Androgen receptor in advanced breast cancer: Is it useful to predict the efficacy of anti-estrogen therapy?

Giuseppe Bronte, Andrea Rocca, Sara Ravaioli, Maurizio Puccetti, Maria Maddalena Tumedei, Emanuela Scarpi, Daniele Andreis, Roberta Maltoni, Samanta Sarti, Lorenzo Cecconetto, Anna Fedeli, Elisabetta Pietri, Valeria De Simone, Silvia Asioli, Sara Bravaccini, Dino Amadori

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Androgen receptor (AR) is widely expressed in breast cancer (BC) but its role in estrogen receptor (ER)-positive tumors is still controversial. The AR/ER ratio has been reported to impact prognosis and response to antiestrogen endocrine therapy (ET). Methods: We assessed whether AR in primary tumors and/or matched metastases is a predictor of efficacy of first-line ET in advanced BC. Patients who had received first-line ET (2002-2011) were recruited, while those given concomitant chemotherapy or trastuzumab or pretreated with > 2 lines of chemotherapy were excluded. ER, progesterone receptor (PgR), Ki67 and AR expression were assessed by immunohistochemistry, and HER2 mainly by fluorescent in-situ hybridization. Cut-offs of 1 and 10% immunostained cells were used to categorize AR expression. Results: Among 102 evaluable patients, biomarkers were assessed in primary tumors in 70 cases and in metastases in 49, with 17 patients having both determinations. The overall concordance rate between primary tumors and metastases was 64.7% (95% CI 42%-87.4%) for AR status. AR status did not affect TTP significantly, whereas PgR and Ki67 status did. AR/PgR ≥0.96 was associated with a significantly shorter TTP (HR = 1.65, 95% CI 1.05-2.61, p = 0.028). AR status in primary tumors or metastases was not associated with progressive disease (PD) as best response. In contrast, Ki67 ≥ 20% and PgR < 10% showed a statistically significant association with PD as best response. Conclusions: AR expression does not appear to be useful to predict the efficacy of ET in advanced BC, whereas Ki67 and PgR exert a greater impact on its efficacy.

Original languageEnglish
Article number348
JournalBMC Cancer
Volume18
Issue number1
DOIs
Publication statusPublished - Mar 27 2018

Fingerprint

Androgen Receptors
Estrogens
Breast Neoplasms
Progesterone Receptors
Estrogen Receptors
Neoplasm Metastasis
Therapeutics
Neoplasms
Drug Therapy
Estrogen Receptor Modulators
Fluorescence In Situ Hybridization
Biomarkers
Immunohistochemistry

Keywords

  • Advanced breast cancer
  • Androgen receptor
  • Anti-estrogen therapy
  • AR/ER ratio
  • Endocrine therapy

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Androgen receptor in advanced breast cancer : Is it useful to predict the efficacy of anti-estrogen therapy? / Bronte, Giuseppe; Rocca, Andrea; Ravaioli, Sara; Puccetti, Maurizio; Tumedei, Maria Maddalena; Scarpi, Emanuela; Andreis, Daniele; Maltoni, Roberta; Sarti, Samanta; Cecconetto, Lorenzo; Fedeli, Anna; Pietri, Elisabetta; De Simone, Valeria; Asioli, Silvia; Bravaccini, Sara; Amadori, Dino.

In: BMC Cancer, Vol. 18, No. 1, 348, 27.03.2018.

Research output: Contribution to journalArticle

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title = "Androgen receptor in advanced breast cancer: Is it useful to predict the efficacy of anti-estrogen therapy?",
abstract = "Background: Androgen receptor (AR) is widely expressed in breast cancer (BC) but its role in estrogen receptor (ER)-positive tumors is still controversial. The AR/ER ratio has been reported to impact prognosis and response to antiestrogen endocrine therapy (ET). Methods: We assessed whether AR in primary tumors and/or matched metastases is a predictor of efficacy of first-line ET in advanced BC. Patients who had received first-line ET (2002-2011) were recruited, while those given concomitant chemotherapy or trastuzumab or pretreated with > 2 lines of chemotherapy were excluded. ER, progesterone receptor (PgR), Ki67 and AR expression were assessed by immunohistochemistry, and HER2 mainly by fluorescent in-situ hybridization. Cut-offs of 1 and 10{\%} immunostained cells were used to categorize AR expression. Results: Among 102 evaluable patients, biomarkers were assessed in primary tumors in 70 cases and in metastases in 49, with 17 patients having both determinations. The overall concordance rate between primary tumors and metastases was 64.7{\%} (95{\%} CI 42{\%}-87.4{\%}) for AR status. AR status did not affect TTP significantly, whereas PgR and Ki67 status did. AR/PgR ≥0.96 was associated with a significantly shorter TTP (HR = 1.65, 95{\%} CI 1.05-2.61, p = 0.028). AR status in primary tumors or metastases was not associated with progressive disease (PD) as best response. In contrast, Ki67 ≥ 20{\%} and PgR < 10{\%} showed a statistically significant association with PD as best response. Conclusions: AR expression does not appear to be useful to predict the efficacy of ET in advanced BC, whereas Ki67 and PgR exert a greater impact on its efficacy.",
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author = "Giuseppe Bronte and Andrea Rocca and Sara Ravaioli and Maurizio Puccetti and Tumedei, {Maria Maddalena} and Emanuela Scarpi and Daniele Andreis and Roberta Maltoni and Samanta Sarti and Lorenzo Cecconetto and Anna Fedeli and Elisabetta Pietri and {De Simone}, Valeria and Silvia Asioli and Sara Bravaccini and Dino Amadori",
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T1 - Androgen receptor in advanced breast cancer

