Androgen receptor levels and association with PIK3CA mutations and prognosis in breast cancer.
OBJECTIVE
To examine the androgen receptor (AR) levels in breast cancer and to assess the impact of AR expression on patient outcomes.


METHODS
Reverse-phase protein arrays were used to measure AR levels and a mass spectroscopy-based approach was used to detect PIK3CA mutations. Means and SDs were generated for AR levels. Linear regression models were used to determine if AR levels differed by tumor subtype and PIK3CA mutation status. Two-sample t tests were used to identify pair-wise differences. Survival probabilities were estimated with the use of the Kaplan-Meier product and log-rank test.


RESULTS
The median age was 59 years (23-89 years). Significant differences in AR levels existed among different breast tumor subtypes (highest in estrogen receptor-positive and/or progesterone receptor-positive tumors) as well as by PIK3CA mutation status (P < 0.0001 for both). AR levels were significantly higher in breast tumors with kinase domain PIK3CA mutations versus tumors that are wild type or with PIK3CA helical mutations (P = 0.017 and P < 0.0001, respectively). In 347 patients, dichotomized AR level by the median was a significant prognostic factor of recurrence-free survival (P = 0.0002) and overall survival (P = 0.004). High AR levels were associated with a significantly improved recurrence-free survival in 207 patients with early-stage estrogen/progesterone receptor-positive tumors after adjuvant hormonal therapy. A trend (P = 0.07) was found toward higher AR expression in PIK3CA mutant versus PIK3CA wild-type triple-negative breast tumors.


CONCLUSIONS
AR levels may represent a prognostic marker in breast cancers and may provide a valuable tool for selecting treatment. There was an association of PIK3CA mutation (kinase domain) with increased AR levels.
Gonzalez-Angulo
Ana M
AM
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. agonzalez@mdanderson.org
Stemke-Hale
Katherine
K
Palla
Shana L
SL
Carey
Mark
M
Agarwal
Roshan
R
Meric-Berstam
Funda
F
Traina
Tiffany A
TA
Hudis
Clifford
C
Hortobagyi
Gabriel N
GN
Gerald
William L
WL
Mills
Gordon B
GB
Hennessy
Bryan T
BT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000145:classification / Q000188:drug therapy / Q000401:mortality*; D058534:Class I Phosphatidylinositol 3-Kinases; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis; D011944:Receptors, Androgen / Q000378:metabolism*
D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human