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Journal of Clinical Oncology, Vol 26, No 2 (January 10), 2008: pp. 258-263
© 2008 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2007.13.0179

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Nodal Stage Classification for Breast Carcinoma: Improving Interobserver Reproducibility Through Standardized Histologic Criteria and Image-Based Training

Roderick R. Turner, Donald L. Weaver, Gabor Cserni, Susan C. Lester, Karen Hirsch, David A. Elashoff, Patrick L. Fitzgibbons, Giuseppe Viale, Giovanni Mazzarol, Julio A. Ibarra, Stuart J. Schnitt, Armando E. Giuliano

From the John Wayne Cancer Institute at Saint John's Health Center, Santa Monica; David Geffen School of Medicine, University of California at Los Angeles, Los Angeles; St Jude Medical Center, Fullerton; Orange Coast Memorial Medical Center, Fountain Valley, CA; University of Vermont College of Medicine, Burlington, VT; Bacs-Kiskun County Teaching Hospital, Kecskemet, Hungary; Brigham and Women's Hospital; Beth Israel Deaconess Medical Center, Boston, MA; and European Institute of Oncology and University of Milan, Milan, Italy

Corresponding author: Roderick R. Turner, MD, Department of Pathology, Saint John's Health Center, 1328 Twenty-Second St, Santa Monica, CA 90404; e-mail: Roderick.Turner{at}stjohns.org

Purpose Reliable pathologic stage classification of axillary lymph nodes is an important determinant of prognosis and therapeutic decision making for patients with invasive breast cancer. Pathologists' distinction between micrometastasis (pN1mi) and isolated tumor cells [ITC; pN0(i+)] is variable using the American Joint Committee on Cancer (AJCC) Staging Manual (Sixth Edition). We sought to determine whether a set of clearly defined histologic criteria could lead to reproducible nodal classification by pathologists.

Patients and Methods Digital images of sentinel lymph node biopsies from 56 patients with small-volume nodal metastases were examined by six experienced breast pathologists (MDs), first as a pre-test, and again as a post-test after studying a training program that outlined and illustrated the classification criteria.

Results Post-test results, after study of the training program, were significantly improved. Compared with the reference MD, agreement improved from 76.2% (pre-test {kappa} = 0.575; standard deviation [SD], 0.25) to 97.3% (post-test {kappa} = 0.947; SD, 0.049). Multirater analysis of agreement among the six MDs improved from 71.5% (pre-test {kappa} = 0.487; ASE, 0.039) to 95.7% (post-test {kappa} = 0.915; ASE, 0.037). Agreement on lobular carcinoma metastasis classification improved from 55% (23 of 42; pre-test) to 100% (42 of 42; post-test) (P < .001), and agreement on ITC classification in nodal parenchyma improved from 67.6% (69 of 102; pre-test) to 98.0% (100 of 102; post-test; P < .001).

Conclusion Application of current definitions for classification of small-volume nodal metastases are inconsistent, leading to variable classification of ITC and micrometastases. Reproducibility of pathologic nodal stage classification is achievable through study of a training set to clarify the AJCC criteria.

Supported by funding from the Ben B. and Joyce E. Eisenberg Foundation (Los Angeles, CA), the Fashion Footwear Association of New York Charitable Foundation (New York, NY), and the Associates for Breast and Prostate Cancer Studies (Santa Monica, CA). Supplemental data are available online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.


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