T2 - Is it useful to predict the efficacy of anti-estrogen therapy?

AU - Bronte, Giuseppe

AU - Rocca, Andrea

AU - Ravaioli, Sara

AU - Puccetti, Maurizio

AU - Tumedei, Maria Maddalena

AU - Scarpi, Emanuela

AU - Andreis, Daniele

AU - Maltoni, Roberta

AU - Sarti, Samanta

AU - Cecconetto, Lorenzo

AU - Fedeli, Anna

AU - Pietri, Elisabetta

AU - De Simone, Valeria

AU - Asioli, Silvia

AU - Bravaccini, Sara

AU - Amadori, Dino

PY - 2018/3/27

Y1 - 2018/3/27

N2 - Background: Androgen receptor (AR) is widely expressed in breast cancer (BC) but its role in estrogen receptor (ER)-positive tumors is still controversial. The AR/ER ratio has been reported to impact prognosis and response to antiestrogen endocrine therapy (ET). Methods: We assessed whether AR in primary tumors and/or matched metastases is a predictor of efficacy of first-line ET in advanced BC. Patients who had received first-line ET (2002-2011) were recruited, while those given concomitant chemotherapy or trastuzumab or pretreated with > 2 lines of chemotherapy were excluded. ER, progesterone receptor (PgR), Ki67 and AR expression were assessed by immunohistochemistry, and HER2 mainly by fluorescent in-situ hybridization. Cut-offs of 1 and 10% immunostained cells were used to categorize AR expression. Results: Among 102 evaluable patients, biomarkers were assessed in primary tumors in 70 cases and in metastases in 49, with 17 patients having both determinations. The overall concordance rate between primary tumors and metastases was 64.7% (95% CI 42%-87.4%) for AR status. AR status did not affect TTP significantly, whereas PgR and Ki67 status did. AR/PgR ≥0.96 was associated with a significantly shorter TTP (HR = 1.65, 95% CI 1.05-2.61, p = 0.028). AR status in primary tumors or metastases was not associated with progressive disease (PD) as best response. In contrast, Ki67 ≥ 20% and PgR < 10% showed a statistically significant association with PD as best response. Conclusions: AR expression does not appear to be useful to predict the efficacy of ET in advanced BC, whereas Ki67 and PgR exert a greater impact on its efficacy.

AB - Background: Androgen receptor (AR) is widely expressed in breast cancer (BC) but its role in estrogen receptor (ER)-positive tumors is still controversial. The AR/ER ratio has been reported to impact prognosis and response to antiestrogen endocrine therapy (ET). Methods: We assessed whether AR in primary tumors and/or matched metastases is a predictor of efficacy of first-line ET in advanced BC. Patients who had received first-line ET (2002-2011) were recruited, while those given concomitant chemotherapy or trastuzumab or pretreated with > 2 lines of chemotherapy were excluded. ER, progesterone receptor (PgR), Ki67 and AR expression were assessed by immunohistochemistry, and HER2 mainly by fluorescent in-situ hybridization. Cut-offs of 1 and 10% immunostained cells were used to categorize AR expression. Results: Among 102 evaluable patients, biomarkers were assessed in primary tumors in 70 cases and in metastases in 49, with 17 patients having both determinations. The overall concordance rate between primary tumors and metastases was 64.7% (95% CI 42%-87.4%) for AR status. AR status did not affect TTP significantly, whereas PgR and Ki67 status did. AR/PgR ≥0.96 was associated with a significantly shorter TTP (HR = 1.65, 95% CI 1.05-2.61, p = 0.028). AR status in primary tumors or metastases was not associated with progressive disease (PD) as best response. In contrast, Ki67 ≥ 20% and PgR < 10% showed a statistically significant association with PD as best response. Conclusions: AR expression does not appear to be useful to predict the efficacy of ET in advanced BC, whereas Ki67 and PgR exert a greater impact on its efficacy.

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KW - Androgen receptor

KW - Anti-estrogen therapy

KW - AR/ER ratio

KW - Endocrine therapy

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