Detection of PIK3CA Mutations in Breast Cancer Bone Metastases

Manijeh Daneshmand,Lisa Vandermeer,Mitra Nabavi,Jennifer E L Hanson,Mark Clemons,Femina Kanji,Susan F Dent,John F Hilton,Ian A J Lorimer

doi:10.5402/2012/492578

Manijeh Daneshmand, Lisa Vandermeer + Show 7 more

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https://doi.org/10.5402/2012/492578

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Abstract

Background. An important goal of personalized cancer therapy is to tailor specific therapies to the mutational profile of individual patients. However, whole genome sequencing studies have shown that the mutational profiles of cancers evolve over time and often differ between primary and metastatic sites. Activating point mutations in the PIK3CA gene are common in primary breast cancer tumors, but their presence in breast cancer bone metastases has not been assessed previously. Results. Fourteen patients with breast cancer bone metastases were biopsied by three methods: CT-guided bone biopsies; bone marrow trephine biopsies; and bone marrow aspiration. Samples that were positive for cancer cells were obtained from six patients. Three of these patients had detectable PIK3CA mutations in bone marrow cancer cells. Primary tumor samples were available for four of the six patients assessed for PIK3CA status in their bone metastases. For each of these, the PIK3CA mutation status was the same in the primary and metastatic sites. Conclusions. PIK3CA mutations occur frequently in breast cancer bone metastases. The PIK3CA mutation status in bone metastases samples appears to reflect the PIK3CA mutation status in the primary tumour. Breast cancer patients with bone metastases may be candidates for treatment with selective PIK3CA inhibitors.

Highlights

An important goal of personalized cancer therapy is to tailor specific therapies to the mutational profile of the individual patient’s cancer
A recent whole genome sequencing study of matched primary and metastatic tumors in pancreatic cancer indicates that both primary tumor heterogeneity and further acquired mutations contribute to differences in mutational profiles between primary and metastatic sites [2]
A total of 5 of 13 bone marrow trephine biopsies were positive for cancer cells, while 4 of 9 CT-guided bone marrow biopsies were positive and only 2 of 13 bone marrow aspirates were positive

Summary

Introduction

An important goal of personalized cancer therapy is to tailor specific therapies to the mutational profile of the individual patient’s cancer. Shah et al used whole genome sequencing to compare the mutation profiles of the primary tumor and a metastatic tumor that occurred many years after the primary and showed that there were multiple additional mutations present in the metastasis [1]. In theory, these differences could arise as a consequence of selection pressures due to therapy or selection pressures for metastatic potential; alternatively, they may arise randomly due to heterogeneity in the primary tumour and/or the high mutation rate in cancer cells. Breast cancer patients with bone metastases may be candidates for treatment with selective PIK3CA inhibitors

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