TY - JOUR
T1 - Androgen receptor levels and association with PIK3CA mutations and prognosis in breast cancer
AU - Gonzaiez-Angulo, Ana M.
AU - Stemke-Hale, Katherine
AU - Palla, Shana L.
AU - Carey, Mark
AU - Agarwal, Roshan
AU - Meric-Berstam, Funda
AU - Traina, Tiffanya
AU - Hudis, Clifford
AU - Hortobagyi, Gabriel N.
AU - Gerald, William L.
AU - Mills, Gordon B.
AU - Hennessy, Bryan T.
PY - 2009/4/1
Y1 - 2009/4/1
N2 - Purpose: To examine the androgen receptor (AR) levels in breast cancer and to assess the impact of AR expression on patient outcomes. Experimental Design: 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 was59 years (23-89 years). Significant differencesin AR levelsexisted 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. Atrend (P = 0.07) wasfound 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.
AB - Purpose: To examine the androgen receptor (AR) levels in breast cancer and to assess the impact of AR expression on patient outcomes. Experimental Design: 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 was59 years (23-89 years). Significant differencesin AR levelsexisted 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. Atrend (P = 0.07) wasfound 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.
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U2 - 10.1158/1078-0432.CCR-08-1763
DO - 10.1158/1078-0432.CCR-08-1763
M3 - Article
C2 - 19276248
AN - SCOPUS:65249139954
VL - 15
SP - 2472
EP - 2478
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 7
ER -