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Schwartz D, Tracy ET, Naik-Mathuria B, Glick RD, Polites SF, Mattei P, Rodeberg D, Espinoza AF, Mansfield SA, Lal DR, Kotagal M, Lautz T, Aldrink J, Rich BS. Management of Pediatric Breast Masses for the Pediatric Surgeon: Expert Consensus Recommendations From the APSA Cancer Committee. J Pediatr Surg 2025; 60:161916. [PMID: 39384492 DOI: 10.1016/j.jpedsurg.2024.161916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 08/29/2024] [Accepted: 09/06/2024] [Indexed: 10/11/2024]
Abstract
BACKGROUND The pathology and management of breast masses in pediatric patients is markedly different than in adults. The vast majority of lesions in children and adolescents are benign, but the rare malignant breast masses require prompt recognition and treatment. Pediatric surgeons navigating clinical evaluation of these masses must balance preservation of the developing breast with appropriate diagnosis and surgical management. METHODS The current English language literature was queried for pediatric and adolescent breast masses. Identified manuscripts were reviewed and classified by level of evidence. Based on these results, as well as expert consensus, an algorithm regarding clinical workup and management was established. RESULTS Evaluation of pediatric breast masses begins with a thorough history and physical exam. Palpable masses should then be further characterized using an ultrasound-guided algorithm. In select cases, observation without surgical resection is appropriate. Surgical management of presumed benign lesions, when performed, should prioritize conserving developing breast tissue and the nipple areolar complex. Excisional biopsy is preferable to core needle biopsy when technically feasible. Surgical management of malignant lesions varies depending on the type of malignancy. CONCLUSION Pediatric surgeons are often the first point of contact after identification of a breast mass in a pediatric or adolescent patient, and therefore play a critical role in management. Based on literature review and expert consensus, we propose an algorithm to guide pediatric surgeons in the diagnosis and treatment of these predominantly benign lesions. For the rare malignant lesions, a multi-disciplinary team approach is recommended to optimize patient care. LEVEL OF EVIDENCE: 5
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Affiliation(s)
- Dana Schwartz
- Division of Pediatric Surgery, Department of Surgery, Nationwide Children's Hospital, The Ohio State University College of Medicine, 700 Children's Drive, Columbus, OH 43205, USA.
| | - Elisabeth T Tracy
- Division of Pediatric Surgery, Department of Surgery, UNC University Medical Center, 2301 Erwin Rd, Durham, NC, 27710, USA
| | - Bindi Naik-Mathuria
- Division Chief of Pediatric Surgery, University of Texas Medical Branch, 301 8th St 7th Floor, Galveston, TX, 77555, USA
| | - Richard D Glick
- Division of Pediatric Surgery, Northwell Health, Cohen Children's Medical Center, 1111 Marcus Ave, New Hyde Park, NY, 11042, USA
| | - Stephanie F Polites
- Division of Pediatric Surgery, Mayo Clinic College of Medicine and Science, 200 1st St SW Rochester, MN, 55905, USA
| | - Peter Mattei
- General, Thoracic and Fetal Surgery, Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, USA
| | - David Rodeberg
- Division of Pediatric Surgery, University of Kentucky Medical College, Kentucky Children's Hospital, 800 Rose Stree 4th Floor, Lexington, KY, 40536, USA
| | - Andres F Espinoza
- Baylor College of Medicine, 6501 Fannin St, NB302, Houston, TX, 77030, USA
| | - Sara A Mansfield
- Division of Pediatric Surgery, Department of Surgery, Nationwide Children's Hospital, The Ohio State University College of Medicine, 700 Children's Drive, Columbus, OH 43205, USA
| | - Dave R Lal
- Division of Pediatric Surgery, Medical College of Wisconsin, Children's Wisconsin, 8915 W Connell Ct, Milwaukee, WI, 53226, USA
| | - Meera Kotagal
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Department of Surgery, University of Cincinnati College of Medicine, 3333 Burnet Ave, Cincinnati, OH, 45229, USA
| | - Timothy Lautz
- Division of Pediatric Surgery, Ann & Robert H Lurie Children's Hospital of Chicago, 225 E Chicago Ave, Chicago, IL, 60611, USA
| | - Jennifer Aldrink
- Division of Pediatric Surgery, Department of Surgery, Nationwide Children's Hospital, The Ohio State University College of Medicine, 700 Children's Drive, Columbus, OH 43205, USA
| | - Barrie S Rich
- Division of Pediatric Surgery, Northwell Health, Cohen Children's Medical Center, 1111 Marcus Ave, New Hyde Park, NY, 11042, USA
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Singh P, Agnese DM, Amin M, Barrio AV, van den Bruele AB, Burke EE, Danforth DN, Dirbas FM, Eladoumikdachi F, Fayanju OM, Kantor O, Kumar S, Lee MC, Matsen C, Nguyen TT, Ozmen T, Park KU, Plichta JK, Reyna C, Showalter SL, Styblo T, Tranakas N, Weiss A, Woodfin A, Laronga C, Boughey JC. Society of Surgical Oncology Breast Disease Site Working Group Statement on Bilateral Risk-Reducing Mastectomy: Indications, Outcomes, and Risks. Ann Surg Oncol 2025; 32:899-911. [PMID: 39538100 DOI: 10.1245/s10434-024-16484-2] [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: 10/15/2024] [Accepted: 10/29/2024] [Indexed: 11/16/2024]
Abstract
Bilateral risk-reducing mastectomy (BRRM) is the surgical removal of both breasts to reduce the risk of cancer. In this Society of Surgical Oncology position statement, we review the literature addressing the indications, outcomes, and risks of BRRM to update the society's 2017 statement. We held a virtual meeting to outline key topics and conducted a literature search using PubMed to identify relevant articles. After literature review, recommendations were made according to group consensus. Individuals with a high lifetime risk of breast cancer due to pathogenic variants in high penetrance breast cancer-predisposition genes, early chest or breast radiation exposure, or a compelling family history should be counseled on the option of BRRM. However, BRRM is not recommended for most patients with high-risk lesions and may be contraindicated in patients who have other competing cancers and/or a high risk of surgical complications. BRRM effectively reduces the risk of breast cancer development, although the survival benefit is unclear. For patients with low-to-moderate breast cancer risk, alternative management strategies should be encouraged, including lifestyle modifications, high-risk screening, and risk-reducing medications. Discussions of BRRM should cover: (1) breast-cancer risk estimates; (2) the procedure's degree of risk reduction and impact on survival; (3) surgical techniques, potential surgical complications and long-term sequelae; and (4) alternatives to surgery. Surgeons should encourage shared and informed decision making with patients who have an elevated lifetime risk of developing breast cancer.
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Affiliation(s)
- Puneet Singh
- Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| | | | | | - Andrea V Barrio
- Memorial Sloan Kettering Cancer Center, New York City, NY, USA
| | | | | | | | | | | | | | - Olga Kantor
- Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Shicha Kumar
- Rutgers Cancer Institute, New Brunswick, NJ, USA
| | | | | | | | - Tolga Ozmen
- Massachusetts General Hospital, Boston, MA, USA
| | - Ko Un Park
- Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | | | | | | | | | | | - Anna Weiss
- University of Rochester Medical Center, Rochester, NY, USA
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3
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Martelli M, Ceriani L, Ciccone G, Ricardi U, Kriachok I, Botto B, Balzarotti M, Tucci A, Usai SV, Zilioli VR, Pennese E, Arcaini L, Dabrowska-Iwanicka A, Ferreri AJM, Merli F, Zhao W, Rigacci L, Cellini C, Hodgson D, Ionescu C, Minoia C, Lucchini E, Spina M, Fosså A, Janikova A, Cwynarski K, Mikhaeel G, Jerkeman M, Di Rocco A, Stepanishyna Y, Vitolo U, Santoro A, Re A, Puccini B, Olivieri J, Petrucci L, Barrington SF, Malkowski B, Metser U, Versari A, Chauvie S, Walewski J, Trneny M, Cavalli F, Gospodarowicz M, Johnson PWM, Davies A, Zucca E. Omission of Radiotherapy in Primary Mediastinal B-Cell Lymphoma: IELSG37 Trial Results. J Clin Oncol 2024; 42:4071-4083. [PMID: 39159403 DOI: 10.1200/jco-24-01373] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 07/25/2024] [Accepted: 08/13/2024] [Indexed: 08/21/2024] Open
Abstract
PURPOSE The role of consolidation radiotherapy in patients with primary mediastinal B-cell lymphoma (PMBCL) is controversial. METHODS The IELSG37 trial, a randomized noninferiority study, aimed to assess whether irradiation can be omitted in patients with PMBCL with complete metabolic response (CMR) after induction immunochemotherapy. The primary end point was progression-free survival (PFS) at 30 months after random assignment. Patients with CMR were randomly assigned to observation or consolidation radiotherapy (30 Gy). With a noninferiority margin of 10% (assuming a 30-month PFS of 85% in both arms), a sample size of 540 patients was planned with 376 expected to be randomly assigned. RESULTS The observed events were considerably lower than expected; therefore, primary end point analysis was conducted when ≥95% of patients were followed for ≥30 months. Of the 545 patients enrolled, 268 were in CMR after induction and were randomly assigned to observation (n = 132) or radiotherapy (n = 136). The 30-month PFS was 96.2% in the observation arm and 98.5% in the radiotherapy arm, with a stratified hazard ratio of 1.47 (95% CI, 0.34 to 6.28) and absolute risk difference of 0.68% (95% CI, -0.97 to 7.46). The 5-year overall survival (OS) was 99% in both arms. Nonrandomized patients were managed according to local policies. Radiotherapy was the only treatment in 86% of those with Deauville score (DS) 4 and in 57% of those with DS 5. The 5-year PFS and OS of patients with DS 4 (95.8% and 97.5%, respectively) were not significantly different from those of randomly assigned patients. Patients with DS5 had significantly poorer 5-year PFS and OS (60.3% and 74.6%, respectively). CONCLUSION This study, the largest randomized trial of radiotherapy in PMBCL, demonstrated favorable outcomes in patients achieving CMR with no survival impairment for those omitting irradiation.
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Affiliation(s)
- Maurizio Martelli
- Sapienza University, Division of Hematology, Department of Translational and Precision Medicine, Rome, Italy
| | - Luca Ceriani
- Institute of Oncology Research (IOR), Bellinzona, Switzerland
- Ente Ospedaliero Cantonale, Imaging Institute of Southern Switzerland, Lugano, Switzerland
- Università della Svizzera Italiana, Faculty of Biomedical Sciences, Lugano, Switzerland
| | - Giovannino Ciccone
- AOU Città della Salute e della Scienza di Torino and CPO Piemonte, Clinical Epidemiology Unit, Turin, Italy
| | | | - Iryna Kriachok
- National Cancer Institute, Onco-Hematology Department, Kyiv, Ukraine
| | - Barbara Botto
- AOU Città della Salute e della Scienza, Department of Hematology, Turin, Italy
| | - Monica Balzarotti
- IRCCS Humanitas Research Hospital, Department of Medical Oncology and Hematology, Rozzano Milan, Italy
| | | | - Sara Veronica Usai
- AO Brotzu - Ospedale Oncologico Businco, Unit of Hematology and Bone Marrow Transplant, Cagliari, Italy
| | | | - Elsa Pennese
- Presidio Ospedaliero Pescara, Unità Operativa Semplice Dipartimentale Centro Diagnosi e Terapia Linfomi, Pescara, Italy
| | - Luca Arcaini
- University of Pavia, Department of Molecular Medicine, Pavia, Italy
- Fondazione IRCCS Policlinico San Matteo, Division of Hematology, Pavia, Italy
| | - Anna Dabrowska-Iwanicka
- Maria Sklodowska-Curie National Research Institute of Oncology, Department of Lymphoid Malignancies, Warsaw, Poland
| | - Andrés J M Ferreri
- IRCCS San Raffaele Scientific Institute, Lymphoma Unit, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Francesco Merli
- Azienda USL-IRCCS of Reggio Emilia, Department of Hematology, Reggio Emilia, Italy
| | - Weili Zhao
- Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Department of Hematology, Shanghai, China
| | - Luigi Rigacci
- AOU Careggi, Department of Hematology, Florence, Italy
| | - Claudia Cellini
- Ospedale Santa Maria delle Croci, Department of Hematology, Ravenna, Italy
| | - David Hodgson
- Princess Margaret Cancer Centre, Radiation Medicine Program, Toronto, Canada
| | - Codruta Ionescu
- Inselspital, Bern University Hospital, University of Bern, Department of Radiation Oncology, Bern, Switzerland
| | - Carla Minoia
- IRCCS Istituto Tumori Giovanni Paolo II, Hematology Unit, Bari, Italy
| | - Elisa Lucchini
- ASU Friuli Centrale, Unit of Hematology, Udine, Italy
- ASU Giuliano Isontina, Ospedale Maggiore, Trieste, Italy
| | - Michele Spina
- Centro di Riferimento Oncologico IRCCS, Division of Medical Oncology and Immunerelated Tumors, Aviano, Italy
| | - Alexander Fosså
- Oslo University Hospital, Department of Oncology, Oslo, Norway
- University of Oslo, KG Jebsen Center for B-cell malignancies, Oslo, Norway
| | | | - Kate Cwynarski
- University College London Hospitals NHS Trust, Department of Hematology, London, United Kingdom
| | - George Mikhaeel
- Guy's and St Thomas' NHS Foundation Trust, Guy's Cancer Center, London, United Kingdom
| | - Mats Jerkeman
- Skane University Hospital, Department of Oncology, Lund University, Lund, Sweden
| | - Alice Di Rocco
- Sapienza University, Division of Hematology, Department of Translational and Precision Medicine, Rome, Italy
| | - Yana Stepanishyna
- National Cancer Institute, Onco-Hematology Department, Kyiv, Ukraine
| | - Umberto Vitolo
- AOU Città della Salute e della Scienza, Department of Hematology, Turin, Italy
- Fondazione del Piemonte per l'Oncologia-IRCCS, Candiolo Cancer Institute, Candiolo, Italy
| | - Armando Santoro
- IRCCS Humanitas Research Hospital, Department of Medical Oncology and Hematology, Rozzano Milan, Italy
- Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Italy
| | - Alessandro Re
- ASST Spedali Civili, Department of Haematology, Brescia, Italy
| | | | | | - Luigi Petrucci
- Sapienza University, Division of Hematology, Department of Translational and Precision Medicine, Rome, Italy
| | - Sally F Barrington
- King's College London and Guy's and St Thomas' PET Centre, School of Biomedical Engineering and Imaging Sciences, King's College London, United Kingdom
| | - Bogdan Malkowski
- Nicolaus Copernicus University, Department of Diagnostics Imagining, Torun, Poland
| | - Ur Metser
- University Health Network, Princess Margaret Hospital, University Medical Imaging Toronto, University of Toronto, Toronto, Canada
| | - Annibale Versari
- Azienda USL-IRCCS of Reggio Emilia, Department of Nuclear Medicine, Oncology and High Technology, Reggio Emilia, Italy
| | - Stephane Chauvie
- AO Santa Croce e Carle, Department of Medical Physics, Cuneo, Italy
| | - Jan Walewski
- Maria Sklodowska-Curie National Research Institute of Oncology, Department of Lymphoid Malignancies, Warsaw, Poland
| | - Marek Trneny
- Charles University, General Hospital, Department of Medical Oncology, Prague, Czech Republic
| | - Franco Cavalli
- Institute of Oncology Research (IOR), Bellinzona, Switzerland
| | - Mary Gospodarowicz
- Princess Margaret Cancer Centre, Radiation Medicine Program, Toronto, Canada
| | - Peter W M Johnson
- University of Southampton, Clinical Trials Unit, School of Cancer Sciences, Southampton, United Kingdom
| | - Andrew Davies
- University of Southampton, Clinical Trials Unit, School of Cancer Sciences, Southampton, United Kingdom
| | - Emanuele Zucca
- Institute of Oncology Research (IOR), Bellinzona, Switzerland
- Università della Svizzera Italiana, Faculty of Biomedical Sciences, Lugano, Switzerland
- Ente Ospedaliero Cantonale, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
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4
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Cassoli JPB, Fernandes Í, Carvalho L, Fernandes M, Centrone AF, Taniwaki L, Lima RDC, Junior UDR, Dias IWR, Taranto P, Beal J, de Lima FT, Moura F, Cendoroglo M, Araújo SEA, Uson Junior PLS. Frequency of Deleterious Germline Variants in HER2-Low Breast Cancer Patients Using a Hereditary Multipanel Gene Testing. Curr Issues Mol Biol 2024; 46:7976-7985. [PMID: 39194688 DOI: 10.3390/cimb46080471] [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: 07/14/2024] [Revised: 07/23/2024] [Accepted: 07/24/2024] [Indexed: 08/29/2024] Open
Abstract
HER2-Low is defined as low levels of HER2 expression, based on a score of 1+ on immunohistochemical (IHC) assay or as an IHC score of 2+ and negative results on in situ hybridization (ISH or FISH). They are a heterogeneous population of breast cancers that vary in prognosis and sensitivity to systemic treatments. The frequency and clinical characteristics of pathogenic germline variants (PGVs) in HER2-Low breast cancer (BC) patients is not defined. We analyzed results from patients with BC who underwent multi-gene panel testing (MGPT) (maximum 145 genes) between 2018-2019. We reclassified HER-2 status accordingly. Relationships between the variables of interest were assessed by adopting the proportional regression Cox models. Of a total of 167 BC patients who underwent MGPT, half were hormone-receptor-positive. The median age was 45 years. About two thirds of the patients were in the earlier stage of BC. A total of 57% of the cases were reclassified as HER-2-negative or -Low. PGVs were found in 19% of the patients overall, as follows: seven BRCA1, four BRCA2, two ATM, one ATR, two CFTR, three CHEK2, one FANCA, one MERTK, one MLH1, three MUTYH, one RAD50, three RAD51C, one RECQL4, and two TP53 mutations. In HER2-Low, 26.5% of the patients had PGVs, and in the overall cohort, this was 19.8%. In conclusion, differences in the prevalence of deleterious germline mutations in HER2-Low BC patients compared to non-HER2-Low BC patients were identified. Similar alterations in BRCA were observed in this group of patients compared to the overall cohort. Germline genetic tests should be evaluated in larger cohorts of patients with HER2-Low status to better address the findings.
