Chronological occurrence of PI3KCA mutations in breast cancer liver metastases after repeat partial liver resection

Aldrick RuizView ORCID ID profile,
Mylène Sebagh,
Raphaël Saffroy,
Marc-Antoine Allard,
Nelly Bosselut,
Giulia Hardoin,
Julie Vasseur,
Jocelyne Hamelin,
René Adam,
Jean-François Morère and
Antoinette LemoineEmail author

BMC Cancer201919:169

https://doi.org/10.1186/s12885-019-5365-2

Received: 15 April 2018
Accepted: 11 February 2019
Published: 22 February 2019

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Abstract

Background

Liver metastases of breast cancer are frequent and can recur even after “complete/R0” resection in combination with systemic and hormonal treatments. The aim of this study was to analyze throughout repeat hepatectomies for liver metastases the evolution of PI3KCA gene mutational status.

Methods

All liver metastases nodules (n = 70) from 19 women who underwent at least 2 liver resections were reexamined. DNA extraction from archived tumoral tissue was performed and the major ‘hot spot’ mutations in the helical and catalytic domains of PI3KCA have been analyzed using Massarray platform (Agena Bioscience) based on allelic discrimination PCR amplification followed by sensitive mass spectrometry detection.

Results

The two major somatic hot spot PI3KCA mutations were found in 27 (38.6%) nodules corresponding to 8 of the 19 patients (42%). The frequency of women whose breast cancer liver metastases (BCLM) carries PI3KCA mutations increased from the first to the third hepatectomy. Tumors carrying PI3KCA mutations are significantly larger and more frequently observed when resections were R0 compared to patients with no PI3KCA mutation.

Conclusion

PI3KCA mutations are frequently observed in BCLM and persist along with the recurrence. Their identification in circulating tumor cells should become a useful biomarker in the routine practice of breast cancer management to prevent tumor recurrence and overcome the problems of intra- and inter-tumoral heterogeneity of the current biomarkers,