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Metastatic breast cancer: comparative genomic hybridisation array and DNA sequencing to direct therapy


Breast cancer is characterised by genomic alterations. Researchers did a multicentre molecular screening study to identify abnormalities in individual patients with the aim of providing targeted therapy matched to individuals' genomic alterations.

During the period 2011-2012, researchers have recruited patients who had breast cancer with a metastasis accessible for biopsy in 18 Centres in France.
Comparative genomic hybridisation ( CGH ) array and Sanger sequencing on PIK3CA ( exon 10 and 21 ) and AKT1 ( exon 4 ) were used to assess metastatic biopsy samples in five centres. Therapeutic targets were decided on the basis of identified genomic alterations.

The primary objective was to include 30% of patients in clinical trials testing a targeted therapy and, therefore, the primary outcome was the proportion of patients to whom a targeted therapy could be offered.
For the primary endpoint, the analyses were done on the overall population registered for the trial.

A total of 423 patients was included, and biopsy samples were obtained from 407 ( metastatic breast cancer was not found in four ).
CGH array and Sanger sequencing were feasible in 283 ( 67% ) and 297 ( 70% ) patients, respectively.

A targetable genomic alteration was identified in 195 ( 46% ) patients, most frequently in PIK3CA ( 74 [ 25% ] of 297 identified genomic alterations ), CCND1 ( 53 [ 19% ] ), and FGFR1 ( 36 [ 13% ] ).

117 ( 39% ) of 297 patients with genomic tests available presented with rare genomic alterations ( defined as occurring in less than 5% of the general population ), including AKT1 mutations, and EGFR, MDM2, FGFR2, AKT2, IGF1R, and MET high-level amplifications.

Therapy could be personalised 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.

Serious ( grade 3 or higher ) adverse events related to biopsy were reported in four ( 1% ) of enrolled patients, including pneumothorax ( grade 3, one patient ), pain ( grade 3, one patient ), haematoma ( grade 3, one patient ), and haemorrhagic shock ( grade 3, one patient ).

Personalisation of medicine for metastatic breast cancer is feasible, including for rare genomic alterations. ( Xagena )

André F et al, The Lancet Oncology 2014; 15: 267-274

XagenaMedicine_2014



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