Genomic Abnormality Screening Helps Personalise Breast Cancer Treatment

Findings from the SAFIR01 breast cancer trial suggest that screening for genomic alterations allows targeted therapy to be matched to such alterations for a personalised treatment approach

medwireNews: Researchers report that comparative genomic Hybridisation (CGH) array and Sanger sequencing are effective for identifying genomic alterations that can then be matched to targeted breast cancer therapies.

Their genomic analyses led to matching of therapy in 55 (13%) of 423 patients with metastatic breast cancer.

This was 28% of the 195 patients who presented with targetable genomic alterations at the time of analysis, say the researchers, led by Fabrice André, from the Institut Gustave Roussy in Villejuif, France.

They note, however, that screening for genomic alterations needs to be successful in more patients if it is to become clinically useful.

Of the 403 patients with biopsy samples suitable for assessment in the study, only 299 had DNA viable for genomic analysis. This was mainly because of a low percentage of tumour cells.

“Overall, the failure to do genomic testing probably arose due to a mixture of tumour-specific characteristics and the relative accessibility of metastatic sites,” the researchers comment in the Lancet Oncology.

Targetable genomic alterations in 195 (46%) of the original 423 patients were most frequently in PIK3CA, CCND1 and FGFR1.
However, rare genomic alterations were also identified, including AKT1 mutations, and EGFR, MDM2, FGFR2, AKT2, IGF1R and MET high-level amplifications, which the researchers say may be relevant in breast cancer.

Only 9% of patients receiving personalised treatment approaches achieved objective responses, which seems disappointing, say the researchers. But they point out that the patients were heavily pretreated. A further 21% of patients had stable disease for more than 16 weeks.

“The low number of patients achieving an objective response justifies the development of multiple strategies to improve efficacy of screening,” say Fabrice André and colleagues.

They suggest an approach that includes improvement of algorithms to interpret genomic data, more highly bioactive drugs for proposed targets, favouring of combination therapies that can target different oncogenic drivers and integration of Oncogene de-addiction with other approaches such as quantification of intratumour heterogeneity, immunotherapy and DNA repair modulation.

“The development of these four strategies along with molecular screening and matching of treatments to genomic alterations might transform the current approach of decreasing tumour growth into a clinically useful strategy,” the researchers conclude.

Commenting on the findings, Charles Swanton, from Cancer Research UK London Research Institute, says that given the challenges highlighted in the SAFIR01 study, “efforts to accelerate genomic analyses for personalised medicine must continue to be embedded within the context of clinical trials, and integrated with scientific and clinical collaborative structures to deliver measurable benefits to patients.”

But adds: “The findings… represent an important first step on this journey.”

References

André F, Bachelot T, Commo F, et al. Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER). Lancet Oncol; Advance online publication February 7, 2014. doi: 10.1016/S1470-2045(13)70611-9

Swanton C. SAFIR01: steps towards precision treatment in breast cancer. Lancet Oncol; Advance online publication February 7, 2014. doi: 10.1016/S1470-12045(14)70003-8

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