title: Breast carcinoma subtypes show different patterns of metastatic behavior.
abstract: The aim of our retrospective study was to analyze patterns of subtype specific metastatic spread and to identify the time course of distant metastases. A consecutive series of 490 patients with breast cancer who underwent surgery and postoperative treatment at Semmelweis University, Hungary, and diagnosed between the years 2000 and 2007 was identified from the archives of the 2nd Department of Pathology, Hungary. Molecular subtypes were defined based on the 2011 St. Gallen recommendations. Statistical analysis was performed with SPSS Statistics for Windows, Version 22.0. Distant metastasis free survival (DMFS) was defined as the time elapsed between the first pathological diagnosis of the tumor and the first distant metastasis detection. Distant metastases were detected in 124 patients. Mean time to develop metastasis was 29 months (range 0-127 months). The longest DMFS was observed in the Luminal A (LUMA) subtype (mean 39 months) whereas the shortest was seen in the HER2-positive (HER2+) subtype (mean 21 months; p = 0.012). We confirmed that HER2+ tumors carry a higher risk for distant metastases (42.1%). LUMA-associated metastases were found to be solitary in 59% of cases, whereas HER2+ tumors showed multiple metastases in 79.2% of cases. LUMA tumors showed a preference for bone-only metastasis as compared with HER2+ and triple negative breast cancer (TNBC) cases, which exhibited a higher rate of brain metastasis. The most frequent second metastatic sites of hormone receptor (HR) positive tumors were the lung and liver, whereas the brain was the most affected organ in HR-negative (HR-) cases. Tumor subtypes differ in DMFS and in pattern of distant metastases. HER2+ tumors featured the most aggressive clinical course. Further identification of subtype-specific factors influencing prognosis might have an impact on clinical care and decision-making.
authors.affiliation: 1st Department of Surgery, Semmelweis University, Üllői út 78, Budapest, 1082, Hungary.
authors.forename: István Artúr
authors.initials: IA
authors.lastname: Molnár
authors.affiliation: 1st Department of Surgery, Semmelweis University, Üllői út 78, Budapest, 1082, Hungary.
authors.forename: Béla Ákos
authors.initials: BÁ
authors.lastname: Molnár
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary.|MTA-SE-NAP, Brain Metastasis Research Group, Semmelweis University, Budapest, Hungary.
authors.forename: Laura
authors.initials: L
authors.lastname: Vízkeleti
authors.affiliation: 1st Department of Surgery, Semmelweis University, Üllői út 78, Budapest, 1082, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Fekete
authors.affiliation: 1st Department of Surgery, Semmelweis University, Üllői út 78, Budapest, 1082, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Tamás
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Deák
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary.
authors.forename: Csilla
authors.initials: C
authors.lastname: Szundi
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary.
authors.forename: Borbála
authors.initials: B
authors.lastname: Székely
authors.affiliation: Department of Tumor Biology, National Korányi Institute of Pulmonology, Semmelweis University, Pihenő út 1, Budapest, 1121, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Moldvay
authors.affiliation: Faculty of Electrical Engineering and Information Technology, University of Oradea, Str. Universitatii nr. 1, Oradea, Romania.
authors.forename: Stefan
authors.initials: S
authors.lastname: Vári-Kakas
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary.
authors.forename: Marcell A
authors.initials: MA
authors.lastname: Szász
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Ács
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary.
authors.forename: Janina
authors.initials: J
authors.lastname: Kulka
authors.affiliation: 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary. tokesa1972@yahoo.co.uk.|MTA-SE Tumor Progression Research Group, 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary. tokesa1972@yahoo.co.uk.
authors.forename: Anna-Mária
authors.initials: AM
authors.lastname: Tőkés
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000032:analysis / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000032:analysis / Q000096:biosynthesis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Bone; Brain; Breast; Distant metastases; Prognosis; Subtypes