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Journal of Clinical Oncology, Vol 23, No 27 (September 20), 2005: pp. 6796-6797 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.02.2046
In Reply:Department of Breast Medical Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX We would like to thank Dr. Katz for his valuable comments on our recent report indicating that patients with a diagnosis of classic infiltrating lobular carcinoma (ILC) who are treated with neoadjuvant chemotherapy have a better long-term outcome compared to primary disease with histological features of infiltrating ductal cancer, despite achieving pathological complete response (pCR) with significantly lower frequency.1 These results are quite intriguing and raise questions that may affect the present management of primary disease. Before we address this issue we would like to take the opportunity to clarify that our manuscript was primarily directed at assessing the prognostic value of pCR and not at providing indication for treatment selection. The conclusion of our study was the demonstration that pCR is not an optimal prognostic factor for women with ILC. This retrospective analysis clearly indicated that these patients achieved a clinical and pathological response to standard neoadjuvant chemotherapy significantly less frequently compared to women with ductal malignancy. However, some patients did respond and many had sufficient reduction in tumor volume to permit breast-conserving surgery. The study was a retrospective review, and it was therefore not an appropriate forum in which to address any treatment-related questions. We recommend that at the present time the management of ILC remain unchanged and continue to follow the current recommendation for use of neoadjuvant therapy in primary disease, particularly with regard to patients presenting with locally advanced disease.2 Moreover, our approach to the follow-up and delivery of adjuvant treatment should not be modified, considering that the results of a large review analysis have clearly defined the benefits of adjuvant chemotherapy without being able to sort out differences among the various subtypes.3 Large prospective neoadjuvant studies conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) (eg, NSABP B-18 and most recently NSABP-B27)4,5 represent a potential resource for confirmation of our data, but once again in a retrospective manner. Moreover, in several of these trials initial diagnosis was obtained by fine-needle aspirates, and this weakens the reliability of the histological diagnosis, unless it was possible to retrieve adequate specimens to assess for the expression of some specific biomarkers (eg, E-cadherin).6 A more definitive approach to defining the most effective systemic therapy for patients diagnosed with ILC will require the design of large, prospective multicenter clinical trials. Neoadjuvant or primary treatments including the use of hormonal agents have been tested already in women with hormone-receptor positive disease and such a design for ILC would be easily accepted by patients and the oncology community.7 Because chemotherapy in patients presenting with lymph nodal involvement (most ILC patients belong to this group) is considered standard, it will be difficult to develop a trial that will directly compare adjuvant hormonal therapy to chemotherapy (followed by hormonal therapy). As a recent retrospective analysis of two NSABP trials with the benefit of a multigene profile (oncotype Dx) indicated, there are subsets of hormone receptor–positive breast cancers that do not seem to respond to chemotherapy, or for which the benefit of chemotherapy is marginal. Whether these data apply to patients with node-positive breast cancer remains to be determined. Therefore, we should continue to refine our ability to predict prognosis in primary disease, benefit from specific treatment regimens, and continue to develop novel and less toxic treatment modalities. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Cristofanilli M, Gonzalez-Angulo A, Sneige N, et al: Invasive lobular carcinoma classic type: Response to primary chemotherapy and survival outcomes. J Clin Oncol 23:41-48, 2005 2. Schwartz GF, Hortobagyi GN: Proceedings of the consensus conference on neoadjuvant chemotherapy in carcinoma of the breast, April 26-28, 2003, Philadelphia, Pennsylvania. Cancer 100:2512-2532, 2004[CrossRef][Medline] 3. Early Breast Cancer Trialists' Collaborative Group. Polichemiotherapy for early breast cancer. An overview of randomized trials. Lancet 352:930-942, 1998[CrossRef][Medline]
4. Fisher B, Brown A, Mamounas E, et al: Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: Findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 15:2483-2493, 1997
5. 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 6. Cleton-Jansen AM: E-cadherin and loss of heterozygosity at chromosome 16 in breast carcinogenesis: Different genetic pathways in ductal and lobular breast cancer? Breast Cancer Res 4:5-8, 2002[Medline]
7. Ellis MJ, Coop A, Singh B, et al: Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: Evidence from a phase III randomized trial. J Clin Oncol 19:3808-3816, 2001
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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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