Outer breast quadrants demonstrate increased levels of genomic instability.
BACKGROUND
Theory holds that the upper outer quadrant of the breast develops more malignancies because of increased tissue volume. This study evaluated genomic patterns of loss of heterozygosity (LOH) and allelic imbalance (AI) in non-neoplastic tissues from quadrants of diseased breasts following mastectomy to characterize relationships between genomic instability and the propensity for tumor development.


METHODS
Tissues from breast quadrants were collected from 21 patients with various stages of breast carcinoma. DNA was isolated from non-neoplastic tissues using standard methods and 26 chromosomal regions commonly deleted in breast cancer were examined to assess genomic instability.


RESULTS
Genomic instability was observed in breast quadrants from patients with ductal carcinomas in situ and advanced carcinomas. Levels of instability by quadrant were not predictive of primary tumor location (P =.363), but outer quadrants demonstrated significantly higher levels of genomic instability than did inner quadrants (P =.017). Marker D8S511 on chromosome 8p22-21.3, one of the most frequently altered chromosomal regions in breast cancer, showed a significantly higher level of instability (P =.039) in outer compared with inner quadrants.


CONCLUSIONS
Non-neoplastic breast tissues often harbor genetic changes that can be important to understanding the local breast environment within which cancer develops. Greater genomic instability in outer quadrants can partially explain the propensity for breast cancers to develop there, rather than simple volume-related concepts. Patterns of field cancerization in the breast appear to be complex and are not a simple function of distance from a developing tumor.
Windber Research Institute, 600 Somerset Avenue, Windber, PA 15963, USA. d.ellsworth@wriwindber.org.
Darrell L
DL
Ellsworth
Rachel E
RE
Ellsworth
Brad
B
Love
Brenda
B
Deyarmin
Susan M
SM
Lubert
Vimal
V
Mittal
Jeffrey A
JA
Hooke
Craig D
CD
Shriver
D001940:Breast / Q000033:anatomy & histology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000601:surgery; D002277:Carcinoma / Q000235:genetics* / Q000601:surgery; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D019656:Loss of Heterozygosity; D008408:Mastectomy; D012307:Risk Factors
D004273:DNA, Neoplasm; D005819:Genetic Markers