Initial experience with genomic profiling of heavily pretreated breast cancers.

Abstract

BACKGROUND:

Rapidly evolving advances in the understanding of theorized unique driver mutations within individual patient's cancers, as well as dramatic reduction in the cost of genomic profiling, have stimulated major interest in the role of such testing in routine clinical practice. The aim of this study was to report our initial experience with genomic testing in heavily pretreated breast cancer patients.

METHODS:

Patients with primary or recurrent breast cancer managed at any of our five hospitals and whose malignancy had failed to respond to therapy or had progressed on all recognized standard-of-care options were offered the opportunity to have their cancer undergo next-generation sequencing genomic profiling.

RESULTS:

Of a total of 101 patients, 98 (97 %) had at least one specific genomic alteration identified. A total of 465 different somatic genetic abnormalities were revealed in this group of patients. Although 52 % of patients were found to have an abnormality for which an U.S. Food and Drug Administration (FDA)-approved drug was available, 69 % of patients had an FDA-approved agent for an indication other than breast cancer. The most common genomic alterations of potential clinical consequence were PIK3 (25 %), FGFR1 (16 %), AKT (11 %), PTEN (10 %), ERBB2 (8 %), JAK2 (6 %), and RAF1 (5 %).

CONCLUSIONS:

Almost all advanced breast cancers possess at least one well-characterized genomic alteration that might be actionable at the clinical level. Further, in most cases, a plausible argument can be advanced for the potential biological and clinical relevance of an FDA-approved antineoplastic agent not currently indicated in the treatment of breast cancer.

• Authors: Edgar D Staren, Donald Braun, Bradford Tan, Digant Gupta, Seungchan Kim, Kim Kramer, Maurie Markman
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 21 Issue 10 Pg. 3216-22 (Oct 2014) ISSN: 1534-4681 [Electronic] United States
• PMID: 25047475 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor

Topics

• Adult
• Aged
• Biomarkers, Tumor (genetics)
• Breast Neoplasms (genetics, pathology, therapy)
• Combined Modality Therapy
• Female
• Follow-Up Studies
• Gene Expression Profiling
• Genetic Predisposition to Disease
• Genomics
• High-Throughput Nucleotide Sequencing
• Humans
• Middle Aged
• Mutation (genetics)
• Neoplasm Metastasis
• Neoplasm Recurrence, Local (genetics, pathology, therapy)
• Neoplasm Staging
• Patient Selection
• Precision Medicine
• Predictive Value of Tests
• Retrospective Studies
• Young Adult