title: PI3K pathway mutations and PTEN levels in primary and metastatic breast cancer.
abstract: The purpose of this work was to determine whether there are differences in PIK3CA mutation status and PTEN protein expression between primary and matched metastatic breast tumors as this could influence patient management. Paraffin sections of 50 μm were used for DNA extraction and slides of 3 μm for immunohistochemistry (IHC) and FISH. Estrogen receptor, progesterone receptor, and HER2 IHC were repeated in a central laboratory for both primary tumors and metastases. PTEN levels were assessed by IHC and phosphoinositide 3-kinase (PI3K) pathway mutations were detected by a mass spectroscopy-based approach. Median age was 48 years (range: 30-83 years). Tumor subtype included 72% hormone receptor positive/HER2 negative, 20% HER2-positive, and less than 7.8% triple receptor negative. Tissues were available for PTEN IHC in 46 primary tumors and 52 metastases. PTEN was lost in 14 (30%) primary tumors and 13 (25%) metastases. There were five cases of PTEN loss and eight cases of PTEN gain from primary tumors to metastases (26% discordance). Adequate DNA was obtained from 46 primary tumors and from 50 metastases for PIK3CA analysis. PIK3CA mutations were detected in 19 (40%) of primary tumors and 21 (42%) of metastases. There were five cases of PIK3CA mutation loss and four cases of mutation gain (18% discordance). There was an increase of the level of PIK3CA mutations in four cases and decrease in one case from primary tumors to metastases. There is a high level of discordance in PTEN level, PIK3CA mutations, and receptor status between primary tumors and metastases that may influence patient selection and response to PI3K-targeted therapies.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Unit 1354, 1515 Holcombe Boulevard, Houston, TX 77030, USA. agonzalez@mdanderson.org
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
authors.forename: Jaime
authors.initials: J
authors.lastname: Ferrer-Lozano
authors.forename: Katherine
authors.initials: K
authors.lastname: Stemke-Hale
authors.forename: Aysegul
authors.initials: A
authors.lastname: Sahin
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
authors.forename: Juan A
authors.initials: JA
authors.lastname: Barrera
authors.forename: Octavio
authors.initials: O
authors.lastname: Burgues
authors.forename: Ana M
authors.initials: AM
authors.lastname: Lluch
authors.forename: Huiqin
authors.initials: H
authors.lastname: Chen
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C484760:PIK3CA protein, human; C494929:PTEN protein, human