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Ki-67 Correlates With In Vivo Bromodeoxyuridine Labeling Index in Operable Breast Cancer

California Pacific Medical Center Research Institute, San Francisco, CA

Frederick M. Waldman

University of California San Francisco, San Francisco, CA

To the Editor:

In their review of Ki-67 and breast cancer, Urruticoechea, Smith, and Dowsett¹ are correct that in vivo labeling of S-phase breast cancer cells with bromodeoxyuridine (BrdU) is "laborious" and that proliferation rate measured with in vivo labeling of S-phase tumor cells with BrdU is a useful "gold standard." However, four of the five references they list report in vitro, not in vivo labeling with BrdU,^2-5 and the fifth reference does not include BrdU at all.⁶

There has been one published comparison of in vivo BrdU and Ki-67 in breast cancer. This study found a high correlation between Ki-67 and in vivo labeling of S-phase cells with BrdU.⁷ Both of these indices of proliferation indicated risk of recurrence in the first 5 years that was comparable to, and not statistically different from, prognostic information based on node status.⁸

This study with in vivo BrdU is unlikely to be repeated because (1) in vivo BrdU cannot be recommended for widespread clinical use and (2) Ki-67 has emerged as a readily obtained marker of proliferation that correlates highly with both in vivo and in vitro labeling of S-phase tumor cells with BrdU.

Authors' Disclosures of Potential Conflicts of Interest

The author or immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Authors Employment Leadership Consultant Stock Honoraria Research Funds Testimony Other William Goodson III Neopharm (A)

Dollar Amount Codes (A) < $10,000 (B) $10,000-99,999 (C) $100,000 (N/R) Not Required

REFERENCES

1. Urruticoechea A, Smith IA, Dowsett M: Proliferation marker Ki-67 in early breast cancer. J Clin Oncol 23:7212-7220, 2005[Abstract/Free Full Text]

2. Saski K, Matsumura K, Tsuji T, et al: Relationship between labeling indices of Ki-67 and BrdUrd in human malignant tumors. Cancer 62:989-993, 1988[CrossRef][Medline]

3. Saski K, Matsumura K, Murakami T, Tsuji T: Measurement of bromodeoxyuridine labeling index, Ki-67 score, and Ag-NOR count in breast carcinomas. Oncology 49:147-153, 1992[CrossRef][Medline]

4. Moriki T, Takahashi T, Kataoka H, et al: Proliferation marker MIB-1 correlates well with proliferative activity evaluated by BrdU in breast cancer: An immunohistochemical study including correlation with PCNA, p53, c-erb-2 and estrogen receptor status. Path Internat 46:953-961, 1996

5. Thor A, Liu S, Moore DH II, et al: Comparison of mitotic index, in vitro bromodeoxyuridine labeling, and MIB-1 assays to quantitate proliferation in breast cancer. J Clin Oncol 17:470-477, 1999[Abstract/Free Full Text]

6. Bouzubar N, Walker KJ, Griffiths K, et al: Ki67 immunostaining in primary breast cancer: Pathological and clinical associations. Br J Cancer 59:943-947, 1989[Medline]

7. Goodson WH III, Moore DH II, Ljung BM, et al: The functional relationship between in vivo bromodeoxyuridine labeling index and Ki-67 proliferation index in human breast cancer. Breast Cancer Res Treat 49:155-164, 1998[CrossRef][Medline]

8. Goodson WH III, Moore DH II, 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[CrossRef][Medline]

Related Reply

• In Reply:
  Mitch Dowsett, Ander Urruticoechea, and Ian E. Smith
  JCO 2006 24: 3809 [Full Text]

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