Whole-Genome Testing Helps Identify Breast Cancer Treatments

A molecular screening study has identified abnormalities in individual patients with breast cancer with the aim of providing targeted therapy matched to individuals' genomic alterations.

Progress in developing effective new chemotherapy or hormonal therapies for metastatic cancer has been slow, though there have been developments in therapies targeting specific genetic mutations in breast cancer.

In a multicenter, prospective trial scientists at the Institute Gustave Roussy (Villejuif, France) and colleagues from other institutions recruited 423 patients who had breast cancer with a metastasis accessible for biopsy in 18 centers in France, from June 16, 2011, to July 30, 2012. Comparative genomic hybridization (CGH) array and Sanger sequencing on phosphatidylinositol-4,5 -bisphosphate 3-kinase, (PIK3CA, exon 10 and 21) and v-akt murine thymoma viral oncogene homolog 1 (AKT1, exon 4) were used to assess metastatic biopsy samples from five medical centers.

DNA concentration was measured with Qubit 2.0 Fluorometer (Life Technologies; Paisley, UK) and sequencing was performed with Life Technologies' BigDye Terminator Cycle Sequencing Kit. For genomic analyses on microarray platforms (Agilent Technologies; Massy, France) tumor and control DNA were labeled by random priming, and then hybridized. To assess robustness of data, normal genomic DNA was used in all analyses to validate the genomic profile findings in tumor samples.

Examining the DNA from the samples, the team found that just under half (46%) of the patients in the study had a genomic alteration that could be targeted, while 39% had rare alterations for which no treatments currently exist. Therapy could be personalized in 55 (13%) of 423 patients. Of the 43 patients who were assessable and received targeted therapy, four (9%) had an objective response, and nine others (21%) had stable disease for more than 16 weeks.

Fabrice André MD, a professor and lead author said, "So far 55 of those enrolled, which is 28% of those with targetable alterations, have been matched with new treatments being tested in clinical trials. This emphasizes the need to increase the range of drug trials. Our goal is to have 30% of patients in clinical trials testing therapies targeting the alterations identified in their tumors." The study was published on February 7, 2014, in the journal Lancet Oncology.

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