
- The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom
| | - N Roche
- The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom.
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Padilla DB, Tsai J, Beck AS, Wapnir IL. Lumpectomy surgery for large ductal carcinoma in situ. Breast Cancer Res Treat 2025; 211:51-58. [PMID: 39928263 DOI: 10.1007/s10549-025-07621-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Accepted: 01/19/2025] [Indexed: 02/11/2025]
Abstract
PURPOSE Breast-conserving surgery for larger ductal carcinoma in situ (DCIS) remains limited. We compare the attempted use and success rates of lumpectomy surgery in patients with DCIS measuring ≥ 4 cm versus < 4 cm. METHODS A retrospective review was conducted using the institutional tumor registry to identify cases of pure DCIS that were surgically treated from 2015 to 2022. Clinical-pathological data were abstracted from electronic medical records. Pathologic tumor size on initial surgery was used to define the two cohorts. Comparisons of variables were made using Chi-square and ANOVA tests. RESULTS A total of 669 patients, 84% (562) with tumors measuring < 4 cm and 16% (107) ≥ 4 cm were identified. Lumpectomy was the initial surgery performed for 89% of women with lesions measuring < 4 cm on preoperative imaging studies compared to 64% of those ≥ 4 cm. Overall, 461 (92.9%) of 496 in the < 4 cm succeeded at lumpectomy compared to 36 (56.3%) of 64 in the ≥ 4 cm group. Re-excision lumpectomies or mastectomy were performed in 27% and 44% of the < 4 cm and ≥ 4 cm subgroups. Lumpectomy was achieved for 70% of women with tumors in the 4 to 5.9 cm range compared to 33% in the 6-7.9 cm and the ≥ 8 cm groups. There were no local recurrences in the ≥ 4 cm group at an average of 4.4 years follow-up. CONCLUSION Lumpectomy is a viable option for many patients with DCIS ≥ 4 cm, especially those measuring < 6 cm, though repeat re-excisions may be required after initial attempt.
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Affiliation(s)
| | - Jacqueline Tsai
- Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | | | - Irene L Wapnir
- Department of Surgery, Stanford University School of Medicine, 300 Pasteur Drive H3625, Stanford, CA, 94305, USA.
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Ofri A, Melanie Tam SK, Gill S, Spillane AJ. Current pattern of care in radiation therapy for DCIS in Australia and New Zealand - where are we heading? Breast 2025; 82:104482. [PMID: 40286763 DOI: 10.1016/j.breast.2025.104482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2025] [Revised: 04/15/2025] [Accepted: 04/22/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND Ductal carcinoma in-situ (DCIS) is a non-obligate precursor breast lesion with variable tendency to become invasive malignancy. Multiple studies have attempted to identify patient groups that could avoid radiation therapy (RT). We investigated the recent surgical management of DCIS in Australia and New Zealand (ANZ) and evaluated the likely rates of RT delivery dependent on differing low risk predictive criteria compared to actual practice. METHOD The BreastSurgANZ Quality Audit identified patients with DCIS from 2018 to 2022. Data were analysed on multiple DCIS characteristics as well as postoperative RT recommendations. Existing potential RT avoidance characteristics, low risk classification criteria (LRCC) and RTOG 9804, were tested against the cohort. RESULTS 7790 cases were analysed with 5323 (68.33 %) undergoing breast conservation surgery (BCS). There was higher median age, lower tumour grade and smaller size in the BCS group compared to mastectomy (p < 0.001). According to the BQA, 25.38 % of patients had RT omitted. Using LRCC, 1659 patients (31.17 %) could omit RT but only 760 (45.81 %) of those patients did. When using RTOG 9804 criterion, 1287 patients (24.18 %) could omit RT but only 447 (34.73 %) did. Of 3477 patients with neither low risk classifying characteristics, 553 (15.9 %) had no RT. CONCLUSION BCS is the preferred surgical management of DCIS in ANZ. Currently RT is omitted following BCS in 25 % of cases. Using LRCC and RTOG 9804 low risk classifiers there was inconsistent avoidance of RT, whereas RT was avoided in 15.9 % of higher risk patients. More consistent and transparent selection methods are desirable and currently genomic testing and clinico-molecular tools appears promising.
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Affiliation(s)
- Adam Ofri
- Breast and Endocrine Department, Mater Hospital, Wollstonecraft, 2065, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Surgery, University of Notre Dame, NSW, Australia.
| | | | - Suki Gill
- Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia; The University of Western Australia, Crawley, WA, Australia
| | - Andrew J Spillane
- Breast and Endocrine Department, Mater Hospital, Wollstonecraft, 2065, NSW, Australia; University of Sydney, Melanoma Institute Australia, Translational Research Hub, Wollstonecraft, NSW, Australia; Breast and Surgical Oncology at the Poche Centre, Wollstonecraft, NSW, Australia; Breast and Melanoma Surgery Department, Royal North Shore Hospital, St Leonards, NSW, Australia
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Brackstone M, Durocher-Allen L, Koch CA, Califaretti N, Eisen A, Knowles S, Plexman T, Salim A. A systematic review on the management of ductal carcinoma in situ of the breast. Surg Oncol 2025; 60:102223. [PMID: 40318551 DOI: 10.1016/j.suronc.2025.102223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 03/13/2025] [Accepted: 04/03/2025] [Indexed: 05/07/2025]
Affiliation(s)
- Muriel Brackstone
- London Health Sciences Centre- London Regional Cancer Program, Victoria Hospital, 800 Commisionners Road East, London, Ontario, N6A 5W9, Canada.
| | - Lisa Durocher-Allen
- Program in Evidence-Based Care, Ontario Health (Cancer Care Ontario), 699 Concession Street, Hamilton, Ontario, L8V 1C3, Canada.
| | - C Anne Koch
- Princess Margaret Cancer Centre, University Health Network, 610 University Ave, Toronto, Ontario, M5G2M9, Canada.
| | - Nadia Califaretti
- Grand River Regional Cancer Centre, 835 King Street W, Kitchener, Ontario, N2G 1G3, Canada.
| | - Andrea Eisen
- Sunnybrook Odette Cancer Centre- Medical Oncology, T2-038- 2075 Bayview Ave, Toronto, Ontario, M4N 3M5, Canada.
| | - Sarah Knowles
- Department of Surgery, Department of Oncology, St Joseph's Health Care Centre, 268 Grosvenor Street, London, Ontario, N6A 4V2, Canada.
| | - Taude Plexman
- Patient and Family Advisor, Ontario Health, 500-525 University Ave, Toronto, ON, M5G 2L3, Canada
| | - Abeer Salim
- Patient and Family Advisor, Ontario Health, 500-525 University Ave, Toronto, ON, M5G 2L3, Canada
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S S, Amirtham U, Gopal C, Arjun R, Jacob L. Prognostic Implications of Concurrent Ductal Carcinoma In Situ in Invasive Breast Cancer: an Observational Nested Cohort Study from a Regional Cancer Center in India. Indian J Surg Oncol 2025; 16:508-515. [PMID: 40337017 PMCID: PMC12052639 DOI: 10.1007/s13193-023-01853-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 11/20/2023] [Indexed: 05/09/2025] Open
Abstract
Ductal Carcinoma In Situ (DCIS) is not an obligate precursor to invasive breast cancer and can exhibit variations in clinical presentation, genetics, biomarkers, and morphological features. There are contrasting views in literature with regard to prognostic significance of DCIS component in invasive cancer. Hence, this study aimed to evaluate how the co-occurrence of DCIS affects the prognosis of people with invasive breast cancer (IBC). A retrospective nested cohort observational study of patients with invasive breast cancer with and without DCIS component was conducted to compare the types of metastases developed on the subsequent follow-up, treatment details, event free survival and other histopathological parameters. There was a significant difference (p = 0.014) in the mean age at diagnosis between patients of IBC with concurrent DCIS (45 ± 11.18 years) and those who had IBC alone (53.24 ± 10.45 years). Invasive cancer with concurrent DCIS component tends to be more common in patients less than 50 years age group (p = 0.03). Majority (75.56%) of the patients were in post-menopausal stage. Patients with concurrent DCIS had higher frequencies of tumors of T1/ T2 stages and zero nodal status. Higher frequencies of local recurrence and visceral metastases were observed in patients with DCIS component compared to patients with IBC alone. Majority had received complete treatment. Longer event free survival was noted in patients with DCIS component compared to those with IBC alone. Our study demonstrated significant association of concurrent DCIS component with mean age at diagnosis in patients with invasive breast cancer. Although a trend towards favorable tumor profile was observed, larger prospective studies are required to enhance the statistical power of our findings. In view of its impact on clinical outcome, it is important to risk stratify invasive breast cancer based on the features of concurrent DCIS component.
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Affiliation(s)
- Shanthala S
- Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore City, Karnataka India
| | - Usha Amirtham
- Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore City, Karnataka India
| | - Champaka Gopal
- Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore City, Karnataka India
| | - Ravi Arjun
- Department of Surgical Oncology, Kidwai Memorial Institute of Oncology, Bangalore City, Karnataka India
| | - Linu Jacob
- Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore City, Karnataka India
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Hwang ES, Hyslop T, Lynch T, Ryser MD, Weiss A, Wolf A, Norris K, Witten M, Grimm L, Schnitt S, Badve S, Factor R, Frank E, Collyar D, Basila D, Pinto D, Watson MA, West R, Davies L, Donovan JL, Shimada A, Li Y, Li Y, Bennett AV, Rosenberg S, Marks J, Winer E, Boisvert M, Giuliano A, Larson KE, Yost K, McAuliffe PF, Krie A, Tamirisa N, Carey LA, Thompson AM, Partridge AH. Active Monitoring With or Without Endocrine Therapy for Low-Risk Ductal Carcinoma In Situ: The COMET Randomized Clinical Trial. JAMA 2025; 333:972-980. [PMID: 39665585 PMCID: PMC11920841 DOI: 10.1001/jama.2024.26698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 11/28/2024] [Indexed: 12/13/2024]
Abstract
Importance Active monitoring for low-risk ductal carcinoma in situ (DCIS) of the breast has been proposed as an alternative to guideline-concordant care, but the safety of this approach is unknown. Objective To compare rates of invasive cancer in patients with low-risk DCIS receiving active monitoring vs guideline-concordant care. Design, Setting, and Participants Prospective, randomized noninferiority trial enrolling 995 women aged 40 years or older with a new diagnosis of hormone receptor-positive grade 1 or grade 2 DCIS without invasive cancer at 100 US Alliance Cancer Cooperative Group clinical trial sites from 2017 to 2023. Interventions Participants were randomized to receive active monitoring (follow-up every 6 months with breast imaging and physical examination; n = 484) or guideline-concordant care (surgery with or without radiation therapy; n = 473). Main Outcomes and Measures The primary outcome was 2-year cumulative risk of ipsilateral invasive cancer diagnosis, according to planned intention-to-treat and per-protocol analyses, with a noninferiority bound of 5%. Results The median age of the 957 participants analyzed was 63.6 (95% CI, 55.5-70.5) years in the guideline-concordant care group and 63.7 (95% CI, 60.0-71.6) years in the active monitoring group. Overall, 15.7% of participants were Black and 75.0% were White. In this prespecified primary analysis, median follow-up was 36.9 months; 346 patients had surgery for DCIS, 264 in the guideline-concordant care group and 82 in the active monitoring group. Forty-six women were diagnosed with invasive cancer, 19 in the active monitoring group and 27 in the guideline-concordant care group. The 2-year Kaplan-Meier cumulative rate of ipsilateral invasive cancer was 4.2% in the active monitoring group vs 5.9% in the guideline-concordant care group, a difference of -1.7% (upper limit of the 95% CI, 0.95%), indicating that active monitoring is not inferior to guideline-concordant care. Invasive tumor characteristics did not differ significantly between groups. Conclusions and Relevance Women with low-risk DCIS randomized to active monitoring did not have a higher rate of invasive cancer in the same breast at 2 years compared with those randomized to guideline-concordant care. Trial Registration ClinicalTrials.gov Identifier: NCT02926911.
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Affiliation(s)
| | - Terry Hyslop
- Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Thomas Lynch
- Department of Surgery, Duke University, Durham, North Carolina
| | - Marc D. Ryser
- Departments of Population Health Sciences and Mathematics, Duke University, Durham, North Carolina
| | - Anna Weiss
- Department of Surgery/Oncology, University of Rochester, Rochester, New York
| | - Anna Wolf
- Alliance Foundation Trials, Boston, Massachusetts
| | | | | | - Lars Grimm
- Department of Radiology, Duke University, Durham, North Carolina
| | - Stuart Schnitt
- Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts
| | - Sunil Badve
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia
| | - Rachel Factor
- Department of Pathology, Duke University, Durham, North Carolina
| | - Elizabeth Frank
- COMET Study Patient Leadership Team, Alliance Foundation Trials, Boston, Massachusetts
| | - Deborah Collyar
- COMET Study Patient Leadership Team, Alliance Foundation Trials, Boston, Massachusetts
| | - Desiree Basila
- COMET Study Patient Leadership Team, Alliance Foundation Trials, Boston, Massachusetts
| | - Donna Pinto
- COMET Study Patient Leadership Team, Alliance Foundation Trials, Boston, Massachusetts
| | - Mark A. Watson
- Department of Pathology and Immunology, Washington University in St Louis, St Louis, Missouri
| | - Robert West
- Department of Pathology, Stanford University, Stanford, California
| | - Louise Davies
- The VA Outcomes Group, Department of Veterans Affairs Medical Center, White River Junction Vermont and Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
| | - Jenny L. Donovan
- Population Health Sciences, University of Bristol, Bristol, United Kingdom
| | - Ayako Shimada
- Division of Biostatistics/Bioinformatics, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Yutong Li
- Division of Biostatistics/Bioinformatics, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Yan Li
- Duke Cancer Institute Biostatistics Shared Resource, Duke University, Durham, North Carolina
| | - Antonia V. Bennett
- Department of Health Policy and Management, University of North Carolina at Chapel Hill
| | | | - Jeffrey Marks
- Department of Surgery, Duke University, Durham, North Carolina
| | - Eric Winer
- School of Medicine, Yale University, New Haven, Connecticut
| | - Marc Boisvert
- Division of Breast Surgery, Medstar Washington Hospital Center, Washington, DC
| | - Armando Giuliano
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California
| | - Kelsey E. Larson
- Department of Surgery, The University of Kansas Health System, Kansas City
| | - Kathleen Yost
- Cancer Research Consortium of West Michigan NCORP, Grand Rapids
| | | | - Amy Krie
- Metro MN Community Oncology Research Consortium, St Louis Park, Minnesota
| | - Nina Tamirisa
- Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston
| | - Lisa A. Carey
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill
| | | | - Ann H. Partridge
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
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7
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Riggi J, Galant C, Vernaeve H, Vassilieff M, Berlière M, Van Bockstal MR. Risk perception of patients with ductal carcinoma in situ (DCIS) of the breast and their healthcare practitioners: The importance of histopathological terminology, and the gaps in our knowledge. Histol Histopathol 2025; 40:297-306. [PMID: 39324807 DOI: 10.14670/hh-18-806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/27/2024]
Abstract
Despite ductal carcinoma in situ (DCIS) being a non-obligatory precursor of invasive breast carcinoma, its diagnosis generates substantial psychological distress. The limited knowledge about the natural history of DCIS contributes to the insufficient transmission of information about DCIS to patients and the general population. The uncertainty about the progression risk to invasive carcinoma hampers adequate communication by clinicians. Breast cancer-related mortality after a DCIS diagnosis is low. However, several studies have demonstrated that DCIS patients generally overestimate the risk of developing loco-regional recurrence or dying from breast cancer. Various factors contribute to this perceived risk. Despite the lack of infiltrative growth, DCIS is treated similarly to invasive breast cancer, with surgery, radiotherapy, and hormonal therapy. Additionally, the term 'carcinoma' in DCIS provokes anxiety. Incorrect risk perception by physicians may result in overtreatment. Here, we provide an overview of epidemiologic data on mortality after DCIS. We discuss the impact of the term "ductal carcinoma in situ" on patients' and physicians' perceptions of risk. The available evidence is mostly limited to patients within the Anglosphere. Recent studies, and European studies in particular, are scarce. We identify this as an area of interest for future large-scale European studies. We discuss the potential value of the "ductal intraepithelial neoplasia" (DIN) terminology, introduced in 1998. Although replacing the concept of "DCIS" with the DIN terminology is unlikely to solve the entire problem of risk overestimation, it could be the first step to optimize doctor-patient communication and alter the current risk perception.
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Affiliation(s)
- Julia Riggi
- Breast Clinic, King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, Brussels, Belgium
- Pôle de Morphologie (MORF), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
- Department of Pathology, Cliniques universitaires Saint-Luc, Brussels, Belgium
| | - Christine Galant
- Breast Clinic, King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, Brussels, Belgium
- Pôle de Morphologie (MORF), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
- Department of Pathology, Cliniques universitaires Saint-Luc, Brussels, Belgium
| | | | - Maud Vassilieff
- Breast Clinic Isala, CHU Saint-Pierre - Site César de Paepe, Brussels, Belgium
| | - Martine Berlière
- Breast Clinic, King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, Brussels, Belgium
- Pôle de Gynécologie (GYNE), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
| | - Mieke R Van Bockstal
- Pôle de Morphologie (MORF), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium
- Department of Pathology, Cliniques universitaires Saint-Luc, Brussels, Belgium
- Breast Clinic, King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, Brussels, Belgium.
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8
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Kanbayashi C, Iwata H. Update on the management of ductal carcinoma in situ of the breast: current approach and future perspectives. Jpn J Clin Oncol 2025; 55:4-11. [PMID: 39223698 PMCID: PMC11708230 DOI: 10.1093/jjco/hyae122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024] Open
Abstract
The standard treatment for ductal carcinoma in situ became well established through the results of several valuable clinical trials, and its therapeutic benefits have now come to be taken for granted. Ductal carcinoma in situ has an extremely good prognosis with the current treatment approach, with a 10-year breast cancer-specific survival rate of 97-98%. According to one retrospective cohort study, the breast cancer-specific survival rate of patients with low-grade ductal carcinoma in situ does not differ significantly between patients undergoing and not undergoing surgery. Some patients with ductal carcinoma in situ are not at a risk of progression to invasive cancer, but the predictors of such progression have not yet been clearly identified. Therefore, the same therapeutic strategies have been used to treat ductal carcinoma in situ and under the assumption that they have risks of invasive breast cancer, and a well-balanced risk/benefit ratio in respect of treatment has not yet been achieved. Based on the results of several recent clinical trials aimed at ensuring provision of a well-balanced treatment for patients with ductal carcinoma in situ which carries a good prognosis, de-escalation of postoperative adjuvant therapy has now begun. Currently, not only is the optimization of postoperative adjuvant therapy accelerating, but also clinical trials to de-escalate basic surgical treatments are under way. There is a possibility of achieving individualized treatment for patients with ductal carcinoma in situ of the breast with reduced treatment intervention. In this review, we present an overview of the current treatment approaches and potential future management strategies for ductal carcinoma in situ of the breast.
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Affiliation(s)
- Chizuko Kanbayashi
- Department of Breast Oncology, Niigata Cancer Center Hospital, Niigata, Japan
| | - Hiroji Iwata
- Department of Medical Research and Developmental Strategy, Core Laboratory, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
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Ueno M, Ueno A, Yamaguchi K, Abe K, Abe M, Kagawa T, Kakisaka K, Ichimoto K, Kamimura H, Komiyama Y, Tsuji K, Tsutsui A, Yamashiki N, Watanabe M, Kayahara T, Takabatake H, Morimoto Y, Takai A, Akahane T, Mochida S, Tanaka A. Survey on Awareness of Tamoxifen-Induced Liver Injury Among Hepatologists in Japan. KANZO 2025; 66:7-18. [DOI: 10.2957/kanzo.66.7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/27/2025]
Affiliation(s)
- Masayuki Ueno
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University
| | - Ayako Ueno
- Department of General Surgery, Kurashiki Central Hospital
| | | | - Kazumichi Abe
- Department of Gastroenterology, Fukushima Medical University School of Medicine
| | - Masanori Abe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine
| | - Tatehiro Kagawa
- Department of Gastroenterology, Tokai University School of Medicine
| | - Keisuke Kakisaka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University
| | | | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University
| | - Yasuyuki Komiyama
- Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Yamanashi
| | - Keiji Tsuji
- Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital
| | - Akemi Tsutsui
- Department of Hepatology, Kagawa Prefectural Central Hospital
| | - Noriyo Yamashiki
- Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center
| | - Masaaki Watanabe
- Department of Gastroenterology, Kitasato University Medical Center
- Tosenen Kitamoto Hospital
| | - Takahisa Kayahara
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital
| | | | - Youichi Morimoto
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital
| | - Atsushi Takai
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University
| | | | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine
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10
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Brackstone M, Durocher-Allen L, Califaretti N, Eisen A, Knowles S, Salim A, Plexman T, Koch CA. Management of Ductal Carcinoma In Situ: An Ontario Health (Cancer Care Ontario) Clinical Practice Guideline. Curr Oncol 2024; 31:7738-7753. [PMID: 39727692 PMCID: PMC11675061 DOI: 10.3390/curroncol31120569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 11/29/2024] [Accepted: 12/01/2024] [Indexed: 12/28/2024] Open
Abstract
(1) Background: To make recommendations on the most effective therapy options for Ductal Carcinoma of the Breast (DCIS) patients; (2) Methods: MEDLINE, EMBASE, Cochrane Library, PROSPERO databases, and main relevant guideline websites were searched. Draft versions of the guideline went through formal internal and external reviews, with a final approval by the Program in Evidence Based Care and the DCIS Expert Panel. The Grading of Recommendations, Assessment, Development, and Evaluation approach was followed; (3) Results: Based on the current evidence from the systematic review and this guideline authors' clinical opinions, initial draft recommendations were developed to improve the management of patients with DCIS. After a comprehensive internal and external review process, ten recommendations and 27 qualifying statements were eventually made. This guideline includes recommendations for the primary treatment of DCIS with surgical treatment and/or radiation therapy and the management of DCIS after primary treatment for patients with DCIS, including DCIS with microinvasion (<1 mm through the duct); (4) Conclusions: The current guideline was created after a systematic review and a comprehensive internal and external review process. We believe this guideline provides valuable insights that will be useful in clinical decision making for health providers.
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Affiliation(s)
- Muriel Brackstone
- London Health Sciences Centre-London Regional Cancer Program, Victoria Hospital, 800 Commissioners Road East, London, ON N6A 5W9, Canada
| | - Lisa Durocher-Allen
- Program in Evidence-Based Care, Ontario Health (Cancer Care Ontario), 699 Concession Street, Hamilton, ON L8V 1C3, Canada
| | - Nadia Califaretti
- Grand River Regional Cancer Centre, 835 King Street W, Kitchener, ON N2G 1G3, Canada;
| | - Andrea Eisen
- Sunnybrook Odette Cancer Centre-Medical Oncology, T2-038-2075 Bayview Ave, Toronto, ON M4N 3M5, Canada;
| | - Sarah Knowles
- Department of Surgery, St Joseph’s Health Care Centre, 268 Grosvenor Street, London, ON N6A 4V2, Canada;
| | - Abeer Salim
- Patient and Family Advisor, Ontario Health, 500-525 University Ave, Toronto, ON M5G 2L3, Canada
| | - Taude Plexman
- Patient and Family Advisor, Ontario Health, 500-525 University Ave, Toronto, ON M5G 2L3, Canada
| | - C. Anne Koch
- Princess Margaret Hospital, 610 University Ave, Toronto, ON M5G2M9, Canada;
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11
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Bowles EJA, Ramin C, Vo JB, Feigelson HS, Gander JC, Veiga LHS, Bodelon C, Curtis RE, Brandt C, de Gonzalez AB, Gierach GL. Endocrine therapy initiation among women diagnosed with ductal carcinoma in situ from 2001 to 2018. Breast Cancer Res Treat 2024; 208:577-587. [PMID: 39148003 DOI: 10.1007/s10549-024-07453-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 07/31/2024] [Indexed: 08/17/2024]
Abstract
PURPOSE Trials demonstrating benefits of tamoxifen for women with ductal carcinoma in situ (DCIS) were published > 20 years ago; yet subsequent uptake of endocrine therapy was low. We estimated endocrine therapy initiation in women with DCIS between 2001 and 2018 in a community setting, reflecting more recent years of diagnosis than previous studies. METHODS This retrospective cohort included adult females ≥ 20 years diagnosed with first primary DCIS between 2001 and 2018, followed through 2019, and enrolled in one of three U.S. integrated healthcare systems. We collected data on endocrine therapy dispensings (tamoxifen, aromatase inhibitors [AIs]) from electronic pharmacy records within 12 months after DCIS diagnosis. Using generalized linear models with a log link and Poisson distribution, we estimated endocrine therapy initiation rates over time and by patient, tumor (including estrogen receptor [ER] status), and treatment characteristics. RESULTS Among 2020 women with DCIS, 587 (29%) initiated endocrine therapy within 12 months after diagnosis (36% among 1208 women with ER-positive DCIS). Among women who used endocrine therapy, 506 (86%) initiated tamoxifen and 81 (14%) initiated AIs. Age-adjusted endocrine therapy initiation declined from 34 to 21% between 2001 and 2017; between 2015 and 2018, AI use increased from 8 to 35%. Women less likely to initiate endocrine therapy were ER-negative or had borderline/unknown or no ER test results, ≥ 65 years at diagnosis, Black, and received no radiotherapy. CONCLUSION One-third of women diagnosed with DCIS initiated endocrine therapy, and use decreased over time. Understanding why women eligible for endocrine therapy do not initiate is important to maximizing disease-free survival following DCIS diagnosis.
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MESH Headings
- Humans
- Female
- Middle Aged
- Breast Neoplasms/drug therapy
- Breast Neoplasms/therapy
- Breast Neoplasms/diagnosis
- Breast Neoplasms/epidemiology
- Carcinoma, Intraductal, Noninfiltrating/drug therapy
- Carcinoma, Intraductal, Noninfiltrating/therapy
- Carcinoma, Intraductal, Noninfiltrating/diagnosis
- Carcinoma, Intraductal, Noninfiltrating/pathology
- Carcinoma, Intraductal, Noninfiltrating/epidemiology
- Aged
- Antineoplastic Agents, Hormonal/therapeutic use
- Tamoxifen/therapeutic use
- Aromatase Inhibitors/therapeutic use
- Retrospective Studies
- Adult
- Aged, 80 and over
- Receptors, Estrogen/metabolism
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Grants
- HHSN 261201800469PP0, HHSN 261201700708P, HHSN 261201600711P, 1R01CA1205621, P01CA154292, HHSN 261201700564P, HHSN75N91019P00076, HHSN 5N910200327, HHSN 61201400010I, HHSN261201800043C, N01-CN-67009, N01-PC-35142, R50CA211115 US National Cancer Institute
- Intramural Research Program NCI NIH HHS
- HHSN 26120090017C RTI International
- Intramural Research Program NCI NIH HHS
- Intramural Research Program NCI NIH HHS
- Intramural Research Program NCI NIH HHS
- Intramural Research Program NCI NIH HHS
- Intramural Research Program NCI NIH HHS
- Intramural Research Program NCI NIH HHS
- Intramural Research Program NCI NIH HHS
- Intramural Research Program NCI NIH HHS
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Affiliation(s)
- Erin J Aiello Bowles
- Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, 1730 Minor Ave, Suite 1360, Seattle, WA, 98101, USA.
| | - Cody Ramin
- Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Jacqueline B Vo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Heather Spencer Feigelson
- Bernard J. Tyson Kaiser Permanente School of Medicine, Pasadena, CA, USA
- Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA
| | - Jennifer C Gander
- Center for Research and Evaluation, Kaiser Permanente Georgia, Atlanta, GA, USA
- Centre College, Danville, KY, USA
| | - Lene H S Veiga
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Clara Bodelon
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
- Department of Population Science, American Cancer Society, Atlanta, GA, USA
| | - Rochelle E Curtis
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Carolyn Brandt
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | | | - Gretchen L Gierach
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
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12
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Diskin B, Sevilimedu V, Morrow M, Van Zee K, Cody HS. Management of Ipsilateral Breast Tumor Recurrence Following Breast Conservation Surgery for Ductal Carcinoma In Situ: A Data-Poor Zone. Ann Surg Oncol 2024; 31:8843-8847. [PMID: 39266787 PMCID: PMC12054159 DOI: 10.1245/s10434-024-16133-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 08/21/2024] [Indexed: 09/14/2024]
Abstract
BACKGROUND Breast conserving surgery (BCS) is well established for the management of ductal carcinoma in situ (DCIS), but neither randomized trials nor guidelines address management of ipsilateral breast tumor recurrence (IBTR) after BCS for DCIS. PATIENTS AND METHODS We identified women treated with BCS for DCIS who developed IBTR as a first event. Between those treated with mastectomy versus re-BCS, we compare the clinicopathologic characteristics, the use of adjuvant radiotherapy (RT) both upfront ("primary RT") and post IBTR ("secondary RT"), of tamoxifen, the rate of third events (local, regional, distant), and both breast cancer specific (BCSS) and overall survival (OS). RESULTS Of 3001 women treated with BCS for DCIS (1978-2010), 383 developed an IBTR as a first event (1983-2023) and were treated by mastectomy (51%) versus re-BCS (49%). Compared with re-BCS, mastectomy patients at initial treatment were higher grade (74% versus 59%, p = 0.004), with more frequent primary RT (61% versus 21%, p < 0.001). Third local events were more frequent for re-BCS than mastectomy (16% versus 3%, p = 0.001), but there were no differences in breast cancer specific or overall survival. CONCLUSIONS For isolated IBTR following BCS for DCIS and treated by mastectomy versus re-BCS (1) mastectomy was associated with less favorable initial pathology and more frequent use of primary RT, (2) re- recurrence was more frequent with re-BCS, and (3) BCSS and OS were comparable. Our data suggest a wider role for re-BCS and further study of the relationship between secondary RT and the rate of third breast events.
