The Genomic Heritage of Lymph Node Metastases: Implications for Clinical Management of Patients with Breast Cancer |
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Authors: | Tyson E Becker Rachel E Ellsworth Brenda Deyarmin Heather L Patney Rick M Jordan Jeffrey A Hooke Craig D Shriver Darrell L Ellsworth |
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Institution: | (1) Clinical Breast Care Project, Windber Research Institute, 620 Seventh Street, Windber, PA 15963, USA;(2) Henry M. Jackson Foundation for the Advancement of Military Medicine, 1401 Rockville Pike, Suite 600, Rockville, MD 20852, USA;(3) Clinical Breast Care Project, Walter Reed Army Medical Center, 6900 Georgia Avenue, NW, Washington, DC 20307, USA |
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Abstract: | Background Metastatic breast cancer is an aggressive disease associated with recurrence and decreased survival. To improve outcomes and
develop more effective treatment strategies for patients with breast cancer, it is important to understand the molecular mechanisms
underlying metastasis.
Methods We used allelic imbalance (AI) to determine the molecular heritage of primary breast tumors and corresponding metastases to
the axillary lymph nodes. Paraffin-embedded samples from primary breast tumors and matched metastases (n = 146) were collected from 26 patients with node-positive breast cancer involving multiple axillary nodes. Hierarchical clustering
was used to assess overall differences in the patterns of AI, and phylogenetic analysis inferred the molecular heritage of
axillary lymph node metastases.
Results Overall frequencies of AI were significantly higher (P < 0.01) in primary breast tumors (23%) than in lymph node metastases (15%), and there was a high degree of discordance in
patterns of AI between primary breast carcinomas and the metastases. Metastatic tumors in the axillary nodes showed different
patterns of chromosomal changes, suggesting that multiple molecular mechanisms may govern the process of metastasis in individual
patients. Some metastases progressed with few genomic alterations, while others harbored many chromosomal alterations present
in the primary tumor.
Conclusions The extent of genomic heterogeneity in axillary lymph node metastases differs markedly among individual patients. Genomic
diversity may be associated with response to adjuvant therapy, recurrence, and survival, and thus may be important in improving
clinical management of breast cancer patients. |
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Keywords: | Metastasis Breast Cancer Allelic Imbalance Axillary Lymph Nodes |
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