Genomic Loss of 18p Predicts an Adverse Clinical Outcome in Patients with High-Risk Breast Cancer

• Published in: Clinical cancer research 2002-12, Vol.8 (12), p.3863-3869
• Main Authors: Climent, Joan, Martinez-Climent, Jose A, Blesa, David, Garcia-Barchino, Maria J, Saez, Rosana, Sánchez-Izquierdo, Dolors, Azagra, Pilar, Lluch, Ana, Garcia-Conde, Javier
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Blotting, Western; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Carcinoma, Ductal, Breast - genetics; Carcinoma, Ductal, Breast - pathology; Carcinoma, Ductal, Breast - therapy; Carcinoma, Lobular - genetics; Carcinoma, Lobular - pathology; Carcinoma, Lobular - therapy; Chromosome Deletion; Chromosome Mapping; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 18 - genetics; Cohort Studies; Female; Gene Amplification; Gynecology. Andrology. Obstetrics; Humans; In Situ Hybridization, Fluorescence; Loss of Heterozygosity; Mammary gland diseases; Mastectomy; Medical sciences; Middle Aged; Neoplasm Staging; Neoplasms, Hormone-Dependent - genetics; Neoplasms, Hormone-Dependent - pathology; Neoplasms, Hormone-Dependent - therapy; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Survival Rate; Tumors
• ISSN: 1078-0432; 1557-3265

The impact of the genomic imbalances on the clinical outcomeof 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.