This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chang, J. Articles by Dowsett, M. Search for Related Content PubMed PubMed Citation Articles by Chang, J. Articles by Dowsett, M.

Prediction of Clinical Outcome from Primary Tamoxifen by Expression of Biologic Markers in Breast Cancer Patients¹

Departments of Medicine and Computing, The Royal Marden Hospital, Sutton, Surrey SM2 5PT, United Kingdom [J. C., T. J. P., S. E. A., A. M., R. K. G., M. D.], and Departments of Medical Oncology and Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-6200 [D. C. A., C. K. O.]

The aim of this study was to evaluate pretreatment clinical features and biological markers together with changes in these factors as predictors of response and relapse in patients receiving tamoxifen for primary breast cancer. Fine-needle aspiration cytology of the primary breast cancer was performed before tamoxifen treatment in 54 patients and repeated after therapy on day 14, day 60, or on both days in a subset of 35 patients. These samples were evaluated for estrogen receptor (ER), progesterone receptor (PgR), Ki67, S-phase fraction and ploidy. The overall response to tamoxifen was 57% (31 of 54 patients). Pretreatment ER and PgR significantly predicted for response by univariate analysis (P < 0.0001 and P < 0.003, respectively). By multivariate analysis, ER expression was the only independent predictor of response, and it was associated with 27 times the likelihood of response (95% confidence interval, 6–136). Increase in PgR and decrease in Ki67 on day 14 significantly predicted for response to tamoxifen (P < 0.03 and P < 0.04, respectively). Lack of ER, clinical node-positive disease, and failure to decrease Ki67 on day 14 were significantly associated with increased risk of relapse (P < 0.05). By multivariate analysis, ER expression was the only independent predictor of relapse (P < 0.005). Pretreatment and early changes in molecular marker expression may assist in the prediction of response and clinical outcome in primary breast cancer patients receiving tamoxifen.

This article has been cited by other articles:

				M. Dowsett and A. K. Dunbier Emerging Biomarkers and New Understanding of Traditional Markers in Personalized Therapy for Breast Cancer Clin. Cancer Res., December 15, 2008; 14(24): 8019 - 8026. [Abstract] [Full Text] [PDF]

				M. Cazzaniga, G. Severi, C. Casadio, L. Chiapparini, U. Veronesi, and A. Decensi Atypia and ki-67 expression from ductal lavage in women at different risk for breast cancer. Cancer Epidemiol. Biomarkers Prev., July 1, 2006; 15(7): 1311 - 1315. [Abstract] [Full Text] [PDF]

				C. E. Wood, A. L. Usborne, M. F. Starost, R. P. Tarara, L. R. Hill, L. M. Wilkinson, K. R. Geisinger, E. A. Feiste, and J. M. Cline Hyperplastic and neoplastic lesions of the mammary gland in macaques. Vet. Pathol., July 1, 2006; 43(4): 471 - 483. [Abstract] [Full Text] [PDF]

				A. Urruticoechea, I. E. Smith, and M. Dowsett Proliferation Marker Ki-67 in Early Breast Cancer J. Clin. Oncol., October 1, 2005; 23(28): 7212 - 7220. [Abstract] [Full Text] [PDF]

				S A Khan, D Bhandare, and R T Chatterton Jr The local hormonal environment and related biomarkers in the normal breast Endocr. Relat. Cancer, September 1, 2005; 12(3): 497 - 510. [Abstract] [Full Text] [PDF]

				C J Fabian, B F Kimler, M S Mayo, and S A Khan Breast-tissue sampling for risk assessment and prevention Endocr. Relat. Cancer, June 1, 2005; 12(2): 185 - 213. [Abstract] [Full Text] [PDF]

				Q. J. Khan, B. F. Kimler, J. Clark, T. Metheny, C. M. Zalles, and C. J. Fabian Ki-67 Expression in Benign Breast Ductal Cells Obtained by Random Periareolar Fine Needle Aspiration Cancer Epidemiol. Biomarkers Prev., April 1, 2005; 14(4): 786 - 789. [Abstract] [Full Text] [PDF]

				C. J. Fabian and B. F. Kimler Selective Estrogen-Receptor Modulators for Primary Prevention of Breast Cancer J. Clin. Oncol., March 10, 2005; 23(8): 1644 - 1655. [Full Text] [PDF]

				B. M. Jacobsen, S. A. Schittone, J. K. Richer, and K. B. Horwitz Progesterone-Independent Effects of Human Progesterone Receptors (PRs) in Estrogen Receptor-Positive Breast Cancer: PR Isoform-Specific Gene Regulation and Tumor Biology Mol. Endocrinol., March 1, 2005; 19(3): 574 - 587. [Abstract] [Full Text] [PDF]

				M. Dowsett, I. E. Smith, S. R. Ebbs, J. M. Dixon, A. Skene, C. Griffith, I. Boeddinghaus, J. Salter, S. Detre, M. Hills, et al. Short-Term Changes in Ki-67 during Neoadjuvant Treatment of Primary Breast Cancer with Anastrozole or Tamoxifen Alone or Combined Correlate with Recurrence-Free Survival Clin. Cancer Res., January 15, 2005; 11(2): 951s - 958s. [Abstract] [Full Text] [PDF]

				C. J. Fabian, B. F. Kimler, J. Anderson, O. W. Tawfik, M. S. Mayo, W. E. Burak Jr., J. A. O'Shaughnessy, K. S. Albain, D. M. Hyams, G. T. Budd, et al. Breast Cancer Chemoprevention Phase I Evaluation of Biomarker Modulation by Arzoxifene, a Third Generation Selective Estrogen Receptor Modulator Clin. Cancer Res., August 15, 2004; 10(16): 5403 - 5417. [Abstract] [Full Text] [PDF]

