Molecular Heterogeneity in Primary Breast Carcinomas and Axillary Lymph Node Metastases Assessed by Genomic Fingerprinting Analysis.
Molecular heterogeneity within primary breast carcinomas and among axillary lymph node (LN) metastases may impact diagnosis and confound treatment. In this study, we used short tandem repeated sequences to assess genomic heterogeneity and to determine hereditary relationships among primary tumor areas and regional metastases from 30 breast cancer patients. We found that primary carcinomas were genetically heterogeneous and sampling multiple areas was necessary to adequately assess genomic variability. LN metastases appeared to originate at different time periods during disease progression from different sites of the primary tumor and the extent of genomic divergence among regional metastases was associated with a less favorable patient outcome (P = 0.009). In conclusion, metastasis is a complex process influenced by primary tumor heterogeneity and variability in the timing of dissemination. Genomic variation in primary breast tumors and regional metastases may negatively impact clinical diagnostics and contribute to therapeutic resistance.
Clinical Breast Care Project, Murtha Cancer Center, Windber, PA, USA.
Rachel E
RE
Ellsworth
Clinical Breast Care Project, Windber Research Institute, Windber, PA, USA.
Allyson L
AL
Toro
Clinical Breast Care Project, Windber Research Institute, Windber, PA, USA.
Heather L
HL
Blackburn
Clinical Breast Care Project, Windber Research Institute, Windber, PA, USA.
Alisha
A
Decewicz
Clinical Breast Care Project, Windber Research Institute, Windber, PA, USA.
Brenda
B
Deyarmin
Clinical Breast Care Project, Windber Research Institute, Windber, PA, USA.
Kimberly A
KA
Mamula
Clinical Breast Care Project, Windber Research Institute, Windber, PA, USA.
Nicholas S
NS
Costantino
Clinical Breast Care Project, Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA.
Jeffrey A
JA
Hooke
Clinical Breast Care Project, Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA.
Craig D
CD
Shriver
Clinical Breast Care Project, Windber Research Institute, Windber, PA, USA.
Darrell L
DL
Ellsworth
allelic imbalance; axillary lymph nodes; breast cancer; intratumor heterogeneity; metastasis