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Affiliation(s)
- Janaina Pontes Batista Cassoli
- Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
- Department of Hematology and Oncology, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
| | - Ítalo Fernandes
- Department of Hematology and Oncology, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
| | - Leonardo Carvalho
- Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
| | - Milena Fernandes
- Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
| | - Ana Fernanda Centrone
- Department of Hematology and Oncology, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
| | - Letícia Taniwaki
- Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
| | - Rita de Cássia Lima
- Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
- Department of Hematology and Oncology, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
| | | | - Igor Wanderley Reis Dias
- Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
| | - Patrícia Taranto
- Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
- Department of Hematology and Oncology, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
| | - Juliana Beal
- Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
- Department of Hematology and Oncology, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
| | - Fernanda Teresa de Lima
- Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
- Department of Hematology and Oncology, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
| | - Fernando Moura
- Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
- Department of Hematology and Oncology, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
| | - Miguel Cendoroglo
- Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
| | - Sergio Eduardo Alonso Araújo
- Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
- Department of Hematology and Oncology, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
| | - Pedro Luiz Serrano Uson Junior
- Center for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
- Department of Hematology and Oncology, Hospital Israelita Albert Einstein, São Paulo 05652000, Brazil
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Stokkevåg CH, Journy N, Vogelius IR, Howell RM, Hodgson D, Bentzen SM. Radiation Therapy Technology Advances and Mitigation of Subsequent Neoplasms in Childhood Cancer Survivors. Int J Radiat Oncol Biol Phys 2024; 119:681-696. [PMID: 38430101 DOI: 10.1016/j.ijrobp.2024.01.206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 12/17/2023] [Accepted: 01/13/2024] [Indexed: 03/03/2024]
Abstract
PURPOSE In this Pediatric Normal Tissue Effects in the Clinic (PENTEC) vision paper, challenges and opportunities in the assessment of subsequent neoplasms (SNs) from radiation therapy (RT) are presented and discussed in the context of technology advancement. METHODS AND MATERIALS The paper discusses the current knowledge of SN risks associated with historic, contemporary, and future RT technologies. Opportunities for research and SN mitigation strategies in pediatric patients with cancer are reviewed. RESULTS Present experience with radiation carcinogenesis is from populations exposed during widely different scenarios. Knowledge gaps exist within clinical cohorts and follow-up; dose-response and volume effects; dose-rate and fractionation effects; radiation quality and proton/particle therapy; age considerations; susceptibility of specific tissues; and risks related to genetic predisposition. The biological mechanisms associated with local and patient-level risks are largely unknown. CONCLUSIONS Future cancer care is expected to involve several available RT technologies, necessitating evidence and strategies to assess the performance of competing treatments. It is essential to maximize the utilization of existing follow-up while planning for prospective data collection, including standardized registration of individual treatment information with linkage across patient databases.
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Affiliation(s)
- Camilla H Stokkevåg
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway; Department of Physics and Technology, University of Bergen, Bergen, Norway.
| | - Neige Journy
- French National Institute of Health and Medical Research (INSERM) Unit 1018, Centre for Research in Epidemiology and Population Health, Paris Saclay University, Gustave Roussy, Villejuif, France
| | - Ivan R Vogelius
- Department of Clinical Oncology, Centre for Cancer and Organ Diseases and University of Copenhagen, Copenhagen, Denmark
| | - Rebecca M Howell
- Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas
| | - David Hodgson
- Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Center, Toronto, Ontario, Canada
| | - Søren M Bentzen
- Department of Epidemiology and Public Health, University of Maryland, Baltimore, Maryland
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Mukherjee S, Mukherjee A, Bytesnikova Z, Ashrafi AM, Richtera L, Adam V. 2D graphene-based advanced nanoarchitectonics for electrochemical biosensors: Applications in cancer biomarker detection. Biosens Bioelectron 2024; 250:116050. [PMID: 38301543 DOI: 10.1016/j.bios.2024.116050] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 01/01/2024] [Accepted: 01/17/2024] [Indexed: 02/03/2024]
Abstract
Low-cost, rapid, and easy-to-use biosensors for various cancer biomarkers are of utmost importance in detecting cancer biomarkers for early-stage metastasis control and efficient diagnosis. The molecular complexity of cancer biomarkers is overwhelming, thus, the repeatability and reproducibility of measurements by biosensors are critical factors. Electrochemical biosensors are attractive alternatives in cancer diagnosis due to their low cost, simple operation, and promising analytical figures of merit. Recently graphene-derived nanostructures have been used extensively for the fabrication of electrochemical biosensors because of their unique physicochemical properties, including the high electrical conductivity, adsorption capacity, low cost and ease of mass production, presence of oxygen-containing functional groups that facilitate the bioreceptor immobilization, increased flexibility and mechanical strength, low cellular toxicity. Indeed, these properties make them advantageous compared to other alternatives. However, some drawbacks must be overcome to extend their use, such as poor and uncontrollable deposition on the substrate due to the low dispersity of some graphene materials and irreproducibility of the results because of the differences in various batches of the produced graphene materials. This review has documented the most recently developed strategies for electrochemical sensor fabrication. It differs in the categorization method compared to published works to draw greater attention to the wide opportunities of graphene nanomaterials for biological applications. Limitations and future scopes are discussed to advance the integration of novel technologies such as artificial intelligence, the internet of medical things, and triboelectric nanogenerators to eventually increase efficacy and efficiency.
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Affiliation(s)
- Soumajit Mukherjee
- Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic
| | - Atripan Mukherjee
- Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic; ELI Beamlines Facility, The Extreme Light Infrastructure ERIC, Za Radnici 835, 252 41, Dolni Breznany, Czech Republic
| | - Zuzana Bytesnikova
- Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic
| | - Amir M Ashrafi
- Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic
| | - Lukas Richtera
- Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic; Central European Institute of Technology, Brno University of Technology, Purkynova 123, CZ-612 00, Brno, Czech Republic
| | - Vojtech Adam
- Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic.
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7
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Soueidy C, Kourie HR. Updates in the Management of Primary Mediastinal B Cell Lymphoma. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2023; 23:866-873. [PMID: 37722943 DOI: 10.1016/j.clml.2023.08.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 08/17/2023] [Accepted: 08/18/2023] [Indexed: 09/20/2023]
Abstract
Primary mediastinal B cell lymphoma (PMBCL) is considered a distinct pathology according to the WHO classification of lymphoid malignancies. Patients have a better prognosis after the addition of Rituximab to anthracycline-based chemotherapy. The role of consolidative radiotherapy is controversial after the approval of dose-adjusted R-EPOCH and the selection of patients to undergo radiotherapy is based on end-of-therapy PET CT. In the relapsed/refractory setting, new approved drugs and other under investigation have improved patient outcomes. This review summarizes the different treatment modalities in (PMBCL) in the frontline and the relapsed/refractory settings.
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Affiliation(s)
- Charbel Soueidy
- Hematology Oncology Department, Hotel Dieu de France Hospital, Beirut, Lebanon.
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Abstract
Importance An estimated 15 000 children and adolescents aged 0 to 19 years are diagnosed with cancer each year in the US, and more than 85% survive for at least 5 years. By 45 years of age, approximately 95% of people who survive childhood cancer will develop a significant health problem related to the childhood cancer diagnosis or its treatment. Observations Approximately 500 000 people currently alive in the US have survived childhood cancer. The most common severe or life-threatening chronic health problems related to childhood cancer or its treatment are endocrine disorders such as hypothyroidism or growth hormone deficiency (44%), subsequent neoplasms such as breast cancer or thyroid cancer (7%), and cardiovascular disease such as cardiomyopathy or congestive heart failure, coronary artery disease, and cerebrovascular disease (5.3%). Medical conditions related to a cancer diagnosis during childhood or adolescence are most commonly caused by the radiation therapy and the chemotherapies used to treat cancer and may develop at varying lengths of time after exposure to these treatments. Individuals at highest risk for developing treatment-related health problems include patients with brain cancer treated with cranial irradiation (approximately 70% develop severe or life-threatening health problems) and allogeneic hematopoietic stem cell transplant recipients (approximately 60% develop severe or life-threatening health problems). Individuals at the lowest risk for developing treatment-related health problems include those who survived solid tumors (such as Wilms tumor) treated with surgical resection alone or with minimal chemotherapy, for whom the prevalence of subsequent health problems is similar to people who did not have cancer during childhood or adolescence. People diagnosed with childhood cancer in the 1990s who survived for at least 5 years after the cancer diagnosis have a shorter lifespan (by about 9 years) vs children who were not diagnosed with cancer in the 1990s. Conclusions and Relevance Approximately 500 000 individuals currently alive in the US have survived childhood cancer. The most common adverse effects in individuals who survived childhood cancer are endocrine disorders, subsequent neoplasms, and cardiovascular disease. There is a need for clinicians and patients to have heightened awareness of these complications.
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Affiliation(s)
- Smita Bhatia
- Institute for Cancer Outcomes and Survivorship, Heersink School of Medicine, University of Alabama at Birmingham
- Department of Pediatrics, Division of Pediatric Hematology/Oncology, Heersink School of Medicine, University of Alabama at Birmingham
| | - Emily S Tonorezos
- Office of Cancer Survivorship, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, Maryland
| | - Wendy Landier
- Institute for Cancer Outcomes and Survivorship, Heersink School of Medicine, University of Alabama at Birmingham
- Department of Pediatrics, Division of Pediatric Hematology/Oncology, Heersink School of Medicine, University of Alabama at Birmingham
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9
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Vachek J, Gebauer J. [Screening for late effects after childhood cancer in adults]. Dtsch Med Wochenschr 2023; 148:731-736. [PMID: 37257474 DOI: 10.1055/a-2055-7388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
In recent decades, long-term survival after childhood/adolescent cancer has steadily improved and 5-year survival rate is over 80% for most entities. Studies have shown that more than two thirds of these long-term survivors develop new diseases associated with the treatment, so-called late effects, that occur years to decades after the end of cancer therapy. Risk-adapted screening examinations are recommended to ensure early diagnosis and treatment of late effects. These examinations are offered by interdisciplinary long-term follow up (LTFU) teams.In order to facilitate standardized LTFU worldwide, the International Guideline Harmonization Group (IGHG) was founded from representatives of various disciplines involved in LTFU. The evidence-based follow-up guidelines created by this group replace national recommendations.Numerous new IGHG guidelines have been published in recent years. The following topics are presents as examples:Breast Cancer Screening: Due to an increased risk of breast cancer, female patients should be included in intensified screening programs after thoracic radiotherapy. This now includes patients exposed to a radiation dose of 10 Gray and more.Bone density: Various cancer treatments elevate the risk for low bone density. Therefore, these patients should receive early bone density measurement.Mental health and fatigue: Mental illness and Fatigue can occur years to decades after cancer and should be regularly addressed during follow-up.
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Affiliation(s)
- Jana Vachek
- Klinik für Kinder- und Jugendmedizin, Bereich Pädiatrische Hämatologie und Onkologie, UKSH, Campus Lübeck
| | - Judith Gebauer
- Medizinische Klinik 1, Bereich Endokrinologie und Diabetologie UKSH, Campus Lübeck
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10
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Gao Y, Perez CA, Chhor C, Heller SL. Breast Cancer Screening in Survivors of Childhood Cancer. Radiographics 2023; 43:e220155. [PMID: 36927127 DOI: 10.1148/rg.220155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
Women who survived childhood cancers or cancers at a young age are at high risk for breast cancer later in life. The accentuated risk is notable among those treated at a young age with a high radiation dose but also extends to survivors treated with therapies other than or in addition to radiation therapy. The predisposing risk factors are complex. Advances in radiation therapy continue to curtail exposure, yet the risk of a second cancer has no dose threshold and a long latency period, and concurrent use of chemotherapy may have an additive effect on long-term risk of cancer. Early screening with annual mammography and MRI is recommended for chest radiation exposure of 10 Gy or greater, beginning 8 years after treatment or at age 25 years, whichever is later. However, there is a lack of recommendations for those at high risk without a history of radiation therapy. Because mortality after breast cancer among survivors is higher than in women with de novo breast cancer, and because there is a higher incidence of a second asynchronous breast cancer in survivors than that in the general population, regular screening is essential and is expected to improve mortality. However, awareness and continuity of care may be lacking in these young patients and is reflected in their poor screening attendance. The transition of care from childhood to adulthood for survivors requires age-targeted and lifelong strategies of education and risk prevention that are needed to improve long-term outcomes for these patients. © RSNA, 2023 See the invited commentary by Chikarmane in this issue. Quiz questions for this article are available through the Online Learning Center.
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Affiliation(s)
- Yiming Gao
- From the Departments of Radiology (Y.G., C.C., S.L.H.) and Pathology (C.A.P.), New York University School of Medicine, 160 E 34th St, New York, NY 10016
| | - Carmen A Perez
- From the Departments of Radiology (Y.G., C.C., S.L.H.) and Pathology (C.A.P.), New York University School of Medicine, 160 E 34th St, New York, NY 10016
| | - Chloe Chhor
- From the Departments of Radiology (Y.G., C.C., S.L.H.) and Pathology (C.A.P.), New York University School of Medicine, 160 E 34th St, New York, NY 10016
| | - Samantha L Heller
- From the Departments of Radiology (Y.G., C.C., S.L.H.) and Pathology (C.A.P.), New York University School of Medicine, 160 E 34th St, New York, NY 10016
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11
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Christopoulos P, Matsas A, Eleftheriades M, Kotsira G, Eleftheriades A, Vlahos NF. Investigating the Link between Early Life and Breast Anomalies. CHILDREN (BASEL, SWITZERLAND) 2023; 10:children10030601. [PMID: 36980159 PMCID: PMC10047184 DOI: 10.3390/children10030601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 02/07/2023] [Accepted: 03/15/2023] [Indexed: 03/30/2023]
Abstract
Several factors during childhood and adolescence are thought to be associated with the development of proliferative benign breast diseases and breast cancer in adulthood. In order to identify them, the authors conducted an extensive review of the literature up to October 2022, searching for clinical studies, reports, and guidelines in English. A thorough Medline/Pubmed and Google scholar database research was performed, investigating the link between diet, exercise, age of menarche, body mass index, ionizing radiation exposure during childhood and adolescence, and proliferative breast diseases and breast cancer in adulthood. A list of keywords, including breast disorders, adolescence, childhood, and breast cancer was included in our search algorithm. Numerous studies concede that the development of breast disease in adulthood is influenced by various risk factors, whose influence begins during early childhood and adolescence.
