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Short-term anastrozole therapy reduces Ki-67 and progesterone receptor expression in invasive breast cancer: a prospective, placebo-controlled, double-blind trial

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Abstract

Purpose

The objective of this study was to compare Ki-67, Bcl-2, Bax, Bak, ER, and PgR expression in postmenopausal women with ER-positive invasive breast cancer (IBC) before and after short-term hormone therapy (HT) with either tamoxifen or anastrozole in order to identify a possible biomarker profile associated with hormone resistance.

Methods

Fifty-eight patients with palpable IBC were assigned to receive neoadjuvant therapy with either anastrozole, placebo, or tamoxifen for 26 days prior to surgery. Tissue microarray blocks were constructed from pre- and post-treatment biopsy samples and used for immunohistochemical analysis. Biomarker (Ki-67, Bcl-2, Bax, Bak, ER, and PgR) levels were assessed semiquantitatively using the Allred score. A statistical analysis was performed using general estimating equations (GEE) and analysis of variance (ANOVA) with a significance level of 0.05.

Results

There was a significant reduction in PgR scores from baseline (mean, 4.22) to post-treatment (mean, 1.94) in the anastrozole group, but only a non-significant trend toward an increase in PgR scores was found in the tamoxifen group. There was a significant reduction in Ki-67 scores from baseline (mean, 3.61) to post-treatment (mean, 2.56) in the anastrozole group (P = 0.01), but only a non-significant trend toward a reduction in Ki-67 scores was found in the tamoxifen group.

Conclusions

There was a significant reduction in PgR and Ki-67 expression in the group treated with anastrozole. In the present study, the short-term HT was not associated with changes in apoptosis-related protein levels, regardless the type of drug used.

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Abbreviations

ANOVA:

Analysis of variance

ER:

Estrogen receptor

GEE:

General estimating equations

HT:

Hormone therapy

IMPACT trial:

Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen trial

IBC:

Invasive breast cancer

PgR:

Progesterone receptor

SD:

Standard deviation

SERM:

Selective estrogen-receptor modulator

UNIFESP:

Universidade Federal de São Paulo

WHO:

World Health Organization

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Acknowledgments

The authors acknowledge all the patients who gave their consent to participate in this trial. The authors declare that they have no competing interests. The authors also declare that they have no financial and/or non-financial competing interests (political, personal, religious, ideological, academic, intellectual, commercial, or any other) in relation to this manuscript. There was no external funding for this study.

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Gynecology, Federal University of São Paulo (UNIFESP), Rua Napoleão de Barros, 715 - 7°.andar, CEP 04024-002, São Paulo, SP, Brazil

    Andre Mattar, Gil Facina & Luiz Henrique Gebrim

  2. Department of Pathology, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil

    Angela Flávia Logullo

  3. Laboratory of Immunohistochemistry, Adolfo Lutz Institute, São Paulo, SP, Brazil

    Suely Nonogaki

  4. Department of Pathology, Antonio Prudente Foundation, São Paulo, SP, Brazil

    Fernando Augusto Soares

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  1. Andre Mattar
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  2. Angela Flávia Logullo
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  4. Suely Nonogaki
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  6. Luiz Henrique Gebrim
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Correspondence to Andre Mattar.

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Mattar, A., Logullo, A.F., Facina, G. et al. Short-term anastrozole therapy reduces Ki-67 and progesterone receptor expression in invasive breast cancer: a prospective, placebo-controlled, double-blind trial. J Cancer Res Clin Oncol 137, 897–905 (2011). https://doi.org/10.1007/s00432-010-0950-4

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  • DOI: https://doi.org/10.1007/s00432-010-0950-4

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