Changes in PIK3CA mutation status are not associated with recurrence, metastatic disease or progression in endocrine-treated breast cancer
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The phosphatidylinositol-3-kinase pathway plays an important role in proliferation, migration and survival in breast cancer and may play a role in resistance to endocrine therapy. Pathway activation occurs as a result of mutations in PIK3CA or loss of functional PTEN. Matched primary and recurrent samples from 120 breast cancer patients treated with endocrine therapy were profiled with a qPCR-based mutation assay covering eight mutational hotspots in PIK3CA. PTEN was assayed by immunohistochemistry. Samples were well characterized with respect to anatomic location of recurrence (metastatic nodal or local recurrence as opposed to contralateral or ipsilateral new primary cancers). In total, 43 % of patients had at least one PIK3CA mutation at diagnosis, and 41 % had a mutation at the time of recurrence. Only 8 % of patients with local recurrence, metastatic disease or progression on primary endocrine treatment changed their PIK3CA mutation status (four gains, two losses, total 76). The most common changes in PIK3CA mutation status were seen in patients who developed a new cancer either in the treated or contralateral breast (64 %, three gains, four losses, total 11). PIK3CA mutation status does not change in the majority of patients with breast cancer and the acquisition of mutations in PIK3CA is not responsible for the development of endocrine resistance. PTEN loss at diagnosis is associated with a significantly shorter time to progression compared with tumours in which PTEN was retained. These are the most comprehensive data currently available correlating PIK3CA status, site of recurrence and endocrine resistance.
KeywordsPIK3CA Breast cancer Mutation PTEN Endocrine Resistance
This work was supported by Breakthrough Breast Cancer and Cancer Research UK who provided infrastructure for assembling and cutting the tissue blocks used in thus study. The authors acknowledge support of the department of pathology who stored these tissues.The authors would like to thank Victoria Brophy and colleagues from Roche Molecular Systems for development and transfer of the PIK3CA mutation assay to the central laboratory.
Conflict of interests
TRW and MRL are employees of Genentech and have equity in Roche.
All patients gave informed consent to be included in the study which had been approved by the local ethics committee (LREC; 2001/8/80 and 2001/8/81).
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