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Affiliation(s)
- Panagiotis Christopoulos
- Second Department of Obstetrics and Gynecology, "Aretaieion" Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Alkis Matsas
- Second Department of Obstetrics and Gynecology, "Aretaieion" Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Makarios Eleftheriades
- Second Department of Obstetrics and Gynecology, "Aretaieion" Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Georgia Kotsira
- Second Department of Obstetrics and Gynecology, "Aretaieion" Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Anna Eleftheriades
- Second Department of Obstetrics and Gynecology, "Aretaieion" Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Nikolaos F Vlahos
- Second Department of Obstetrics and Gynecology, "Aretaieion" Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
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12
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Wong FL, Lee JM, Leisenring WM, Neglia JP, Howell RM, Smith SA, Oeffinger KC, Moskowitz CS, Henderson TO, Mertens A, Nathan PC, Yasui Y, Landier W, Armstrong GT, Robison LL, Bhatia S. Health Benefits and Cost-Effectiveness of Children's Oncology Group Breast Cancer Screening Guidelines for Chest-Irradiated Hodgkin Lymphoma Survivors. J Clin Oncol 2023; 41:1046-1058. [PMID: 36265088 PMCID: PMC9928841 DOI: 10.1200/jco.22.00574] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 08/02/2022] [Accepted: 08/25/2022] [Indexed: 11/20/2022] Open
Abstract
PURPOSE To evaluate the outcomes and cost-effectiveness of the Children's Oncology Group Guideline recommendation for breast cancer (BC) screening using mammography (MAM) and breast magnetic resonance imaging (MRI) in female chest-irradiated childhood Hodgkin lymphoma (HL) survivors. Digital breast tomosynthesis (DBT), increasingly replacing MAM in practice, was also examined. METHODS Life years (LYs), quality-adjusted LYs (QALYs), BC mortality, health care costs, and false-positive screen frequencies of undergoing annual MAM, DBT, MRI, MAM + MRI, and DBT + MRI from age 25 to 74 years were estimated by microsimulation. BC risks and non-BC mortality were estimated from female 5-year survivors of HL in the Childhood Cancer Survivor Study and the US population. Test performance of MAM and MRI was synthesized from HL studies, and that of DBT from the general population. Costs (2017 US dollars [USD]) and utility weights were obtained from the medical literature. Incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS With 100% screening adherence, annual BC screening extended LYs by 0.34-0.46 years over no screening. If the willingness-to-pay threshold to gain a quality-adjusted LY was ICER < $100,000 USD, annual MAM at age 25-74 years was the only cost-effective strategy. When nonadherence was taken into consideration, only annual MAM at age 30-74 years (ICER = $56,972 USD) was cost-effective. Supplementing annual MAM with MRI costing $545 USD was not cost-effective under either adherence condition. If MRI costs were reduced to $300 USD, adding MRI to annual MAM at age 30-74 years could become more cost-effective, particularly in the reduced adherence condition (ICER = $133,682 USD). CONCLUSION Annual BC screening using MAM at age 30-74 years is effective and cost-effective in female chest-irradiated HL survivors. Although annual adjunct MRI is not cost-effective at $545 USD cost, it could become cost-effective as MRI cost is reduced, a plausible scenario with the emergent use of abbreviated MRI.
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Affiliation(s)
| | - Janie M. Lee
- University of Washington School of Medicine, Seattle, WA
| | | | | | | | - Susan A. Smith
- The University of Texas MD Anderson Cancer Center, Houston, TX
| | | | | | | | - Ann Mertens
- Emory University School of Medicine, Atlanta, GA
| | - Paul C. Nathan
- The Hospital for Sick Children, University of Toronto, Toronto, ON
| | - Yutaka Yasui
- St Jude Children's Research Hospital, Memphis, TN
| | | | | | | | - Smita Bhatia
- University of Alabama at Birmingham, Birmingham, AL
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13
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Zadravec Zaletel L, Cesen Mazic M, Jazbec J, Kos G, Toplak M, Štrbac D. Excellent results of screening for subsequent breast cancers in long-term survivors of childhood Hodgkin's lymphoma-Results of a population-based study. Front Pediatr 2023; 11:1161128. [PMID: 37077334 PMCID: PMC10106574 DOI: 10.3389/fped.2023.1161128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 03/16/2023] [Indexed: 04/21/2023] Open
Abstract
Introduction Subsequent breast cancer (SBC) represents a major complication in childhood cancer survivors and screening for SBC in survivors after incidental irradiation of breasts is recommended. In this article, we report the results and discuss benefits of SBC screening in female pts treated for Hodgkin's lymphoma (HL) in Slovenia in a period of 45 years. Methods Between 1966 and 2010, 117 females were treated for HL under the age of 19 in Slovenia. One hundred five of them survived for 5 years and were included in our study. They were 3-18 (med. 15) years old at diagnosis and followed for 6-52 (med. 28) years. Eighty-three percent of them had chest RT with a median dose of 30 Gy. Ninety-seven (92%) of 105 pts were regularly followed according to the international guidelines including yearly screening mammography/breast MRI in those who received chest RT. Results We diagnosed 10 SBCs in eight pts 14-39 (med. 24) years after diagnosis at the age of 28-52 (med. 42) years. At 40 years of follow-up, cumulative incidence of SBCs in females who got chest RT was 15.2%. Seven of eight patients (with 9 SBCs) got chest RT with 24-80 (med. 36) Gy at the age of 12 to 18 (median 17) years. Two patients in this group got bilateral SBC. One patient got invasive SBC after being treated with ChT containing high-dose of anthracyclines without chest RT at the age of 13. All eight invasive SBCs were invasive ductal cancers, HER2 receptors negative, all but one with positive hormonal receptors. Six invasive cancers were of stage T1N0, one T1N1mi, only one, diagnosed before era of screening, was of T2N1. None of 8 pts died of SBC. Conclusion After introduction of regular breast screening in our female patients, who received chest RT in childhood, all SBCs were of early stage and no patients died of SBC. Survivors of pediatric HL should be informed about the risk of late sequelae of treatment for HL, including SBC. Regular follow-up with breast cancer screening and breast self-examination is of vital importance in those treated with chest RT.
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Affiliation(s)
- Lorna Zadravec Zaletel
- Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Correspondence: Lorna Zadravec Zaletel
| | - Maja Cesen Mazic
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Department of Oncology and Haematology, University Children’s Hospital, University Medical Centre, Ljubljana, Slovenia
| | - Janez Jazbec
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Department of Oncology and Haematology, University Children’s Hospital, University Medical Centre, Ljubljana, Slovenia
| | - Gregor Kos
- Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Miha Toplak
- Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Danijela Štrbac
- Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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14
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Khoramdad M, Solaymani-Dodaran M, Kabir A, Ghahremanzadeh N, Hashemi EOS, Fahimfar N, Omidi Z, Mansournia MA, Olfatbakh A, Salehiniya H, Haghighat S. Breast cancer risk factors in Iranian women: a systematic review and meta-analysis of matched case-control studies. Eur J Med Res 2022; 27:311. [PMID: 36575538 PMCID: PMC9793603 DOI: 10.1186/s40001-022-00952-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 12/14/2022] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Identifying breast cancer risk factors is a critical component of preventative strategies for this disease. This study aims to identify modifiable and non-modifiable risk factors of breast cancer in Iranian women. METHODS We used international databases (PubMed/Medline, Scopus, Web of Knowledge, and Embase) and national databases (SID, Magiran, and ISC) to retrieve relevant studies until November 13, 2022. The odds ratio (OR) with a 95% confidence interval using the random-effect model was used to estimate the pooled effect. The publication bias was assessed by the Egger and Begg test. A sensitivity analysis was conducted to evaluate the effect of each included study on the final measurement. RESULTS Of the 30,351 retrieved articles, 24 matched case-control records were included with 12,460 participants (5675 newly diagnosed cases of breast cancer and 6785 control). This meta-analysis showed that of the known modifiable risk factors for breast cancer, obesity (vs normal weight) had the highest risk (OR = 2.17, 95% CI 1.47 to 3.21; I2 = 85.7) followed by age at marriage (25-29 vs < 18 years old) (OR = 2.00, 95% CI 1.53 to 2.61; I2 = 0), second-hand smoking (OR = 1.86, 95% CI 1.58 to 2.19; I2 = 0), smoking (OR = 1.83, 95% CI 1.41 to 2.38; I2 = 18.9), abortion history (OR = 1.44, 95% CI 1.02 to 2.05; I2 = 66.3), oral contraceptive use (OR = 1.35, 95% CI 1.11 to 1.63; I2 = 74.1), age at marriage (18-24 vs < 18 years old) (OR: 1.22, 95% CI 1.02 to 1.47; I2 = 0). Of non-modifiable risk factors, history of radiation exposure (OR = 3.48, 95% CI 2.17 to 5.59; I2 = 0), family history of breast cancer (OR = 2.47, 95% CI 1.83 to 3.33; I2 = 73), and age at menarche (12-13 vs ≥ 14 years old) (OR = 1.67, 95% CI 1.31-2.13; I2 = 25.4) significantly increased the risk of breast cancer. CONCLUSIONS Since most risk factors related to breast cancer incidence are modifiable, promoting healthy lifestyles can play an influential role in preventing breast cancer. In women with younger menarche age, a family history of breast cancer, or a history of radiation exposure, screening at short intervals is recommended.
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Affiliation(s)
- Malihe Khoramdad
- Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Masoud Solaymani-Dodaran
- Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
- Minimally Invasive Surgery Research Center, Hazrat-E-Rasool Hospital, Iran University of Medical Science, Tehran, Iran.
| | - Ali Kabir
- Minimally Invasive Surgery Research Center, Hazrat-E-Rasool Hospital, Iran University of Medical Science, Tehran, Iran
| | - Neda Ghahremanzadeh
- Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | | | - Noushin Fahimfar
- Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Omidi
- Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
| | - Mohammad Ali Mansournia
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Asiie Olfatbakh
- Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
| | - Hamid Salehiniya
- Social Determinants of Health Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Shahpar Haghighat
- Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
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15
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Current Considerations in Surgical Treatment for Adolescents and Young Women with Breast Cancer. Healthcare (Basel) 2022; 10:healthcare10122542. [PMID: 36554065 PMCID: PMC9777860 DOI: 10.3390/healthcare10122542] [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] [Received: 09/22/2022] [Revised: 12/06/2022] [Accepted: 12/09/2022] [Indexed: 12/23/2022] Open
Abstract
Adolescents and young women (AYA) with breast cancer represent a unique patient population, compared to the general population with breast cancer. We performed a literature review to evaluate the factors that influenced the surgical outcomes in this patient population. Fifty-two studies were identified, which evaluated breast surgery type, axillary surgery, contralateral prophylactic mastectomy (CPM), surgical timing, psychological factors, disparities, and imaging use. AYA patients had equivalent oncologic outcomes with breast conserving surgery (BCS) or mastectomy. CPM did not improve survival. There are limited data on axillary management in the AYA population, and while more data would be beneficial, this is currently extrapolated from the general breast cancer population. A shorter time to initiate treatment correlated to better outcomes, and disparities need to be overcome for optimal outcomes. AYA patients appreciated involvement in clinical decisions, and shared decision making should be considered whenever possible. Providers must keep these factors in mind when counseling AYA patients, regarding the surgical management of breast cancer.
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16
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Krul IM, Boekel NB, Kramer I, Janus CPM, Krol ADG, Nijziel MR, Zijlstra JM, van der Maazen RWM, Roesink JM, Jacobse JN, Schaapveld M, Schmidt MK, Opstal-van Winden AWJ, Sonke GS, Russell NS, Aleman BMP, van Leeuwen FE. Breast cancer and cardiovascular outcomes after breast cancer in survivors of Hodgkin lymphoma. Cancer 2022; 128:4285-4295. [PMID: 36281718 DOI: 10.1002/cncr.34464] [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: 12/04/2021] [Revised: 02/25/2022] [Accepted: 03/24/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND Hodgkin lymphoma (HL) survivors treated with chest radiotherapy have an increased risk of breast cancer (BC). Prior HL treatment and associated cardiovascular disease (CVD) risk may limit BC treatment options. It is unknown how treatment adaptations affect BC and CVD outcomes. METHODS The authors compared 195 BC patients treated with chest/axillary radiotherapy for HL (BC-HL) with 5988 age- and calendar year-matched patients with first primary BC (BC-1). Analyses included cumulative incidence functions and Cox regression models, accounting for tumor characteristics and BC treatment. RESULTS Compared to BC-1 patients, BC-HL patients received anthracycline-containing chemotherapy (23.7% vs. 43.8%, p < .001) and breast-conserving surgery followed by radiotherapy (7.1% vs. 57.7%, p < .001) less often. BC treatment considerations were reported for 71% of BC-HL patients. BC-HL patients had a significantly higher risk of 15-year overall mortality than BC-1 patients (61% vs. 23%). Furthermore, risks of BC-specific mortality and nonfatal BC events were significantly increased among BC-HL patients, also when accounting for tumor and treatment characteristics (2.2- to 4.5-fold). BC-HL patients with a screen-detected BC had a significantly reduced (61%) BC-specific mortality. One-third of BC-HL patients had CVD at BC-diagnosis, compared to <0.1% of BC-1 patients. Fifteen-year CVD-specific mortality and CVD incidence were significantly higher in BC-HL patients than in BC-1 patients (15.2% vs. 0.4% and 40.4% vs. 6.8%, respectively), which was due to HL treatment rather than BC treatment. CONCLUSIONS BC-HL patients experience a higher burden of CVD and worse BC outcomes than BC-1 patients. Clinicians should be aware of increased CVD risk when selecting BC treatment for HL survivors. LAY SUMMARY Patients with breast cancer after Hodgkin lymphoma (BC-HL) may have limited options for BC treatment, due to earlier HL treatment and an associated increased risk of cardiovascular disease (CVD). BC treatment considerations were reported for 71% of BC-HL patients. We examined whether BC-HL patients have a higher risk of CVD or BC events (recurrences/metastases) compared to patients with breast cancer that had no earlier tumors (BC-1). We observed a higher burden of CVD and worse BC outcomes in HL patients compared to BC-1 patients. Clinicians should be aware of increased CVD risk when selecting BC treatment for HL survivors.
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Affiliation(s)
- Inge M Krul
- Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Naomi B Boekel
- Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Iris Kramer
- Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Cécile P M Janus
- Department of Radiation Oncology, Erasmus University MC Cancer Institute, Rotterdam, The Netherlands
| | - Augustinus D G Krol
- Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands
| | - Marten R Nijziel
- Department of Hematology, Catharina Hospital, Eindhoven, The Netherlands
| | - Josée M Zijlstra
- Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | | | - Judith M Roesink
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Judy N Jacobse
- Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Michael Schaapveld
- Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Marjanka K Schmidt
- Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | | | - Gabe S Sonke
- Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Nicola S Russell
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Berthe M P Aleman
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Flora E van Leeuwen
- Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
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17
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Bhatia S. Germline risk factors for second malignant neoplasms after treatment for pediatric hematologic malignancies. HEMATOLOGY. AMERICAN SOCIETY OF HEMATOLOGY. EDUCATION PROGRAM 2022; 2022:245-250. [PMID: 36485122 PMCID: PMC9820434 DOI: 10.1182/hematology.2022000399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Survivors of childhood hematologic malignancies are at a substantially higher risk of developing subsequent neoplasms (SNs) when compared with the general population. SNs commonly observed in this population include basal cell carcinoma, brain tumors, thyroid cancer, breast cancer, bone tumors, and sarcoma. Radiation is the primary therapeutic exposure associated with the development of these SNs. There is emerging evidence of an association between chemotherapeutic exposures (alkylating agents/anthracyclines) and the development of SNs. Despite a strong dose-dependent association between therapeutic exposures and SN risk, there is significant interindividual variability in the risk for SNs for any given dose of therapeutic exposure. This interindividual variability in risk suggests the role of genetic susceptibility. This article describes the clinical and molecular epidemiology of SNs commonly observed in survivors of childhood hematologic malignancies and also highlights some of the work focusing on the development of risk prediction models to facilitate targeted interventions.
