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Park S.,Yonsei University | Park S.,Target Molecule Study Group | Koo J.S.,Target Molecule Study Group | Koo J.S.,Yonsei University | And 9 more authors.
Annals of Oncology | Year: 2011

Background: The objective of the study was to evaluate the implications of androgen receptor (AR) in breast cancers. Patients and methods: We investigated immunohistochemical AR expression from the tissue microarrays of 931 patients between 1999 and 2005, and analyzed demographics and outcomes using uni-/multivariate analyses. Tumors with ≥10% nuclear-stained cells were considered positive for AR. Results: AR was expressed in 58.1% of patients. AR was significantly related to older age at diagnosis, smaller size, well-differentiated tumors, higher positivity of hormone receptors, non-triple-negative breast cancers (non-TNBCs), and lower proliferative index. In estrogen receptor (ER)-negative tumors, AR was distinctively associated with human epidermal growth factor receptor type 2 (HER2) overexpression. With a mean follow-up of 72.7 months, AR was positively related to survival in ER-positive but not in ER-negative tumors. In Cox's models, AR was an independent prognostic factor for disease-free survival in ER-positive cancers. Interestingly, molecular apocrine tumors (ER negative and AR positive) with HER2 positive status showed trends of poorer outcome, but AR had no impact on survival in patients with TNBC. Conclusions: AR is significantly associated with favorable features in breast cancers and related to better outcomes in ER-positive not in ER-negative tumors. These results suggest that AR could be an additional marker for endocrine responsiveness in ER-positive cancers and a candidate for therapeutic targeting of ER-negative tumors. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Park S.,Yonsei University | Park S.,Target Molecule Study Group | Koo J.S.,Target Molecule Study Group | Koo J.S.,Yonsei University | And 8 more authors.
Breast | Year: 2012

To investigate the significance of immunohistochemical molecular subtyping, we evaluated outcomes of subtypes based on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Using tissue microarrays, 1006 breast cancer patients between November 1999 and August 2005 were categorized into four subtypes: luminal A (ER+ and/or PR+, HER2-, Ki-67<14%), luminal B (ER+ and/or PR+, HER2-, Ki-67≥14% or ER+ and/or PR+, HER2+), HER2-enriched (ER-, PR-, HER2+), and triple-negative breast cancer (TNBC) (ER-, PR-, HER2-). Demographics, recurrence patterns, and survival were retrospectively analyzed using uni-/multivariate analyses. Luminal A, luminal B, HER2-enriched, and TNBC accounted for 53.1%, 21.7%, 9.0%, and 16.2% of cases, respectively. Luminal A presented well-differentiation and more co-expression of hormone receptors comparing to luminal B. HER2-enriched showed larger size and higher nodal metastasis. TNBC demonstrated younger age at diagnosis, larger size, undifferentiation, higher proliferation, and frequent visceral metastases. The peak of recurrence for luminal A was at 36 months postoperatively, while that for HER2-enriched and TNBC peaked at 12 months. The relapse risk of luminal B was mixed. Luminal A showed the best survival, but no difference was observed between the other three subtypes. When matched by nodal status, however, TNBC showed the worst outcomes in node-positive patients. In multivariate analyses, luminal A remained a positive prognostic significance. Immunohistochemically-defined subtypes showed different features, recurrence patterns, and survival. Therefore, molecular subtypes using four biomarkers could provide clinically useful information of tumor biology and clinical behaviors, and could be used for determining treatment and surveillance strategies. © 2011 Elsevier Ltd.

Park S.,Yonsei University | Park S.,Target Molecule Study Group | Park H.S.,Yonsei University | Koo J.S.,Target Molecule Study Group | And 6 more authors.
Cancer | Year: 2012

Background: The aims of this study were to compare human epidermal growth factor receptor 2 (HER2) results between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and to investigate the clinicopathological characteristics and outcomes according to their results. Methods: Using consecutive tissue microarrays, IHC and FISH were performed as guidelines in 950 invasive breast cancers treated between November 1999 and August 2005. Characteristics and outcomes were retrospectively analyzed using a chi-square test, the Kaplan-Meier method, and Cox's model. Results: FISH-positivity was observed in 2.6%, 4.8%, 28.1%, and 93.8% of IHC 0, 1+, 2+, and 3+, respectively, and the concordance rate between the 2 assays was 95.5%. IHC-positive or FISH-positive cases were associated with poorer differentiation, negative expression of hormone receptors, and higher proliferative index. Among IHC-equivocal or IHC-negative patients, positive FISH was negatively associated with survival in univariate and multivariate analyses. Among IHC-negative patients, tumors showing luminal B subtype features such as estrogen receptor (ER)-positive, grade II/III, and high Ki-67 presented discordantly high FISH-positivity. Among IHC-positive cases, FISH was not related to outcomes. Conclusions: The result of FISH is significantly related to prognosis of patients with IHC-negative or IHC-equivocal result. Therefore, FISH should be performed in IHC-equivocal cases. FISH assay might be considered for a selected group of patients with IHC-negative tumors showing luminal B subtype features of ER-positive, grade II/III, and high Ki-67 expression. © 2011 American Cancer Society.

Park S.,Yonsei University | Park S.,Target Molecule Study Group | Park H.S.,Yonsei University | Koo J.S.,Yonsei University | And 6 more authors.
Breast Cancer Research and Treatment | Year: 2012

The aim was to investigate the implications of androgen receptor (AR) expression levels on outcomes for estrogen receptor (ER)-positive tumors. Immunohistochemically AR levels were determined from tissue microarrays of 614 ER-positive patients who received adjuvant endocrine with or without chemotherapy between November 1999 and August 2005. Characteristics and survival were analyzed using a Chi-square test, Kaplan-Meier methods, and Cox's models. AR levels were categorized into 3 subgroups as follows: low, AR < 10%; intermediate, 10% AR < 50%; high, AR 50%. Low, intermediate, and high AR levels were observed in 29.0, 44.0, and 27.0% of patients, respectively. High AR was associated with smaller size, nodal uninvolvement, grade I/II tumor, higher progesterone receptor expression, and lower proliferation index. With a median follow-up of 70.9 months, the high AR subgroup showed better survival, and these associations were maintained in 119 patients who received endocrine therapy alone [hazard ratio (HR), 0.111; 95% CI, 0.013-0.961 for disease-free survival (DFS); HR, 0.135; 95% CI, 0.015-1.208 for overall survival (OS)]. No significant benefits from chemotherapy were demonstrated in the high AR subgroup; however, the benefit from chemotherapy was significant among 448 AR-intermediate or -low patients (HR, 2.679; 95% CI, 1.452-4.944 for DFS; HR, 3.371; 95% CI, 1.611-7.052 for OS). High AR is an independent prognostic factor and a significant predictor for better endocrine-responsiveness in ER-positive tumors. AR-low or -intermediate levels could give an additional indication for use of chemotherapy in ER-positive tumors. © 2012 Springer Science+Business Media, LLC.

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