Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers : results from the Consortium of Investigators of Modifiers of BRCA1/2.

Abstract Introduction Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. Methods We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach. Results The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status. Conclusions The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers

Calidad del informe de solicitud de estudio anatomopatológico y motivos de consulta en cirugía menor ambulatoria de atención primaria

ObjetivosDeterminar la proporción de biopsias procedentes de cirugía menor enTabla 1 Diagnóstico anatomopatológico de las biopsias procedentes de cirugía menor en atención primariaDiagnósticoFrecuenciaPorcentajeNevo (intradérmico, compuesto, etc.)22826,6%Quiste de inclusión epidérmica, tricolemales y otros13215,4%Queratosis seborreica12214,2%Dermatofibroma8610,0%Carcinoma de células basales485,6%Pólipo fibroepitelial455,2%Lipoma263,0%Tumores vasculares benignos263,0%Queratosis actínica252,9%Carcinoma de células escamosas222,6%Nevo displásico182,1%Lesiones virales101,2%Otras lesiones melanocíticas benignas101,2%Queratoacantoma101,2%Tumores anexiales benignos101,2%Hiperplasia epidérmica benigna91,1%Tumores fasciculados benignos60,7%Hiperqueratosis40,5%Granuloma a cuerpo extraño30,4%Melanoma30,4%Otros131,5%Total856100,0%atención primaria (CMAP) que se reciben en un servicio hospitalario de anatomía patológica (SAP), la calidad de los informes de petición de estudio anatomopatológico (IPEAP) y la frecuencia de las diversas enfermedades remitidas para estudio.DiseñoDescriptivo, transversal.EmplazamientoServicio de Anatomía Patológica del Hospital Universitario Virgen del Rocío de Sevilla (HUVRS).ParticipantesSe han analizado 856 IPEAP consecutivos recibidos entre enero de 2005 y junio de 2006, procedentes de 25 centros de atención primaria (CAP).Mediciones principalesSe ha clasificado la calidad de los IPEAP según la tabla realizada por Irazábal y Gutiérrez1 en 3 niveles: buena, aceptable y mala. Se han recogido la edad, el sexo, el centro de procedencia (urbano o no urbano) y el diagnóstico anatomopatológico (DAP).ResultadosLas biopsias procedentes de CMAP supusieron en el período de estudio un 1,9% del total (43.976) y el 8,2% de las correspondientes a lesiones cutáneas (10.400). La media de edad de los pacientes cuyas muestras se remitieron fue de 46,5±18,9 años), sin diferencias entre sexos ni CAP de procedencia. Predominaban las mujeres (57,7%; intervalo de confianza [IC] del 95%, 54,3-61,0). La calidad del informe era buena en 689 casos (80,5%), aceptable en 106 (12,4%) y mala en 61 (7,1%), sin diferencias según la procedencia, el sexo o la edad de los pacientes. En el 7,3% (63 casos) de los IPEAP no constaba la localización de la lesión, en el 6% (52 casos), la edad y en el 5,1% (44 casos) no se reflejaban suficientes datos clínicos. El IPEAP resultó ilegible en 8 casos (0,9% del total). La relación de los DAP se expone en la tabla 1.Discusión y conclusionesLa generalización de diversos programas de salud en los CAP, como es el caso de la CMAP, ha convertido a los médicos de familia en clients de los servicios de anatomía patológica. El correcto funcionamiento de estos programas exige una adecuada comunicación entre los ámbitos de atención1.La CMAP es un programa de salud seguro, eficiente2 y que genera satisfacción en los usuarios y los profesionales sanitarios3. Las biopsias procedentes de CMAP suponen un pequeño pero significativo porcentaje del total de las recibidas en un SAP y presentan una gran variedad de lesiones, algunas de gran complejidad.La calidad de los IPEAP provenientes de CMAP es, en general, buena y suficiente para el DAP. Sin embargo, hay algunos casos con información insuficiente.El presumible aumento de la demanda de servicio hacia los SAP desde los CAP obliga a establecer vías de comunicación entre dos ámbitos que hace unos años no tenían contacto. En este sentido, proponemos la elaboración de formularios protocolizados específicos para la solicitud de IPEAP desde la CMAP, consensuados entre ámbitos, que contengan una suficiente información y que sean fáciles y rápidos de cumplimentar en los CAP

Phenotypic characterization of hereditary epithelial ovarian cancer based on a tissue microarray study

The pathologic and immunohistochemical features of familial epithelial ovarian cancers are not well understood. We have carried out a comprehensive immunohistochemical study of familial ovarian carcinomas from women with and without BRCA1 or BRCA2 mutations, in order to identify specific and/or common features among these different familial case groups (BRCA1, BRCA2 and non-BRCA1/2) and to identify markers of diagnostic value that might help to select more specific treatments. 73 familial primary ovarian carcinomas were analyzed for the expression of 40 antibodies involved in different genetic pathways using a tissue microarray. Serous carcinomas comprised the majority of all three familial case groups. On the other hand, BRCA1 and BRCA2 carcinomas have similar histopathologic features; i.e. they are often highgrade and are usually diagnosed at a more advanced FIGO stage than non-BRCA1/2 carcinomas. In our series, BRCA1 carcinomas had better clinical evolution and they also more frequently over-expressed PR and P53 than BRCA2 and non-BRCA1/2carcinomas. Unsupervised cluster analysis and survival analysis identified ERCC1 as a potential marker of better clinical outcome for hereditary epithelial ovarian cancer

Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2.

Abstract Introduction Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. Methods We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach. Results The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status. Conclusions The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers