Genomic loss of 18p predicts an adverse clinical outcome in patients with high-risk breast cancer.
The impact of the genomic imbalances on the clinical outcome of 34 patients with lymph-node positive high-risk breast cancer (HRBC) was investigated using comparative genomic hybridization. All of the patients were uniformly treated with high-dose chemotherapy and autologous stem cell transplantation. The average number of chromosomal imbalances per tumor was 11 (range, 2-24), including DNA overrepresentation on chromosomes 1q (59%), 17q (38%), 8q and 16p (35% each), 20q (32%), and 19p (26%), and genomic losses involving 9p and 18q (41%), 8p, 11q, and 18p (38%), 17p (32%), 4p and Xq (29%), and 16q (26%). The most significant association among genomic changes and clinical-pathological features was the correlation of the loss of 8p with progesterone receptor positivity (P < 0.005). With a median follow-up time of 74 months, 15 patients (44%) have relapsed. In the univariate analysis, patients with gain/amplification of 17q including the HER-2/neu gene locus had a longer disease-free survival (P = 0.02), whereas those with genomic loss of 18p had a higher probability of relapse (P = 0.003). In multivariate analysis, the loss of 18p was the only parameter correlated with shorter disease-free survival (relative risk, 4.8; 95% confidence interval, 1.57-14.8; P = 0.006). In summary, our data indicate that the tumoral genomic profile may represent a valuable marker for predicting the clinical outcome in HRBC. Furthermore, the genomic loss of 18p may identify a poor prognostic subgroup of patients with HRBC.
Climent
Joan
J
Department of Hematology and Medical Oncology, Hospital Clinico, University of Valencia, Valencia, Spain 46010.
Martinez-Climent
Jose A
JA
Blesa
David
D
Garcia-Barchino
Maria J
MJ
Saez
Rosana
R
Sánchez-Izquierdo
Dolors
D
Azagra
Pilar
P
Lluch
Ana
A
Garcia-Conde
Javier
J
D000328:Adult; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology / Q000628:therapy; D018275:Carcinoma, Lobular / Q000235:genetics / Q000473:pathology / Q000628:therapy; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008408:Mastectomy; D008875:Middle Aged; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000473:pathology / Q000628:therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate
D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone