|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Originally published as JCO Early Release 10.1200/JCO.2008.20.3208 on February 2 2009 © 2009 American Society of Clinical Oncology.
In ReplyFox Chase Cancer Center, Philadelphia, PA
Montefiore-Einstein Cancer Center, Bronx, NY We appreciate the comments by Dimitrios H. Roukas concerning our report recently published in Journal of Clinical Oncology.1 We found that the 21-gene assay (Oncotype DX Recurrence Score [RS]; Genomic Health Inc, Redwood City, CA) was a more accurate predictor of recurrence than classical clinicopathologic features in patients with operable breast cancer and zero to three positive axillary nodes who were treated with adjuvant doxorubicin-containing chemotherapy in trial E2197.2 The 21-gene assay also provided information that was complementary to an integrator algorithm modeled after Adjuvant! that was adjusted for 5-year outcomes rather than 10-year outcomes (by multiplying the projected 10-year recurrence rate by one half). As we pointed out in the report, the purpose of including the integrator analysis was not to determine which method for estimating recurrence was superior, but rather to provide a more stringent test of the prognostic utility of the 21-gene assay in the population studied. To emphasize and clarify the point that the integrator used in our analysis and Adjuvant! are not equivalent, we have requested that the editors replace the term "Adjuvant!" (which appeared in Figs 2 through 5 and the running title in the original version of this publication) with the term "integrator" to ensure consistent terminology throughout the publication. Nevertheless, our results with the integrator do recapitulate the findings of Bryant et al with Adjuvant! that were presented at the ninth International Conference on the Primary Therapy of Early Breast Cancer in 2005 (http://www.oncoconferences.ch/2005/home/home.htm); that analysis demonstrated that RS likewise provides information that is complementary to Adjuvant!, in this case using 10-year outcomes in patients with node-negative disease who were treated with a 5-year course of tamoxifen. Roukos pointed out several limitations of our analysis, including its retrospective nature and other methodologic issues, the study population, and changing standards of care that now often include aromatase inhibitor (AI) therapy rather than tamoxifen. First, although this was retrospective study, it was a prospectively planned analysis that used specimens from a completed trial whose methods were consistent with the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) guidelines.3 Second, consistent with our findings, Albain et al4 have reported that the 21-gene assay provides prognostic information in postmenopausal patients with node-positive disease treated with adjuvant tamoxifen; this study also confirmed that high RS predicts benefit from adjuvant cyclophosphamide, doxorubicin, and fluorouracil chemotherapy in node-positive disease, as had previously been shown for cyclophosphamide, methotrexate, fluorouracil chemotherapy in node-negative disease.5 Third, regarding the limited use of AI therapy in the E2197 trial, it was performed before AIs had been shown to be an acceptable alternative to tamoxifen. A recent analysis presented at the 2008 San Antonio Breast Cancer Symposium demonstrated the prognostic utility of RS in patients with adjuvant AI therapy.6 We agree with Roukus that the successful completion of prospective, randomized trials such as Trials Assigning Individualized Options for Treatment (TAILORx) and Microarray in Node-Negative Disease May Avoid Chemotherapy (MINDACT) is critical for moving the field forward. We also agree that newer technologies offer opportunities to improve the prognostic and predictive utility of somatic multigene markers, and that host genetic markers are also likely to play an important role in the creation of individualized therapeutic approaches in the near future. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. 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. Employment or Leadership Position: None Consultant or Advisory Role: Joseph A. Sparano, Sanofi-aventis (C); Lori J. Goldstein, Sanofi-aventis (C); Genomic Health (C) Stock Ownership: None Honoraria: Joseph A. Sparano, Sanofi-aventis Research Funding: Joseph A. Sparano, Sanofi-aventis Expert Testimony: None Other Remuneration: None Acknowledgment Supported in part by the US Department of Health and Human Services, by National Cancer Institutes of Health grants (CA23318 to the Eastern Cooperative Oncology Group [ECOG] statistical center, CA66636 to the ECOG data management center, CA21115 to the ECOG coordinating center, CA25224 to the North Central Cancer Treatment Group, CA32291 to Cancer and Leukemia Group B, and CA32012 to the Southwest Oncology Group), and by a grant from Sanofi-aventis. REFERENCES
1. Goldstein LJ, Gray R, Badve S, et al: Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features. J Clin Oncol 26:4063–4071, 2008. 2. Goldstein LJ, O'Neill A, Sparano JA, et al: Concurrent doxorubicin plus docetaxel is not more effective than concurrent doxorubicin plus cyclophosphamide in operable breast cancer with 0 to 3 positive axillary nodes: North American Breast Cancer Intergroup Trial E 2197. J Clin Oncol 26:4092–4099, 2008. 3. McShane LM, Altman DG, Sauerbrei W, et al: Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst 97:1180–1184, 2005. 4. Albain K, Barlow W, Shak S, et al: Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal, node-positive, ER-positive breast cancer (S8814, INT0100). Breast Cancer Res Treat 106:1; 2007 (suppl) abstr 10.[Medline] 5. Paik S, Tang G, Shak S, et al: Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor–positive breast cancer. J Clin Oncol 24:3726–3734, 2006. 6. Dowsett M, Cuzick J, Wales C, et al; on behalf of the ATAC Trialists. Risk of distant recurrence using oncotype DX in postmenopausal primary breast cancer patients treated with anastrozole or tamoxifen: A TransATAC study. Breast Cancer Res Treat 107:1; 2008 (suppl) abstr 53.[CrossRef][Medline]
Related Article
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
