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The prognostic value of proliferation indices: a study with in vivo bromodeoxyuridine and Ki-67

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Abstract

Proliferation indices are intended to help patients and clinicians make treatment decisions. We have previously demonstrated that a proliferation index based on in vivo labeling of S-phase cells with bromodeoxyuridine (BrdUrd) correlates with Ki-67 labeling index (LI). We now compare the prognostic value of these indices.

With written consent, we gave 129 women with biopsy confirmed breast cancer 200 mg/M2 BrdUrd during 30 min immediately preceding surgery. We used IU-4 anti BrdUrd antibody to count the immunohistochemical labeling index (LI) of DNA-incorporated BrdUrd in 2,000 cells and MIB-1 to count Ki-67 (118 cases). Patients received standard surgical and adjuvant treatment. No patients were lost to follow-up and patients were followed a minimum of 2 (median 5.1) years. We compared survival and recurrence in tumors with high vs low labeling indices. We found that women in the low BrdUrd LI group had better disease free survival (92% vs 67% 5-yr DFS p = 0.001) and overall survival (94% vs 70% 5-yr OS, p = 0.0001) than those with a high LI. In comparison, a low Ki-67 index predicted better OS (87% vs 80% 5-yr OS, p = 0.020) and a trend for better DFS (84% vs 72% DFS p = 0.055). The apparent superiority of BrdUrd LI over Ki-67 LI is likely due to chance (p = 0.18). In multivariate survival analyses we found that BrdUrd LI proliferative index significantly improves prediction of DFS or OS even when node status, age or tumor size is in the model. We conclude that markers of proliferation are useful adjuncts in predicting patient prognosis.

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Authors and Affiliations

  1. Department of Surgery, California Pacific Medical Research Institute, San Francisco, California, USA

    William H. Goodson III

  2. The Geraldine Brush Cancer Research Institute, California Pacific Medical Center, San Francisco, USA

    Dan H. Moore II & Helene S. Smith

  3. Departments of Epidemiology Biostatistics & Biostatistics, California, USA

    Dan H. Moore II

  4. Department of Pathology, University of California, San Francisco, California, USA

    Britt-Marie Ljung & Karen Chew

  5. Laboratory Medicine, University of California, San Francisco, California, USA

    Brian Mayall & Frederic M. Waldman

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  1. William H. Goodson III
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Goodson, W.H., Moore, D.H., Ljung, BM. et al. The prognostic value of proliferation indices: a study with in vivo bromodeoxyuridine and Ki-67. Breast Cancer Res Treat 59, 113–123 (2000). https://doi.org/10.1023/A:1006344010050

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