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Journal of Clinical Oncology, Vol 23, No 16 (June 1), 2005: pp. 3859-3860 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.05.248
Inflammatory Breast Cancer and High-Dose Chemotherapy: Back to the PastThe University of Texas, M.D. Anderson Cancer Center, Houston, TX To the Editor: We read with interest the article from Somlo et al1 published in the May 15, 2004, issue of the Journal of Clinical Oncology, and we would like to comment on the content and conclusions of the manuscript. The overall conclusion of the authors is that patients with inflammatory breast cancer (IBC) can be stratified in their prognosis by including several tumor-related factors (tumor size, nuclear grade, estrogen receptor [ER] and HER-2/neu status, number of involved axillary lymph nodes) and treatment-related factors (use of doxorubicin-containing regimens). Furthermore, a treatment with an intensified chemotherapy regimen can improve outcome in patients that according to the proposed model are classified as having favorable or intermediate features. There are several issues raised by this article that we will try to analyze sequentially. The diagnosis of IBC is primarily clinical and is supported by the pathologic evidence of tumor emboli in the dermal lymphatics.2 Patients included in this analysis had their initial diagnostic biopsy in the community. They received induction chemotherapy, had surgery, and subsequently were referred for high-dose chemotherapy. In an attempt to derive critical information on the initial diagnosis, the investigators reviewed "representative sections" of the primary tumor, but they failed to report in the patient characteristics information regarding the number of cases reviewed and the percentage of those with dermal tumor emboli. ER and HER-2/neu status were determined and reported in 62% of cases. Only positive or unknown cases are described for ER, and HER-2/neu 2+ cases are considered positive. All of these missing clinical and pathologic data in ER, HER-2/neu and p53 status (the most relevant to describe the peculiarity of IBC3-7), raise questions on the appropriate clinical diagnosis and pathologic review of IBC. IBC is inoperable by definition. The standard management of this entity is multidisciplinary, including neoadjuvant chemotherapy, mastectomy, locoregional radiotherapy, and hormonal therapy for hormone receptor–positive disease.8 Eighty-eight patients (73%) in this study received appropriate neoadjuvant treatment, but surprisingly the remaining 32 patients (27%) had mastectomy as primary treatment. The population at risk for recurrence was heterogeneous: 16 patients (13%) had residual microscopic margins, and 14 patients had more than one metastatic site. Pathologic complete response (pCR) in breast and axilla to induction chemotherapy has been identified has the strongest prognostic factor for locally advanced breast cancer, including IBC.9,10 The cohort of IBC patients that achieved pCR after induction chemotherapy was 6% (7 patients), a low percentage for anthracycline-based primary chemotherapy.11 Moreover, a taxane was included in the standard treatment of 48 patients (40%) and the addition of taxanes to primary chemotherapy has been shown to increase pCR rates.12 The number of positive lymph nodes reported after induction chemotherapy is uncertain, because the data provided includes also patients treated with primary surgery. These considerations raise the possibility that these patients received a suboptimal standard treatment for their disease, and make a risk-adapted stratification quite challenging. Patients received postoperative high-dose treatment (dose-intense chemotherapy), as part of a late intensification strategy, with eight different regimens, either single (five patients) or tandem (three patients). Forty-eight percent of the patients received doxorubicin again as part of the dose-intense program. Six different regimens enrolled less than 15% (range 1% to 13%) each of the entire population. At the time of the analysis, approximately 50% of patients had developed recurrence. Data on survival are comparable to other high-dose and/ or conventional anthracycline-taxane–containing regimens for IBC.13,14 Cautious approach to these data should be considered and efforts should continue on the development of more biologically targeted therapy that could integrate and improve our present knowledge in the management of this aggressive form of breast cancer. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Somlo G, Frankel P, Chow W, et al: Prognostic indicators and survival in patients with stage IIIB inflammatory breast carcinoma after dose-intense chemotherapy. J Clin Oncol 22:1839-1848, 2004 2. Gruber G, Ciriolo M, Altermatt HJ, et al: Prognosis of dermal lymphatic invasion with or without clinical signs of inflammatory breast cancer Int J Cancer 109:144-148, 2004[Medline]
3. Anderson WF, Chu KC, Chang S: Inflammatory breast cancer and noninflammatory locally advanced breast cancer carcinoma: Distinct clinicopathologic entities? J Clin Oncol 21:2254-2259, 2003
4. Bonnefoi H, Diebold-Berger S, Therasse P, et al: Locally advanced/inflammatory breast cancers treated with intensive epirubicin-based neoadjuvant chemotherapy: Are there molecular markers in the primary tumour that predict for 5-year clinical outcome. Ann Oncol 14:406-413, 2003 5. Parton M, Dowsett M, Ashley S, et al: High incidence of HER-2 positivity in inflammatory breast cancer Breast 13:97-103, 2004[CrossRef][Medline] 6. Charafe-Jauffret E, Tarpin C, Bardou VJ, et al: Immunophenotypic analysis of inflammatory breast cancers: Identification of an "inflammatory signature. " J Path 202:265-273, 2004
7. Gonzalez Angulo, Sneige N, Buzdar AU, et al: p53 Expression as a Prognostic Marker in Inflammatory Breast Cancer. Clin Cancer Res, 10: 6215-6221, 2004
8. Cristofanilli M, Buzdar AU, Hortobagyi GN: Update on the management of inflammatory breast cancer. Oncologist 8:141-148, 2003
9. Kuerer HM, Newman LA, Smith TL, et al: Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 17:460-469, 1999 10. Buchholz TA, Katz A, Strom EA, et al: Pathologic tumor size and lymph node status predict for different rates of locoregional recurrence after mastectomy for breast cancer patients treated with neoadjuvant versus adjuvant chemotherapy. Int J Radiat Oncol Biol Phys 53:880-888, 2002[CrossRef][Medline] 11. Fisher B, Bryant J, Wolmark N, et al: Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16:2672-2685, 1998[Abstract]
12. Bear HD, Anderson S, Brown A, et al: The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: Preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 21:4165-4174, 2003 13. Cristofanilli M, Gonzalez-Angulo AM, Buzdar AU, et al: Paclitaxel improves the prognosis in estrogen receptor negative inflammatory breast cancer: The M. D. Anderson Cancer Center experience. Clin Breast Cancer 4:415-419, 2004[Medline] 14. Bertucci F, Tarpin C, Charafe-Jauffret E, et al: Multivariate analysis on survival in inflammatory breast cancer: Impact of intensity of chemotherapy in multimodality treatment. Bone Marrow Transplant 3:913-920, 2004 Related Reply
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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