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Affiliation(s)
- Smita Bhatia
- Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL
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18
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Wang Y, Kremer LCM, van Leeuwen FE, Armstrong GT, Leisenring W, de Vathaire F, Hudson MM, Kuehni CE, Arnold MA, Haddy N, Demoor-Goldschmidt C, Diallo I, Howell RM, Ehrhardt MJ, Moskowitz CS, Neglia JP, van der Pal HJH, Robison LL, Schaapveld M, Turcotte LM, Waespe N, Ronckers CM, Teepen JC. Cohort profile: Risk and risk factors for female breast cancer after treatment for childhood and adolescent cancer: an internationally pooled cohort. BMJ Open 2022; 12:e065910. [PMID: 36344003 PMCID: PMC9644351 DOI: 10.1136/bmjopen-2022-065910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
PURPOSE The International Consortium for Pooled Studies on Subsequent Malignancies after Childhood and Adolescent Cancer was established in 2018 to address gaps in knowledge of risk and risk factors for breast cancer subsequent to childhood/adolescent cancer by pooling individual patient data from seven cohorts. Initially, the pooled cohort will focus on three clinically relevant questions regarding treatment-related subsequent breast cancer risk in female survivors, which are the risk related to low-dose radiotherapy exposure to the chest, specific chemotherapy agents and attained age. PARTICIPANTS The consortium database includes pooled data on 21 892 female survivors from seven cohorts in North America and Europe with a primary cancer diagnosis at <21 years of age, and survival ≥5 years from diagnosis. FINDINGS TO DATE This is a newly established pooled study. The cohort profile summarised the data collected from each included cohort, including childhood cancer diagnosis information and treatment details (ie, radiotherapy fields and cumulative doses, and chemotherapy agents and cumulative doses for each agent). Included cohorts' follow-up started 1951-1981 and ended 2013-2021, respectively, for a median follow-up duration of 24.3 (IQR 18.0-32.8) years since primary cancer diagnosis. The median age at primary cancer diagnosis was 5.4 (IQR 2.5-11.9) years. And the median attained age at last follow-up was 32.2 (IQR 24.0-40.4) years. In all, 4240 (19.4%) survivors were treated with radiotherapy to the chest and 9308 (42.5%) with anthracyclines. At the end of the follow-up, 835 females developed a first subsequent breast cancer, including 635 invasive breast cancer only, 184 carcinomas in situ only (172 ductal carcinomas in situ and 12 lobular carcinomas in situ), and 16 with both an invasive and in situ diagnosis at the same moment. The cumulative incidences of subsequent breast cancer (both invasive and in situ) 25 and 35 years after primary cancer diagnosis were 2.2% and 6.2%, respectively. FUTURE PLANS The consortium is intended to serve as a model and robust source of childhood/adolescent cancer survivor data for elucidating other knowledge gaps on subsequent breast cancer risk, and risk of other subsequent malignancies (including data on males) in the future.
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Affiliation(s)
- Yuehan Wang
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
| | - Leontien C M Kremer
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
- University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands
- Emma Children's Hospital, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, The Netherlands
| | | | | | - Wendy Leisenring
- Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Florent de Vathaire
- Radiation Epidemiology Team, INSERM U1018, Gustave Roussy, Villejuif, France
| | | | - Claudia E Kuehni
- Childhood Cancer Research Group, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
- Pediatric Hematology and Oncology, University Children's Hospital Bern, University of Bern, Bern, Switzerland
| | - Michael A Arnold
- Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, Colorado, USA
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Nadia Haddy
- Radiation Epidemiology Team, INSERM U1018, Gustave Roussy, Villejuif, France
| | - Charlotte Demoor-Goldschmidt
- Radiation Epidemiology Team, INSERM U1018, Gustave Roussy, Villejuif, France
- Department of Pediatric Hematology and Oncology, University-Hospital of Angers, Angers, France
- Radiotherapy department, Francois Baclesse center, Caen, France
- Supportive care department, Francois Baclesse center, Caen, France
| | - Ibrahima Diallo
- Radiation Epidemiology Team, INSERM U1018, Gustave Roussy, Villejuif, France
| | - Rebecca M Howell
- University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
| | | | | | - Joseph P Neglia
- University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota, USA
| | | | | | | | - Lucie M Turcotte
- University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota, USA
| | - Nicolas Waespe
- Childhood Cancer Research Group, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
- Pediatric Hematology and Oncology, University Children's Hospital Bern, University of Bern, Bern, Switzerland
- CANSEARCH research platform in pediatric oncology and hematology, University of Geneva, Geneva, Switzerland
| | - Cécile M Ronckers
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
- Department of Health Services Research, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany
| | - Jop C Teepen
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
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19
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Roginski M, Sifaki-Pistolla D, Stomby A, Velivasaki G, Faresjö T, Lionis C, Faresjö Å. Paradoxes of breast cancer incidence and mortality in two corners of Europe. BMC Cancer 2022; 22:1123. [PMID: 36319987 PMCID: PMC9628067 DOI: 10.1186/s12885-022-10243-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 10/27/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Breast cancer incidence is rising globally, while mortality rates show a geographical heterogenous pattern. Early detection and treatment have been proven to have a profound impact on breast cancer prognosis. The aim of his study was to compare breast cancer incidence, mortality, and survival rates in two contrasting corners of Europe, Sweden and Crete, to better understand cancer determinants with focus on disease burden and sociocultural factors. METHODS Breast cancer data from Sweden and Crete was derived from registries. Incidence and mortality were expressed as Age-Standardized Incidence Rates (ASIR), Age-Standardized Mortality Rates (ASMR). FINDINGS Breast cancer incidence has for decades risen in Sweden and on Crete. In 2019, ASIR was 217.5 in Sweden and 58.9 on Crete, (p < 0.001). Mortality rates showed opposite trends. ASMR in Sweden was reduced from 25.5 to 16.8 (2005-2019) while on Crete, ASMR increased from 22.1 to 25.3. A successive rise in survival rate in Sweden with a 5-year survival rate of 92% since 2015, but a converse development on Crete with 85% 5-year survival rate the same year. INTERPRETATION The incidence of breast cancer is slowly rising in both studied regions, but mortality increases on Crete in contrast to Sweden with sinking mortality rates. The interpretation of these findings is that differences in health care systems and health policies including differences in early detection like screening programs and early treatment, as well as sociocultural factors in the two countries might play an important role on the differences found in breast cancer burden.
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Affiliation(s)
- Mikaela Roginski
- grid.5640.70000 0001 2162 9922Department of Health, Medicine and Caring Sciences, Linköping University, SE-581 83 Linköping, Sweden
| | - Dimitra Sifaki-Pistolla
- grid.8127.c0000 0004 0576 3437Clinic of Social and Family Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece
| | - Andreas Stomby
- grid.5640.70000 0001 2162 9922Department of Health, Medicine and Caring Sciences, Linköping University, SE-581 83 Linköping, Sweden
| | - Georgia Velivasaki
- grid.8127.c0000 0004 0576 3437Clinic of Social and Family Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece
| | - Tomas Faresjö
- grid.5640.70000 0001 2162 9922Department of Health, Medicine and Caring Sciences, Linköping University, SE-581 83 Linköping, Sweden
| | - Christos Lionis
- grid.5640.70000 0001 2162 9922Department of Health, Medicine and Caring Sciences, Linköping University, SE-581 83 Linköping, Sweden ,grid.8127.c0000 0004 0576 3437Clinic of Social and Family Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece
| | - Åshild Faresjö
- grid.5640.70000 0001 2162 9922Department of Health, Medicine and Caring Sciences, Linköping University, SE-581 83 Linköping, Sweden
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20
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Henderson TO, Liu Q, Turcotte LM, Neglia JP, Leisenring W, Hodgson D, Diller L, Kenney L, Morton L, Berrington de Gonzalez A, Arnold M, Bhatia S, Howell RM, Smith SA, Robison LL, Armstrong GT, Oeffinger KC, Yasui Y, Moskowitz CS. Association of Changes in Cancer Therapy Over 3 Decades With Risk of Subsequent Breast Cancer Among Female Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study (CCSS). JAMA Oncol 2022; 8:2797487. [PMID: 36227603 PMCID: PMC9562103 DOI: 10.1001/jamaoncol.2022.4649] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 07/26/2022] [Indexed: 01/25/2023]
Abstract
Importance Breast cancer is the most common invasive subsequent malignant disease in childhood cancer survivors, though limited data exist on changes in breast cancer rates as primary cancer treatments have evolved. Objective To quantify the association between temporal changes in cancer treatment over 3 decades and subsequent breast cancer risk. Design, Setting, and Participants Retrospective cohort study of 5-year cancer survivors diagnosed when younger than 21 years between 1970 and 1999, with follow-up through December 5, 2020. Exposures Radiation and chemotherapy dose changes over time. Main Outcomes and Measures Breast cancer cumulative incidence rates and age-specific standardized incidence ratios (SIRs) compared across treatment decades (1970-1999). Piecewise exponential models estimated invasive breast cancer and ductal carcinoma in situ (DCIS) risk and associations with treatment exposures, adjusted for age at childhood cancer diagnosis and attained age. Results Among 11 550 female survivors (median age, 34.2 years; range 5.6-66.8 years), 489 developed 583 breast cancers: 427 invasive, 156 DCIS. Cumulative incidence was 8.1% (95% CI, 7.3%-9.0%) by age 45 years. An increased breast cancer risk (SIR, 6.6; 95% CI, 6.1-7.2) was observed for survivors compared with the age-sex-calendar-year-matched general population. Changes in therapy by decade included reduced rates of chest (34% in the 1970s, 22% in the 1980s, and 17% in the 1990s) and pelvic radiotherapy (26%, 17%, and 13% respectively) and increased rates of anthracycline chemotherapy exposures (30%, 51%, and 64%, respectively). Adjusting for age and age at diagnosis, the invasive breast cancer rate decreased 18% every 5 years of primary cancer diagnosis era (rate ratio [RR], 0.82; 95% CI, 0.74-0.90). When accounting for chest radiotherapy exposure, the decline attenuated to an 11% decrease every 5 years (RR, 0.89; 95% CI, 0.81-0.99). When additionally adjusted for anthracycline dose and pelvic radiotherapy, the decline every 5 years increased to 14% (RR, 0.86; 95% CI, 0.77-0.96). Although SIRs of DCIS generally increased over time, there were no statistically significant changes in incidence. Conclusions and Relevance Invasive breast cancer rates in childhood cancer survivors have declined with time, especially in those younger than 40 years. This appears largely associated with the reduced use of chest radiation therapy, but was tempered by concurrent changes in other therapies.
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Affiliation(s)
| | - Qi Liu
- University of Alberta, Alberta, Canada
| | | | | | | | | | - Lisa Diller
- Dana-Farber Cancer Institute/Children’s Hospital Boston, Boston, Massachusetts
| | - Lisa Kenney
- Dana-Farber Cancer Institute/Children’s Hospital Boston, Boston, Massachusetts
| | | | | | - Michael Arnold
- Children’s Hospital of Colorado, Denver, Colorado
- University of Colorado, Anschutz Medical Campus, Aurora
| | | | | | | | | | | | | | - Yutaka Yasui
- St. Jude Children’s Research Hospital, Memphis, Tennessee
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21
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Shalabi SF, LaBarge MA. Cellular and molecular mechanisms of breast cancer susceptibility. Clin Sci (Lond) 2022; 136:1025-1043. [PMID: 35786748 DOI: 10.1042/cs20211158] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 06/16/2022] [Accepted: 06/22/2022] [Indexed: 11/17/2022]
Abstract
There is a plethora of recognized risk factors for breast cancer (BC) with poorly understood or speculative biological mechanisms. The lack of prevention options highlights the importance of understanding the mechanistic basis of cancer susceptibility and finding new targets for breast cancer prevention. Until now, we have understood risk and cancer susceptibility primarily through the application of epidemiology and assessing outcomes in large human cohorts. Relative risks are assigned to various human behaviors and conditions, but in general the associations are weak and there is little understanding of mechanism. Aging is by far the greatest risk factor for BC, and there are specific forms of inherited genetic risk that are well-understood to cause BC. We propose that bringing focus to the biology underlying these forms of risk will illuminate biological mechanisms of BC susceptibility.
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Affiliation(s)
- Sundus F Shalabi
- Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, U.S.A
- Medical Research Center, Al-Quds University, Jerusalem, Palestine
| | - Mark A LaBarge
- Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, U.S.A
- Center for Cancer and Aging, Beckman Research Institute, City of Hope, Duarte, CA, U.S.A
- Center for Cancer Biomarkers Research (CCBIO), Bergen, Norway
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22
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Second Primary Malignancies in Diffuse Large B-cell Lymphoma Survivors with 40 Years of Follow-Up: Influence of Chemotherapy and Radiotherapy. Adv Radiat Oncol 2022; 7:101035. [DOI: 10.1016/j.adro.2022.101035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 07/15/2022] [Indexed: 11/20/2022] Open
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23
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Smolarz B, Nowak AZ, Romanowicz H. Breast Cancer-Epidemiology, Classification, Pathogenesis and Treatment (Review of Literature). Cancers (Basel) 2022; 14:2569. [PMID: 35626173 PMCID: PMC9139759 DOI: 10.3390/cancers14102569] [Citation(s) in RCA: 178] [Impact Index Per Article: 59.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 05/12/2022] [Accepted: 05/23/2022] [Indexed: 12/22/2022] Open
Abstract
Breast cancer is the most-commonly diagnosed malignant tumor in women in the world, as well as the first cause of death from malignant tumors. The incidence of breast cancer is constantly increasing in all regions of the world. For this reason, despite the progress in its detection and treatment, which translates into improved mortality rates, it seems necessary to look for new therapeutic methods, and predictive and prognostic factors. Treatment strategies vary depending on the molecular subtype. Breast cancer treatment is multidisciplinary; it includes approaches to locoregional therapy (surgery and radiation therapy) and systemic therapy. Systemic therapies include hormone therapy for hormone-positive disease, chemotherapy, anti-HER2 therapy for HER2-positive disease, and quite recently, immunotherapy. Triple negative breast cancer is responsible for more than 15-20% of all breast cancers. It is of particular research interest as it presents a therapeutic challenge, mainly due to its low response to treatment and its highly invasive nature. Future therapeutic concepts for breast cancer aim to individualize therapy and de-escalate and escalate treatment based on cancer biology and early response to therapy. The article presents a review of the literature on breast carcinoma-a disease affecting women in the world.
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Affiliation(s)
- Beata Smolarz
- Laboratory of Cancer Genetics, Department of Pathology, Polish Mother’s Memorial Hospital Research Institute, Rzgowska 281/289, 93-338 Lodz, Poland;
| | - Anna Zadrożna Nowak
- Department of Chemotherapy, Medical University of Lodz, Copernicus Memorial Hospital, 93-513 Lodz, Poland;
| | - Hanna Romanowicz
- Laboratory of Cancer Genetics, Department of Pathology, Polish Mother’s Memorial Hospital Research Institute, Rzgowska 281/289, 93-338 Lodz, Poland;
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24
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Modulation of Secondary Cancer Risks from Radiation Exposure by Sex, Age and Gonadal Hormone Status: Progress, Opportunities and Challenges. J Pers Med 2022; 12:jpm12050725. [PMID: 35629147 PMCID: PMC9146871 DOI: 10.3390/jpm12050725] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/18/2022] [Accepted: 04/27/2022] [Indexed: 11/29/2022] Open
Abstract
Available data on cancer secondary to ionizing radiation consistently show an excess (2-fold amount) of radiation-attributable solid tumors in women relative to men. This excess risk varies by organ and age, with the largest sex differences (6- to more than 10-fold) found in female thyroid and breasts exposed between birth until menopause (~50 years old) relative to age-matched males. Studies in humans and animals also show large changes in cell proliferation rates, radiotracer accumulation and target density in female reproductive organs, breast, thyroid and brain in conjunction with physiological changes in gonadal hormones during the menstrual cycle, puberty, lactation and menopause. These sex differences and hormonal effects present challenges as well as opportunities to personalize radiation-based treatment and diagnostic paradigms so as to optimize the risk/benefit ratios in radiation-based cancer therapy and diagnosis. Specifically, Targeted Radionuclide Therapy (TRT) is a fast-expanding cancer treatment modality utilizing radiopharmaceuticals with high avidity to specific molecular tumor markers, many of which are influenced by sex and gonadal hormone status. However, past and present dosimetry studies of TRT agents do not stratify results by sex and hormonal environment. We conclude that cancer management using ionizing radiation should be personalized and informed by the patient sex, age and hormonal status.
