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Ki67 expression in the primary tumor predicts for clinical benefit and time to progression on first-line endocrine therapy in estrogen receptor-positive metastatic breast cancer

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Abstract

We examined whether baseline Ki67 expression in estrogen receptor-positive (ER+) primary breast cancer correlates with clinical benefit and time to progression on first-line endocrine therapy and survival in metastatic disease. Ki67 values and outcome information were retrieved from a prospectively maintained clinical database and validated against the medical records; 241 patients with metastatic breast cancer were included—who had ER+ primary cancer with known Ki67 expression level—and received first-line endocrine therapy for metastatic disease. Patients were assigned to low (<10 %), intermediate (10–25 %), or high (>25 %) Ki67 expression groups. Kaplan–Meier survival curves were plotted and multivariate analysis was performed to assess association between clinical and immunohistochemical variables and outcome. The clinical benefit rates were 81, 65, and 55 % in the low (n = 32), intermediate (n = 103), and high (n = 106) Ki67 expression groups (P = 0.001). The median times to progression on first-line endocrine therapy were 20.3 (95 % CI, 17.5–38.5), 10.8 (95 % CI, 8.9–18.8), and 8 (95 % CI, 6.1–11.1) months, respectively (P = 0.0002). The median survival times after diagnosis of metastatic disease were also longer for the low/intermediate compared to the high Ki67 group, 52 versus 30 months (P < 0.0001). In multivariate analysis, high Ki67 expression in the primary tumor remained an independent adverse prognostic factor in metastatic disease (P = 0.001). Low Ki67 expression in the primary tumor is associated with higher clinical benefit and longer time to progression on first-line endocrine therapy and longer survival after metastatic recurrence.

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Acknowledgments

Grants from “La Fondation de France” and “La Fondation pour la recherche médicale” to YD and Research Grant from Merck to LP.

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, PO Box 301439, Houston, TX, 77230-1439, USA

    Y. Delpech, L. Hsu, R. Natowicz, G. N. Hortobagyi & L. Pusztai

  2. Department of Gynecology and Obstetrics, Lariboisiere Hospital/AP-HP, Paris, France

    Y. Delpech & E. Barranger

  3. The University Denis Diderot, Paris 7, France

    Y. Delpech & E. Barranger

  4. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Y. Wu

  5. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    K. R. Hess

  6. Merck & Co., Inc., One Merck Drive, Whitehouse Station, NJ, USA

    M. Ayers & D. Mauro

  7. ESIEE-PARIS, University of Paris-Est, Noisy le Grand, France

    R. Natowicz

  8. Department of Surgical Oncology, Georges Francois Leclerc Cancer Center, Dijon, France

    C. Coutant

  9. The University of Bourgogne, Dijon, France

    C. Coutant

  10. Department of Gynecology and Obstetrics, Tenon Hospital/AP-HP, Paris, France

    R. Rouzier

  11. The University Pierre and Marie Curie, Paris 6, France

    R. Rouzier

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  1. Y. Delpech
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  2. Y. Wu
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  9. E. Barranger
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  10. G. N. Hortobagyi
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  11. D. Mauro
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  12. L. Pusztai
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Corresponding author

Correspondence to L. Pusztai.

Electronic supplementary material

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10549_2012_2194_MOESM1_ESM.docx

Supplementary Table 1. Clinical benefit rates by Ki67 group for patients who presented with stage I-III disease at diagnosis. (DOCX 15 kb)

10549_2012_2194_MOESM2_ESM.tif

Supplementary Figure 1. Survival after metastasis (A) and time to progression on first-line endocrine therapy for metastatic disease (B) in low (Ki67 < 10 %), intermediate (Ki67 10-25 %) and high (Ki67 > 25 %) proliferation groups for patients who first presented with stage I-III breast cancer. Ki67 levels were determined in the primary cancer. (TIFF 847 kb)

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Delpech, Y., Wu, Y., Hess, K.R. et al. Ki67 expression in the primary tumor predicts for clinical benefit and time to progression on first-line endocrine therapy in estrogen receptor-positive metastatic breast cancer. Breast Cancer Res Treat 135, 619–627 (2012). https://doi.org/10.1007/s10549-012-2194-2

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  • DOI: https://doi.org/10.1007/s10549-012-2194-2

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