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Persistence of Tumor DNA in Plasma of Breast Cancer Patients After Mastectomy

From the Department of Medical Oncology, Clinica Puerta de Hierro (JMS, JMG, GD, JS, CM, BC, MP, PE, FB); and the Department of Pathology, Hospital Militar del Aire (SC), Madrid, Spain.

Correspondence: Address correspondence and reprint requests to: Felix Bonilla, Department of Medical Oncology, Molecular Genetics Unit, Clinica Puerta de Hierro, C/San Martin de Porres, 4, 28035-Madrid, Spain; Fax: 34-91-373 7667; E-mail: felixbv{at}stnet.es

Background: We investigated tumor DNA changes before and after mastectomy in the plasma of breast cancer patients with no disseminated disease and eventually investigated these changes’ relationship to specific pathological parameters of the tumors.

Methods: We studied 41 patients. DNA extracted from tumor and normal breast tissues, mononuclear blood cells, and plasma was used for molecular studies. Alterations in the microsatellite markers D17S855, D17S654, D16S421, TH₂, D10S197, and D9S161, as well as point mutations in the p53 gene and aberrant methylation of p16^INK4a, were used to identify and characterize tumor and plasma DNA. A number of tumor clinicopathological parameters were analyzed in each patient.

Results: We found that 18 (44%) of the 27 patients with alterations in tumor DNA presented the same plasma DNA alteration before mastectomy, and persistence of the same molecular features was detected in plasma DNA 4 to 6 weeks postmastectomy in 8 (19.5%) patients. Patients with vascular invasion, more than three lymph node metastases, and higher histological grade at diagnosis displayed plasma DNA after mastectomy with a significant difference.

Conclusions: Persistence of plasma DNA with features of tumor DNA may be present after mastectomy in breast cancer patients, and its relation to bad-prognosis histological parameters may suggest undetectable micrometastatic disease.

Key Words: Postmastectomy • Mammary malignancies • Circulating DNA • Poor prognosis • Genetic markers

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