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25
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Yan Z, Ao X, Liang X, Chen Z, Liu Y, Wang P, Wang D, Liu Z, Liu X, Zhu J, Zhou S, Zhou P, Gu Y. Transcriptional inhibition of miR-486-3p by BCL6 upregulates Snail and induces epithelial-mesenchymal transition during radiation-induced pulmonary fibrosis. Respir Res 2022; 23:104. [PMID: 35484551 PMCID: PMC9052631 DOI: 10.1186/s12931-022-02024-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 04/09/2022] [Indexed: 12/14/2022] Open
Abstract
Background Ionizing radiation (IR) can induce pulmonary fibrosis by causing epithelial mesenchymal transition (EMT), but the exact mechanism has not been elucidated. To investigate the molecular mechanism of how radiation induces pulmonary fibrosis by altering miR-486-3p content and thus inducing EMT. Methods The changes of miR-486-3p in cells after irradiation were detected by RT-qPCR. Western blot was used to detect the changes of cellular epithelial marker protein E-cadherin, mesenchymal marker N-cadherin, Vimentin and other proteins. The target gene of miR-486-3p was predicted by bioinformatics method and the binding site was verified by dual luciferase reporter system. In vivo experiments, adeno-associated virus (AAV) was used to carry miR-486-3p mimic to lung. Radiation-induced pulmonary fibrosis (RIPF) model was constructed by 25Gy60Co γ-rays. The structural changes of mouse lung were observed by HE and Masson staining. The expression of relevant proteins in mice was detected by immunohistochemistry. Results IR could decrease the miR-486-3p levels in vitro and in vivo, and that effect was closely correlated to the occurrence of RIPF. The expression of Snail, which induces EMT, was shown to be restrained by miR-486-3p. Therefore, knockdown of Snail blocked the EMT process induced by radiation or knockdown of miR-486-3p. In addition, the molecular mechanism underlying the IR-induced miRNA level reduction was explored. The increased in BCL6 could inhibit the formation of pri-miR-486-3p, thereby reducing the levels of miR-486-3p in the alveolar epithelial cells, which would otherwise promote EMT and contribute to RIPF by targeting Snail. Conclusion IR can exacerbate RIPF in mice by activating the transcription factor BCL6, which inhibits the transcription of miR-486-3p and decreases its content, which in turn increases the content of the target gene slug and triggers EMT.
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Affiliation(s)
- Ziyan Yan
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China
| | - Xingkun Ao
- Hengyang Medical College, University of South China, Hengyang, Hunan, China
| | - Xinxin Liang
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.,Hengyang Medical College, University of South China, Hengyang, Hunan, China
| | - Zhongmin Chen
- PLA Rocket Force Characteristic Medical Center, Beijing, China
| | - Yuhao Liu
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China
| | - Ping Wang
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China
| | - Duo Wang
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China
| | - Zheng Liu
- School of Public Health, University of South China, Hengyang, Hunan, China
| | - Xiaochang Liu
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China
| | - Jiaojiao Zhu
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China
| | - Shenghui Zhou
- Hengyang Medical College, University of South China, Hengyang, Hunan, China
| | - Pingkun Zhou
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.
| | - Yongqing Gu
- Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China. .,Hengyang Medical College, University of South China, Hengyang, Hunan, China.
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26
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Pensabene M, Von Arx C, De Laurentiis M. Male Breast Cancer: From Molecular Genetics to Clinical Management. Cancers (Basel) 2022; 14:2006. [PMID: 35454911 PMCID: PMC9030724 DOI: 10.3390/cancers14082006] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 04/01/2022] [Accepted: 04/04/2022] [Indexed: 12/18/2022] Open
Abstract
MBC is a rare disease accounting for almost 1% of all cancers in men and less than 1% of breast cancer. Emerging data on the genetic drivers of predisposition for MBC are available and different risk factors have been associated with its pathogenesis. Genetic alterations, such as pathogenetic variants in BRCA1/2 and other moderate-/low-penetrance genes, along with non-genetic risk factors, have been recognized as pathogenic factors for MBC. Preventive and therapeutic implications could be related to the detection of alterations in predisposing genes, especially BRCA1/2, and to the identification of oncogenic drivers different from FBC. However, approved treatments for MBC remain the same as FBC. Cancer genetic counseling has to be considered in the diagnostic work-up of MBC with or without positive oncological family history. Here, we review the literature, reporting recent data about this malignancy with a specific focus on epidemiology, and genetic and non-genetic risk factors. We introduce the perspective of cancer genetic counseling for MBC patients and their healthy at-risk family members, with a focus on different hereditary cancer syndromes.
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Affiliation(s)
- Matilde Pensabene
- National Cancer Institute, IRCCS Fondazione G. Pascale, 80131 Naples, Italy; (C.V.A.); (M.D.L.)
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27
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Ramachandran L, Patel G, Fatima S, Khan M. Breast Cancer Secondary to Radiation Therapy in a Patient With Wilms Tumor. Cureus 2022; 14:e23597. [PMID: 35505703 PMCID: PMC9053353 DOI: 10.7759/cureus.23597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/29/2022] [Indexed: 11/22/2022] Open
Abstract
Wilms tumor, one of the most common childhood malignancies, is typically treated with a combination of chemotherapy, radiation, and surgical resection. Wilms tumor survivors who received radiation therapy are, however, at a higher risk of secondary malignancies and need vigilant monitoring. We present the case of a 35-year-old female with history of Wilms tumor at age five, who received radiation therapy for pulmonary metastasis, and was found to have breast cancer at the age of 35. We discuss different protocols in treatment of Wilms tumor and current secondary malignancy screening recommendations. We also recognize the importance of screening guideline awareness among primary care physicians and its mortality and morbidity implications.
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28
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Green VL. Breast Cancer Risk Assessment and Management of the High-Risk Patient. Obstet Gynecol Clin North Am 2022; 49:87-116. [DOI: 10.1016/j.ogc.2021.11.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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29
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Breast Cancer Management in 2021: A Primer for the OB GYN. Best Pract Res Clin Obstet Gynaecol 2022; 82:30-45. [DOI: 10.1016/j.bpobgyn.2022.02.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 02/07/2022] [Accepted: 02/09/2022] [Indexed: 12/18/2022]
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30
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Lee MV, Aharon S, Kim K, Sunn Konstantinoff K, Appleton CM, Stwalley D, Olsen MA. Recent Trends in Screening Breast MRI. JOURNAL OF BREAST IMAGING 2022; 4:39-47. [PMID: 35103253 PMCID: PMC8794012 DOI: 10.1093/jbi/wbab088] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The objective of this study was to assess trends in screening breast MRI utilization among privately insured women in the U.S. from 2007 to 2017. METHODS The utilization of screening breast MRI among women aged 25-64 years from January 1, 2007, to December 31, 2017, was obtained using the MarketScan Commercial Database. We used Current Procedural Terminology codes to exclude breast MRI exams performed in women with a new breast cancer diagnosis and in women imaged to assess response to neoadjuvant therapy in the preceding 90 days. During the 11-year study, 351 763 study-eligible women underwent 488 852 MRI scans. RESULTS An overall 55.0% increase in screening breast MRI utilization was observed over the study period, with a steadily increasing trend. The greatest annual increase in percent utilization was from 2007 to 2008 at 16.6%. The highest utilization rate was in 2017, in which 0.4% of women aged 25-64 years underwent screening breast MRI. Of the women who underwent screening MRI with sufficient follow-up, 76.5% underwent only one examination during the study period. CONCLUSION Utilization of screening breast MRI has increased steadily in the past decade to a peak of 0.4% of adult women. However, an estimated 9% of U.S. women are eligible for high-risk breast MRI screening; thus, utilization falls short of optimal compliance. Further studies to evaluate the barriers to screening compliance may help optimize utilization.
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Affiliation(s)
- Michelle V Lee
- Medical College of Georgia, Department of Radiology, Augusta, GA, USA
| | - Shani Aharon
- Medical School at the University of Massachusetts, Worcester, MA, USA
| | - Kevin Kim
- Washington University in St. Louis, Department of Medicine, St. Louis, MO, USA
| | | | | | - Dustin Stwalley
- Washington University in St. Louis, Department of Medicine, St. Louis, MO, USA
| | - Margaret A Olsen
- Washington University in St. Louis, Department of Medicine, St. Louis, MO, USA
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31
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Wong SM, Ajjamada L, Weiss AC, Prakash I, Skamene S, Boileau JF, Pollak MN, Basik M. Clinicopathologic features of breast cancers diagnosed in women treated with prior radiation therapy for Hodgkin lymphoma: Results from a population-based cohort. Cancer 2021; 128:1365-1372. [PMID: 34919263 DOI: 10.1002/cncr.34065] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 11/22/2021] [Accepted: 11/23/2021] [Indexed: 11/06/2022]
Abstract
BACKGROUND Childhood and young adult survivors of Hodgkin lymphoma (HL) are at elevated risk of developing breast cancer, yet little data exist on the tumor characteristics that develop in this high-risk patient population. METHODS The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify breast cancers diagnosed between 1990 and 2016 in women who had received prior radiation therapy for HL at age 30 years or younger. Clinicopathologic features of subsequent breast cancers (breast cancer after radiation therapy for HL [BC-HL]) were examined and compared with breast cancers diagnosed in women who had no prior malignancy (breast cancer with no prior malignancy [BC-NPM]). RESULTS In total, 321 breast cancers were identified in 257 women who had a history of radiation therapy for HL. The median age at HL diagnosis was 22 years (interquartile range, 18-26 years), and nearly all patients in the BC-HL group (97.9%) were diagnosed ≥8 years after radiation therapy. Overall, 56 patients in the BC-HL group (21.8%) developed bilateral breast cancer. Compared with women who had BC-NPM, those who had BC-HL were younger (43 vs 60 years; P < .001) and were less likely to present with ductal carcinoma in situ (8.4% vs 14.9%; P = .001). On multivariable analysis that included adjustment for age, invasive BC-HL was associated with smaller (≤2 cm) tumor size (odds ratio, 1.64; 95% CI, 1.25-2.15) and upper outer quadrant tumors (odds ratio, 1.37; 95% CI, 1.04-1.81) compared with BC-NPM. In a subset analysis of 102 women who had HER2/neu status available, the distribution of biologic subtype was not significantly different between BC-HL and BC-NPM (P = .16). CONCLUSIONS Breast cancers in women who previously received radiation therapy for HL are characterized by earlier onset disease, although most remain estrogen receptor-positive and have early stage disease at presentation. LAY SUMMARY Women who have had radiation therapy for Hodgkin lymphoma at a young age are at increased risk of developing early onset breast cancer; however, most of these breast cancers are sensitive to hormones (estrogen receptor-positive) and are diagnosed at early stages. Because these breast tumors are estrogen receptor-positive, medications that prevent breast cancer by blocking the effect of or lowering hormone levels (also termed endocrine prevention) may be useful in this group of high-risk women.
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Affiliation(s)
- Stephanie M Wong
- Department of Surgery, McGill University Medical School, Montreal, Quebec, Canada.,Jewish General Hospital Stroll Cancer Prevention Center, Montreal, Quebec, Canada.,Department of Oncology, McGill University Medical School, Montreal, Quebec, Canada
| | - Lissa Ajjamada
- Department of Hematology Oncology, McGill University Medical School, Montreal, Quebec, Canada.,Department of Hematology Oncology, University of Montreal, Montreal, Quebec, Canada
| | - Anna C Weiss
- Division of Breast Surgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts
| | - Ipshita Prakash
- Department of Surgery, McGill University Medical School, Montreal, Quebec, Canada.,Department of Oncology, McGill University Medical School, Montreal, Quebec, Canada
| | - Sonia Skamene
- Department of Radiation Oncology, McGill University Medical School, Montreal, Quebec, Canada
| | - Jean Francois Boileau
- Department of Surgery, McGill University Medical School, Montreal, Quebec, Canada.,Department of Oncology, McGill University Medical School, Montreal, Quebec, Canada
| | - Michael N Pollak
- Jewish General Hospital Stroll Cancer Prevention Center, Montreal, Quebec, Canada.,Department of Oncology, McGill University Medical School, Montreal, Quebec, Canada
| | - Mark Basik
- Department of Surgery, McGill University Medical School, Montreal, Quebec, Canada.,Department of Oncology, McGill University Medical School, Montreal, Quebec, Canada
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Tamam N, Salah H, Rabbaa M, Abuljoud M, Sulieman A, Alkhorayef M, Bradley D. Evaluation of patients radiation dose during mammography imaging procedure. Radiat Phys Chem Oxf Engl 1993 2021. [DOI: 10.1016/j.radphyschem.2021.109680] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Fakhri B, Ai W. Current and emerging treatment options in primary mediastinal B-cell lymphoma. Ther Adv Hematol 2021; 12:20406207211048959. [PMID: 34659697 PMCID: PMC8511915 DOI: 10.1177/20406207211048959] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Accepted: 07/21/2021] [Indexed: 11/24/2022] Open
Abstract
Previously considered a subtype of diffuse large B-cell lymphoma (DLBCL), primary
mediastinal B-cell lymphoma (PMBCL) is now recognized by the World Health
Organization as an independent entity. PMBCL has clinicopathologic features that
are separate from systemic DLBCL and harbors some biologic characteristics which
overlap with nodular sclerosing classic Hodgkin’s lymphoma (cHL). Similar to
cHL, copy number alterations of 9p24.1 are frequently seen in PMBCL, which leads
to increased expression of key genes in the region, including programmed
death-ligand 1( PD-L1), PD-L2, and JAK2. In addition, PMBCL cells express CD30
in a mostly patchy fashion. In the upfront setting, dose-adjusted etoposide,
prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (i.e.,
DA-EPOCH-R) is the only regimen that has been shown in a prospective setting to
result in outstanding outcomes without consolidative radiation to the
mediastinum, with a 5-year event-free survival rate of 93% and overall survival
rate of 97%. Thus, in recent years, DA-EPOCH-R has been recognized as the
preferred frontline regimen. Despite the encouraging results in the frontline
setting, the outcomes in the relapsed/refractory setting remain poor. The
current approach of salvage chemotherapy followed by autologous stem cell
transplantation, as used in patients with DLBCL, does not result in high rates
of cure in patients with rrPMBCL. In recent years, the characteristic molecular
features identified in PMBCL have provided more treatment opportunities for this
patient population. In the relapsed setting, single-agent PD-1 inhibitor
pembrolizumab have demonstrated high and durable remission rates. Despite the
expression of CD30, the CD30 antibody drug-conjugate brentuximab vedotin (BV) as
a single agent has been deemed inactive in this disease. On the contrary, the
combinations of BV and PD-1 inhibitor have shown higher response rates than PD-1
inhibitor alone. Moreover, anti-CD19 chimeric antigen receptor T-cell (CAR
T-cell) therapy has been positioned as another successful strategy for patients
with rrPMBCL. Axicabtagene ciloleucel and lisocabtagene maraleucel are two
products used in rrPMBCL.
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Affiliation(s)
- Bita Fakhri
- Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
| | - Weiyun Ai
- Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
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Bao S, Jiang M, Wang X, Hua Y, Zeng T, Yang Y, Yang F, Yan X, Sun C, Yang M, Fu Z, Huang X, Li J, Wu H, Li W, Tang J, Yin Y. Nonmetastatic breast cancer patients subsequently developing second primary malignancy: A population-based study. Cancer Med 2021; 10:8662-8672. [PMID: 34643330 PMCID: PMC8633251 DOI: 10.1002/cam4.4351] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 09/04/2021] [Accepted: 09/05/2021] [Indexed: 12/24/2022] Open
Abstract
Background With life span extending, breast cancer (BC) survivors may face the possibility of developing second primary cancer (SPC) and considerably shorten survivorship. However, little is known about multiple primary cancer (MPC) patients with nonmetastatic breast cancer as a first primary malignancy (BCFPM). Methods Here, we retrospectively analyzed data on cancer survivors with BCFPM diagnosed between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. The prognostic factors for breast cancer‐specific survival (BCSS) were ascertained by the stepwise regression analysis and a competing risk model, and were integrated to the establishment of prognostic nomogram, of which the accuracy was measured by the calibration curve and the concordance index (C‐index). Results In total, 8616 patients were identified with 4.6% of 3‐year breast cancer‐ specific death (BCSD) and 8.6% of 5‐year BCSD. The most common SPC among BCFPM patients were female BC and lung cancer. Besides, the median latency time between BC and SPC was 22 months. At a ratio of 7:3, all patients were randomly categorized into a training cohort (n = 6032) and a validation cohort (n = 2584). By a proportional subdistribution hazards regression analysis, the following factors were considered to own independent prognostic abilities of BCSS: subtypes, grade, T classification, N classification, radiation, and sites of SPC. The nomogram could accurately predict 3‐year and 5‐year breast cancer‐associated survival of BCFPM patients with high internal and external validated C‐index, 0.715 (95% CI, 0.691–0.739), and 0.683 (95% CI, 0.642–0.724), respectively. Conclusions BC survivors remained a high risk of developing SPC and considerably shortened survival time. In this study, a favorable nomogram was constructed to as a prediction model for 3‐year and 5‐year BCSS of BCFPM patients, largely intending to prolong the life of these patients by assisting clinicians to make individualized follow‐up plans.
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Affiliation(s)
- Shengnan Bao
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,The First Clinical College of Nanjing Medical University, Nanjing, China
| | - Mengping Jiang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,The First Clinical College of Nanjing Medical University, Nanjing, China
| | - Xi Wang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,The First Clinical College of Nanjing Medical University, Nanjing, China
| | - Yijia Hua
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,The First Clinical College of Nanjing Medical University, Nanjing, China
| | - Tianyu Zeng
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,The First Clinical College of Nanjing Medical University, Nanjing, China
| | - Yiqi Yang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,The First Clinical College of Nanjing Medical University, Nanjing, China
| | - Fan Yang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,The First Clinical College of Nanjing Medical University, Nanjing, China
| | - Xueqi Yan
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,The First Clinical College of Nanjing Medical University, Nanjing, China
| | - Chunxiao Sun
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Mengzhu Yang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ziyi Fu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiang Huang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jun Li
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hao Wu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wei Li
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jinhai Tang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yongmei Yin
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing, China
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Khanna L, Prasad SR, Yedururi S, Parameswaran AM, Marcal LP, Sandrasegaran K, Tirumani SH, Menias CO, Katabathina VS. Second Malignancies after Radiation Therapy: Update on Pathogenesis and Cross-sectional Imaging Findings. Radiographics 2021; 41:876-894. [PMID: 33891523 DOI: 10.1148/rg.2021200171] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
A wide spectrum of second cancers occur as late complications of radiation therapy (RT) used to treat various malignancies. In addition to the type and dose of radiation, lifestyle, environmental, and genetic factors are important to the development of second malignancies in cancer survivors. Typically, RT-induced malignancies (RTIMs) are biologically aggressive cancers with a variable period of 5-10 years for hematologic malignancies and 10-60 years for solid tumors between RT and the development of the second cancer. Although carcinomas and leukemias commonly develop after low-dose RT, sarcomas occur in tissues or organs that receive high-dose RT. Angiosarcomas and unclassified pleomorphic sarcomas are the two most common RT-associated sarcomas; other sarcomas include malignant peripheral nerve sheath tumors, leiomyosarcomas, osteosarcomas, chondrosarcomas, and dedifferentiated or pleomorphic liposarcomas. Select RTIMs show tumor genetic characteristics that allow accurate diagnosis. Nearly all cutaneous angiosarcomas after RT for breast cancer and 90% of RT-associated malignant peripheral nerve sheath tumors are characterized by MYC gene amplifications and loss of H3 K27me3 expression, respectively. Classic papillary thyroid carcinomas that develop after RT frequently harbor RET/PTC rearrangements and have a favorable prognosis, despite their advanced stage at patient presentation. Select RTIMs demonstrate characteristic imaging findings and typically develop in the prior radiation field. Imaging is essential to early diagnosis, characterization, localization, and staging of RTIMs. Familiarity of radiologists with the diverse spectrum of RTIMs is essential for early diagnosis and optimal management. An invited commentary by Shapiro is available online. ©RSNA, 2021.
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Affiliation(s)
- Lokesh Khanna
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
| | - Srinivasa R Prasad
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
| | - Sireesha Yedururi
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
| | - Anand M Parameswaran
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
| | - Leonardo P Marcal
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
| | - Kumar Sandrasegaran
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
| | - Sree Harsha Tirumani
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
| | - Christine O Menias
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
| | - Venkata S Katabathina
- From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (L.K., A.M.P., V.S.K.); Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (S.R.P., S.Y., L.P.M.); Department of Radiology, Mayo Clinic, Scottsdale, Ariz (K.S., C.O.M.); and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (S.H.T.)
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Apodaca-Ramos I, Maciel-Roman DA, Tenorio-Torres JA, Kershenovich-Gersson J, Moncada-Madrazo M, Said-Lemus FM, Mendoza-Elizarraraz D, Domínguez-Reyes CA. Intracystic Papillary Breast Cancer in a 16-Year-Old Patient. J Pediatr Adolesc Gynecol 2021; 34:213-216. [PMID: 33152468 DOI: 10.1016/j.jpag.2020.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 10/14/2020] [Accepted: 10/27/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND Primary breast cancer in the pediatric population is rare. To our knowledge, no cases of intracystic papillary carcinoma have been reported in patients younger than 21 years. CASE A 16-year-old patient presented with a retroareolar mass and bloody nipple discharge in her left breast. A biopsy established papillary intracystic carcinoma. The patient was treated surgically and a risk reduction strategy developed in a multidisciplinary session was implemented.
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Hoeller U, Borgmann K, Oertel M, Haverkamp U, Budach V, Eich HT. Late Sequelae of Radiotherapy—The Effect of Technical and Conceptual Innovations in Radiation Oncology. DEUTSCHES ARZTEBLATT INTERNATIONAL 2021; 118:205-211. [PMID: 34024324 PMCID: PMC8278127 DOI: 10.3238/arztebl.m2021.0024] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 03/25/2020] [Accepted: 11/20/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Approximately half of all patients with tumors need radiotherapy. Long-term survivors may suffer from late sequelae of the treatment. The existing radiotherapeutic techniques are being refined so that radiation can be applied more precisely, with the goal of limiting the radiation exposure of normal tissue and reducing late sequelae. METHODS This review is based on the findings of a selective search in PubMed for publications on late sequelae of conventional percutaneous radiotherapy, January 2000 to May 2020. Late sequelae affecting the central nervous system, lungs, and heart and the development of second tumors are presented, and radiobiological mechanisms and the relevant technical and conceptual considerations are discussed. RESULTS The current standard of treatment involves the use of linear accelerators, intensity-modulated radiotherapy (IMRT), image-guided and respiratory-gated radiotherapy, and the integration of positron emission tomography combined with computed tomography (PET-CT) in radiation treatment planning. Cardiotoxicity has been reduced with regard to the risk of coronary heart disease after radiotherapy for Hodgkin's lymphoma (hazard ratio [HR] 0.44 [0.23; 0.85]). It was also found that the rate of radiation- induced pneumonitis dropped from 7.9% with conformal treatment to 3.5% with IMRT in a phase III lung cancer trial. It is hoped that neurocognitive functional impairment will be reduced by hippocampal avoidance in modern treatment planning: an initial phase III trial yielded a hazard ratio of 0.74 [0.58; 0.94]. It is estimated that 8% of second solid tumors in adults are induced by radiotherapy (3 additional tumors per 1000 patients at 10 years). CONCLUSION Special challenges for research in this field arise from the long latency of radiation sequelae and the need for largescale, well-documented patient collectives in order to discern dose-effect relationships, and take account of cofactors, when the overall number of events is small. It is hoped that further technical and conceptual advances will be made in the areas of adaptive radiotherapy, proton and heavy-ion therapy, and personalized therapy.
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Zang Y, Qi F, Cheng Y, Xia T, Xiao R, Li X, Yang N. Survival outcomes in prostate cancer patients with a prior cancer. Transl Androl Urol 2021; 10:741-753. [PMID: 33718076 PMCID: PMC7947467 DOI: 10.21037/tau-20-897] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background To shed light on the survival outcomes of prostate cancer (PCa) patients diagnosed after a prior cancer and identify prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in PCa patients. Methods In the primary group, a total of 1,778 PCa patients with a prior cancer were identified in the Surveillance, Epidemiology, and End Results (SEER) database from 2005 to 2015, retrospectively. Baseline characteristics and causes of death (COD) of these patients were collected and compared. In the second group, a total of 10,296 PCa patients [5,148 patients with PCa as the only malignancy and 5,148 patients with PCa as their second primary malignancy (SPM)] diagnosed between 2010 and 2011 were extracted to investigate the impact of prior cancers on survival outcomes. Results In PCa patients with a prior cancer, the most common type of prior cancer was from gastrointestinal system (29.92%), followed by urinary system (21.37%). Patients were more likely to die of the prior caner, and those with prior cancer from respiratory system had the worst survival outcomes. Moreover, the overall ratios in patients with stage (PCa) I–II and III–IV diseases were 0.21 and 1.65, indicating that patients with higher stage diseases were more likely to die of PCa. In the second group, patients with PCa as the SPM had worse OS than those with PCa as the first primary cancer. Lastly, prognostic factors for OS and CSS in PCa patients were explored. Conclusions PCa remains to be an important COD for patients with a prior malignancy, especially for those with high-stage diseases. PCa patients with a prior cancer had worse survival outcomes than those without.
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Affiliation(s)
- Yan Zang
- Department of Bariatric and Metabolic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Feng Qi
- Department of Urologic Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Yifei Cheng
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Tian Xia
- Department of Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Rongrong Xiao
- Department of Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Xiao Li
- Department of Urologic Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Ningli Yang
- Department of Bariatric and Metabolic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Ma L, Gonzalez-Junca A, Zheng Y, Ouyang H, Illa-Bochaca I, Horst KC, Krings G, Wang Y, Fernandez-Garcia I, Chou W, Barcellos-Hoff MH. Inflammation Mediates the Development of Aggressive Breast Cancer Following Radiotherapy. Clin Cancer Res 2021; 27:1778-1791. [PMID: 33402361 DOI: 10.1158/1078-0432.ccr-20-3215] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Revised: 10/23/2020] [Accepted: 12/28/2020] [Indexed: 11/16/2022]
Abstract
PURPOSE Women treated with radiotherapy before 30 years of age have increased risk of developing breast cancer at an early age. Here, we sought to investigate mechanisms by which radiation promotes aggressive cancer. EXPERIMENTAL DESIGN The tumor microenvironment (TME) of breast cancers arising in women treated with radiotherapy for Hodgkin lymphoma was compared with that of sporadic breast cancers. To investigate radiation effects on carcinogenesis, we analyzed tumors arising from Trp53-null mammary transplants after irradiation of the target epithelium or host using immunocompetent and incompetent mice, some of which were treated with aspirin. RESULTS Compared with age-matched specimens of sporadic breast cancer, radiation-preceded breast cancers (RP-BC) were characterized by TME rich in TGFβ, cyclooxygenase 2, and myeloid cells, indicative of greater immunosuppression, even when matched for triple-negative status. The mechanism by which radiation impacts TME construction was investigated in carcinomas arising in mice bearing Trp53-null mammary transplants. Immunosuppressive TMEs (iTME) were recapitulated in mice irradiated before transplantation, which implicated systemic immune effects. In nu/nu mice lacking adaptive immunity irradiated before Trp53-null mammary transplantation, cancers also established an iTME, which pointed to a critical role for myeloid cells. Consistent with this, irradiated mammary glands contained more macrophages and human cells cocultured with polarized macrophages underwent dysplastic morphogenesis mediated by IFNγ. Treating mice with low-dose aspirin for 6 months postirradiation prevented establishment of an iTME and resulted in less aggressive tumors. CONCLUSIONS These data show that radiation acts via nonmutational mechanisms to promote markedly immunosuppressive features of aggressive, RP-BCs.
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Affiliation(s)
- Lin Ma
- Department of Radiation Oncology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California
| | - Alba Gonzalez-Junca
- Department of Radiation Oncology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California
| | - Yufei Zheng
- Department of Radiation Oncology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California
| | - Haoxu Ouyang
- Department of Radiation Oncology, New York University School of Medicine, New York, New York
| | - Irineu Illa-Bochaca
- Department of Radiation Oncology, New York University School of Medicine, New York, New York
| | - Kathleen C Horst
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California
| | - Gregor Krings
- Department of Pathology, University of California, San Francisco, San Francisco, California
| | - Yinghao Wang
- Department of Radiation Oncology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California
| | | | - William Chou
- Department of Radiation Oncology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California
| | - Mary Helen Barcellos-Hoff
- Department of Radiation Oncology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
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Mulder RL, Hudson MM, Bhatia S, Landier W, Levitt G, Constine LS, Wallace WH, van Leeuwen FE, Ronckers CM, Henderson TO, Moskowitz CS, Friedman DN, Ng AK, Jenkinson HC, Demoor-Goldschmidt C, Skinner R, Kremer LC, Oeffinger KC. Updated Breast Cancer Surveillance Recommendations for Female Survivors of Childhood, Adolescent, and Young Adult Cancer From the International Guideline Harmonization Group. J Clin Oncol 2020; 38:4194-4207. [PMID: 33078972 PMCID: PMC7723685 DOI: 10.1200/jco.20.00562] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/17/2020] [Indexed: 01/02/2023] Open
Abstract
PURPOSE As new evidence is available, the International Late Effects of Childhood Cancer Guideline Harmonization Group has updated breast cancer surveillance recommendations for female survivors of childhood, adolescent, and young adult cancer. METHODS We used evidence-based methods to apply new knowledge in refining the international harmonized recommendations developed in 2013. The guideline panel updated the systematic literature review, developed evidence summaries, appraised the evidence, and updated recommendations on the basis of evidence, clinical judgement, and consideration of benefits versus the harms of the surveillance interventions while attaining flexibility in implementation across different health care systems. The GRADE Evidence-to-Decision framework was used to translate evidence to recommendations. A survivor information form was developed to counsel survivors about the potential harms and benefits of surveillance. RESULTS The literature update identified new study findings related to the effects of prescribed moderate-dose chest radiation (10 to 19 Gy), radiation dose-volume, anthracyclines and alkylating agents in non-chest irradiated survivors, and the effects of ovarian function on breast cancer risk. Moreover, new data from prospective investigations were available regarding the performance metrics of mammography and magnetic resonance imaging among survivors of Hodgkin lymphoma. Modified recommendations include the performance of mammography and breast magnetic resonance imaging for survivors treated with 10 Gy or greater chest radiation (strong recommendation) and upper abdominal radiation exposing breast tissue at a young age (moderate recommendation) at least annually up to age 60 years. As a result of inconsistent evidence, no recommendation could be formulated for routine breast cancer surveillance for survivors treated with any type of anthracyclines in the absence of chest radiation. CONCLUSION The newly identified evidence prompted significant change to the recommendations formulated in 2013 related to moderate-dose chest radiation and anthracycline exposure as well as breast cancer surveillance modality.
