RESUMEN
BACKGROUND: HER2 is one of the predominant therapeutic targets in breast cancer. The metastatic selection process may lead to discrepancies between the HER2 status of the primary tumor and circulating tumor cells (CTCs). This study analyzed the HER2 status of CTCs in patients with HER2-positive primary breast cancer at the time of diagnosis. Aim of the study was to assess potential discordance of HER2 status between primary tumor and CTCs, as this may have important implications for the use of HER2-targeted therapy. METHODS: The number and HER2 status of CTCs out of 30ml peripheral blood were assessed in 642 patients using the CellSearch System (Janssen Diagnostics, USA). The cutoff for CTC positivity was the presence of at least 1 CTC, and the cutoff for HER2 positivity of CTCs was the presence of at least 1 CTC with a strong HER2 staining. RESULTS: 258 (40.2%) of the 642 patients were positive for CTCs (median 2; range 1-1,689). 149 (57.8%) of these 258 patients had at least 1 CTC with strong HER2 staining. The presence of HER2-positive CTCs was not associated with tumor size (p = 0.335), histopathological grading (p = 0.976), hormone receptor status (ER: p = 0.626, PR: p = 0.263) or axillary lymph node involvement (p = 0.430). Overall, 83 (32.2%) of the CTC-positive patients exclusively had CTCs with strong HER2 staining, whereas 31 (12.0%) had only CTCs with negative HER2 staining. Within-sample variation in the HER2 status of CTCs was found in 86 (57.8%) of the 149 patients with more than 1 CTC. CONCLUSION: This study demonstrated that discordance between the HER2 expression of CTCs and that of the primary tumor frequently occurs in early breast cancer. Future follow-up evaluation will assess whether this discrepancy may contribute to trastuzumab resistance.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Células Neoplásicas Circulantes/patología , Receptor ErbB-2/genética , Adulto , Anciano , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Receptor ErbB-2/sangre , Investigación Biomédica Traslacional , Trastuzumab/administración & dosificaciónRESUMEN
Forty-one children with Crohn's disease were seen over a 10 year period. Fifty percent of these patients were diagnosed at ages 13 to 16 years. The colon and small bowel were involved in half of the patients. Twenty-six patients required surgery for resection of bowel or diversionary procedures. Sixty percent of the patients with small bowel disease alone responded to medical therapy. We have been unable to document that growth failure can be predictably reversed by surgery. There were no deaths in this series and no patient was lost to follow-up. At present, only one patient is unable to perform the full-time activities of daily living. The longest period of follow-up is 10 years.