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MESH Headings
- Humans
- Female
- Mastectomy, Segmental
- Neoplasm Recurrence, Local/pathology
- Neoplasm Recurrence, Local/surgery
- Carcinoma, Intraductal, Noninfiltrating/surgery
- Carcinoma, Intraductal, Noninfiltrating/pathology
- Middle Aged
- Breast Neoplasms/pathology
- Breast Neoplasms/surgery
- Breast Neoplasms/mortality
- Survival Rate
- Radiotherapy, Adjuvant
- Follow-Up Studies
- Aged
- Prognosis
- Adult
- Tamoxifen/therapeutic use
- Carcinoma, Ductal, Breast/surgery
- Carcinoma, Ductal, Breast/pathology
- Disease Management
- Mastectomy
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Affiliation(s)
- Brian Diskin
- Breast Service, Department of Surgery, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Varadan Sevilimedu
- Biostastistical Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Monica Morrow
- Breast Service, Department of Surgery, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kimberly Van Zee
- Breast Service, Department of Surgery, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Hiram S Cody
- Breast Service, Department of Surgery, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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13
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Pan K, Nelson RA, Chlebowski RT, Piela R, Mullooly M, Simon MS, Rohan TE, Wactawski-Wende J, Manson JE, Mortimer JE, Lane D, Kruper L. Ductal carcinoma in situ and cause-specific mortality among younger and older postmenopausal women: the Women's Health Initiative. Breast Cancer Res Treat 2024; 207:65-79. [PMID: 38730133 DOI: 10.1007/s10549-024-07327-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 03/28/2024] [Indexed: 05/12/2024]
Abstract
BACKGROUND Whether DCIS is associated with higher breast cancer-specific and all-cause mortality is unclear with few studies in older women. Therefore, we examined DCIS and breast cancer-specific, cardiovascular (CVD)-specific, and all-cause mortality among Women's Health Initiative (WHI) Clinical Trial participants overall and by age (< 70 versus ≥ 70 years). METHODS Of 68,132 WHI participants, included were 781 postmenopausal women with incident DCIS and 781 matched controls. Serial screening mammography was mandated with high adherence. DCIS cases were confirmed by central medical record review. Adjusted multivariable Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Kaplan Meier (KM) plots were used to assess 10-year and 20-year mortality rates. RESULTS After 20.3 years total, and 13.2 years median post-diagnosis follow-up, compared to controls, DCIS was associated with higher breast cancer-specific mortality (HR 3.29; CI = 1.32-8.22, P = 0.01). The absolute difference in 20-year breast cancer mortality was 1.2% without DCIS and 3.4% after DCIS, log-rank P = 0.026. Findings were similar by age (< 70 versus ≥ 70 years) with no interaction (P interaction = 0.80). Incident DCIS was not associated with CVD-specific mortality (HR 0.77; CI-0.54-1.09, P = 0.14) or with all-cause mortality (HR 0.96; CI = 0.80-1.16, P = 0.68) with similar findings by age. CONCLUSIONS In postmenopausal women, incident DCIS was associated with over three-fold higher breast cancer-specific mortality, with similar findings in younger and older postmenopausal women. These finding suggest caution in using age to adjust DCIS clinical management or research strategies.
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Grants
- N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32 NHLBI NIH HHS
- N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32 NHLBI NIH HHS
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Affiliation(s)
- Kathy Pan
- The Lundquist Institute, 1124 W. Carson St, Torrance, CA, USA
| | | | | | - Rita Piela
- The Lundquist Institute, 1124 W. Carson St, Torrance, CA, USA
| | - Maeve Mullooly
- The Lundquist Institute, 1124 W. Carson St, Torrance, CA, USA
| | - Michael S Simon
- The Lundquist Institute, 1124 W. Carson St, Torrance, CA, USA
| | - Thomas E Rohan
- The Lundquist Institute, 1124 W. Carson St, Torrance, CA, USA
| | | | - JoAnn E Manson
- The Lundquist Institute, 1124 W. Carson St, Torrance, CA, USA
| | | | - Dorothy Lane
- The Lundquist Institute, 1124 W. Carson St, Torrance, CA, USA
| | - Laura Kruper
- The Lundquist Institute, 1124 W. Carson St, Torrance, CA, USA
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14
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Li H, Aggarwal A, Toro P, Fu P, Badve SS, Cuzick J, Madabhushi A, Thorat MA. A prognostic and predictive computational pathology immune signature for ductal carcinoma in situ: retrospective results from a cohort within the UK/ANZ DCIS trial. Lancet Digit Health 2024; 6:e562-e569. [PMID: 38987116 DOI: 10.1016/s2589-7500(24)00116-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Revised: 04/21/2024] [Accepted: 05/23/2024] [Indexed: 07/12/2024]
Abstract
BACKGROUND The density of tumour-infiltrating lymphocytes (TILs) could be prognostic in ductal carcinoma in situ (DCIS). However, manual TIL quantification is time-consuming and suffers from interobserver and intraobserver variability. In this study, we developed a TIL-based computational pathology biomarker and evaluated its association with the risk of recurrence and benefit of adjuvant treatment in a clinical trial cohort. METHODS In this retrospective cohort study, a computational pathology pipeline was developed to generate a TIL-based biomarker (CPath TIL categories). Subsequently, the signature underwent a masked independent validation on H&E-stained whole-section images of 755 patients with DCIS from the UK/ANZ DCIS randomised controlled trial. Specifically, continuous biomarker CPath TIL score was calculated as the average TIL density in the DCIS microenvironment and dichotomised into binary biomarker CPath TIL categories (CPath TIL-high vs CPath TIL-low) using the median value as a cutoff. The primary outcome was ipsilateral breast event (IBE; either recurrence of DCIS [DCIS-IBE] or invasive progression [I-IBE]). The Cox proportional hazards model was used to estimate the hazard ratio (HR). FINDINGS CPath TIL-score was evaluable in 718 (95%) of 755 patients (151 IBEs). Patients with CPath TIL-high DCIS had a greater risk of IBE than those with CPath TIL-low DCIS (HR 2·10 [95% CI 1·39-3·18]; p=0·0004). The risk of I-IBE was greater in patients with CPath TIL-high DCIS than those with CPath TIL-low DCIS (3·09 [1·56-6·14]; p=0·0013), and the risk of DCIS-IBE was non-significantly higher in those with CPath TIL-high DCIS (1·61 [0·95-2·72]; p=0·077). A significant interaction (pinteraction=0·025) between CPath TIL categories and radiotherapy was observed with a greater magnitude of radiotherapy benefit in preventing IBE in CPath TIL-high DCIS (0·32 [0·19-0·54]) than CPath TIL-low DCIS (0·40 [0·20-0·81]). INTERPRETATION High TIL density is associated with higher recurrence risk-particularly of invasive recurrence-and greater radiotherapy benefit in patients with DCIS. Our TIL-based computational pathology signature has a prognostic and predictive role in DCIS. FUNDING National Cancer Institute under award number U01CA269181, Cancer Research UK (C569/A12061; C569/A16891), and the Breast Cancer Research Foundation, New York (NY, USA).
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Affiliation(s)
- Haojia Li
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
| | - Arpit Aggarwal
- Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA
| | - Paula Toro
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
| | - Pingfu Fu
- Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
| | - Sunil S Badve
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA; Winship Cancer Institute, Atlanta, GA, USA
| | - Jack Cuzick
- Centre for Cancer Screening, Prevention and Early Diagnosis, Wolfson Institute of Population Health, Queen Mary University of London, London, UK
| | - Anant Madabhushi
- Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA; Joseph Maxwell Cleland Atlanta VA Medical Center, Atlanta, GA, USA.
| | - Mangesh A Thorat
- Centre for Cancer Screening, Prevention and Early Diagnosis, Wolfson Institute of Population Health, Queen Mary University of London, London, UK; School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK; Breast Surgery, Homerton University Hospital, London, UK; Breast Surgery, Guy's Hospital, Great Maze Pond, London, UK.
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15
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Jiang G, Ren X, Shang X. Impact of surgical types on overall survival in patients with ductal carcinoma in situ: an analysis based on the SEER database. Gland Surg 2024; 13:910-926. [PMID: 39015717 PMCID: PMC11247566 DOI: 10.21037/gs-23-468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 05/30/2024] [Indexed: 07/18/2024]
Abstract
Background Breast cancer, as one of the most common malignancies among women globally, presents a concerning incidence rate, underscoring the importance of addressing the treatment of its precursor lesion, ductal carcinoma in situ (DCIS). Treatment decisions for DCIS, involving the balance between breast-conserving surgery (BCS) and mastectomy, remain an area requiring further investigation. This study aimed to compare influence of different surgical types on overall survival (OS) of patients with DCIS and identify specific subgroups with improved OS to develop an effective survival nomogram for patients. Methods Patient data from the Surveillance, Epidemiology, and End Results (SEER) database for DCIS cohort from 2010 to 2020 were retrieved. Kaplan-Meier (K-M) survival curves were utilized to compare prognostic OS of patients with different surgical methods. Cox regression analysis was employed to determine prognostic factors and establish a nomogram to predict 3-, 5-, and 10-year survival rates. The model was confirmed by Concordance Index (C-index), calibration curves, and receiver operating characteristic (ROC) curves. Results A total of 71,675 patients with DCIS were included. Patients who underwent subcutaneous mastectomy (SM) demonstrated the best OS compared to other surgical types. Additionally, adjuvant radiotherapy or chemotherapy in combination with surgery significantly improved OS compared to surgery alone. Among DCIS patients aged ≤74 years, those who underwent SM benefited the most in terms of OS, while in the age group of 63-74 years, patients who underwent BCS had significantly higher OS than those who underwent total (simple) mastectomy (TM)/modified radical mastectomy (MRM). Multiple factors were associated with improved OS in DCIS patients, and these factors were integrated into the nomogram to establish OS predictions. The C-index, calibration curves, and ROC curves indicated that the nomogram was suitable for assessing patient prognosis. Conclusions This study demonstrated that SM treatment yielded the best survival rates for DCIS patients, providing important guidance for future surgical decision-making. Moreover, identifying multiple independent factors related to survival and establishing reliable survival nomograms can assist physicians in developing personalized treatment plans and prolonging patient survival.
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Affiliation(s)
- Guobin Jiang
- Thyroid and Breast Surgery Department, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, China
- Thyroid and Breast Surgery Department, Enze Hospital, Taizhou Enze Medical Center (Group), Taizhou, China
| | - Xia Ren
- Thyroid and Breast Surgery Department, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, China
- Thyroid and Breast Surgery Department, Enze Hospital, Taizhou Enze Medical Center (Group), Taizhou, China
| | - Xi Shang
- Thyroid and Breast Surgery Department, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, China
- Thyroid and Breast Surgery Department, Enze Hospital, Taizhou Enze Medical Center (Group), Taizhou, China
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16
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Delaloge S, Khan SA, Wesseling J, Whelan T. Ductal carcinoma in situ of the breast: finding the balance between overtreatment and undertreatment. Lancet 2024; 403:2734-2746. [PMID: 38735296 DOI: 10.1016/s0140-6736(24)00425-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 01/10/2024] [Accepted: 02/29/2024] [Indexed: 05/14/2024]
Abstract
Ductal carcinoma in situ (DCIS) accounts for 15-25% of all breast cancer diagnoses. Its prognosis is excellent overall, the main risk being the occurrence of local breast events, as most cases of DCIS do not progress to invasive cancer. Systematic screening has greatly increased the incidence of this non-obligate precursor of invasion, lending urgency to the need to identify DCIS that is prone to invasive progression and distinguish it from non-invasion-prone DCIS, as the latter can be overdiagnosed and therefore overtreated. Treatment strategies, including surgery, radiotherapy, and optional endocrine therapy, decrease the risk of local events, but have no effect on survival outcomes. Active surveillance is being evaluated as a possible new option for low-risk DCIS. Considerable efforts to decipher the biology of DCIS have led to a better understanding of the factors that determine its variable natural history. Given this variability, shared decision making regarding optimal, personalised treatment strategies is the most appropriate course of action. Well designed, risk-based de-escalation studies remain a major need in this field.
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Affiliation(s)
- Suzette Delaloge
- Department of Cancer Medicine, Interception Programme, Gustave Roussy, Villejuif, France.
| | - Seema Ahsan Khan
- Department of Surgery, Northwestern University, Chicago, IL, USA
| | - Jelle Wesseling
- Divisions of Molecular Pathology & Department of Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands; Department of Pathology, Leiden University Medical Center, Leiden, Netherlands
| | - Timothy Whelan
- Department of Oncology, McMaster University, Hamilton, ON, Canada
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17
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Coschi CH, Dodbiba L, Guerry D. Oncology: What You May Have Missed in 2023. Ann Intern Med 2024; 177:S57-S70. [PMID: 38621244 DOI: 10.7326/m24-0520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/17/2024] Open
Abstract
Advances in oncology treatment methods have improved outcomes and quality of life for patients with cancer. However, care of these patients can be complex, and the contribution of physicians from different specialties is crucial. This article highlights important publications from 2023 on topics across a wide spectrum relating to the management of oncology patients. The literature was screened for significant new evidence that is relevant to internal medicine specialists and subspecialists whose focus is not oncology. Two articles address the importance of social interventions targeting end-of-life care for low-income and minority patients and the well-being of caregivers. Two additional articles address screening considerations in patients at risk for colorectal and lung cancer. Two more articles address safe use of hormone-related therapies to treat symptoms of menopause and prevent disease recurrence or progression in patients diagnosed with noninvasive breast neoplasia. Finally, several articles were included on topics related to COVID-19 vaccination in patients with cancer, use of cannabinoids for cancer pain control, chronic autoimmune adverse effects related to use of immune checkpoint inhibitors, and the incidence of second primary neoplasms.
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Affiliation(s)
- Courtney H Coschi
- Division of Medical Oncology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada (C.H.C., L.D.)
| | - Lorin Dodbiba
- Division of Medical Oncology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada (C.H.C., L.D.)
| | - DuPont Guerry
- Associate Editor, Annals of Internal Medicine, and Emeritus Professor of Medicine, Perelman School of Medicine, Philadelphia, Pennsylvania (D.G.)
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18
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Leonardi MC, Zerella MA, Lazzeroni M, Fusco N, Veronesi P, Galimberti VE, Corso G, Dicuonzo S, Rojas DP, Morra A, Gerardi MA, Lorubbio C, Zaffaroni M, Vincini MG, Orecchia R, Jereczek-Fossa BA, Magnoni F. Tools to Guide Radiation Oncologists in the Management of DCIS. Healthcare (Basel) 2024; 12:795. [PMID: 38610216 PMCID: PMC11011767 DOI: 10.3390/healthcare12070795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 03/27/2024] [Accepted: 04/03/2024] [Indexed: 04/14/2024] Open
Abstract
Similar to invasive breast cancer, ductal carcinoma in situ is also going through a phase of changes not only from a technical but also a conceptual standpoint. From prescribing radiotherapy to everyone to personalized approaches, including radiotherapy omission, there is still a lack of a comprehensive framework to guide radiation oncologists in decision making. Many pieces of the puzzle are finding their place as high-quality data mature and are disseminated, but very often, the interpretation of risk factors and the perception of risk remain very highly subjective. Sharing the therapeutic choice with patients requires effective communication for an understanding of risks and benefits, facilitating an informed decision that does not increase anxiety and concerns about prognosis. The purpose of this narrative review is to summarize the current state of knowledge to highlight the tools available to radiation oncologists for managing DCIS, with an outlook on future developments.
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Affiliation(s)
- Maria Cristina Leonardi
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (M.C.L.); (S.D.); (D.P.R.); (A.M.); (M.A.G.); (C.L.); (M.Z.); (M.G.V.); (B.A.J.-F.)
| | - Maria Alessia Zerella
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (M.C.L.); (S.D.); (D.P.R.); (A.M.); (M.A.G.); (C.L.); (M.Z.); (M.G.V.); (B.A.J.-F.)
| | - Matteo Lazzeroni
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy;
| | - Nicola Fusco
- Department of Oncology and Hemato-Oncology, University of Milan, 20141 Milan, Italy; (N.F.); (P.V.); (G.C.)
- Division of Pathology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy
| | - Paolo Veronesi
- Department of Oncology and Hemato-Oncology, University of Milan, 20141 Milan, Italy; (N.F.); (P.V.); (G.C.)
- Division of Breast Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (V.E.G.); (F.M.)
| | - Viviana Enrica Galimberti
- Division of Breast Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (V.E.G.); (F.M.)
| | - Giovanni Corso
- Department of Oncology and Hemato-Oncology, University of Milan, 20141 Milan, Italy; (N.F.); (P.V.); (G.C.)