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Affiliation(s)
- Renée L. Mulder
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
| | - Melissa M. Hudson
- Departments of Epidemiology and Cancer Control, and Oncology, St Jude Children’s Research Hospital, Memphis, TN
| | - Smita Bhatia
- Institute for Cancer Outcomes and Survivorship and Department of Pediatrics, School of Medicine, University of Alabama at Birmingham, Birmingham, AL
| | - Wendy Landier
- Institute for Cancer Outcomes and Survivorship and Department of Pediatrics, School of Medicine, University of Alabama at Birmingham, Birmingham, AL
| | - Gill Levitt
- Department of Oncology/Haematology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
| | - Louis S. Constine
- Departments of Radiation Oncology and Pediatrics, University of Rochester Medical Center, Rochester, NY
| | - W. Hamish Wallace
- Department of Paediatric Oncology, Royal Hospital for Sick Children, Edinburgh, United Kingdom
| | - Flora E. van Leeuwen
- Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Cécile M. Ronckers
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
- Institute for Biostatistics and Registry Research, Medical University Brandenburg, Theodor Fontane, Neuruppin, Germany
| | - Tara O. Henderson
- Department of Pediatrics, University of Chicago Pritzker School of Medicine, Chicago, IL
| | - Chaya S. Moskowitz
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Danielle N. Friedman
- Departments of Pediatrics and Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | | | - Helen C. Jenkinson
- Department of Paediatric Oncology, Birmingham Children’s Hospital, NHS Foundation Trust, Birmingham, United Kingdom
| | - Charlotte Demoor-Goldschmidt
- Centre for Research in Epidemiology and Population Health, Cancer and Radiation team, University of Paris-Sud, Villejuif, France
- Department of Pediatric and Adolescent Hematology/Oncology, CHU Angers, Angers, France
| | - Roderick Skinner
- Department of Paediatric and Adolescent Haematology/Oncology, Great North Children’s Hospital and Newcastle University Centre for Cancer, Newcastle upon Tyne, United Kingdom
| | - Leontien C.M. Kremer
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
- Department of Pediatric Oncology, Emma Children’s Hospital, Amsterdam University Medical Center, University of Amsterdam, the Netherlands
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Bakkach J, Pellegrino B, Elghazawy H, Novosad O, Agrawal S, Bennani Mechita M. Current overview and special considerations for second breast cancer in Hodgkin lymphoma survivors. Crit Rev Oncol Hematol 2020; 157:103175. [PMID: 33321295 DOI: 10.1016/j.critrevonc.2020.103175] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Revised: 06/28/2020] [Accepted: 11/05/2020] [Indexed: 12/15/2022] Open
Abstract
Second breast cancer (SBC) is the most common solid cancer among Hodgkin Lymphoma (HL) female survivors. We reviewed the related modifying risk factors, radiation-induced carcinogenesis, tumors characteristics, management specificities, prevention and surveillance modalities based on current evidence. The risk of developing SBC may be influenced essentially by the age at HL treatment, follow-up latency, dose of irradiation received and the extent of irradiated field. SBCs generally develop at younger age, they are often bilateral, and exhibit more aggressive biological features and worse prognosis. No firm answer about the benefits of breast surveillance is provided by literature, but compelling evidence tends toward a clinical benefit in early detection. Increasing awareness among health providers' care and current survivors as well as the implementation of screening measures is crucial. Great efforts are ongoing in individualizing treatment strategies for future HL patients and response-adapted approaches are holding promise in prevention of these second malignancies.
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Affiliation(s)
- Joaira Bakkach
- Biomedical Genomics and Oncogenetics Research Laboratory, Faculty of Sciences and Techniques of Tangier, Abdelmalek Essaâdi University, Morocco.
| | | | - Hagar Elghazawy
- Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Egypt.
| | - Olga Novosad
- Onco-Hematology Department, National Cancer Institute of the MPH Ukraine, Kiev, Ukraine.
| | - Sanjit Agrawal
- Department of Breast Oncosurgery, Tata Medical Center, Kolkata, West Bengal, India.
| | - Mohcine Bennani Mechita
- Biomedical Genomics and Oncogenetics Research Laboratory, Faculty of Sciences and Techniques of Tangier, Abdelmalek Essaâdi University, Morocco.
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Yeh JM, Lowry KP, Schechter CB, Diller LR, Alagoz O, Armstrong GT, Hampton JM, Leisenring W, Liu Q, Mandelblatt JS, Miglioretti DL, Moskowitz CS, Oeffinger KC, Trentham-Dietz A, Stout NK. Clinical Benefits, Harms, and Cost-Effectiveness of Breast Cancer Screening for Survivors of Childhood Cancer Treated With Chest Radiation : A Comparative Modeling Study. Ann Intern Med 2020; 173:331-341. [PMID: 32628531 PMCID: PMC7510774 DOI: 10.7326/m19-3481] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Surveillance with annual mammography and breast magnetic resonance imaging (MRI) is recommended for female survivors of childhood cancer treated with chest radiation, yet benefits, harms, and costs are uncertain. OBJECTIVE To compare the benefits, harms, and cost-effectiveness of breast cancer screening strategies in childhood cancer survivors. DESIGN Collaborative simulation modeling using 2 Cancer Intervention and Surveillance Modeling Network breast cancer models. DATA SOURCES Childhood Cancer Survivor Study and published data. TARGET POPULATION Women aged 20 years with a history of chest radiotherapy. TIME HORIZON Lifetime. PERSPECTIVE Payer. INTERVENTION Annual MRI with or without mammography, starting at age 25, 30, or 35 years. OUTCOME MEASURES Breast cancer deaths averted, false-positive screening results, benign biopsy results, and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS Lifetime breast cancer mortality risk without screening was 10% to 11% across models. Compared with no screening, starting at age 25 years, annual mammography with MRI averted the most deaths (56% to 71%) and annual MRI (without mammography) averted 56% to 62%. Both strategies had the most screening tests, false-positive screening results, and benign biopsy results. For an ICER threshold of less than $100 000 per quality-adjusted life-year gained, screening beginning at age 30 years was preferred. RESULTS OF SENSITIVITY ANALYSIS Assuming lower screening performance, the benefit of adding mammography to MRI increased in both models, although the conclusions about preferred starting age remained unchanged. LIMITATION Elevated breast cancer risk was based on survivors diagnosed with childhood cancer between 1970 and 1986. CONCLUSION Early initiation (at ages 25 to 30 years) of annual breast cancer screening with MRI, with or without mammography, might reduce breast cancer mortality by half or more in survivors of childhood cancer. PRIMARY FUNDING SOURCE American Cancer Society and National Institutes of Health.
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Affiliation(s)
- Jennifer M. Yeh
- Department of Pediatrics, Harvard Medical School and Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115
| | - Kathryn P. Lowry
- University of Washington, Seattle Cancer Care Alliance, 825 Eastlake Ave. E., Seattle, WA 98109
| | - Clyde B. Schechter
- Department of Family and Social Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Block Building 406, Bronx, NY 10461
| | - Lisa R. Diller
- Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, 450 Brookline Avenue, Boston, MA 02115
| | - Oguzhan Alagoz
- University of Wisconsin–Madison, 1513 University Avenue, Madison, WI 53706
| | - Gregory T. Armstrong
- Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105
| | - John M. Hampton
- University of Wisconsin Carbone Cancer Center, 610 Walnut Street, WARF Room 307, Madison, WI 53726
| | - Wendy Leisenring
- Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA, 98109
| | - Qi Liu
- University of Alberta, 11405 87th Avenue, Edmonton, Alberta, Canada T6G 1C9
| | - Jeanne S. Mandelblatt
- Lombardi Comprehensive Cancer Center, Georgetown University, 3300 Whitehaven Street Northwest, Suite 4100, Washington, DC 20007
| | - Diana L. Miglioretti
- Department of Public Health Sciences, University of California Davis School of Medicine, One Shields Avenue, Med-Sci 1C, Room 145, Davis, CA 95616
| | - Chaya S. Moskowitz
- Memorial Sloan Kettering Cancer Center, 485 Lexington Ave, 2nd floor, NY, NY 10017
| | | | - Amy Trentham-Dietz
- University of Wisconsin Carbone Cancer Center, 610 Walnut Street, WARF Room 307, Madison, WI 53726
| | - Natasha K. Stout
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Landmark Center, 401 Park Drive, Suite 401, Boston, MA 02215
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Chiarelli AM, Blackmore KM, Muradali D, Done SJ, Majpruz V, Weerasinghe A, Mirea L, Eisen A, Rabeneck L, Warner E. Performance Measures of Magnetic Resonance Imaging Plus Mammography in the High Risk Ontario Breast Screening Program. J Natl Cancer Inst 2020; 112:136-144. [PMID: 31233143 DOI: 10.1093/jnci/djz079] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Revised: 03/11/2019] [Accepted: 04/16/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The Ontario Breast Screening Program expanded in July 2011 to screen high-risk women age 30-69 years with annual magnetic resonance imaging (MRI) and digital mammography. This study examined the benefits of screening with mammography and MRI by age and risk criteria. METHODS This prospective cohort study included 8782 women age 30-69 years referred to the High Risk Ontario Breast Screening Program from July 2011 to June 2015, with final results to December 2016. Cancer detection rates, sensitivity, and specificity of MRI and mammography combined were compared with each modality individually within risk groups stratified by age using generalized estimating equation models. Prognostic features of screen-detected breast cancers were compared by modality using Fisher exact test. All P values are two-sided. RESULTS Among 20 053 screening episodes, there were 280 screen-detected breast cancers (cancer detection rate = 14.0 per 1000, 95% confidence interval [CI] = 12.4 to 15.7). The sensitivity of mammography was statistically significantly lower than that of MRI plus mammography (40.8%, 95% CI = 29.3% to 53.5% vs 96.0%, 95% CI = 92.2% to 98.0%, P < .001). In mutation carriers age 30-39 years, sensitivity of the combination was comparable with MRI alone (100.0% vs 96.8%, 95% CI = 79.2% to 100.0%, P = .99) but with statistically significantly decreased specificity (78.0%, 95% CI = 74.7% to 80.9% vs 86.2%, 95% CI = 83.5% to 88.5%, P < .001). In women age 50-69 years, combining MRI and mammography statistically significantly increased sensitivity compared with MRI alone (96.3%, 95% CI = 90.6% to 98.6% vs 90.9%, 95% CI = 83.6% to 95.1%, P = .02), with a small but statistically significant decrease in specificity (84.2%, 95% CI = 83.1% to 85.2% vs 90.0%, 95% CI = 89.2% to 90.9%, P < .001). CONCLUSIONS Screening high risk women age 30-39 years with annual MRI only may be sufficient for cancer detection and should be evaluated further, particularly for mutation carriers. Among women age 50-69 years, detection is most effective when mammography is included with annual MRI.
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Affiliation(s)
- Anna M Chiarelli
- Prevention and Cancer Control, Cancer Care Ontario, Toronto, Ontario, Canada.,Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | | | - Derek Muradali
- Prevention and Cancer Control, Cancer Care Ontario, Toronto, Ontario, Canada.,St. Michael's Hospital, Toronto, Ontario, Canada.,Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada
| | - Susan J Done
- Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada
| | - Vicky Majpruz
- Prevention and Cancer Control, Cancer Care Ontario, Toronto, Ontario, Canada
| | - Ashini Weerasinghe
- Prevention and Cancer Control, Cancer Care Ontario, Toronto, Ontario, Canada
| | - Lucia Mirea
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.,Phoenix Children's Hospital, Phoenix, AZ
| | - Andrea Eisen
- Division of Medical Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Linda Rabeneck
- Prevention and Cancer Control, Cancer Care Ontario, Toronto, Ontario, Canada.,Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.,Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Ellen Warner
- Division of Medical Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.,Department of Medicine, University of Toronto, Toronto, Ontario, Canada
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McDonald AM, Chen Y, Wu J, Hageman L, Francisco L, Kung M, Wong FL, Ness E, Landier W, Battles K, Salzman D, Weisdorf DJ, Forman SJ, Arora M, Armenian SH, Bhatia S. Total Body Irradiation and Risk of Breast Cancer After Blood or Marrow Transplantation: A Blood or Marrow Transplantation Survivor Study Report. J Clin Oncol 2020; 38:2872-2882. [PMID: 32673169 DOI: 10.1200/jco.20.00231] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE To examine the association between total body irradiation (TBI) and subsequent breast cancer in women treated with blood or marrow transplantation (BMT) for hematologic malignancies. PATIENTS AND METHODS Participants were drawn from the BMT Survivor Study (BMTSS), a retrospective cohort study that included patients who underwent transplantation between 1974 and 2014 and survived for ≥ 2 years after BMT. Patients with pre-BMT chest radiation or a history of breast cancer were excluded. Participants completed the BMTSS survey, which included details regarding breast cancer diagnosis. Subsequent breast cancer was confirmed by pathology report review or physician notes. Cox proportional hazards models assessed the association between TBI and subsequent breast cancer. Standardized incidence ratios were calculated to determine the excess risk of subsequent breast cancer compared with that in the general population. RESULTS A total of 1,464 female BMT survivors (allogeneic: n = 788; autologous: n = 676) participated, with a median follow-up of 9.3 years from BMT. TBI was used in 660 patients (46%). Thirty-seven women developed subsequent breast cancer (allogeneic: n = 19; autologous: n = 18). Multivariable analysis revealed that exposure to TBI was associated with an increased risk of subsequent breast cancer among allogeneic BMT survivors (hazard ratio [HR], 3.7 [95% CI, 1.2 to 11.8]; P = .03) and autologous BMT survivors (HR, 2.6 [95% CI, 1.0 to 6.8]; P = .048). Pre-BMT exposure to alkylating agents was associated with an increased risk of subsequent breast cancer among autologous BMT survivors (HR, 3.3 [95% CI, 1.0 to 9.0]; P = .05). Compared with that in the general population, exposure to TBI at age < 30 years was associated with a 4.4-fold higher risk of subsequent breast cancer in allogeneic BMT survivors and a 4.6-fold higher risk in autologous BMT survivors. CONCLUSION The association between TBI and subsequent breast cancer, especially among those exposed at a young age, as well as pre-BMT exposure to alkylating agents, should inform breast cancer screening for early detection.
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Affiliation(s)
- Andrew M McDonald
- Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL.,Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL
| | - Yanjun Chen
- Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL
| | - Jessica Wu
- Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL
| | - Lindsey Hageman
- Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL
| | - Liton Francisco
- Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL
| | - Michelle Kung
- Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL
| | - F Lennie Wong
- Department of Population Sciences, City of Hope, Los Angeles, CA
| | - Emily Ness
- Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL
| | - Wendy Landier
- Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL.,Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL
| | - Kevin Battles
- Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL
| | - Donna Salzman
- Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL
| | - Daniel J Weisdorf
- Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN
| | - Stephen J Forman
- Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Los Angeles, CA
| | - Mukta Arora
- Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN
| | - Saro H Armenian
- Department of Population Sciences, City of Hope, Los Angeles, CA
| | - Smita Bhatia
- Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL.,Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL
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Hiatt RA, Engmann NJ, Balke K, Rehkopf DH. A Complex Systems Model of Breast Cancer Etiology: The Paradigm II Conceptual Model. Cancer Epidemiol Biomarkers Prev 2020; 29:1720-1730. [PMID: 32641370 DOI: 10.1158/1055-9965.epi-20-0016] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 03/09/2020] [Accepted: 06/04/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The etiology of breast cancer is a complex system of interacting factors from multiple domains. New knowledge about breast cancer etiology continues to be produced by the research community, and the communication of this knowledge to other researchers, practitioners, decision makers, and the public is a challenge. METHODS We updated the previously published Paradigm model (PMID: 25017248) to create a framework that describes breast cancer etiology in four overlapping domains of biologic, behavioral, environmental, and social determinants. This new Paradigm II conceptual model was part of a larger modeling effort that included input from multiple experts in fields from genetics to sociology, taking a team and transdisciplinary approach to the common problem of describing breast cancer etiology for the population of California women in 2010. Recent literature was reviewed with an emphasis on systematic reviews when available and larger epidemiologic studies when they were not. Environmental chemicals with strong animal data on etiology were also included. RESULTS The resulting model illustrates factors with their strength of association and the quality of the available data. The published evidence supporting each relationship is made available herein, and also in an online dynamic model that allows for manipulation of individual factors leading to breast cancer (https://cbcrp.org/causes/). CONCLUSIONS The Paradigm II model illustrates known etiologic factors in breast cancer, as well as gaps in knowledge and areas where better quality data are needed. IMPACT The Paradigm II model can be a stimulus for further research and for better understanding of breast cancer etiology.
