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1.
Breast Cancer Res Treat ; 165(2): 411-420, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28612228

RESUMEN

PURPOSE: The natural history of pleomorphic lobular carcinoma in situ (PLCIS) remains largely unknown. METHODS: A pathology database search (1995-2012) was performed to identify patients diagnosed with an LCIS variant. Patients with synchronous breast cancer and/or no evidence of pleomorphism were excluded. Original slides were re-evaluated by three pathologists to identify a consensus cohort of PLCIS. Borderline lesions with focal atypia were classified as LCIS with pleomorphic features (LCIS-PF). Clinical data were obtained from medical records. RESULTS: From 233 patients, we identified 32 with an LCIS variant diagnosis and no concurrent breast cancer. Following review, 16 cases were excluded due to lack of pleomorphism. The remaining 16 were classified as PLCIS (n = 11) and LCIS-PF (n = 5). 12/16 patients were treated with surgical excision ± chemoprevention. Patients with a prior breast cancer history and those having mastectomy were excluded from outcome analysis. Among the remaining 7 patients with PLCIS/LCIS-PF, 4/7 (57%) developed ipsilateral breast cancer at a median follow-up of 67 months. Median age at the time of breast cancer diagnosis was 56 years old and median time from PLCIS/LCIS-PF to cancer diagnosis was 59 months (range 45-66 months). The four cancers included 1 invasive lobular carcinoma (ILC), 1 microinvasive ILC, 1 invasive ductal carcinoma, and 1 ductal carcinoma in situ. CONCLUSIONS: We confirm that PLCIS in isolation is indeed a rare entity, further contributing to the difficulty in determining the actual risk conferred by this lesion. Long-term follow-up data on larger cohorts are needed to define standardized management and outcomes for patients with PLCIS.


Asunto(s)
Carcinoma de Mama in situ/patología , Carcinoma Lobular/patología , Adulto , Anciano , Biomarcadores de Tumor , Biopsia , Carcinoma de Mama in situ/diagnóstico , Carcinoma de Mama in situ/terapia , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/terapia , Terapia Combinada , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Imagen Multimodal/métodos
2.
Mol Oncol ; 9(4): 772-82, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25601220

RESUMEN

PURPOSE: Lobular carcinoma in situ (LCIS) is both a risk indicator and non-obligate precursor of invasive lobular carcinoma (ILC). We sought to characterize the transcriptomic features of LCIS and ILC, with a focus on the identification of intrinsic molecular subtypes of LCIS and the changes involved in the progression from normal breast epithelium to LCIS and ILC. METHODS: Fresh-frozen classic LCIS, classic ILC, and normal breast epithelium (N) from women undergoing prophylactic or therapeutic mastectomy were prospectively collected, laser-capture microdissected, and subjected to gene expression profiling using Affymetrix HG-U133A 2.0 microarrays. RESULTS: Unsupervised hierarchical clustering of 40 LCIS samples identified 2 clusters of LCIS distinguished by 6431 probe sets (p < 0.001). Genes identifying the clusters included proliferation genes and other genes related to cancer canonical pathways such as TGF beta signaling, p53 signaling, actin cytoskeleton, apoptosis and Wnt-Signaling pathway. A supervised analysis to identify differentially expressed genes (p < 0.001) between normal epithelium, LCIS, and ILC, using 23 patient-matched triplets of N, LCIS, and ILC, identified 169 candidate precursor genes, which likely play a role in LCIS progression, including PIK3R1, GOLM1, and GPR137B. These potential precursor genes map significantly more frequently to 1q and 16q, regions frequently targeted by gene copy number alterations in LCIS and ILC. CONCLUSION: Here we demonstrate that classic LCIS is a heterogeneous disease at the transcriptomic level and identify potential precursor genes in lobular carcinogenesis. Understanding the molecular heterogeneity of LCIS and the potential role of these potential precursor genes may help personalize the therapy of patients with LCIS.


Asunto(s)
Neoplasias de la Mama/genética , Carcinoma in Situ/genética , Carcinoma Lobular/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Estudios de Asociación Genética , Invasividad Neoplásica/genética , Neoplasias de la Mama/patología , Carcinoma in Situ/patología , Carcinoma Lobular/patología , Cromosomas Humanos/genética , Análisis por Conglomerados , Variaciones en el Número de Copia de ADN/genética , Progresión de la Enfermedad , Regulación hacia Abajo/genética , Epitelio/patología , Femenino , Genes Relacionados con las Neoplasias , Heterogeneidad Genética , Humanos , Programas Informáticos
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