- Division of Breast Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (V.E.G.); (F.M.)
| | - Samantha Dicuonzo
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (M.C.L.); (S.D.); (D.P.R.); (A.M.); (M.A.G.); (C.L.); (M.Z.); (M.G.V.); (B.A.J.-F.)
| | - Damaris Patricia Rojas
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (M.C.L.); (S.D.); (D.P.R.); (A.M.); (M.A.G.); (C.L.); (M.Z.); (M.G.V.); (B.A.J.-F.)
| | - Anna Morra
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (M.C.L.); (S.D.); (D.P.R.); (A.M.); (M.A.G.); (C.L.); (M.Z.); (M.G.V.); (B.A.J.-F.)
| | - Marianna Alessandra Gerardi
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (M.C.L.); (S.D.); (D.P.R.); (A.M.); (M.A.G.); (C.L.); (M.Z.); (M.G.V.); (B.A.J.-F.)
| | - Chiara Lorubbio
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (M.C.L.); (S.D.); (D.P.R.); (A.M.); (M.A.G.); (C.L.); (M.Z.); (M.G.V.); (B.A.J.-F.)
- Department of Oncology and Hemato-Oncology, University of Milan, 20141 Milan, Italy; (N.F.); (P.V.); (G.C.)
| | - Mattia Zaffaroni
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (M.C.L.); (S.D.); (D.P.R.); (A.M.); (M.A.G.); (C.L.); (M.Z.); (M.G.V.); (B.A.J.-F.)
| | - Maria Giulia Vincini
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (M.C.L.); (S.D.); (D.P.R.); (A.M.); (M.A.G.); (C.L.); (M.Z.); (M.G.V.); (B.A.J.-F.)
| | - Roberto Orecchia
- Scientific Directorate, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy;
| | - Barbara Alicja Jereczek-Fossa
- Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (M.C.L.); (S.D.); (D.P.R.); (A.M.); (M.A.G.); (C.L.); (M.Z.); (M.G.V.); (B.A.J.-F.)
- Department of Oncology and Hemato-Oncology, University of Milan, 20141 Milan, Italy; (N.F.); (P.V.); (G.C.)
| | - Francesca Magnoni
- Division of Breast Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (V.E.G.); (F.M.)
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Wang J, Li B, Luo M, Huang J, Zhang K, Zheng S, Zhang S, Zhou J. Progression from ductal carcinoma in situ to invasive breast cancer: molecular features and clinical significance. Signal Transduct Target Ther 2024; 9:83. [PMID: 38570490 PMCID: PMC10991592 DOI: 10.1038/s41392-024-01779-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 02/14/2024] [Accepted: 02/26/2024] [Indexed: 04/05/2024] Open
Abstract
Ductal carcinoma in situ (DCIS) represents pre-invasive breast carcinoma. In untreated cases, 25-60% DCIS progress to invasive ductal carcinoma (IDC). The challenge lies in distinguishing between non-progressive and progressive DCIS, often resulting in over- or under-treatment in many cases. With increasing screen-detected DCIS in these years, the nature of DCIS has aroused worldwide attention. A deeper understanding of the biological nature of DCIS and the molecular journey of the DCIS-IDC transition is crucial for more effective clinical management. Here, we reviewed the key signaling pathways in breast cancer that may contribute to DCIS initiation and progression. We also explored the molecular features of DCIS and IDC, shedding light on the progression of DCIS through both inherent changes within tumor cells and alterations in the tumor microenvironment. In addition, valuable research tools utilized in studying DCIS including preclinical models and newer advanced technologies such as single-cell sequencing, spatial transcriptomics and artificial intelligence, have been systematically summarized. Further, we thoroughly discussed the clinical advancements in DCIS and IDC, including prognostic biomarkers and clinical managements, with the aim of facilitating more personalized treatment strategies in the future. Research on DCIS has already yielded significant insights into breast carcinogenesis and will continue to pave the way for practical clinical applications.
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Affiliation(s)
- Jing Wang
- The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Department of Breast Surgery and Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, China
| | - Baizhou Li
- Department of Pathology, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China
| | - Meng Luo
- The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, China
- Department of Plastic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jia Huang
- The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, China
| | - Kun Zhang
- Department of Breast Surgery and Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shu Zheng
- The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, China
| | - Suzhan Zhang
- The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, China.
| | - Jiaojiao Zhou
- The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- Department of Breast Surgery and Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, China.
- Cancer Center, Zhejiang University, Hangzhou, China.
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20
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Joo JH, Kim W, Nam J, Kim D, Kim HY, Jung YJ, Choo KS, Nam KJ, Nam SB, Kim JJ, Ki Y. 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]. Gland Surg 2024; 13:131-143. [PMID: 38455345 PMCID: PMC10915430 DOI: 10.21037/gs-23-433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 01/23/2024] [Indexed: 03/09/2024]
Abstract
Background 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. Methods 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. Results 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. Conclusions 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.
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Affiliation(s)
- Ji Hyeon Joo
- Department of Radiation Oncology, Pusan National University School of Medicine, Yangsan, Republic of Korea
- Department of Radiation Oncology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Wontaek Kim
- Department of Radiation Oncology, Pusan National University School of Medicine, Yangsan, Republic of Korea
- Department of Radiation Oncology, Pusan National University Hospital, Busan, Republic of Korea
| | - Jiho Nam
- Department of Radiation Oncology, Pusan National University Hospital, Busan, Republic of Korea
| | - Donghyun Kim
- Department of Radiation Oncology, Pusan National University School of Medicine, Yangsan, Republic of Korea
- Department of Radiation Oncology, Pusan National University Hospital, Busan, Republic of Korea
| | - Hyun Yul Kim
- Department of Surgery, Pusan National University School of Medicine, Yangsan, Republic of Korea
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Youn Joo Jung
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Ki Seok Choo
- Department of Radiology, Pusan National University School of Medicine, Yangsan, Republic of Korea
- Department of Radiology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Kyung Jin Nam
- Department of Radiology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Su Bong Nam
- Department of Plastic and Reconstructive Surgery, Pusan National University School of Medicine, Yangsan, Republic of Korea
- Department of Plastic and Reconstructive Surgery, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Jae-Joon Kim
- Department of Oncology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
| | - Yongkan Ki
- Department of Radiation Oncology, Pusan National University School of Medicine, Yangsan, Republic of Korea
- Department of Radiation Oncology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
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21
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Wright JL, Gray R, Rahbar H, Comstock CE, Tjoe JA, Badve S, Recht A, Sparano JA, Davidson NE, Wolff AC. Lumpectomy without radiation for ductal carcinoma in situ of the breast: 20-year results from the ECOG-ACRIN E5194 study. NPJ Breast Cancer 2024; 10:16. [PMID: 38396024 PMCID: PMC10891055 DOI: 10.1038/s41523-024-00622-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Accepted: 02/08/2024] [Indexed: 02/25/2024] Open
Abstract
We report the 20-year rate of ipsilateral breast event (IBE) for patients with ductal carcinoma in situ (DCIS) treated with lumpectomy without radiation on a non-randomized prospective clinical trial. Patients were enrolled in cohort 1: low- or intermediate-grade DCIS, size ≤ 2.5 cm (n = 561); or cohort 2: high-grade DCIS, size ≤ 1 cm (n = 104). The Kaplan-Meier method was used to estimate time-to-event distributions. Cox proportional hazard methods were used to estimate hazard ratios (HRs) and tests for significance for event times. 561 patients were enrolled in cohort 1 and 104 in cohort 2. After central pathology review, 26% in cohort 1 were recategorized as high-grade and 26% in cohort 2 as low- or intermediate-grade. Mean DCIS size was similar at 7.5 mm in cohort 1 and 7.8 mm in cohort 2. Surgical margin was ≥3 mm in 96% of patients, and about 30% received tamoxifen. Median follow-up was 19.2 years. There were 104 IBEs, of which 54 (52%) were invasive. The IBE and invasive IBE rates increased in both cohorts up to 15 years, then plateaued. The 20-year IBE rates were 17.8% for cohort 1 and 28.7% for cohort 2 (p = 0.005), respectively. Invasive IBE occurred in 9.8% and 15.1% (p = 0.09), respectively. On multivariable analysis, IBE risk increased with size and was higher in cohort 2, but grade and margin width were not significantly associated with IBE. For patients with DCIS treated with excision without radiation, the rate of IBE increased with size and assigned cohort mostly in the first 15 years.
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Affiliation(s)
- Jean L Wright
- Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| | - Robert Gray
- Dana Farber Cancer Institute, Boston, MA, USA
| | - Habib Rahbar
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | | | - Judy A Tjoe
- Department of Surgical Oncology, Green Bay Oncology, Green Bay, WI, USA
| | - Sunil Badve
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Emory University Winship Cancer Institute, Atlanta, GA, USA
| | - Abram Recht
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Joseph A Sparano
- Division of Hematology and Medical Oncology, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Nancy E Davidson
- Fred Hutchinson Cancer Center and University of Washington, Seattle, WA, USA
| | - Antonio C Wolff
- Johns Hopkins Women's Malignancies Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Skjerven HK, Myklebust EM, Korvald C, Stubberud K, Hovda T, Porojnicu AC, Kaaresen R, Hofvind S, Schlicting E, Sahlberg KK. Long-term follow-up of complex oncoplastic breast-conserving surgery, standard breast conservation and skin-sparing mastectomy in DCIS - a register-based study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:107938. [PMID: 38199004 DOI: 10.1016/j.ejso.2023.107938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 12/10/2023] [Accepted: 12/25/2023] [Indexed: 01/12/2024]
Abstract
BACKGROUND Few studies evaluate oncological safety in complex oncoplastic breast-conserving surgery(C-OBCS) for DCIS. It still needs to be defined whether it is equivalent to standard breast conservation(S-BCS) or an alternative to skin-sparing mastectomy(SSM). This study compares local recurrence rates(LR), disease-free survival(DFS) and overall survival (OS) between the three surgical techniques. METHODS We conducted a retrospective register-based study on LR, DFS and OS of patients operated with S-BCS(n=1388), C-OBCS (n=106) or skin-sparing mastectomy (n=218) for DCIS diagnosed 2007-2020. Data was extracted from the Norwegian Breast Cancer Registry. RESULTS In the S-BCS, C-OBCS and SSM groups, median age was 60, 58 and 51 years (p<0.001), median size 15, 25, and 40 mm (p<0.001) and median follow-up 55, 48 and 76 months. At ten years, the overall LR was 12.7%, 14.3% for S-BCS, 11.2% for C-OBCS and 6.8% for SSM. Overall DFS at ten years was 82.3%, 80.5% for S-BCS, 82.4% for C-OBCS and 90.4% for SSM. At ten years, the OS was 93.8%, 93.0% in S-BCS, 93.3% in C-OBCS and 96.6% in the SSM group. Weighted Kaplan Meier plots showed that SSM had a significantly higher DFS than S-BCS (p=0.003) and C-OBCS (p=0.029). DFS in C-OBCS versus S-BCS and the difference in OS was not significant (p=0.264). CONCLUSION SSM had a significantly higher DFS than S-BCS and C-OBCS. The difference in DFS between S-BCS and C-OBCS, and OS between the three groups was not statistically significant. Our study suggests that C-OBCS is a safe alternative to S-BCS and SSM.
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Affiliation(s)
- Helle Kristine Skjerven
- Section for Breast and Endocrine Surgery, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
| | - Even Moa Myklebust
- Oslo Centre for Biostatistics and Epidemiology, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Research and Innovation, Vestre Viken Hospital Trust, Drammen, Norway
| | - Christian Korvald
- Department of Plastic and Reconstructive Surgery, Oslo University Hospital, Oslo, Norway
| | - Kjetil Stubberud
- Section for Breast and Endocrine Surgery, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway
| | - Tone Hovda
- Section for Breast and Endocrine Surgery, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway
| | | | - Rolf Kaaresen
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Solveig Hofvind
- Department of Health and Care Sciences, The Artic University, UiT, Tromsø, Norway; Section for Breast Cancer Screening, Cancer Registry of Norway, Oslo, Norway
| | - Ellen Schlicting
- Section for Breast and Endocrine Surgery, Oslo University Hospital, Oslo, Norway
| | - Kristine Kleivi Sahlberg
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Research and Innovation, Vestre Viken Hospital Trust, Drammen, Norway
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23
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Wang Y, Peng D, Zhou X, Hu W, Li F. Treatments and Prognosis of the Breast Ductal Carcinoma In Situ. Clin Breast Cancer 2024; 24:122-130.e2. [PMID: 38016910 DOI: 10.1016/j.clbc.2023.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 11/06/2023] [Accepted: 11/06/2023] [Indexed: 11/30/2023]
Abstract
INTRODUCTION With 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 METHODS This 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. RESULTS Among 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. CONCLUSION In 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.
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Affiliation(s)
- Yaxue Wang
- State Key Laboratory of Oncology, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Dingsheng Peng
- Department of Radiation Oncology, Huizhou Central People's Hospital, Huizhou, PR China
| | - Xinhui Zhou
- State Key Laboratory of Oncology, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Wendie Hu
- State Key Laboratory of Oncology, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China
| | - Fengyan Li
- State Key Laboratory of Oncology, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
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O’Keefe T, Yau C, Iaconetti E, Jeong E, Brabham C, Kim P, McGuire J, Griffin A, Wallace A, Esserman L, Harismendy O, Hirst G. Duration of Endocrine Treatment for DCIS impacts second events: Insights from a large cohort of cases at two academic medical centers. RESEARCH SQUARE 2024:rs.3.rs-3403438. [PMID: 38260526 PMCID: PMC10802747 DOI: 10.21203/rs.3.rs-3403438/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/24/2024]
Abstract
Ductal carcinoma in situ (DCIS) incidence has risen rapidly with the introduction of screening mammography, yet 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 registry of retrospective DCIS cases (N = 1,916) with median follow up of 8.2 years. We show that patients with DCIS who took less than 2 years of adjuvant ET alone have a similar second event rate as BCS. However, patients 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.
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Affiliation(s)
- Thomas O’Keefe
- Department of Surgery, University of California, San Diego
| | - Christina Yau
- Department of Surgery, University of California, San Francisco, CA
| | - Emma Iaconetti
- Department of Surgery, University of California, San Francisco, CA
| | - Eliza Jeong
- Moores Cancer Center, Division of Biomedical Informatics, UCSD School of
Medicine University of California, San Diego, La Jolla, CA
| | - Case Brabham
- Department of Surgery, University of California, San Francisco, CA
| | - Paul Kim
- Department of Surgery, University of California, San Francisco, CA
| | | | - Ann Griffin
- UCSF Helen Diller Family Comprehensive Cancer Center
| | - Anne Wallace
- Department of Surgery, University of California, San Diego
| | - Laura Esserman
- Department of Surgery, University of California, San Francisco, CA
| | - Olivier Harismendy
- Moores Cancer Center, Division of Biomedical Informatics, UCSD School of
Medicine University of California, San Diego, La Jolla, CA
| | - Gillian Hirst
- Department of Surgery, University of California, San Francisco, CA
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25
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de Sousa CFPM, Pereira AAL, Arruda GV, Gouveia AG, Hanna SA, Cruz MRDS, Dos Anjos CH, Bevilacqua JLB, Alcantara Filho P, de Moraes FY, Marta GN. Real-World Evidence on the Use of Endocrine Therapy for Ductal Carcinoma In Situ in Patients Treated With Breast-Conserving Surgery Followed by Postoperative Radiation Therapy: A Brazilian Retrospective Cohort Study. Clin Breast Cancer 2023; 23:e499-e506. [PMID: 37758557 DOI: 10.1016/j.clbc.2023.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 08/06/2023] [Accepted: 08/20/2023] [Indexed: 09/29/2023]
Abstract
INTRODUCTION/BACKGROUND This study aims to evaluate the reproducibility of findings from randomized controlled trials regarding adjuvant hormone therapy (HT) for breast ductal carcinoma in situ (DCIS) in a real-life scenario. MATERIALS/METHODS This retrospective cohort study used Fundação Oncocentro de São Paulo database. It included DCIS patients DCIS who received breast-conserving surgery and postoperative radiation therapy. The endpoints were local control (LC), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS We analyzed 2192 patients treated between 2000 and 2020. The median FU was 48.99 months. Most patients (53.33%; n = 1169) received adjuvant HT. Patients not receiving adjuvant HT tend to be older (P = .021) and have a lower educational level (P < .001). At the end of FU, 1.5% of patients had local recurrence, and there was no significant difference between groups (P = .19). The 10-year OS and BCSS were 89.4% and 97.5% for adjuvant HT versus 91.5% and 98.5% for no adjuvant HT, respectively, and there were no significant differences between groups. The 10-year OS was 93.25% for medium/high education level versus 87.31% for low (HR for death 0.51; 95% CI, 0.32-0.83; P = .007). CONCLUSIONS The benefits of adjuvant HT for DCIS were not reproduced in a Brazilian cohort. Education significantly impacted survival and HT usage, reflecting the influence of socioeconomic factors. These findings can allow for more precise interventions.
