title: Study of breast cancer incidence in patients of lymphangioleiomyomatosis.
abstract: Molecular evidence has linked the pathophysiology of lymphangioleiomyomatosis (LAM) to that of metastatic breast cancer. Following on this observation, we assessed the association between LAM and subsequent breast cancer. An epidemiological study was carried out using three LAM country cohorts, from Japan, Spain, and the United Kingdom. The number of incident breast cancer cases observed in these cohorts was compared with the number expected on the basis of the country-specific incidence rates for the period 2000-2014. Immunohistochemical studies and exome sequence analysis were performed in two and one tumors, respectively. All cohorts revealed breast cancer standardized incidence ratios (SIRs) ≥ 2.25. The combined analysis of all cases or restricted to pre-menopausal age groups revealed significantly higher incidence of breast cancer: SIR = 2.81, 95 % confidence interval (CI) = 1.32-5.57, P = 0.009; and SIR = 4.88, 95 % CI = 2.29-9.99, P = 0.0007, respectively. Immunohistochemical analyses showed positivity for known markers of lung metastatic potential. This study suggests the existence of increased breast cancer risk among LAM patients. Prospective studies may be warranted to corroborate this result, which may be particularly relevant for pre-menopausal women with LAM.
authors.affiliation: Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, and Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Sinesio Delgado 6, 28029, Madrid, Spain.
authors.forename: Olivier
authors.initials: O
authors.lastname: Nuñez
authors.affiliation: Lung Transplant Unit, Department of Pulmonology, Lymphangioleiomyomatosis Clinic, Vall d'Hebron University Hospital, 08035, Barcelona, Catalonia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Román
authors.affiliation: National Centre for Lymphangioleiomyomatosis, Nottingham University Hospitals NHS Trust, Nottingham, Nottinghamshire, UK Division of Respiratory Medicine and Respiratory Research Unit, University of Nottingham, Nottingham, NG7 2UH, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Johnson
authors.affiliation: National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, 591-8555, Osaka, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, 591-8555, Osaka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hirose
authors.affiliation: Department of Pneumology, Henares Hospital, 28882, Madrid, Spain.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Casanova
authors.affiliation: ProCURE, Breast Cancer and Systems Biology, Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), Gran via 199, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain.
authors.forename: Gorka Ruiz
authors.initials: GR
authors.lastname: de Garibay
authors.affiliation: ProCURE, Breast Cancer and Systems Biology, Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), Gran via 199, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Herranz
authors.affiliation: Department of Biochemistry, Autonomous University of Madrid (UAM), Biomedical Research Institute "Alberto Sols" (Spanish National Research Council (CSIC)-UAM), Hospital La Paz Institute for Health Research (IdiPAZ), 28029, Madrid, Spain.|MD Anderson International Foundation, 28033, Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Bueno-Moreno
authors.affiliation: ProCURE, Breast Cancer and Systems Biology, Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), Gran via 199, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Boni
authors.affiliation: ProCURE, Breast Cancer and Systems Biology, Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), Gran via 199, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mateo
authors.affiliation: Department of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Petit
authors.affiliation: Department of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain.
authors.forename: Fina
authors.initials: F
authors.lastname: Climent
authors.affiliation: Department of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Soler
authors.affiliation: Department of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain.
authors.forename: August
authors.initials: A
authors.lastname: Vidal
authors.affiliation: Cancer Epigenetics and Biology Program, IDIBELL, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain.
authors.forename: José Vicente
authors.initials: JV
authors.lastname: Sánchez-Mut
authors.affiliation: Cancer Epigenetics and Biology Program, IDIBELL, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain.|Department of Physiological Sciences II, School of Medicine, University of Barcelona, 08908, Barcelona, Catalonia, Spain.|Catalan Institution for Research and Advanced Studies (ICREA), 08010, Barcelona, Catalonia, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.affiliation: Cruces University Hospital, BioCruces Research Institute, University of the Basque Country, 48903, Barakaldo, Spain.
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: López
authors.affiliation: ProCURE, Breast Cancer and Systems Biology, Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), Gran via 199, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain.
authors.forename: Nadia
authors.initials: N
authors.lastname: García
authors.affiliation: Department of Radiology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Gumà
authors.affiliation: Department of Radiology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Ortega
authors.affiliation: Breast Cancer Functional Unit, Department of Gynecology, University Hospital of Bellvitge, ICO, IDIBELL, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Plà
authors.affiliation: Breast Cancer Functional Unit, Department of Medical Oncology, ICO, IDIBELL, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Campos
authors.affiliation: Lung Transplant and Cystic Fibrosis Unit, Hospital Universitario y Politecnico La Fe, 46026, Valencia, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Ansótegui
authors.affiliation: Department of Pneumology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain.|Consortium for Biomedical Research in Respiratory Diseases (CIBERES), 28029, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Molina-Molina
authors.affiliation: Department of Pneumology, Instituto de Investigación Sanitaria La Princesa, Hospital La Princesa, 28006, Madrid, Spain.
authors.forename: Claudia
authors.initials: C
authors.lastname: Valenzuela
authors.affiliation: Department of Pneumology, University Hospital Clínica Puerta del Hierro, 28222, Madrid, Spain.
authors.forename: Piedad
authors.initials: P
authors.lastname: Ussetti
authors.affiliation: Department of Pneumology, University Hospital Clínica Puerta del Hierro, 28222, Madrid, Spain.
authors.forename: Rosalía
authors.initials: R
authors.lastname: Laporta
authors.affiliation: Department of Pneumology, Instituto de Investigación Sanitaria La Princesa, Hospital La Princesa, 28006, Madrid, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Ancochea
authors.affiliation: Consortium for Biomedical Research in Respiratory Diseases (CIBERES), 28029, Madrid, Spain.|Department of Pneumology, Hospital Clinic of Barcelona, August Pi Suñer Biomedical Research Institute (IDIBAPS), 08036, Barcelona, Catalonia, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Xaubet
authors.affiliation: Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, and Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Sinesio Delgado 6, 28029, Madrid, Spain. mpollan@isciii.es.
authors.forename: Marina
authors.initials: M
authors.lastname: Pollán
authors.affiliation: ProCURE, Breast Cancer and Systems Biology, Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), Gran via 199, L'Hospitalet del Llobregat, 08908, Barcelona, Catalonia, Spain. mapujana@iconcologia.net.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Pujana
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D018192:Lymphangioleiomyomatosis / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis; D017422:Sequence Analysis, DNA; D013030:Spain / Q000453:epidemiology; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D014408:Biomarkers, Tumor
keywords: Breast cancer; Incidence; Lymphangioleiomyomatosis; TSC1; TSC2; mTOR