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Journal of Clinical Oncology, Vol 22, No 2 (January 15), 2004: pp. 383 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.99.183
In Reply:National Cancer Institute/Division of Cancer Prevention; Center to Reduce Cancer Health Disparities; and Division of Cancer Prevention; Bethesda, MD We thank Drs Cristofanilli, Singletary, and Hortobagyi for carefully reading our article and for providing the opportunity to further discuss our results. Their comments reflect concerns regarding: (1) the accuracy of our Surveillance, Epidemiology, and End-Results (SEER)-defined inflammatory breast carcinoma (IBC) patients, and (2) the heterogeneity among our patients with noninflammatory locally advanced breast carcinoma (LABC). First, IBC patients (n = 2,237) were defined with SEER extent of disease (EOD) code 70, corresponding to AJCC T4 d and consistent with Haagensen's classic diagnostic criteria [1-3]. Sixty-six percent (n = 1,488 of 2,237 [66.5%]) of patients with SEER-defined IBCs (EOD 70, T4 d) had matching International Classification of Diseases for Oncology (ICDO)-2 pathologic code 8530 because of documented dermal lymphatic invasion [4]. The remaining 33% (n = 749 of 2,237) had ICDO-2 pathologic codes other than 8530, including designations for ductal, tubular, lobular, medullary, and other morphologic subtypes. Undoubtedly, some of the remaining 33% had dermal lymphatic infiltration but for uncertain reasons did not receive ICDO-2 code 8530 from their local pathologists. Cristofanilli et al suggested that there was no information for the remaining 33% to support the distinction from LABC. However, Figure 4 in our article demonstrated identical age-specific incidence rate patterns for the 66.5% and 33% of our SEER-defined IBC cases (EOD 70, T4 d), irrespective of ICDO-2 code 8530 [5]. A major thesis of our article was that similar age-specific rate curves suggested similar biology [5,6]. However, differing rate patterns between IBC and LABC implied that all SEER-defined IBC cases (EOD 70, T4 d) were distinct from LABC. Second, Cristofanilli et al correctly noted that our LABC patients (n = 7,985) included those with operable (stage IIIA) as well as inoperable (stage IIIB) disease. In fact, 61% of the LABC cases were operable stage IIIA (4,845 of 7,985 cases), compared with 39% with inoperable stage IIIB (n = 3,140 of 7,985). SEER EOD codes 40 to 60 defined inoperable LABC (stage IIIB), corresponding to AJCC T4a-c [1,2]. Cristofanilli et al suspected that operable stage IIIA biased our results. However, conclusions were not affected by removing operable stage IIIA from our analysis, as shown in the accompanying Figure 1A. Age-specific rate curves for SEER-defined IBC (EOD 70, T4 d) increased rapidly to age 50 years and then flattened. However, rates for inoperable LABC (stage IIIB, T4a-c) rose continuously with aging, as did rates for stage IIIA + IIIB in the original article. Moreover, actuarial survival was worse (P < .001) for IBC (EOD 70, T4 d) compared with inoperable LABC (stage IIIB, T4a-c; Fig 1B). IBC (EOD 70, T4 d) also was more likely to be associated with positive lymph nodes, poor nuclear grade, and estrogen receptor-negative expression (P < .001) than was inoperable LABC (stage IIIB, T4a-c). Given that our analysis was unaffected by stage IIIA, we simply chose the more conservative statistical approach of reporting all the data in the original article. In sum, different age-specific rate patterns and prognostic factor profiles for IBC and LABC were robust to SEER coding, implying fundamental biologic differences for these two types of locally advanced breast carcinoma. With that said and for all the important diagnostic and therapeutic aspects discussed by Cristofanilli et al, we agree that inoperable LABC (stage IIIB, T4a-c) would be the more appropriate comparison group for future studies. We also hope this dialogue will guide the reader in the interpretation of our data. We appreciated the comments of the investigators at the University of Texas M.D. Anderson Cancer Center, and we commend them for their long-standing commitment to all forms of breast carcinoma. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES 1. SEER Extent of Disease—1988 Codes and Coding Instructions. http://seer.cancer.gov/Publications/Manuals/EOD10Dig.3rd.pdf 2. Breast, in Greene FL, Page DL, Fleming ID, et al (eds): AJCC Cancer Staging Handbook (ed 6). New York, NY, Springer, 2002, pp 255-281 3. Haagensen CD: Inflammatory carcinoma, Diseases of the Breast (ed 2). Philadelphia, PA, W.B. Saunders, 1971, pp 576-584 4. Berg JW, Hutter RV: Breast cancer. Cancer 75:257-269, 1995[CrossRef][Medline]
5. Anderson WF, Chu KC, Chang S: Inflammatory breast carcinoma and non-inflammatory locally advanced breast carcinoma: Distinct clinicopathologic entities? J Clin Oncol 21:2254-2259, 2003
6. Harlan LC, Hankey BF: The surveillance, epidemiology, and end-results program database as a resource for conducting descriptive epidemiologic and clinical studies. J Clin Oncol 21:2232-2233, 2003
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Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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