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MESH Headings
- Female
- Humans
- Antineoplastic Agents, Hormonal/therapeutic use
- Brazil/epidemiology
- Breast Neoplasms/pathology
- Carcinoma, Intraductal, Noninfiltrating/drug therapy
- Carcinoma, Intraductal, Noninfiltrating/radiotherapy
- Carcinoma, Intraductal, Noninfiltrating/surgery
- Mastectomy, Segmental
- Neoplasm Recurrence, Local/pathology
- Radiotherapy, Adjuvant
- Randomized Controlled Trials as Topic
- Reproducibility of Results
- Retrospective Studies
- Cohort Studies
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Affiliation(s)
| | | | - Gustavo Viani Arruda
- Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP, Ribeirão Preto, SP, Brazil
| | - Andre Guimaraes Gouveia
- Department of Oncology, Division of Radiation Oncology, Juravinski Cancer Centre, Hamilton, ON, Canada
| | | | | | | | | | | | | | - Gustavo Nader Marta
- Department of Radiation Oncology, Hospital Sírio Libanês, São Paulo, SP, Brazil; Latin America Cooperative Oncology Group (LACOG), Porto Alegre, RS, Brazil
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26
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Nakashima A, Yamazaki H, Suzuki G, Yamada K, Norihiro A, Kimoto T, Masui K, Nakatsuka K, Taguchi T, Naoi Y. The Feasibility of Omitting Postoperative Radiotherapy in Japanese Patients With Ductal Carcinoma In Situ of Breast Treated With Breast-Conserving Surgery. Cureus 2023; 15:e48187. [PMID: 38054154 PMCID: PMC10695091 DOI: 10.7759/cureus.48187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/01/2023] [Indexed: 12/07/2023] Open
Abstract
Background To analyze the feasibility of omitting postoperative radiotherapy (PORT) after breast-conserving surgery (BCS) in Japanese patients with ductal carcinoma in situ (DCIS). Materials and methods We retrospectively analyzed 88 patients with small pure DCIS (median diameter 1.1 cm, ≤ 4 cm) who underwent BCS with (n = 39) or without (n = 49) PORT. The primary and secondary endpoints were ipsilateral breast tumor recurrence (IBTR) and overall survival (OS), respectively, between the groups that received PORT and those that did not. Results The PORT group included a high number of margin-positive cases. The incidence of IBTR was 2.4% (95% confidence interval (CI), 0.3-15.7%) and 2.8% (95% CI, 0.4-18.2%) at five years and 5.5% (95% CI, 1.4-20.6%) and 2.8% (95% CI, 0.4-18.2%) at 10 years in patients without and with PORT, respectively (p = 0.686). In the margin-negative group, only one patient showed IBTR without RT (2.3%), whereas no patient with PORT experienced IBTR (0%). To date, there have been no regional or distant metastases; therefore, no patient has experienced breast cancer-related deaths. The OS rates were 97.7% (95% CI, 84.9-99.6%) and 100% at 10 years in patients without and with PORT, respectively (p = 0.372). Conclusion This study suggests that the omission of PORT after BCS could be a feasible option for selected Japanese patients but requires further investigation to identify the low-risk factor in patients who can omit PORT.
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Affiliation(s)
| | - Hideya Yamazaki
- Radiology, Kyoto Prefectural University of Medicine, Kyoto, JPN
| | - Gen Suzuki
- Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, JPN
| | - Kei Yamada
- Radiology, Kyoto Prefectural University of Medicine, Kyoto, JPN
| | - Aibe Norihiro
- Radiology, Kyoto Prefectural University of Medicine, Kyoto, JPN
| | - Takuya Kimoto
- Radiology, Kyoto Prefectural University of Medicine, Kyoto, JPN
| | - Koji Masui
- Radiology, Kyoto Prefectural University of Medicine, Kyoto, JPN
| | - Katsuhiko Nakatsuka
- Endocrine and Breast Surgery, Kyoto Prefectural University of Medicine, Kyoto, JPN
| | - Tetsuya Taguchi
- Endocrine and Breast Surgery, Kyoto Prefectural University of Medicine, Kyoto, JPN
| | - Yasuto Naoi
- Endocrine and Breast Surgery, Kyoto Prefectural University of Medicine, Kyoto, JPN
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Gligorov J, Benderra MA, Barthere X, de Forceville L, Antoine EC, Cottu PH, Delaloge S, Pierga JY, Belkacemi Y, Houvenaegel G, Pujol P, Rivera S, Spielmann M, Penault-Llorca F, Namer M. Recommandations francophones pour la pratique clinique concernant la prise en charge des cancers du sein de Saint-Paul-de-Vence 2022-2023. Bull Cancer 2023; 110:10S1-10S43. [PMID: 38061827 DOI: 10.1016/s0007-4551(23)00473-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
With more than 60,000 new cases of breast cancer in mainland France in 2023 and 8% of all cancer deaths, breast cancer is the leading cancer in women in terms of incidence and mortality. While the number of new cases has almost doubled in 30 years, the percentage of patients at all stages alive at 5 years (87%) and 10 years (76%) testifies to the major progress made in terms of screening, characterisation and treatment. However, this progress, rapid as it is, needs to be evaluated and integrated into an overall strategy, taking into account the characteristics of the disease (stage and biology), as well as those of the patients being treated. These are the objectives of the St Paul-de-Vence recommendations for clinical practice. We report here the summary of the votes, discussions and conclusions of the Saint-Paul-de-Vence 2022-2023 RPCs.
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Affiliation(s)
- Joseph Gligorov
- Institut universitaire de cancérologie AP-HP Sorbonne université, Paris, France.
| | | | - Xavier Barthere
- Institut universitaire de cancérologie AP-HP Sorbonne université, Paris, France
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Schmitz RSJM, van den Belt-Dusebout AW, Clements K, Ren Y, Cresta C, Timbres J, Liu YH, Byng D, Lynch T, Menegaz BA, Collyar D, Hyslop T, Thomas S, Love JK, Schaapveld M, Bhattacharjee P, Ryser MD, Sawyer E, Hwang ES, Thompson A, Wesseling J, Lips EH, Schmidt MK. Association of DCIS size and margin status with risk of developing breast cancer post-treatment: multinational, pooled cohort study. BMJ 2023; 383:e076022. [PMID: 37903527 PMCID: PMC10614034 DOI: 10.1136/bmj-2023-076022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/27/2023] [Indexed: 11/01/2023]
Abstract
OBJECTIVE To examine the association between size and margin status of ductal carcinoma in situ (DCIS) and risk of developing ipsilateral invasive breast cancer and ipsilateral DCIS after treatment, and stage and subtype of ipsilateral invasive breast cancer. DESIGN Multinational, pooled cohort study. SETTING Four large international cohorts. PARTICIPANTS Patient level data on 47 695 women with a diagnosis of pure, primary DCIS between 1999 and 2017 in the Netherlands, UK, and US who underwent surgery, either breast conserving or mastectomy, often followed by radiotherapy or endocrine treatment, or both. MAIN OUTCOME MEASURES The main outcomes were 10 year cumulative incidence of ipsilateral invasive breast cancer and ipsilateral DCIS estimated in relation to DCIS size and margin status, and adjusted hazard ratios and 95% confidence intervals, estimated using multivariable Cox proportional hazards analyses with multiple imputed data RESULTS: The 10 year cumulative incidence of ipsilateral invasive breast cancer was 3.2%. In women who underwent breast conserving surgery with or without radiotherapy, only adjusted risks for ipsilateral DCIS were significantly increased for larger DCIS (20-49 mm) compared with DCIS <20 mm (hazard ratio 1.38, 95% confidence interval 1.11 to 1.72). Risks for both ipsilateral invasive breast cancer and ipsilateral DCIS were significantly higher with involved compared with clear margins (invasive breast cancer 1.40, 1.07 to 1.83; DCIS 1.39, 1.04 to 1.87). Use of adjuvant endocrine treatment was not significantly associated with a lower risk of ipsilateral invasive breast cancer compared to treatment with breast conserving surgery only (0.86, 0.62 to 1.21). In women who received breast conserving treatment with or without radiotherapy, higher DCIS grade was not significantly associated with ipsilateral invasive breast cancer, only with a higher risk of ipsilateral DCIS (grade 1: 1.42, 1.08 to 1.87; grade 3: 2.17, 1.66 to 2.83). Higher age at diagnosis was associated with lower risk (per year) of ipsilateral DCIS (0.98, 0.97 to 0.99) but not ipsilateral invasive breast cancer (1.00, 0.99 to 1.00). Women with large DCIS (≥50 mm) more often developed stage III and IV ipsilateral invasive breast cancer compared to women with DCIS <20 mm. No such association was found between involved margins and higher stage of ipsilateral invasive breast cancer. Associations between larger DCIS and hormone receptor negative and human epidermal growth factor receptor 2 positive ipsilateral invasive breast cancer and involved margins and hormone receptor negative ipsilateral invasive breast cancer were found. CONCLUSIONS The association of DCIS size and margin status with ipsilateral invasive breast cancer and ipsilateral DCIS was small. When these two factors were added to other known risk factors in multivariable models, clinicopathological risk factors alone were found to be limited in discriminating between low and high risk DCIS.
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Affiliation(s)
- Renée S J M Schmitz
- Division of Molecular Pathology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 Amsterdam, Netherlands
| | | | | | - Yi Ren
- Department of Biostatistics and Bioinformatics, Biostatistics Shared Resource Duke Cancer Institute, Durham, NC, USA
| | - Chiara Cresta
- Division of Molecular Pathology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 Amsterdam, Netherlands
| | - Jasmine Timbres
- School of Cancer and Pharmaceutical Science, King's College London, London, UK
| | - Yat-Hee Liu
- Division of Molecular Pathology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 Amsterdam, Netherlands
| | - Danalyn Byng
- Department of Population Health Sciences, Duke University Medical Center, Durham, NC, USA
| | - Thomas Lynch
- Department of Surgery, Duke Cancer Institute, Durham, NC, USA
| | - Brian A Menegaz
- Department of Surgical Oncology, Baylor College of Medicine, Houston, TX, USA
| | | | - Terry Hyslop
- Department of Biostatistics and Bioinformatics, Biostatistics Shared Resource Duke Cancer Institute, Durham, NC, USA
| | - Samantha Thomas
- Department of Biostatistics and Bioinformatics, Biostatistics Shared Resource Duke Cancer Institute, Durham, NC, USA
| | - Jason K Love
- Department of Breast Surgical Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Michael Schaapveld
- Division of Psycho-oncology and Epidemiology, Netherlands Cancer Institute- Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands
| | - Proteeti Bhattacharjee
- Division of Molecular Pathology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 Amsterdam, Netherlands
| | - Marc D Ryser
- Department of Population Health Sciences, Duke University Medical Center, Durham, NC, USA
- Department of Mathematics, Duke University, Durham, NC, USA
| | - Elinor Sawyer
- School of Cancer and Pharmaceutical Science, King's College London, London, UK
| | - E Shelley Hwang
- Department of Surgery, Duke Cancer Institute, Durham, NC, USA
| | - Alastair Thompson
- Department of Surgical Oncology, Baylor College of Medicine, Houston, TX, USA
| | - Jelle Wesseling
- Division of Molecular Pathology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 Amsterdam, Netherlands
- Division of Diagnostic Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands
- Department of Pathology, Leiden University Medical Centre, Leiden, Netherlands
| | - Esther H Lips
- Division of Molecular Pathology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 Amsterdam, Netherlands
| | - Marjanka K Schmidt
- Division of Molecular Pathology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, 1066 Amsterdam, Netherlands
- Department of Clinical Genetics, Leiden University Medical Centre, Leiden, Netherlands
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Shah C, Vicini F. Adjuvant Radiation Therapy for Ductal Carcinoma In Situ of the Breast: A Clinician's Dilemma. Ann Surg Oncol 2023; 30:6281-6283. [PMID: 37280311 DOI: 10.1245/s10434-023-13691-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 05/17/2023] [Indexed: 06/08/2023]
MESH Headings
- Humans
- Female
- Carcinoma, Intraductal, Noninfiltrating/radiotherapy
- Carcinoma, Intraductal, Noninfiltrating/surgery
- Radiotherapy, Adjuvant
- Breast/pathology
- Carcinoma, Ductal, Breast/radiotherapy
- Carcinoma, Ductal, Breast/surgery
- Carcinoma, Ductal, Breast/pathology
- Breast Neoplasms/radiotherapy
- Breast Neoplasms/surgery
- Mastectomy, Segmental
- Neoplasm Recurrence, Local/pathology
- Carcinoma in Situ/pathology
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Affiliation(s)
- Chirag Shah
- Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
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Record SM, Hwang ESS, Chiba A. How to Navigate the Treatment Spectrum from Multimodality Therapy to Observation Alone for ductal carcinoma in situ. Surg Oncol Clin N Am 2023; 32:663-673. [PMID: 37714635 DOI: 10.1016/j.soc.2023.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/17/2023]
Abstract
DCIS detection has increased dramatically since the introduction of screening mammography. Current guidance concordant care recommends surgical intervention for all patients with DCIS, followed by radiation and/or endocrine therapy for some. Adjuvant therapies after surgical excision have reduced recurrence rates but not breast cancer mortality. Given the lack of evidence of current treatment regimens and the morbidity associated with these treatments, there is concern that DCIS is over-treated. Active surveillance may be a favorable alternative for selected patients and is currently being investigated through four international clinical trials.
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Affiliation(s)
- Sydney M Record
- Department of Surgery, Duke University Medical Center, 40 Duke Medicine Circle, 124 Davison Building, Durham, NC 27710, USA. https://twitter.com/sydney_record
| | - Eun-Sil Shelley Hwang
- Department of Surgery, Duke University Medical Center, 40 Duke Medicine Circle, 124 Davison Building, Durham, NC 27710, USA; Duke Cancer Institute, 20 Duke Medicine Circle, Durham, NC 27710, USA. https://twitter.com/drshelleyhwang
| | - Akiko Chiba
- Department of Surgery, Duke University Medical Center, 40 Duke Medicine Circle, 124 Davison Building, Durham, NC 27710, USA; Duke Cancer Institute, 20 Duke Medicine Circle, Durham, NC 27710, USA; Department of Surgery, 508 Fulton Street, Durham, NC 27705, USA.
