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Study opens new prospects for developing new targeted therapies for breast cancer
Date:5/2/2013

t rate versus placebo plus exemestane. Although benefits were seen in all prospectively defined subgroups of women who took part, the researchers noted some variations, partially due to genetic differences in molecular determinants of everolimus sensitivity and interactions between the oestrogen receptor and mTOR pathways.

In the current analysis, researchers used next-generation sequencing to assess genetic alterations in archival tumour specimens from 230 tumours. They analysed coding regions of 182 cancer-related genes for sequence and copy number variations.

All patients had at least one genetic alteration, and 98% had more than 2, the researchers report. A total of 173 different genes were altered in at least one of the tumour samples. Among the frequently mutated genes were PIK3CA, TP53 and ARID1A.

"Some mutations were found to cluster into similar pathways, for which targeted therapies could potentially be used," Dr Piccart said.

"Although in many cases we cannot be sure what effect the mutations have on the tumour characteristics or the clinical efficacy of treatments, we did find that mutations in the tumour suppressor gene PTEN were associated with loss of protein expression and function."

The authors also found an increased mutation rate for the oestrogen receptor, a key player in breast cancer, between primary and metastatic samples, which highlights potentially clinically relevant differences between the primary and metastatic disease for this group of hormone-receptor positive patients.

More generally, the results illustrate that this kind of sequencing is feasible in phase III studies, the researchers say.

"The ability to carry on large-scale sequencing in phase III trials will potentially help us understand why some patients did show a good clinical response to the investigated drugs whereas others did not. Also, being able to sequence cancer genes in well-described clinically homogeneous cohorts of clinical trials w
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Contact: Vanessa Pavinato
media@esmo.org
European Society for Medical Oncology
Source:Eurekalert

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