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Affiliation(s)
- Robert A Hiatt
- Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, California. .,Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California
| | | | - Kaya Balke
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California
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Paluch-Shimon S, Cardoso F, Partridge AH, Abulkhair O, Azim HA, Bianchi-Micheli G, Cardoso MJ, Curigliano G, Gelmon KA, Harbeck N, Merschdorf J, Poortmans P, Pruneri G, Senkus E, Spanic T, Stearns V, Wengström Y, Peccatori F, Pagani O. ESO-ESMO 4th International Consensus Guidelines for Breast Cancer in Young Women (BCY4). Ann Oncol 2020; 31:674-696. [PMID: 32199930 DOI: 10.1016/j.annonc.2020.03.284] [Citation(s) in RCA: 167] [Impact Index Per Article: 33.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 03/07/2020] [Indexed: 12/16/2022] Open
Abstract
The 4th International Consensus Conference for Breast Cancer in Young Women (BCY4) took place in October 2018, in Lugano, Switzerland, organized by the European School of Oncology (ESO) and the European Society of Medical Oncology (ESMO). Consensus recommendations for the management of breast cancer in young women were updated from BCY3 with incorporation of new evidence to inform the guidelines. Areas of research priorities were also identified. This article summarizes the ESO-ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).
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Affiliation(s)
| | - F Cardoso
- Breast Unit Champalimaud Clinical Centre/Champalimaud Foundation, Lisbon, Portugal
| | - A H Partridge
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA
| | - O Abulkhair
- King Abdulaziz Medical City for National Guard, Riyadh, Saudi Arabia
| | - H A Azim
- School of Medicine, Monterrey Institute of Technology, Monterrey, MX
| | | | - M-J Cardoso
- Breast Unit Champalimaud Clinical Centre/Champalimaud Foundation, Lisbon, Portugal; Nova Medical School Lisbon, Portugal
| | - G Curigliano
- European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - K A Gelmon
- British Columbia Cancer, Vancouver, Canada
| | - N Harbeck
- Breast Center, Dept. OB&GYN, University of Munich (LMU), Munich, Germany
| | | | - P Poortmans
- Institut Curie, Department of Radiation Oncology & Paris Sciences & Lettres - PSL University, Paris, France
| | - G Pruneri
- National Cancer Institute, IRCCS Foundation, Milan, Italy
| | - E Senkus
- Medical University of Gdansk, Gdansk, Poland
| | - T Spanic
- Europa Donna Slovenia, Ljubljana, Slovenia
| | - V Stearns
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, USA
| | - Y Wengström
- Department of Neurobiology Cancer Science and Society, Karolinska Institute and Theme Cancer Karolinska University Hospital, Sweden
| | - F Peccatori
- European Institute of Oncology IRCCS & European School of Oncology, Milan, Italy
| | - O Pagani
- Oncology Institute of Southern Switzerland and Breast Unit of Southern Switzerland, Geneva University Hospitals, Swiss Group for Clinical Cancer Research (SAKK), Bellinzona, Switzerland
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Chelmow D, Pearlman MD, Young A, Bozzuto L, Dayaratna S, Jeudy M, Kremer ME, Scott DM, O'Hara JS. Executive Summary of the Early-Onset Breast Cancer Evidence Review Conference. Obstet Gynecol 2020; 135:1457-1478. [PMID: 32459439 PMCID: PMC7253192 DOI: 10.1097/aog.0000000000003889] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 02/23/2020] [Accepted: 03/12/2020] [Indexed: 12/23/2022]
Abstract
The Centers for Disease Control and Prevention launched the Bring Your Brave campaign to increase knowledge about early-onset breast cancer, defined as breast cancer in women aged 18-45 years. The American College of Obstetricians and Gynecologists convened a panel of experts in breast disease from the Society for Academic Specialists in General Obstetrics and Gynecology to review relevant literature, validated tools, best practices, and practice guidelines as a first step toward developing educational materials for women's health care providers about early-onset breast cancer. Panel members conducted structured literature reviews, which were then reviewed by other panel members and discussed at an in-person meeting of stakeholder professional and patient advocacy organizations in April 2019. This article summarizes the relevant literature, existing guidance, and validated tools to guide health care providers in the prevention, early detection, and special considerations of early-onset breast cancer. Substantive knowledge gaps were noted and summarized to provide guidance for future research.
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Affiliation(s)
- David Chelmow
- Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine, Richmond, Virginia; the Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, Michigan; the Department of Women's Health, the University of Texas at Austin Dell Medical School, Austin, Texas; the Departments of Obstetrics and Gynecology and Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; the Department of Obstetrics and Gynecology, Thomas Jefferson University Hospital, Sidney Kimmel Medical College, Philadelphia, Pennsylvania; Southeast Kaiser Permanente Medical Group, Atlanta, Georgia; the Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington; the Department of Obstetrics and Gynecology, University of Connecticut Medical School, Farmington, Connecticut; and the American College of Obstetricians and Gynecologists, Washington, DC
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48
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Helm JS, Rudel RA. Adverse outcome pathways for ionizing radiation and breast cancer involve direct and indirect DNA damage, oxidative stress, inflammation, genomic instability, and interaction with hormonal regulation of the breast. Arch Toxicol 2020; 94:1511-1549. [PMID: 32399610 PMCID: PMC7261741 DOI: 10.1007/s00204-020-02752-z] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 04/16/2020] [Indexed: 12/15/2022]
Abstract
Knowledge about established breast carcinogens can support improved and modernized toxicological testing methods by identifying key mechanistic events. Ionizing radiation (IR) increases the risk of breast cancer, especially for women and for exposure at younger ages, and evidence overall supports a linear dose-response relationship. We used the Adverse Outcome Pathway (AOP) framework to outline and evaluate the evidence linking ionizing radiation with breast cancer from molecular initiating events to the adverse outcome through intermediate key events, creating a qualitative AOP. We identified key events based on review articles, searched PubMed for recent literature on key events and IR, and identified additional papers using references. We manually curated publications and evaluated data quality. Ionizing radiation directly and indirectly causes DNA damage and increases production of reactive oxygen and nitrogen species (RONS). RONS lead to DNA damage and epigenetic changes leading to mutations and genomic instability (GI). Proliferation amplifies the effects of DNA damage and mutations leading to the AO of breast cancer. Separately, RONS and DNA damage also increase inflammation. Inflammation contributes to direct and indirect effects (effects in cells not directly reached by IR) via positive feedback to RONS and DNA damage, and separately increases proliferation and breast cancer through pro-carcinogenic effects on cells and tissue. For example, gene expression changes alter inflammatory mediators, resulting in improved survival and growth of cancer cells and a more hospitable tissue environment. All of these events overlap at multiple points with events characteristic of "background" induction of breast carcinogenesis, including hormone-responsive proliferation, oxidative activity, and DNA damage. These overlaps make the breast particularly susceptible to ionizing radiation and reinforce that these biological activities are important characteristics of carcinogens. Agents that increase these biological processes should be considered potential breast carcinogens, and predictive methods are needed to identify chemicals that increase these processes. Techniques are available to measure RONS, DNA damage and mutation, cell proliferation, and some inflammatory proteins or processes. Improved assays are needed to measure GI and chronic inflammation, as well as the interaction with hormonally driven development and proliferation. Several methods measure diverse epigenetic changes, but it is not clear which changes are relevant to breast cancer. In addition, most toxicological assays are not conducted in mammary tissue, and so it is a priority to evaluate if results from other tissues are generalizable to breast, or to conduct assays in breast tissue. Developing and applying these assays to identify exposures of concern will facilitate efforts to reduce subsequent breast cancer risk.
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Affiliation(s)
- Jessica S Helm
- Silent Spring Institute, 320 Nevada Street, Suite 302, Newton, MA, 02460, USA
| | - Ruthann A Rudel
- Silent Spring Institute, 320 Nevada Street, Suite 302, Newton, MA, 02460, USA.
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49
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Ji F, Yang CQ, Li XL, Zhang LL, Yang M, Li JQ, Gao HF, Zhu T, Cheng MY, Li WP, Wu SY, Zhong AL, Wang K. Risk of breast cancer-related death in women with a prior cancer. Aging (Albany NY) 2020; 12:5894-5906. [PMID: 32250967 PMCID: PMC7185107 DOI: 10.18632/aging.102984] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 03/24/2020] [Indexed: 12/14/2022]
Abstract
The overall risk of developing a second primary cancer is increasing. The purpose of this study was to analyze the survival of patients with breast cancer diagnosed after a prior cancer and identify risk factors of breast cancer death in this population. Using the SEER database, we identified 1,310 woman diagnosed with breast cancer between 2010 and 2015 after a prior cancer as the primary cohort. Clinicopathological characteristics were compared using the Student t-test and chi-square test. Fine and Gray’s regression was used to evaluate the effect of treatments on breast cancer death. After propensity score matching (PSM), 9,845 pairs of patients with breast cancer as the prior or second cancer diagnosed between 2010 and 2011 were included as a second cohort. PSM-adjusted Kaplan-Meier and Cox hazards models were used to evaluate the impact of prior cancer on survival. The results showed that survivors of gynecologic cancers (e.g., ovarian cancer) had a higher risk of developing breast cancer than survivors of gastrointestinal and urinary tract cancers. More patients died of breast cancer than of prior urinary cancer (53.3% vs. 40%, P < 0.05) and melanoma (66.7% vs. 33.3%, P < 0.05). The ratio of breast cancer deaths to prior cancer deaths was significantly higher in patients with diagnoses interval ≥ 3 years than in those with the interval < 3 years (2.67 vs. 0.69, P < 0.001). Breast cancer-specific survival and overall survival rates were significantly lower in women with breast cancer as the second primary cancer than in those with breast cancer as the prior cancer, especially among hormone receptor-positive women. However, breast cancer treatment decreased the risk of breast cancer -specific death (hazard ratio = 0.695, 95% confidence interval: 0.586–0.725, P < 0.001). Breast cancer patients with prior cancers must be carefully considered for clinical trials.
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Affiliation(s)
- Fei Ji
- Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P.R. China.,School of Medicine, South China University of Technology, Guangzhou 510006, P.R. China
| | - Ci-Qiu Yang
- Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P.R. China.,School of Medicine, South China University of Technology, Guangzhou 510006, P.R. China
| | - Xiao-Ling Li
- Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P.R. China.,School of Medicine, South China University of Technology, Guangzhou 510006, P.R. China
| | - Liu-Lu Zhang
- Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P.R. China.,School of Medicine, South China University of Technology, Guangzhou 510006, P.R. China
| | - Mei Yang
- Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P.R. China.,School of Medicine, South China University of Technology, Guangzhou 510006, P.R. China
| | - Jie-Qing Li
- Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P.R. China.,School of Medicine, South China University of Technology, Guangzhou 510006, P.R. China
| | - Hong-Fei Gao
- Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P.R. China.,School of Medicine, South China University of Technology, Guangzhou 510006, P.R. China
| | - Teng Zhu
- Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P.R. China.,School of Medicine, South China University of Technology, Guangzhou 510006, P.R. China
| | - Min-Yi Cheng
- Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P.R. China.,School of Medicine, South China University of Technology, Guangzhou 510006, P.R. China
| | - Wei-Ping Li
- Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P.R. China.,School of Medicine, South China University of Technology, Guangzhou 510006, P.R. China
| | - Si-Yan Wu
- Department of Operation Room, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P.R. China.,School of Medicine, South China University of Technology, Guangzhou 510006, P.R. China
| | - Ai-Ling Zhong
- Department of Operation Room, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P.R. China.,School of Medicine, South China University of Technology, Guangzhou 510006, P.R. China
| | - Kun Wang
- Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P.R. China.,School of Medicine, South China University of Technology, Guangzhou 510006, P.R. China
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50
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Fiorelli A, D'Andrilli A, Carlucci A, Vicidomini G, Loizzi D, Ardò NP, Marasco RD, Ventura L, Ampollini L, Carbognani P, Bocchialini G, Lococo F, Paci M, Di Stefano TS, Ardissone F, Gagliasso M, Mendogni P, Rosso L, Mazzucco A, Vanni C, Marinucci BT, Potenza R, Matricardi A, Ragusa M, Tassi V, Anile M, Poggi C, Serra N, Sica A, Nosotti M, Sollitto F, Venuta F, Rendina EA, Puma F, Santini M. Prognostic factors of lung cancer in lymphoma survivors (the LuCiLyS study). Transl Lung Cancer Res 2020; 9:90-102. [PMID: 32206557 PMCID: PMC7082280 DOI: 10.21037/tlcr.2019.12.28] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Background Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment. Methods This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival. Results Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58–85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P<0.0001); incidental diagnosis of lung cancer (HR: 1.71; P<0.0001); and lung cancer resection (HR: 2.79; P<0.0001) were favorable prognostic factors. At multivariable analysis, no-active lymphoma (HR: 2.68; P=0.004); early lung cancer stage (HR: 2.37; P<0.0001); incidental diagnosis of lung cancer (HR: 2.00; P<0.0001); and lung cancer resection (HR: 2.07; P<0.0001) remained favorable prognostic factors. Patients with non-active lymphoma (n=146) versus those with active lymphoma (n=18) at lung cancer diagnosis presented better median survival (64 vs. 37 months; HR: 2.4; P=0.02), but median lung cancer specific survival showed no significant difference (27 vs. 19 months; HR: 0.3; P=0.17). Conclusions The presence and/or a history of lymphoma should not be a contraindication to resection of lung cancer. Inclusion of lymphoma survivors in a lung cancer-screening program may lead to early detection of lung cancer, and improve the survival.
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Affiliation(s)
- Alfonso Fiorelli
- Translational Medical and Surgical Science, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Antonio D'Andrilli
- Thoracic Surgery, Università La Sapienza, Sant'Andrea Hospital, Rome, Italy
| | - Annalisa Carlucci
- Translational Medical and Surgical Science, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Giovanni Vicidomini
- Translational Medical and Surgical Science, University of Campania Luigi Vanvitelli, Naples, Italy
| | | | | | | | - Luigi Ventura
- Medicine and Surgery, Thoracic Surgery, University Hospital of Parma, Parma, Italy
| | - Luca Ampollini
- Medicine and Surgery, Thoracic Surgery, University Hospital of Parma, Parma, Italy
| | - Paolo Carbognani
- Medicine and Surgery, Thoracic Surgery, University Hospital of Parma, Parma, Italy
| | - Giovanni Bocchialini
- Medicine and Surgery, Thoracic Surgery, University Hospital of Parma, Parma, Italy
| | - Filippo Lococo
- Department of General Thoracic Surgery, Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Massimiliano Paci
- Unit of Thoracic Surgery, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | | | - Francesco Ardissone
- Department of Oncology, Thoracic Surgery Unit, University of Torino, San Luigi Hospital, Orbassano, Italy
| | - Matteo Gagliasso
- Department of Oncology, Thoracic Surgery Unit, University of Torino, San Luigi Hospital, Orbassano, Italy
| | - Paolo Mendogni
- Thoracic Surgery and Lung Transplant Unit, Foundation IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Lorenzo Rosso
- Thoracic Surgery and Lung Transplant Unit, Foundation IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Alessandra Mazzucco
- Thoracic Surgery and Lung Transplant Unit, Foundation IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Camilla Vanni
- Thoracic Surgery, Università La Sapienza, Sant'Andrea Hospital, Rome, Italy
| | | | | | | | - Mark Ragusa
- Thoracic Surgery Unit, S. Maria Hospital at Terni, Perugia University Medical School, Terni, Italy
| | - Valentina Tassi
- Thoracic Surgery Unit, S. Maria Hospital at Terni, Perugia University Medical School, Terni, Italy
| | - Marco Anile
- Unit of Thoracic Surgery, Policlinico Umberto I, University of Rome La Sapienza, Rome, Italy
| | - Camilla Poggi
- Unit of Thoracic Surgery, Policlinico Umberto I, University of Rome La Sapienza, Rome, Italy
| | - Nicola Serra
- Statistic Unit, Department of Public Health, University of Federico II, Naples, Italy
| | - Antonello Sica
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Mario Nosotti
- Thoracic Surgery and Lung Transplant Unit, Foundation IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy
| | | | - Federico Venuta
- Unit of Thoracic Surgery, Policlinico Umberto I, University of Rome La Sapienza, Rome, Italy
| | | | | | - Mario Santini
- Translational Medical and Surgical Science, University of Campania Luigi Vanvitelli, Naples, Italy
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