Molecular Prediction of Recurrence of Breast Cancer
http://www.100md.com
《新英格兰医药杂志》
To the Editor: The use of the Oncotype DX assay in the study reported by Paik et al. (Dec. 30 issue)1 is an example of a conflict of interest. Most of the authors of the report are employed by, receive consulting fees from, or hold equity positions or stock options in Genomic Health, the manufacturer of Oncotype DX. These authors support the adoption of a $3,000 test in lieu of information already contained in a standard surgical pathology report — the tumor grade. Table 1 of their article shows risk categories as determined by the Oncotype DX assay and the associated rates of distant recurrence at 10 years and compares the results to the inverse of the estimated proportion of patients free of distant recurrence at 10 years according to tumor grade (Figure 3 of the article). It is evident that tumor grade is as robust a predictor of outcome for all risk categories as the Oncotype DX assay. This interpretation is bolstered by the results of multicenter studies that have demonstrated the accuracy and reproducibility of the Nottingham combined histologic grade for the prediction of outcomes and responses to therapy.2,3
James F. Lombardo, M.D.
Ogden Regional Medical Center
Ogden, UT 84405
james.lombardo@mountainstarhealth.com
References
Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004;351:2817-2826.
Page DL, Gray R, Allred DC, et al. Prediction of node-negative breast cancer outcome by histologic grading and S-phase analysis by flow cytometry: an Eastern Cooperative Oncology Group Study (2192). Am J Clin Oncol 2001;24:10-18.
Pinder SE, Murray S, Ellis IO, et al. The importance of the histologic grade of invasive breast carcinoma and response to chemotherapy. Cancer 1998;83:1529-1539.
The authors reply: Our article was based on a scientific collaboration between the National Surgical Adjuvant Breast and Bowel Project (NSABP) and Genomic Health, and any potential conflict of interest is stated in the article. The protocol was finalized before the tissues were assayed, and data transfer from Genomic Health to the NSABP Biostatistical Center was administered by an intermediary group that is independent of Genomic Health and the NSABP. The NSABP statistician primarily responsible for the data analysis has no conflict of interest that might undermine the objectivity of the analysis.
There is no doubt that tumor grade provides important prognostic information. The problem is poor reproducibility. In the study published by Pinder et al.,1 that is cited by Dr. Lombardo, interobserver agreement for a grade 1 tumor was only 66.6 percent, a finding similar to reports by others.2,3,4,5 Although this level of tumor-grade reproducibility might be acceptable to some investigators, we believe that it is inadequate.
Soonmyung Paik, M.D.
Gong Tang, Ph.D.
National Surgical Adjuvant Breast and Bowel Project
Pittsburgh, PA 15212
spaik.nejm@nsabp.org
Dr. Paik reports being a coinventor on patent applications for the Oncotype DX assay, with all rights assigned to the NSABP Foundation, and having received lecture fees from Genomic Health.
References
Pinder SE, Murray S, Ellis IO, et al. The importance of the histologic grade of invasive breast carcinoma and response to chemotherapy. Cancer 1998;83:1529-1539.
Hopton DS, Thorogood J, Clayden AD, MacKinnon D. Observer variation in histological grading of breast cancer. Eur J Surg Oncol 1989;15:21-23.
Theissig F, Kunze KD, Haroske G, Meyer W. Histological grading of breast cancer: interobserver reproducibility and prognostic significance. Pathol Res Pract 1990;186:732-736.
Gilchrist KW, Kalish L, Gould VE, et al. Interobserver reproducibility of histopathological features in stage II breast cancer: an ECOG study. Breast Cancer Res Treat 1985;5:3-10.
Meyer JS, Alvarez C, Milikowski C, et al. Breast carcinoma malignancy grading by Bloom-Richardson system vs proliferation index: reproducibility of grade and advantages of proliferation index. Mod Pathol 2005;18:1067-1078.
James F. Lombardo, M.D.
Ogden Regional Medical Center
Ogden, UT 84405
james.lombardo@mountainstarhealth.com
References
Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004;351:2817-2826.
Page DL, Gray R, Allred DC, et al. Prediction of node-negative breast cancer outcome by histologic grading and S-phase analysis by flow cytometry: an Eastern Cooperative Oncology Group Study (2192). Am J Clin Oncol 2001;24:10-18.
Pinder SE, Murray S, Ellis IO, et al. The importance of the histologic grade of invasive breast carcinoma and response to chemotherapy. Cancer 1998;83:1529-1539.
The authors reply: Our article was based on a scientific collaboration between the National Surgical Adjuvant Breast and Bowel Project (NSABP) and Genomic Health, and any potential conflict of interest is stated in the article. The protocol was finalized before the tissues were assayed, and data transfer from Genomic Health to the NSABP Biostatistical Center was administered by an intermediary group that is independent of Genomic Health and the NSABP. The NSABP statistician primarily responsible for the data analysis has no conflict of interest that might undermine the objectivity of the analysis.
There is no doubt that tumor grade provides important prognostic information. The problem is poor reproducibility. In the study published by Pinder et al.,1 that is cited by Dr. Lombardo, interobserver agreement for a grade 1 tumor was only 66.6 percent, a finding similar to reports by others.2,3,4,5 Although this level of tumor-grade reproducibility might be acceptable to some investigators, we believe that it is inadequate.
Soonmyung Paik, M.D.
Gong Tang, Ph.D.
National Surgical Adjuvant Breast and Bowel Project
Pittsburgh, PA 15212
spaik.nejm@nsabp.org
Dr. Paik reports being a coinventor on patent applications for the Oncotype DX assay, with all rights assigned to the NSABP Foundation, and having received lecture fees from Genomic Health.
References
Pinder SE, Murray S, Ellis IO, et al. The importance of the histologic grade of invasive breast carcinoma and response to chemotherapy. Cancer 1998;83:1529-1539.
Hopton DS, Thorogood J, Clayden AD, MacKinnon D. Observer variation in histological grading of breast cancer. Eur J Surg Oncol 1989;15:21-23.
Theissig F, Kunze KD, Haroske G, Meyer W. Histological grading of breast cancer: interobserver reproducibility and prognostic significance. Pathol Res Pract 1990;186:732-736.
Gilchrist KW, Kalish L, Gould VE, et al. Interobserver reproducibility of histopathological features in stage II breast cancer: an ECOG study. Breast Cancer Res Treat 1985;5:3-10.
Meyer JS, Alvarez C, Milikowski C, et al. Breast carcinoma malignancy grading by Bloom-Richardson system vs proliferation index: reproducibility of grade and advantages of proliferation index. Mod Pathol 2005;18:1067-1078.