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31
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van Walle L, Verhoeven D, Marotti L, Ponti A, Tomatis M, Rubio IT. Trends and variation in treatment of early breast cancer in European certified breast centres: an EUSOMA-based analysis. Eur J Cancer 2023; 192:113244. [PMID: 37633095 DOI: 10.1016/j.ejca.2023.113244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 07/07/2023] [Indexed: 08/28/2023]
Abstract
BACKGROUND Practice indicators (PI) measure provided care making use of real-world data. This study describes trends and variations in adjuvant treatment of early breast cancer (EBC) using the European Society of Breast Cancer Specialists (EUSOMA) database. METHODS The analysis was conducted on anonymous cumulative data registered by 56 certified breast centres, which all entered at least 500 new diagnoses in the database in the 10-year period 2010-2019. Practice trends of radiotherapy, endocrine treatment, chemotherapy, and anti-HER2 therapy were evaluated. The association with age group (<50, 50-69, ≥70) and geographical area of the centre (Northern, Central, Southern Europe; NE, CE, SE) was assessed with the Pearson Chi2 test for independence in contingency tables. RESULTS In total, 150,150 patients with EBC were selected. Overall, radiotherapy was administered more frequently in NE centres, and conversely, endocrine, chemo-, and anti-HER2 therapy were used more frequently in SE centres (p<0.001). 46.9% of the pN1 patients received postmastectomy radiotherapy, with significant differences by age and geographical region (p < 0.001). Adjuvant endocrine treatment for endocrine-sensitive carcinoma in situ was administered in 46.1%, with a decreasing trend during the study period (58.5-34.5%; p < 0.001). Anti-HER2 therapy was delivered in 75.6% of all patients with HER2BC T1a/bN0, patients older than 70 received anti-HER2 in 67.6% in SE compared to 31.3% in NE centres. CONCLUSION Important variations in EBC management between European certified breast centres have been demonstrated. PI using real-world data can help to monitor, evaluate, and eventually guide and align good clinical practice in the management of breast cancer.
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Affiliation(s)
| | - Didier Verhoeven
- Department of Medical Oncology, Breast Centre Voorkempen, AZ Klina, Brasschaat, Belgium; University of Antwerp, Antwerpen, Belgium
| | - Lorenza Marotti
- European Society of Breast Cancer Specialists (EUSOMA), Florence, Italy
| | - Antonio Ponti
- CPO Piemonte, Turin and European Society of Breast Cancer Specialists (EUSOMA), Florence, Italy
| | - Mariano Tomatis
- European Society of Breast Cancer Specialists (EUSOMA), Florence, Italy
| | - Isabel T Rubio
- Breast Surgical Oncology, Clinica Universidad de Navarra, Madrid, Spain
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Kuo SH, Tseng LM, Chen ST, Sagara Y, Chang YC, Yeh HT, Kuo YL, Hung CC, Lu TP, Lee YH, Toi M, Huang CS. Radiotherapy versus low-dose tamoxifen following breast-conserving surgery for low-risk and estrogen receptor-positive breast ductal carcinoma in situ: an international open-label randomized non-inferiority trial (TBCC-ARO DCIS Trial). BMC Cancer 2023; 23:865. [PMID: 37710198 PMCID: PMC10500726 DOI: 10.1186/s12885-023-11291-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 08/11/2023] [Indexed: 09/16/2023] Open
Abstract
BACKGROUND Radiotherapy (RT) following breast-conserving surgery (BCS) is mainly used to decrease the rate of ipsilateral breast tumor recurrence (IBTR) in women with breast ductal carcinoma in situ (DCIS). Recent studies have demonstrated that low-dose tamoxifen significantly reduces IBTR in breast DCIS. Here, we aim to determine whether the administration of low-dose tamoxifen is non-inferior to RT in preventing IBTR in patients with low-risk characteristics of breast DCIS. METHODS/DESIGN This is a prospective, international, open-label, randomized, non-inferiority trial. Patients with low-risk clinicopathologic features (> 40 years old, low risk of breast cancer susceptibility gene (BRCA) 1 and BRCA2 mutations, mammographically detected unicentric and non-mass lesions, low- or intermediate-grade without comedo or necrosis, measuring < 2.5 cm with margins ≥ 3 mm, and estrogen receptor-positive status) of DCIS who underwent BCS will be randomized at a 1:1 ratio to either receive tamoxifen (5 mg/day) for 5 years or undergo RT with conventional fractions (50 Gy in 25 fractions) or hypofractionations (40.05 Gy in 15 fractions). Randomization will be stratified by the Taiwan Breast Cancer Consortium. As approximately 5% of patients cannot tolerate the side effects of low-dose tamoxifen and will receive RT, we estimate that 405 patients will be randomized to a low-dose tamoxifen arm and 405 patients to the RT arm, according to a non-inferiority margin within 5% of IBTR difference and 90% β-power noticing non-inferiority. The primary endpoints are breast tumor recurrence, including ipsilateral, regional, contralateral, and distant recurrence of breast DCIS or invasive cancer. The secondary endpoints are overall survival and adverse effects of RT and tamoxifen. Translational studies will also be conducted for this trial. DISCUSSION This is the first non-inferiority trial on breast DCIS. This study will provide an important recommendation for clinical physicians on whether to use low-dose adjuvant tamoxifen for patients with low-risk breast DCIS who do not want to receive adjuvant RT. TRIAL REGISTRATION ClinicalTrials.gov, ID: NCT04046159, Registered on April 30, 2019.
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Affiliation(s)
- Sung-Hsin Kuo
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Radiation Oncology, National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ling-Ming Tseng
- Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shou-Tung Chen
- Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan
| | - Yasuaki Sagara
- Department of Breast Surgical Oncology, Hakuaikai Social Cooperation, Sagara Hospital, Kagoshima, Japan
| | | | - Hsien-Tang Yeh
- Department of Surgery, Lotung Poh-Ai Hospital, Yilan, Taiwan
| | - Yao-Lung Kuo
- Division of Breast Surgery, Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Chih-Chiang Hung
- Department of Surgery, Division of Breast Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Tzu-Pin Lu
- Department of Public Health, National, Institute of Epidemiology and Preventive Medicine, Taiwan University, Taipei, Taiwan
| | - Yi-Hsuan Lee
- Department of Pathology, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan
| | - Masakazu Toi
- Tokyo Metropolitan Cancer and Infectious Disease Centre, Komagome Hospital, Tokyo, Japan
| | - Chiun-Sheng Huang
- Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan South Rd, Taipei, Taiwan.
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Dreyfuss AD, Max D, Flynn J, Zhang Z, Gillespie EF, Xu A, Cuaron J, Mueller B, Khan AJ, Cahlon O, Powell SN, McCormick B, Braunstein LZ. Locoregional Control Benefit of a Tumor Bed Boost for Ductal Carcinoma In Situ. Adv Radiat Oncol 2023; 8:101254. [PMID: 37250283 PMCID: PMC10220256 DOI: 10.1016/j.adro.2023.101254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 04/12/2023] [Indexed: 05/31/2023] Open
Abstract
Purpose Radiation therapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) reduces invasive and in situ recurrences. Whereas landmark studies suggest that a tumor bed boost improves local control for invasive breast cancer, the benefit in DCIS remains less certain. We evaluated outcomes of patients with DCIS treated with or without a boost. Methods and Materials The study cohort comprised patients with DCIS who underwent BCS at our institution from 2004 to 2018. Clinicopathologic features, treatment parameters, and outcomes were ascertained from medical records. Patient and tumor characteristics were evaluated relative to outcomes using univariable and multivariable Cox models. Recurrence-free survival (RFS) estimates were generated using the Kaplan-Meier method. Results We identified 1675 patients who underwent BCS for DCIS (median age, 56 years; interquartile range, 49-64 years). Boost RT was used in 1146 cases (68%) and hormone therapy in 536 (32%). At a median follow-up of 4.2 years (interquartile range, 1.4-7.0 years), we observed 61 locoregional recurrence events (56 local, 5 regional) and 21 deaths. Univariable logistic regression demonstrated that boost RT was more common among younger patients (P < .001) with positive or close margins (P < .001) and with larger tumors (P < .001) of higher grade (P = .025). The 10-year RFS rate was 88.8% among those receiving a boost and 84.3% among those without a boost (P = .3), and neither univariable nor multivariable analyses revealed an association between boost RT and locoregional recurrence. Conclusions Among patients with DCIS who underwent BCS, use of a tumor bed boost was not associated with locoregional recurrence or RFS. Despite a preponderance of adverse features among the boost cohort, outcomes were similar to those of patients not receiving a boost, suggesting that a boost may mitigate risk of recurrence among patients with high-risk features. Ongoing studies will elucidate the extent to which a tumor bed boost influences disease control rates.
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Affiliation(s)
- Alexandra D. Dreyfuss
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Danielle Max
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
- Department of Radiation Oncology, UCLA Health, Los Angeles, California
| | - Jessica Flynn
- Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Zhigang Zhang
- Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Erin F. Gillespie
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Amy Xu
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - John Cuaron
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Boris Mueller
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Atif J. Khan
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Oren Cahlon
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Simon N. Powell
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Beryl McCormick
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Lior Z. Braunstein
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
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Jatoi I, Shaaban AM, Jou E, Benson JR. The Biology and Management of Ductal Carcinoma in Situ of the Breast. Curr Probl Surg 2023; 60:101361. [PMID: 37596033 DOI: 10.1016/j.cpsurg.2023.101361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Accepted: 06/27/2023] [Indexed: 08/20/2023]
Affiliation(s)
- Ismail Jatoi
- Division of Surgical Oncology and Endocrine Surgery, University of Texas Health Science Center, San Antonio, TX.
| | - Abeer M Shaaban
- Department of Cellular Pathology, Queen Elizabeth Hospital Birmingham and Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
| | - Eric Jou
- Oxford University Hospitals NHS Trust, University of Oxford, Oxford, UK
| | - John R Benson
- Addenbrooke's Hospital, University of Cambridge, Cambridge; School of Medicine, Anglia Ruskin University, Cambridge and Chelmsford, UK
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Dejthevaporn T, Patanayindee P. Clinical Treatment Score Post-5 Years as a Tool for Risk Estimation of Late Recurrence in Thai Patients With Estrogen-Receptor-Positive, Early Breast Cancer: A Validation Study. Breast Cancer (Auckl) 2023; 17:11782234231186869. [PMID: 37533837 PMCID: PMC10392218 DOI: 10.1177/11782234231186869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 06/22/2023] [Indexed: 08/04/2023] Open
Abstract
Background The risk of late distant recurrence (LDR) of estrogen receptor (ER)-positive breast cancer continues even after 5 years of endocrine treatment. Clinical Treatment Score after 5 years (CTS5) was developed and validated as a tool to assess the risk of LDR using data from Tamoxifen, Arimidex Alone or in Combinations (ATAC) and Breast International Group 1-98 (BIG1-98) trials. This study aimed to externally validate CTS5 in a real-world cohort of patients treated at an academic center in Thailand. Methods The study was a retrospective analytical research study of early-stage, ER-positive breast cancer patients. The primary endpoint was LDR. The risk of LDR was determined using the CTS5 calculator. Cox regression model and Kaplan-Meier survival analysis were applied for prognostic validation of CTS5. Calibration was performed by comparing observed LDR to expected LDR using the Hosmer-Lemeshow (H-L) test. Results A total of 323 women were included with a median follow-up period of 11.6 years. The rate of LDR was 10.8%. The CTS5 was prognostic for LDR. C-index of the area under the ROC curve was 0.672. There was no significant difference between actual and expected numbers of LDR with an observed (O) LDR events to expected (E) number of LDR events ratio of 0.99 (0.86-1.12) (H-L P = .79) indicating a proper calibration in this cohort. Conclusions Our study validated that CTS5 is accurate in predicting the risk of LDR in ER-positive breast cancer cases in Thai patients. Its performance seemed to be better in postmenopausal patients. CTS5 could be applied in routine clinical practice to improve decisions regarding prolonged endocrine therapy, particularly in resource-limited countries where molecular profiling are inaccessible.
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Affiliation(s)
- Thitiya Dejthevaporn
- Division of Medical Oncology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Panchanin Patanayindee
- Division of Medical Oncology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
- Medical Oncology Unit, Department of Medicine, Faculty of Medicine, Thammasat University, Bangkok, Thailand
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Moyer CL, Brown PH. Targeting nuclear hormone receptors for the prevention of breast cancer. Front Med (Lausanne) 2023; 10:1200947. [PMID: 37583424 PMCID: PMC10424511 DOI: 10.3389/fmed.2023.1200947] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Accepted: 06/30/2023] [Indexed: 08/17/2023] Open
Abstract
Advancements in research have led to the steady decline of breast cancer mortality over the past thirty years. However, breast cancer incidence has continued to rise, resulting in an undue burden on healthcare costs and highlighting a great need for more effective breast cancer prevention strategies, including targeted chemo preventative agents. Efforts to understand the etiology of breast cancer have uncovered important roles for nuclear receptors in the development and progression of breast cancer. Targeted therapies to inhibit estrogen receptor (ER) and progesterone receptor (PR) signaling (selective ER modulators, aromatase inhibitors and selective PR modulators) have shown great promise for the treatment and prevention of hormone receptor (HR)-positive breast cancer. However, these drugs do not prevent HR-negative disease. Therefore, recent efforts have focused on novel targeted therapies with the potential to prevent both HR-positive and HR-negative breast cancer. Among these include drugs that target other nuclear receptors, such as retinoic acid receptor (RAR), retinoid X receptor (RXR) and vitamin D receptor (VDR). In this review we provide an overview of recent preclinical and clinical trials targeting members of the nuclear receptor superfamily for the prevention of breast cancer.
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Affiliation(s)
- Cassandra L. Moyer
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Powel H. Brown
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States
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Hahn E, Rodin D, Sutradhar R, Nofech-Mozes S, Trebinjac S, Paszat LF, Rakovitch E. Can Molecular Biomarkers Help Reduce the Overtreatment of DCIS? Curr Oncol 2023; 30:5795-5806. [PMID: 37366916 DOI: 10.3390/curroncol30060433] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 05/23/2023] [Accepted: 06/05/2023] [Indexed: 06/28/2023] Open
Abstract
Ductal carcinoma in situ (DCIS), especially in the era of mammographic screening, is a commonly diagnosed breast tumor. Despite the low breast cancer mortality risk, management with breast conserving surgery (BCS) and radiotherapy (RT) is the prevailing treatment approach in order to reduce the risk of local recurrence (LR), including invasive LR, which carries a subsequent risk of breast cancer mortality. However, reliable and accurate individual risk prediction remains elusive and RT continues to be standardly recommended for most women with DCIS. Three molecular biomarkers have been studied to better estimate LR risk after BCS-Oncotype DX DCIS score, DCISionRT Decision Score and its associated Residual Risk subtypes, and Oncotype 21-gene Recurrence Score. All these molecular biomarkers represent important efforts towards improving predicted risk of LR after BCS. To prove clinical utility, these biomarkers require careful predictive modeling with calibration and external validation, and evidence of benefit to patients; on this front, further research is needed. Most trials do not incorporate molecular biomarkers in evaluating de-escalation of therapy for DCIS; however, one-the Prospective Evaluation of Breast-Conserving Surgery Alone in Low-Risk DCIS (ELISA) trial-incorporates the Oncotype DX DCIS score in defining a low-risk population and is an important next step in this line of research.