				P J van Diest, E van der Wall, and J P A Baak Prognostic value of proliferation in invasive breast cancer: a review J. Clin. Pathol., July 1, 2004; 57(7): 675 - 681. [Abstract] [Full Text] [PDF]

				S. Sellappan, R. Grijalva, X. Zhou, W. Yang, M. B. Eli, G. B. Mills, and D. Yu Lineage Infidelity of MDA-MB-435 Cells: Expression of Melanocyte Proteins in a Breast Cancer Cell Line Cancer Res., May 15, 2004; 64(10): 3479 - 3485. [Abstract] [Full Text] [PDF]

				R. S. Herbst and P. A. Bunn Jr. Targeting the Epidermal Growth Factor Receptor in Non-Small Cell Lung Cancer Clin. Cancer Res., December 1, 2003; 9(16): 5813 - 5824. [Abstract] [Full Text] [PDF]

				K. Wu and P. Brown Is Low-Dose Tamoxifen Useful for the Treatment and Prevention of Breast Cancer? J Natl Cancer Inst, June 4, 2003; 95(11): 766 - 767. [Full Text] [PDF]

				A. Decensi, C. Robertson, G. Viale, F. Pigatto, H. Johansson, E. R. Kisanga, P. Veronesi, R. Torrisi, M. Cazzaniga, S. Mora, et al. A Randomized Trial of Low-Dose Tamoxifen on Breast Cancer Proliferation and Blood Estrogenic Biomarkers J Natl Cancer Inst, June 4, 2003; 95(11): 779 - 790. [Abstract] [Full Text] [PDF]

				C. L. Arteaga and J. Baselga Clinical Trial Design and End Points for Epidermal Growth Factor Receptor-targeted Therapies: Implications for Drug Development and Practice Clin. Cancer Res., May 1, 2003; 9(5): 1579 - 1589. [Full Text] [PDF]

				C. J. Fabian, B. F. Kimler, D. A. Brady, M. S. Mayo, C. H. J. Chang, J. A. Ferraro, C. M. Zalles, A. L. Stanton, S. Masood, W. E. Grizzle, et al. A Phase II Breast Cancer Chemoprevention Trial of Oral {alpha}-Difluoromethylornithine: Breast Tissue, Imaging, and Serum and Urine Biomarkers Clin. Cancer Res., October 1, 2002; 8(10): 3105 - 3117. [Abstract] [Full Text] [PDF]

				S. E. Singletary, E. N. Atkinson, A. Hoque, N. Sneige, A. A. Sahin, H. A. Fritsche Jr., R. Lotan, T. Lu, W. N. Hittelman, T. B. Bevers, et al. Phase II Clinical Trial of N-(4-Hydroxyphenyl)retinamide and Tamoxifen Administration before Definitive Surgery for Breast Neoplasia Clin. Cancer Res., September 1, 2002; 8(9): 2835 - 2842. [Abstract] [Full Text] [PDF]

				A. Bowman, H. Gabra, S. P. Langdon, A. Lessells, M. Stewart, A. Young, and J. F. Smyth CA125 Response Is Associated with Estrogen Receptor Expression in a Phase II Trial of Letrozole in Ovarian Cancer: Identification of an Endocrine-sensitive Subgroup Clin. Cancer Res., July 1, 2002; 8(7): 2233 - 2239. [Abstract] [Full Text] [PDF]

				C. L. Harper-Wynne, N. P.M. Sacks, K. Shenton, F. A. MacNeill, P. Sauven, I. J. Laidlaw, Z. Rayter, S. Miall, A. Howes, J. Salter, et al. Comparison of the Systemic and Intratumoral Effects of Tamoxifen and the Aromatase Inhibitor Vorozole in Postmenopausal Patients With Primary Breast Cancer J. Clin. Oncol., February 15, 2002; 20(4): 1026 - 1035. [Abstract] [Full Text] [PDF]

				M. Dowsett, C. Harper-Wynne, I. Boeddinghaus, J. Salter, M. Hills, M. Dixon, S. Ebbs, G. Gui, N. Sacks, and I. Smith HER-2 Amplification Impedes the Antiproliferative Effects of Hormone Therapy in Estrogen Receptor-positive Primary Breast Cancer Cancer Res., December 1, 2001; 61(23): 8452 - 8458. [Abstract] [Full Text] [PDF]

				J. A. Lawrence, P. C. Adamson, R. Caruso, C. Chow, D. Kleiner, R. F. Murphy, D. J. Venzon, M. Shovlin, M. Noone, M. Merino, et al. Phase I Clinical Trial of Alitretinoin and Tamoxifen in Breast Cancer Patients: Toxicity, Pharmacokinetic, and Biomarker Evaluations J. Clin. Oncol., May 15, 2001; 19(10): 2754 - 2763. [Abstract] [Full Text] [PDF]

				E. S. Lee, J. M. Schafer, K. Yao, G. England, R. M. O’Regan, A. D. L. Reyes, and V. C. Jordan Cross-Resistance of Triphenylethylene-type Antiestrogens but not ICI 182,780 in Tamoxifen-stimulated Breast Tumors Grown in Athymic Mice Clin. Cancer Res., December 1, 2000; 6(12): 4893 - 4899. [Abstract] [Full Text]