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Journal of Clinical Oncology, Vol 26, No 18 (June 20), 2008: pp. 3094 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2008.16.7817
Measurement of Residual Disease After Neoadjuvant ChemotherapyCentre Jean Perrin and INSERM, Clermont-Ferrand, France
Centre Jean Perrin and INSERM; and Faculté de Médecine, Université d'Auvergne, Clermont-Ferrand, France
Centre Jean Perrin and INSERM; Faculté de Médecine, Université d'Auvergne; and Centre d'Investigation Clinique, Clermont-Ferrand, France To the Editor: A complete pathologic response after induction chemotherapy for a bulky breast cancer is accepted as a favorable prognosis factor. Conversely, residual disease in breast and nodes is adverse and must be evaluated, but has not been fully classified until now. It is the reason why Symmans et al1 have done a useful task in proposing an index (residual cancer burden) that combines pathologic measurement of primary tumor (size and cellularity) and nodal metastases (number and size) for prediction of distant relapse-free survival with multivariate Cox regression analyses. This index seems to be relevant but warrants additional discussion, given that it is not directly usable from the publication. First, as it was proposed by Symmans et al,1 it seems necessary to take into account the size of the residual disease and the axillary lymph nodes status. These parameters are the main criteria representing the residual disease and their combination after neoadjuvant chemotherapy is of high prognostic value.2 Moreover, the authors have considered the bidimensional size of the tumor, because, as they correctly noted, the asymmetry of the residual disease is not usually precise in pathology reports—a factor that could determinate more accurately the prognostic value of this parameter. In addition, the index has taken into account the size of the largest node metastasis. Again, this information is not always indicated in pathology reports, but could be informative in a prognostic study because it reflects the residual tumor bulk. Second, as mentioned by the authors, a variable hypocellularity after treatment is not usually quantified in pathology reports. However, Symmans et al reported that, according to the literature, the reduction in cellularity is often greatest when the residual tumor is small, suggesting a direct relationship between residual size and cellularity.3 Thus, it seems interesting to study this parameter, and the authors have added this factor in their index. Moreover, this factor is somewhat subjective, and to facilitate its use, they proposed a tutorial (available on the Internet) to show the pathologists how to assess the hypocellularity of the residual tumor. Nevertheless, the use of this parameter suggests its routine assessment and reproducibility of its evaluation. Third, the authors mentioned that each factor they used in their model had a prognostic significance. Their aim was to combine different parameters used separately in other studies and to include them in their model. However, in the literature, another factor with prognostic significance when assessed separately and in combination is available: the Scarff-Bloom-Richardson grade that retains its value after induction chemotherapy.4-6 It should certainly be interesting to add it to the index proposed by Symmans et al, given that it is a basic parameter for breast pathology reports, and retains its value after primary chemotherapy. To conclude, this index proposed by Symmans et al seems promising and is interesting to complete. It is mandatory to test it on another data sets to verify its predictive power and transferability to general users. Hence, our comments reflect the current pitfalls encountered in measuring the residual disease because of the multitude of parameters that can be studied and because of the difficulty of a standardized assessment of histopathologic parameters. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Symmans WF, Peintinger F, Hatzis C, et al: Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 25:4414-4422, 2007 2. Carey LA, Metzger R, Dees EC, et al: American Joint Committee on Cancer tumor-node-metastasis stage after neoadjuvant chemotherapy and breast cancer outcome. J Natl Cancer Inst 97:1137-1142, 2005 3. Rajan R, Poniecka A, Smith TL, et al: Change in tumor cellularity of breast carcinoma after neoadjuvant chemotherapy as a variable in the pathologic assessment of response. Cancer 100:1365-1373, 2004[CrossRef][Medline] 4. Chollet P, Amat S, Belembaogo E, et al: Is Nottingham prognostic index useful after induction chemotherapy in operable breast cancer? Br J Cancer 89:1185-1191, 2003[CrossRef][Medline] 5. Amat S, Abrial C, Penault-Llorca F, et al: High prognostic significance of residual disease after neoadjuvant chemotherapy: A retrospective study in 710 patients with operable breast cancer. Breast Cancer Res Treat 94:255-263, 2005[CrossRef][Medline] 6. Amat S, Penault-Llorca F, Curé H, et al: Scarff-Bloom-Richardson (SBR) grading: a pleiotropic marker of chemosensitivity in invasive ductal breast carcinomas treated by neoadjuvant chemotherapy. Int J Oncol 20:791-796, 2002[Medline]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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