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Affiliation(s)
- Ezra Hahn
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON M5G 2C4, Canada
- Department of Radiation Oncology, University of Toronto, Toronto, ON M5T 1P5, Canada
| | - Danielle Rodin
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON M5G 2C4, Canada
- Department of Radiation Oncology, University of Toronto, Toronto, ON M5T 1P5, Canada
| | - Rinku Sutradhar
- Institute for Clinical Evaluative Sciences, Toronto, ON M4N 3M5, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada
| | - Sharon Nofech-Mozes
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
- Department of Pathology, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada
| | - Sabina Trebinjac
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada
| | - Lawrence Frank Paszat
- Department of Radiation Oncology, University of Toronto, Toronto, ON M5T 1P5, Canada
- Institute for Clinical Evaluative Sciences, Toronto, ON M4N 3M5, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada
| | - Eileen Rakovitch
- Department of Radiation Oncology, University of Toronto, Toronto, ON M5T 1P5, Canada
- Institute for Clinical Evaluative Sciences, Toronto, ON M4N 3M5, Canada
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada
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Oses G, Mension E, Pumarola C, Castillo H, Francesc L, Torras I, Cebrecos I, Caparrós X, Ganau S, Ubeda B, Bargallo X, González B, Sanfeliu E, Vidal-Sicart S, Moreno R, Muñoz M, Santamaría G, Mollà M. Analysis of Local Recurrence Risk in Ductal Carcinoma In Situ and External Validation of the Memorial Sloan Kettering Cancer Center Nomogram. Cancers (Basel) 2023; 15:2392. [PMID: 37190320 PMCID: PMC10136555 DOI: 10.3390/cancers15082392] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Revised: 04/05/2023] [Accepted: 04/19/2023] [Indexed: 05/17/2023] Open
Abstract
BACKGROUND Adjuvant radiotherapy and hormonotherapy after breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) have been shown to reduce the risk of local recurrence. To predict the risk of ipsilateral breast tumor relapse (IBTR) after BCS, the Memorial Sloan Kettering Cancer Center (MSKCC) developed a nomogram to analyze local recurrence (LR) risk in our cohort and to assess its external validation. METHODS A historical cohort study using data from 296 patients treated for DCIS at the Hospital Clínic of Barcelona was carried out. Patients who had had a mastectomy were excluded from the analysis. RESULTS The mean age was 58 years (42-75), and the median follow-up time was 10.64 years. The overall local relapse rate was 13.04% (27 patients) during the study period. Actuarial 5- and 10-year IBTR rates were 5.8 and 12.9%, respectively. The external validation of the MSKCC nomogram was performed using a multivariate logistic regression analysis on a total of 207 patients, which did not reach statistical significance in the studied population for predicting LR (p = 0.10). The expression of estrogen receptors was significantly associated with a decreased risk of LR (OR: 0.25; p = 0.004). CONCLUSIONS In our series, the LR rate was 13.4%, which was in accordance with the published series. The MSKCC nomogram did not accurately predict the IBTR in this Spanish cohort of patients treated for DCIS (p = 0.10).
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Affiliation(s)
- Gabriela Oses
- Department of Radiation Oncology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Eduard Mension
- Department of Obstetrics and Gynecology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Claudia Pumarola
- Department of Obstetrics and Gynecology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Helena Castillo
- Department of Obstetrics and Gynecology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - León Francesc
- Department of Radiation Oncology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Inés Torras
- Department of Obstetrics and Gynecology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Isaac Cebrecos
- Department of Obstetrics and Gynecology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Xavier Caparrós
- Department of Obstetrics and Gynecology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Sergi Ganau
- Department of Radiology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Belén Ubeda
- Department of Radiology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Xavier Bargallo
- Department of Radiology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Blanca González
- Departament of Pathology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Esther Sanfeliu
- Departament of Pathology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Sergi Vidal-Sicart
- Departament of Nuclear Medicine, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Reinaldo Moreno
- Department of Medical Oncology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Montserrat Muñoz
- Department of Medical Oncology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
| | - Gorane Santamaría
- Department of Radiology, Princess Alexandra Hospital, Brisbane 4102, Australia
| | - Meritxell Mollà
- Department of Radiation Oncology, Hospital Clínic of Barcelona, 08036 Barcelona, Spain
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Fauveau LR, Dao TN, Wallace LB, Mamawala MK, Obaid A, Waddimba AC, Grant MD. Positive surgical margins after breast-conserving surgery for ductal carcinoma in-situ: does histologic grade or estrogen receptor status matter? Breast Cancer Res Treat 2023; 199:215-220. [PMID: 37027122 DOI: 10.1007/s10549-023-06905-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 02/24/2023] [Indexed: 04/08/2023]
Abstract
PURPOSE DCIS has been shown to have a higher rate of positive margins following breast-conserving surgery (BCS) than invasive breast cancer. We aim to analyze certain factors of DCIS, specifically histologic grade and estrogen receptor (ER) status, in patients with positive surgical margins following BCS to determine if there is an association. METHODS A retrospective review of our institutional patient registry was performed to identify women with DCIS and microinvasive DCIS who underwent BCS by a single surgeon from 1999 to 2021. Demographics and clinicopathologic characteristics between patients with and without positive surgical margins were compared using chi-square or Student's t-test. We assessed factors associated with positive margins using univariate and multivariable logistic regression. RESULTS Of the 615 patients evaluated, there was no significant difference in demographics between the patients with and without positive surgical margins. Increasing tumor size was an independent risk factor for margin positivity (P = < 0.001). On univariate analysis both high histologic grade (P = 0.009) and negative ER status (P = < 0.001) were significantly associated with positive surgical margins. However, when adjusted in multivariable analysis, only negative ER status remained significantly associated with margin positivity (OR = 0.39 [95% CI 0.20-0.77]; P = 0.006). CONCLUSION The study confirms increased tumor size as a risk factor for positive surgical margins. We also demonstrated that ER negative DCIS was independently associated with a higher rate of positive margins after BCS. Given this information, we can modify our surgical approach to reduce rate of positive margins in patients with large-sized ER negative DCIS.
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Affiliation(s)
- Lindsey R Fauveau
- Division of Surgical Oncology, Department of Surgery, Baylor University Medical Center, 3410 Worth Street, Suite 235, Dallas, TX, 75246, USA.
- Baylor Scott and White Research Institute, 3500 Gaston Ave, Dallas, TX, 75246, USA.
- Department of Surgery, Health Systems Science, Baylor University Medical Center, 3500 Gaston Ave, Dallas, TX, 75246, USA.
- Division of Breast Surgical Oncology, Department of Surgery, Ochsner Health, 10310 The Grove Boulevard, Baton Rouge, LA, 70836, USA.
| | - Tuoc N Dao
- Division of Surgical Oncology, Department of Surgery, Baylor University Medical Center, 3410 Worth Street, Suite 235, Dallas, TX, 75246, USA
| | - Lucy B Wallace
- Division of Surgical Oncology, Department of Surgery, Baylor University Medical Center, 3410 Worth Street, Suite 235, Dallas, TX, 75246, USA
| | - Mufaddal K Mamawala
- Baylor Scott and White Research Institute, 3500 Gaston Ave, Dallas, TX, 75246, USA
| | - Ala Obaid
- Baylor Scott and White Research Institute, 3500 Gaston Ave, Dallas, TX, 75246, USA
| | - Anthony C Waddimba
- Baylor Scott and White Research Institute, 3500 Gaston Ave, Dallas, TX, 75246, USA
- Department of Surgery, Health Systems Science, Baylor University Medical Center, 3500 Gaston Ave, Dallas, TX, 75246, USA
| | - Michael D Grant
- Division of Surgical Oncology, Department of Surgery, Baylor University Medical Center, 3410 Worth Street, Suite 235, Dallas, TX, 75246, USA
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Nash AL, Hwang ES. The Landmark Series-Ductal Carcinoma in Situ: The Evolution of Treatment. Ann Surg Oncol 2023; 30:3206-3214. [PMID: 37024766 DOI: 10.1245/s10434-023-13370-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 03/06/2023] [Indexed: 04/08/2023]
Abstract
The evolution of ductal carcinoma in situ (DCIS) management has been driven by a parallel evolution in our understanding of its natural history. Early trials established the benefit of adjuvant therapies in all patients with DCIS. In contrast, subsequent studies have stratified patients to determine their eligibility for progressively less invasive and less intensive therapies. Large, randomized trials and meta-analyses have supported this shift away from treating DCIS as an homogenous disease treated with similar intensity to invasive breast cancer. This review describes the landmark studies on which current DCIS management is based.
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Affiliation(s)
- Amanda L Nash
- Department of Surgery, Duke University Medical Center, Durham, NC, USA.
- Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
| | - E Shelley Hwang
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
- Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA
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Goldberg M, Parpia S, Rakovitch E, Chang L, Bowen J, Lukka H, Perera F, Fyles A, Wright J, Sussman J, Whelan T. Long-term outcomes and effects of hypofractionated radiotherapy in microinvasive breast cancer: Analysis from a randomized trial. Breast 2023; 68:189-193. [PMID: 36827900 PMCID: PMC9988653 DOI: 10.1016/j.breast.2023.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 02/06/2023] [Accepted: 02/09/2023] [Indexed: 02/12/2023] Open
Abstract
PURPOSE The natural history of microinvasive (T1mi) breast cancer is uncertain. The objective was to evaluate long-term local and distant recurrence rates following breast conserving surgery (BCS) in a prospective cohort of patients with T1mi compared to T1a-2 disease who received whole breast irradiation (WBI) in the context of a randomized trial of hypofractionation. METHODS 1234 patients with T1-2 N0 breast cancer were randomized to receive adjuvant WBI of 42.5Gy in 16 daily fractions, or 50Gy in 25 daily fractions after BCS. An analysis of patients with T1mi tumors compared with T1a-2 disease was performed. Kaplan-Meier estimates of local recurrence (LR), distant recurrence, and overall survival (OS) were compared using the log-rank test. RESULTS Median follow-up was 12 years. T1mi was found in 3% (n = 38) of patients. The 10-year LR rate was 22.6% in T1mi vs. 6.9% in T1a-2 breast cancer [hazard ratio (HR) = 3.73; 95% confidence interval (CI): 1.93, 7.19; p < 0.001]. The 10-year risk of distant recurrence was 5.1% for T1mi, and 12.1% for T1a-2 disease (HR = 0.56; 95% CI: 0.19, 1.84; p = 0.36). Ten-year OS was 91.5% in T1mi and 84.4% in T1a-2 disease, (HR = 0.48; 95% CI: 0.18, 1.30; p = 0.14). Rates of LR did not differ whether treated by hypofractionation or conventional fractionation (HR = 1.21; 95% CI: 0.35, 4.18; p = 0.77). CONCLUSIONS The risk of LR was considerably higher in patients with T1mi compared to T1a-2 tumors, but OS remained very good. Future research should evaluate the utility of wider local excision and boost radiation to optimize local control for microinvasive breast cancer.
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Affiliation(s)
| | | | | | - Lynn Chang
- University of Ottawa, Ottawa, ON, Canada
| | - Julie Bowen
- Northeastern Ontario Regional Cancer Centre, Sudbury, ON, Canada
| | | | | | - Anthony Fyles
- Princess Margaret Cancer Centre, Toronto, ON, Canada
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Hepel JT, Loap P, Fourquet A, Kirova YM. DCIS Update: Escalation or De-escalation? Boost, Fractionation, and Omission of Radiation. Int J Radiat Oncol Biol Phys 2023; 115:813-816. [PMID: 36822780 DOI: 10.1016/j.ijrobp.2022.11.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 11/06/2022] [Indexed: 02/23/2023]
Affiliation(s)
- Jaroslaw T Hepel
- Department of Radiation Oncology, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island.
| | - Pierre Loap
- Department of Radiation Oncology, Institut Curie, Paris, France
| | - Alain Fourquet
- Department of Radiation Oncology, Institut Curie, Paris, France
| | - Youlia M Kirova
- Department of Radiation Oncology, Institut Curie, Paris, France
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De-escalation in DCIS Care. CURRENT BREAST CANCER REPORTS 2023. [DOI: 10.1007/s12609-023-00475-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/17/2023]
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Skjerven HK, Myklebust EM, Korvald C, Porojnicu AC, Kaaresen R, Hofvind S, Schlicting E, Sahlberg KK. Oncological outcomes after simple and skin-sparing mastectomy of ductal carcinoma in situ: A register-based cohort study of 576 Norwegian women. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:575-582. [PMID: 36509629 DOI: 10.1016/j.ejso.2022.11.594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 11/18/2022] [Accepted: 11/30/2022] [Indexed: 12/03/2022]
Abstract
BACKGROUND For Ductal Carcinoma in Situ (DCIS), recurrence is shown to be higher after skin-sparing (SSM) versus simple (SM) mastectomy. This study aimed to compare the two groups recurrence rates, disease-free survival (DFS), and overall (OS) survival. METHODS We conducted a retrospective register-based cohort study of women operated with SSM (n = 338) or SM (n = 238) for DCIS between 2007 and 2017. Data from the Norwegian Breast Cancer Registry was used to estimate recurrences rates, DFS and OS. RESULTS Mean age was 51 and 61 years in the SSM and SM groups, respectively. Median follow-up time was 77 months for SSM (range: 21-152 months) vs 84 months for SM (range: 7-171 months). After five years of follow-up, the overall recurrence rate (OR) was 2.1%; 3.9% for SSM and 0.9% for SM. After ten years, the rates were 3.0%, 6.2% for SSM and still 0.9% for SM. DFS was after ten years 92.2%; 91.8% for SSM, and 92.4% for SM. OS was 95.0%; 97.5% for SSM and 93.3% for SM at ten years. For SSM, involved margins represented a significant risk for recurrence. CONCLUSION The recurrence rate was higher in the SSM versus the SM group. Whether the difference is due to the operating procedures or underlying risk factors remains unknown. When stratifying for the difference in age, there was no statistical difference in DFS or OS. Involved margins in the SSM group were associated with an increased risk of recurrence.
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Affiliation(s)
- Helle Kristine Skjerven
- Section for Breast and Endocrine Surgery, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
| | - Even Moa Myklebust
- Oslo Centre for Biostatistics and Epidemiology, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Research and Innovation, Vestre Viken Hospital Trust, Drammen, Norway
| | - Christian Korvald
- Department of Plastic and Reconstructive Surgery, Oslo University Hospital, Oslo, Norway
| | | | - Rolf Kaaresen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Solveig Hofvind
- Department of Health and Care Sciences, The Artic University, UiT, Tromsø, Norway; Section for Breast Cancer Screening, Cancer Registry of Norway, Oslo, Norway
| | - Ellen Schlicting
- Section for Breast and Endocrine Surgery, Oslo University Hospital, Oslo, Norway
| | - Kristine Kleivi Sahlberg
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Research and Innovation, Vestre Viken Hospital Trust, Drammen, Norway
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Gellings JA, Cortina CS, Jorns JM, Johnson MK, Huang CC, Kong AL. Annual cost-savings with the implementation of estrogen-receptor-only testing on Ductal Carcinoma in Situ specimens. Am J Surg 2023; 225:304-308. [PMID: 36283883 DOI: 10.1016/j.amjsurg.2022.09.060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 09/08/2022] [Accepted: 09/29/2022] [Indexed: 11/01/2022]
Abstract
BACKGROUND In DCIS, ER status is an important marker. The utility of concomitant PR testing remains unclear. METHODS A single-institution retrospective cohort study was performed with a comparative analysis of the NCDB to assess annual cost-savings with omission of routine PR testing. National Medicare payment standards determined PR staining costs to be $124.92. RESULTS 150 institutional DCIS cases with receptor data were identified. 104 (69%) were ER+/PR+, 16 (11%) were ER+/PR-, and none were ER-/PR+. Omission of routine PR testing would have resulted in $18,738 saved annually. Within the NCDB, 34,100 DCIS cases had receptor data: 29,277 (85.9%) patients were ER+, and 26,008 (76%) were both ER/PR+. 211 (0.6%) patients were ER-/PR+. Annual national cost-savings with omission of routine PR-testing would have been $4.3 million. CONCLUSION PR testing for DCIS should be reserved only for patients with ER- DCIS undergoing breast conservation to determine the utility of adjuvant endocrine therapy.
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Affiliation(s)
- Jaclyn A Gellings
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
| | - Chandler S Cortina
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA; Medical College of Wisconsin Cancer Center, Milwaukee, WI, USA.
| | - Julie M Jorns
- Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA.
| | - Morgan K Johnson
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Chiang-Ching Huang
- Joseph J. Zilber School of Public Health, University of Wisconsin, 1240 N 10th St., Milwaukee, WI, 53205, USA.
| | - Amanda L Kong
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA; Medical College of Wisconsin Cancer Center, Milwaukee, WI, USA.
