title: Changes in PIK3CA mutation status are not associated with recurrence, metastatic disease or progression in endocrine-treated breast cancer.
abstract: 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.
authors.affiliation: Edinburgh Breast Unit, Western General Hospital, Edinburgh, EH4 2XU, UK.
authors.forename: L M
authors.initials: LM
authors.lastname: Arthur
authors.forename: A K
authors.initials: AK
authors.lastname: Turnbull
authors.forename: L
authors.initials: L
authors.lastname: Renshaw
authors.forename: J
authors.initials: J
authors.lastname: Keys
authors.forename: J S
authors.initials: JS
authors.lastname: Thomas
authors.forename: T R
authors.initials: TR
authors.lastname: Wilson
authors.forename: M R
authors.initials: MR
authors.lastname: Lackner
authors.forename: A H
authors.initials: AH
authors.lastname: Sims
authors.forename: J M
authors.initials: JM
authors.lastname: Dixon
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000556:secondary; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000556:secondary; D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D016609:Neoplasms, Second Primary / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000556:secondary; D051059:PTEN Phosphohydrolase / Q000235:genetics; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D058539:Phosphatidylinositol 3-Kinase; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human