SPECIAL DEPARTMENTS
Authors: K. Mokbel, A.C. A. Leris, J. Chang, T.J. Powles, D.C. Allred, S.E. Ashley, G.M. Clark, M. Dowsett
Journal: Journal of Clinical Oncology (2000)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.7.1601 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10735910 K. MokbelxK. MokbelSearch for articles by this author , A.C. A. LerisxA.C. A. LerisSearch for articles by this author J. ChangxJ. ChangSearch for articles by this author , T.J. PowlesxT.J. PowlesSearch for articles by this author , D.C. AllredxD.C. AllredSearch for articles by this author , S.E. AshleyxS.E. AshleySearch for articles by this author , G.M. ClarkxG.M. ClarkSearch for articles by this author , M. DowsettxM. DowsettSearch for articles by this author Show More St Bartholomew’s Hospital LondonUnited KingdomBaylor College of Medicine HoustonTX https://doi.org/10.1200/JCO.2000.18.7.1601 Full Text PDF Figures and Tables "." Journal of Clinical Oncology, 18(7), pp. 1601–1602© 2000 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse07042000In Reply:Immunocytochemical analysis of biologic markers on samples obtained by fine-needle aspiration (FNA) has shown high correlation with results from paraffin sections and biochemical assays.1,2 We have previously validated the assays used in this study3 by demonstrating a high concordance between measurements obtained by FNAs and histologic paraffin sections.4 We have also reported no significant change in the level of expression of hormone receptors, Ki67, S-phase fraction, or ploidy from FNA cytology taken 2 weeks apart in a study involving 20 control patients who had not received any systemic therapy.5 Hence, the measurements of changes in biologic markers by repeat FNA before and after exposure to treatment may be used as additional predictive markers of response to therapy. Inconsistencies in the literature on the role of these biologic markers are more likely to reflect different chemotherapy regimens, timing of repeat biopsies, and different technical approaches to detecting a single biologic feature (eg, hormone receptors measured by ligand binding assays or immunohistochemistry).Assessing changes in Ki67 as a continuous variable would be problematic, especially since percentage change scores cannot be calculated if pretreatment values are zero. Moreover, good clinical response (GCR) was assessed as a dichotomous variable in this study3; hence, evaluation of correlation coefficient with change in Ki67 expression would be inappropriate. The relative likelihood from the logistic regression analysis in this study would provide the measure of association between change in Ki67 and GCR. There are several studies evaluating the relationship between bcl-2 expression and response to therapy. Expression of bcl-2 is positively correlated with estrogen receptor (ER) expression in a number of studies, and together with ER predicts for tamoxifen responsiveness.6 Conversely, other studies have shown that bcl-2 expression may be associated with resistance to chemotherapy.7 In this study,3 the majority of patients received chemoendocrine treatment, and this may explain the lack of predictive value of bcl-2 expression and response. Increased bcl-2 expression was associated with a 2.2-fold increased likelihood of clinical response (defined as complete and partial response), but there was no significant association with GCR. Moreover, there is increasing evidence that bcl-XL rather than bcl-2 may be a more important determinant of chemotherapy-induced apoptosis.8Finally, the National Institutes of Health consensus statement defined useful predictive factors for breast cancer as those with independent and significant predictive value and therapeutic implications that have been validated by clinical testing. Their determination should be feasible, reproducible, and readily interpreted by the clinician.9 Measurements of new predictive and prognostic variables should be standardized and validated by clinical outcome in large patient populations without selection bias.10 We note the comments regarding telomerase activity, which should be evaluated according to these guidelines. 2. Frigo B, Pilotti S, Zurrida S, et al: Analysis of estrogen and progesterone receptors on preoperative fine-needle aspirates. Breast Cancer Res Treat 33::179,1995-184, Crossref, Medline, Google Scholar2. Bozzetti C, Nizzoli R, Naldi N, et al: Fine-needle aspiration technique for the concurrent immunocytochemical evaluation of multiple biologic parameters in primary breast carcinoma. Breast Cancer Res Treat 32::221,1994-228, Crossref, Medline, Google Scholar2. Chang J, Powles TJ, Allred DC, et al: Biologic markers as predictors of clinical outcome from systemic therapy for primary operable breast cancer. J Clin Oncol 17::3058,1999-3063, Link, Google Scholar2. Makris A, Allred DC, Powles TJ, et al: Cytological evaluation of biological prognostic markers from primary breast carcinomas. Breast Cancer Res Treat 44::65,1997-74, Crossref, Medline, Google Scholar2. Makris A, Powles TJ, Allred DC, et al: Quantitative changes in cytological molecular markers during primary medical treatment of breast cancer: A pilot study. Breast Cancer Res Treat 53::51,1999-59, Crossref, Medline, Google Scholar2. Elledge RM, Green S, Howes L, et al: bcl-2, p53, and response to tamoxifen in estrogen receptor-positive metastatic breast cancer: A Southwest Oncology Group study. J Clin Oncol 15::1916,1997-1922, Link, Google Scholar2. Bonetti A, Zaninelli M, Leone R, et al: bcl-2 but not p53 expression is associated with resistance to chemotherapy in advanced breast cancer. Clin Cancer Res 4::2331,1998-2336, Medline, Google Scholar2. Liu JR, Fletcher B, Page C, et al: Bcl-xL is expressed in ovarian carcinoma and modulates chemotherapy-induced apoptosis. Gynecol Oncol 70::398,1998-403, Crossref, Medline, Google Scholar2. NIH consensus conference: Treatment of early-stage breast cancer. JAMA 265:391-397, 1991 Google Scholar2. McGuire WL: Breast cancer prognostic factors: Evaluation guidelines. J Natl Cancer Inst 83::154,1991-155, Crossref, Medline, Google Scholar