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Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer.
- Source :
-
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2010 Mar 01; Vol. 28 (7), pp. 1145-53. Date of Electronic Publication: 2010 Jan 25. - Publication Year :
- 2010
-
Abstract
- PURPOSE Cisplatin is a chemotherapeutic agent not used routinely for breast cancer treatment. As a DNA cross-linking agent, cisplatin may be effective treatment for hereditary BRCA1-mutated breast cancers. Because sporadic triple-negative breast cancer (TNBC) and BRCA1-associated breast cancer share features suggesting common pathogenesis, we conducted a neoadjuvant trial of cisplatin in TNBC and explored specific biomarkers to identify predictors of response. PATIENTS AND METHODS Twenty-eight women with stage II or III breast cancers lacking estrogen and progesterone receptors and HER2/Neu (TNBC) were enrolled and treated with four cycles of cisplatin at 75 mg/m(2) every 21 days. After definitive surgery, patients received standard adjuvant chemotherapy and radiation therapy per their treating physicians. Clinical and pathologic treatment response were assessed, and pretreatment tumor samples were evaluated for selected biomarkers. Results Six (22%) of 28 patients achieved pathologic complete responses, including both patients with BRCA1 germline mutations;18 (64%) patients had a clinical complete or partial response. Fourteen (50%) patients showed good pathologic responses (Miller-Payne score of 3, 4, or 5), 10 had minor responses (Miller-Payne score of 1 or 2), and four (14%) progressed. All TNBCs clustered with reference basal-like tumors by hierarchical clustering. Factors associated with good cisplatin response include young age (P = .001), low BRCA1 mRNA expression (P = .03), BRCA1 promoter methylation (P = .04), p53 nonsense or frameshift mutations (P = .01), and a gene expression signature of E2F3 activation (P = .03). CONCLUSION Single-agent cisplatin induced response in a subset of patients with TNBC. Decreased BRCA1 expression may identify subsets of TNBCs that are cisplatin sensitive. Other biomarkers show promise in predicting cisplatin response.
- Subjects :
- Adult
Aged
Breast Neoplasms chemistry
Breast Neoplasms genetics
Cisplatin adverse effects
DNA Methylation
DNA-Binding Proteins analysis
Female
Genes, BRCA1
Genes, p53
Humans
Middle Aged
Mutation
Neoadjuvant Therapy
Nuclear Proteins analysis
Oligonucleotide Array Sequence Analysis
Promoter Regions, Genetic
Tumor Protein p73
Tumor Suppressor Proteins analysis
Antineoplastic Agents therapeutic use
Breast Neoplasms drug therapy
Cisplatin therapeutic use
Receptor, ErbB-2 analysis
Receptors, Estrogen analysis
Receptors, Progesterone analysis
Subjects
Details
- Language :
- English
- ISSN :
- 1527-7755
- Volume :
- 28
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 20100965
- Full Text :
- https://doi.org/10.1200/JCO.2009.22.4725