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Higher expression of androgen receptor is a significant predictor for better endocrine-responsiveness in estrogen receptor-positive breast cancers

  • Epidemiology
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Abstract

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.

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Abbreviations

AIs:

Aromatase inhibitors

ANOVA:

Analysis of variance

AR:

Androgen receptor

ASCO/CAP:

American Society of Clinical Oncology/College of American Pathologists

CMF:

Cyclophosphamide, methotrexate, and fluorouracil

DAPI:

4′,6-diamidino-2-phenylindole

DFS:

Disease-free survival

ER:

Estrogen receptor

FISH:

Fluorescence in situ hybridization

H&E:

Hematoxylin and eosin

HER2:

Human epidermal growth factor receptor 2

HR:

Hazard ratio

IHC:

Immunohistochemistry

NCCN:

National Comprehensive Cancer Network

OS:

Overall survival

SERMs:

Selective estrogen receptor modulators

STROBE:

Strengthening the reporting of observational studies in epidemiology

TMA:

Tissue microarray

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Acknowledgments

The author(s) indicate no potential conflicts of interest. A major part of this study was presented at the Sixth International Symposium on Hormonal Oncogenesis, Poster Presentations, September 12–16, 2010 in Tokyo, Japan. This study was supported by the Brain Korea 21 Project for Medical Science, Yonsei University, and in part by a grant-in-aid from Sanofi-Aventis Pharmaceutical Co. and Dong-A Pharmaceutical Co.

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Authors and Affiliations

  1. Department of Surgery, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea

    Seho Park, Hyung Seok Park, Seung Il Kim & Byeong-Woo Park

  2. Department of Pathology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea

    Ja Seung Koo & Woo Ick Yang

  3. Target Molecule Study Group, The Korean Breast Cancer Society, Seoul, Korea

    Seho Park, Ja Seung Koo, Seung Il Kim & Byeong-Woo Park

  4. Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea

    Byeong-Woo Park

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  1. Seho Park
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Correspondence to Byeong-Woo Park.

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Park, S., Park, H.S., Koo, J.S. et al. Higher expression of androgen receptor is a significant predictor for better endocrine-responsiveness in estrogen receptor-positive breast cancers. Breast Cancer Res Treat 133, 311–320 (2012). https://doi.org/10.1007/s10549-011-1950-z

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