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Relationship between tamoxifen and cataracts: a nationwide cohort study of women in South Korea. Breast Cancer Res Treat 2023; 197:603-612. [PMID: 36495379 DOI: 10.1007/s10549-022-06765-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 10/06/2022] [Indexed: 12/14/2022]
Abstract
PURPOSE Although prospective randomized clinical trials have reported that the use of prophylactic tamoxifen in patients at a high risk of breast cancer is associated with an increased risk of cataracts development, such findings are inconsistent. This study aimed to clarify the relationship between adjuvant tamoxifen use and cataracts risk using a nationwide longitudinal population-based registry. METHODS This retrospective cohort study was conducted using the Korean National Health Insurance claims database over a 15-year period (January 2007-December 2021). Data from all female patients diagnosed with ductal carcinoma in situ (DCIS) between 2009 and 2015 were extracted. We evaluated the incidence of cataracts diagnosis and surgery after adjuvant tamoxifen administration in patients with DCIS. RESULTS A total of 43,434 patients who met the inclusion criteria were diagnosed with DCIS between 2009 and 2015. Data from 2849 patients receiving tamoxifen and 1615 patients not receiving tamoxifen were analyzed before matching. After matching for comorbidities, type of breast surgery, and age, both groups consisted of 1597 patients. Both before and after matching, adjuvant tamoxifen was not a significant factor for an increased risk of cataracts diagnosis alone or with surgery. CONCLUSION Our study showed that adjuvant tamoxifen was not a risk factor for increased cataracts diagnosis and surgery in patients with DCIS. This finding provides a basis for physicians to reduce their ocular toxicity concerns regarding the risk of patients developing cataracts by tamoxifen treatment.
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Sprague BL, Chen S, Miglioretti DL, Gard CC, Tice JA, Hubbard RA, Aiello Bowles EJ, Kaufman PA, Kerlikowske K. Cumulative 6-Year Risk of Screen-Detected Ductal Carcinoma In Situ by Screening Frequency. JAMA Netw Open 2023; 6:e230166. [PMID: 36808238 PMCID: PMC9941892 DOI: 10.1001/jamanetworkopen.2023.0166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 12/15/2022] [Indexed: 02/22/2023] Open
Abstract
Importance Detection of ductal carcinoma in situ (DCIS) by mammography screening is a controversial outcome with potential benefits and harms. The association of mammography screening interval and woman's risk factors with the likelihood of DCIS detection after multiple screening rounds is poorly understood. Objective To develop a 6-year risk prediction model for screen-detected DCIS according to mammography screening interval and women's risk factors. Design, Setting, and Participants This Breast Cancer Surveillance Consortium cohort study assessed women aged 40 to 74 years undergoing mammography screening (digital mammography or digital breast tomosynthesis) from January 1, 2005, to December 31, 2020, at breast imaging facilities within 6 geographically diverse registries of the consortium. Data were analyzed between February and June 2022. Exposures Screening interval (annual, biennial, or triennial), age, menopausal status, race and ethnicity, family history of breast cancer, benign breast biopsy history, breast density, body mass index, age at first birth, and false-positive mammography history. Main Outcomes and Measures Screen-detected DCIS defined as a DCIS diagnosis within 12 months after a positive screening mammography result, with no concurrent invasive disease. Results A total of 916 931 women (median [IQR] age at baseline, 54 [46-62] years; 12% Asian, 9% Black, 5% Hispanic/Latina, 69% White, 2% other or multiple races, and 4% missing) met the eligibility criteria, with 3757 screen-detected DCIS diagnoses. Screening round-specific risk estimates from multivariable logistic regression were well calibrated (expected-observed ratio, 1.00; 95% CI, 0.97-1.03) with a cross-validated area under the receiver operating characteristic curve of 0.639 (95% CI, 0.630-0.648). Cumulative 6-year risk of screen-detected DCIS estimated from screening round-specific risk estimates, accounting for competing risks of death and invasive cancer, varied widely by all included risk factors. Cumulative 6-year screen-detected DCIS risk increased with age and shorter screening interval. Among women aged 40 to 49 years, the mean 6-year screen-detected DCIS risk was 0.30% (IQR, 0.21%-0.37%) for annual screening, 0.21% (IQR, 0.14%-0.26%) for biennial screening, and 0.17% (IQR, 0.12%-0.22%) for triennial screening. Among women aged 70 to 74 years, the mean cumulative risks were 0.58% (IQR, 0.41%-0.69%) after 6 annual screens, 0.40% (IQR, 0.28%-0.48%) for 3 biennial screens, and 0.33% (IQR, 0.23%-0.39%) after 2 triennial screens. Conclusions and Relevance In this cohort study, 6-year screen-detected DCIS risk was higher with annual screening compared with biennial or triennial screening intervals. Estimates from the prediction model, along with risk estimates of other screening benefits and harms, could help inform policy makers' discussions of screening strategies.
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Affiliation(s)
- Brian L. Sprague
- Office of Health Promotion Research, University of Vermont, Burlington
- Department of Surgery, University of Vermont, Burlington
- University of Vermont Cancer Center, Burlington
| | - Shuai Chen
- Division of Biostatistics, Department of Public Health Sciences, University of California, Davis
| | - Diana L. Miglioretti
- Division of Biostatistics, Department of Public Health Sciences, University of California, Davis
- Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle
| | - Charlotte C. Gard
- Department of Economics, Applied Statistics, and International Business, New Mexico State University, Las Cruces
| | - Jeffrey A. Tice
- Division of General Internal Medicine, Department of Medicine, University of California, San Francisco
| | - Rebecca A. Hubbard
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia
| | - Erin J. Aiello Bowles
- Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle
| | - Peter A. Kaufman
- Division of Hematology/Oncology, University of Vermont Cancer Center, Burlington
| | - Karla Kerlikowske
- Department of Medicine, University of California, San Francisco
- Department of Epidemiology and Biostatistics, University of California, San Francisco
- General Internal Medicine Section, Department of Veterans Affairs, University of California, San Francisco
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Udayasiri RI, Luo T, Gorringe KL, Fox SB. Identifying recurrences and metastasis after ductal carcinoma in situ (DCIS) of the breast. Histopathology 2023; 82:106-118. [PMID: 36482277 PMCID: PMC10953414 DOI: 10.1111/his.14804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/06/2022] [Accepted: 09/11/2022] [Indexed: 12/13/2022]
Abstract
Ductal carcinoma in situ (DCIS) of the breast is a non-invasive tumour that has the potential to progress to invasive ductal carcinoma (IDC). Thus, it represents a treatment dilemma: alone it does not present a risk to life, however, left untreated it may progress to a life-threatening condition. Current clinico-pathological features cannot accurately predict which patients with DCIS have invasive potential, and therefore clinicians are unable to quantify the risk of progression for an individual patient. This leads to many women being over-treated, while others may not receive sufficient treatment to prevent invasive recurrence. A better understanding of the molecular features of DCIS, both tumour-intrinsic and the microenvironment, could offer the ability to better predict which women need aggressive treatment, and which can avoid therapies carrying significant side-effects and such as radiotherapy. In this review, we summarise the current knowledge of DCIS, and consider future research directions.
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Affiliation(s)
- Ruwangi I Udayasiri
- Peter MacCallum Cancer Centre and the Sir Peter MacCallum Department of OncologyThe University of MelbourneMelbourneVICAustralia
| | - Tongtong Luo
- Peter MacCallum Cancer Centre and the Sir Peter MacCallum Department of OncologyThe University of MelbourneMelbourneVICAustralia
| | - Kylie L Gorringe
- Peter MacCallum Cancer Centre and the Sir Peter MacCallum Department of OncologyThe University of MelbourneMelbourneVICAustralia
| | - Stephen B Fox
- Peter MacCallum Cancer Centre and the Sir Peter MacCallum Department of OncologyThe University of MelbourneMelbourneVICAustralia
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Nachmanson D, Pagadala M, Steward J, Cheung C, Bruce LK, Lee NQ, O'Keefe TJ, Lin GY, Hasteh F, Morris GP, Carter H, Harismendy O. Accurate genome-wide genotyping from archival tissue to explore the contribution of common genetic variants to pre-cancer outcomes. J Transl Med 2022; 20:623. [PMID: 36575447 PMCID: PMC9793518 DOI: 10.1186/s12967-022-03810-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Accepted: 12/05/2022] [Indexed: 12/28/2022] Open
Abstract
PURPOSE The contribution of common genetic variants to pre-cancer progression is understudied due to long follow-up time, rarity of poor outcomes and lack of available germline DNA collection. Alternatively, DNA from diagnostic archival tissue is available, but its somatic nature, limited quantity and suboptimal quality would require an accurate cost-effective genome-wide germline genotyping methodology. EXPERIMENTAL DESIGN Blood and tissue DNA from 10 individuals were used to benchmark the accuracy of Single Nucleotide Polymorphisms (SNP) genotypes, Polygenic Risk Scores (PRS) or HLA haplotypes using low-coverage whole-genome sequencing (lc-WGS) and genotype imputation. Tissue-derived PRS were further evaluated for 36 breast cancer patients (11.7 years median follow-up time) diagnosed with DCIS and used to model the risk of Breast Cancer Subsequent Events (BCSE). RESULTS Tissue-derived germline DNA profiling resulted in accurate genotypes at common SNPs (blood correlation r2 > 0.94) and across 22 disease-related polygenic risk scores (PRS, mean correlation r = 0.93). Imputed Class I and II HLA haplotypes were 96.7% and 82.5% concordant with clinical-grade blood HLA haplotypes, respectively. In DCIS patients, tissue-derived PRS was significantly associated with BCSE (HR = 2, 95% CI 1.2-3.8). The top and bottom decile patients had an estimated 28% and 5% chance of BCSE at 10 years, respectively. CONCLUSIONS Archival tissue DNA germline profiling using lc-WGS and imputation, represents a cost and resource-effective alternative in the retrospective design of long-term disease genetic studies. Initial results in breast cancer suggest that common risk variants contribute to pre-cancer progression.
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Affiliation(s)
- Daniela Nachmanson
- Bioinformatics and Systems Biology Graduate Program, University of California San Diego, 9500 Gilman Drive, San Diego, CA, 92093, USA
| | - Meghana Pagadala
- Biomedical Science Graduate Program, University of California San Diego, 9500 Gilman Drive, San Diego, CA, 92093, USA
| | - Joseph Steward
- Moores Cancer Center, University of California San Diego, 3855 Health Science Drive, San Diego, CA, 92093, USA
| | - Callie Cheung
- Moores Cancer Center, University of California San Diego, 3855 Health Science Drive, San Diego, CA, 92093, USA
| | - Lauryn Keeler Bruce
- Bioinformatics and Systems Biology Graduate Program, University of California San Diego, 9500 Gilman Drive, San Diego, CA, 92093, USA
| | - Nicole Q Lee
- Moores Cancer Center, University of California San Diego, 3855 Health Science Drive, San Diego, CA, 92093, USA
| | - Thomas J O'Keefe
- Department of Surgery, University of California San Diego, 9500 Gilman Drive, San Diego, CA, 92093, USA
| | - Grace Y Lin
- Department of Pathology, University of California San Diego, 9500 Gilman Drive, San Diego, CA, 92093, USA
| | - Farnaz Hasteh
- Department of Pathology, University of California San Diego, 9500 Gilman Drive, San Diego, CA, 92093, USA
| | - Gerald P Morris
- Department of Pathology, University of California San Diego, 9500 Gilman Drive, San Diego, CA, 92093, USA
| | - Hannah Carter
- Moores Cancer Center, University of California San Diego, 3855 Health Science Drive, San Diego, CA, 92093, USA
- Division of Medical Genetics, Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA
| | - Olivier Harismendy
- Moores Cancer Center, University of California San Diego, 3855 Health Science Drive, San Diego, CA, 92093, USA.
- Division of Biomedical Informatics, Department of Medicine, University of California San Diego, 9500 Gilman Drive, San Diego, CA, 92093, USA.
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50
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Glencer AC, Miller PN, Greenwood H, Maldonado Rodas CK, Freimanis R, Basu A, Mukhtar RA, Brabham C, Kim P, Hwang ES, Rosenbluth JM, Hirst GL, Campbell MJ, Borowsky AD, Esserman LJ. Identifying Good Candidates for Active Surveillance of Ductal Carcinoma In Situ: Insights from a Large Neoadjuvant Endocrine Therapy Cohort. CANCER RESEARCH COMMUNICATIONS 2022; 2:1579-1589. [PMID: 36970720 PMCID: PMC10035518 DOI: 10.1158/2767-9764.crc-22-0263] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 09/12/2022] [Accepted: 11/16/2022] [Indexed: 11/23/2022]
Abstract
Ductal carcinoma in situ (DCIS) is a biologically heterogenous entity with uncertain risk for invasive ductal carcinoma (IDC) development. Standard treatment is surgical resection often followed by radiation. New approaches are needed to reduce overtreatment. This was an observational study that enrolled patients with DCIS who chose not to pursue surgical resection from 2002 to 2019 at a single academic medical center. All patients underwent breast MRI exams at 3- to 6-month intervals. Patients with hormone receptor-positive disease received endocrine therapy. Surgical resection was strongly recommended if clinical or radiographic evidence of disease progression developed. A recursive partitioning (R-PART) algorithm incorporating breast MRI features and endocrine responsiveness was used retrospectively to stratify risk of IDC. A total of 71 patients were enrolled, 2 with bilateral DCIS (73 lesions). A total of 34 (46.6%) were premenopausal, 68 (93.2%) were hormone-receptor positive, and 60 (82.1%) were intermediate- or high-grade lesions. Mean follow-up time was 8.5 years. Over half (52.1%) remained on active surveillance without evidence of IDC with mean duration of 7.4 years. Twenty patients developed IDC, of which 6 were HER2 positive. DCIS and subsequent IDC had highly concordant tumor biology. Risk of IDC was characterized by MRI features after 6 months of endocrine therapy exposure; low-, intermediate-, and high-risk groups were identified with respective IDC rates of 8.7%, 20.0%, and 68.2%. Thus, active surveillance consisting of neoadjuvant endocrine therapy and serial breast MRI may be an effective tool to risk-stratify patients with DCIS and optimally select medical or surgical management. Significance A retrospective analysis of 71 patients with DCIS who did not undergo upfront surgery demonstrated that breast MRI features after short-term exposure to endocrine therapy identify those at high (68.2%), intermediate (20.0%), and low risk (8.7%) of IDC. With 7.4 years mean follow-up, 52.1% of patients remain on active surveillance. A period of active surveillance offers the opportunity to risk-stratify DCIS lesions and guide decisions for operative management.
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Affiliation(s)
- Alexa C. Glencer
- Department of Surgery, University of California San Francisco, San Francisco, California
| | - Phoebe N. Miller
- University of California San Francisco School of Medicine, San Francisco, California
| | - Heather Greenwood
- Department of Radiology, University of California San Francisco, San Francisco, California
| | | | - Rita Freimanis
- Department of Radiology, University of California San Francisco, San Francisco, California
| | - Amrita Basu
- Department of Surgery, University of California San Francisco, San Francisco, California
| | - Rita A. Mukhtar
- Department of Surgery, University of California San Francisco, San Francisco, California
| | | | - Paul Kim
- Quinnipiac University School of Medicine, North Haven, Connecticut
| | | | - Jennifer M. Rosenbluth
- Department of Medicine, University of California San Francisco, San Francisco, California
| | - Gillian L. Hirst
- Department of Surgery, University of California San Francisco, San Francisco, California
| | - Michael J. Campbell
- Department of Surgery, University of California San Francisco, San Francisco, California
| | | | - Laura J. Esserman
- Department of Surgery, University of California San Francisco, San Francisco, California
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