This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions 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.

Biologic Markers as Predictors of Clinical Outcome From Systemic Therapy for Primary Operable Breast Cancer

From the Departments of Medicine and Computing, The Royal Marsden Hospital, Sutton, Surrey, United Kingdom; and the Departments of Medical Oncology and Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX.

Address reprint requests to Jenny Chang, MD, Department of Medical Oncology, National University Hospital, Lower Kent Ridge Rd, Singapore 119074, Singapore; email mdcccn{at}nus.edu.sg

PURPOSE: To determine whether pretreatment clinical features and molecular markers, together with changes in these factors, can predict treatment response and survival in patients with primary operable breast cancer who receive neoadjuvant therapy.

PATIENTS AND METHODS: Mitoxantrone, methotrexate (with or without mitomycin), and tamoxifen chemoendocrine therapy was administered to 158 patients before surgery. Clinical response was assessed after four cycles of treatment. Fine-needle aspiration cytology for estrogen receptor (ER), progesterone receptor (PgR), c-erbB-2, p53, bcl-2, Ki67, S-phase fraction (SPF), and ploidy were performed pretreatment and repeated on day 10 or day 21 after the first cycle of treatment.

RESULTS: Good clinical response (GCR, defined as complete response or minimal residual disease) was achieved in 31% of patients (49 of 158). Tumor size, nodal disease, response, ER, PgR, c-erbB-2, p53, bcl-2, Ki67, SPF, and ploidy were analyzed as predictors of survival. By univariate analysis, node-positive disease (P = .05), lack of ER (P < .05) and PgR (P < .05), and failure to attain GCR (P = .008) were associated with a significantly increased risk of relapse. A significantly increased risk of death was associated with node-positive disease (P = .02), lack of ER expression (P = .04), and failure to attain GCR. By multivariate analysis, GCR was an independent predictor for survival (P = .05). ER expression (P = .03), absence of c-erbB-2 (P = .03), and a decrease in Ki67 on day 10 or day 21 of the first cycle (P < .05) significantly predicted for subsequent GCR.

CONCLUSION: Molecular markers may be used to predict the likelihood of achieving GCR, which seems to be a valid surrogate marker for survival.

Presented in part at the Thirty-Fourth Annual Meeting of the American Society of Clinical Oncology, Los Angeles, CA, May 16-18, 1998.

This article has been cited by other articles:

				R A Walker Immunohistochemical markers as predictive tools for breast cancer J. Clin. Pathol., June 1, 2008; 61(6): 689 - 696. [Abstract] [Full Text] [PDF]

				G. Viale, M. M. Regan, M. G. Mastropasqua, F. Maffini, E. Maiorano, M. Colleoni, K. N. Price, R. Golouh, T. Perin, R. W. Brown, et al. Predictive Value of Tumor Ki-67 Expression in Two Randomized Trials of Adjuvant Chemoendocrine Therapy for Node-Negative Breast Cancer J Natl Cancer Inst, February 6, 2008; 100(3): 207 - 212. [Abstract] [Full Text] [PDF]

				K. C. Lee, B. A. Moffat, A. F. Schott, R. Layman, S. Ellingworth, R. Juliar, A. P. Khan, M. Helvie, C. R. Meyer, T. L. Chenevert, et al. Prospective Early Response Imaging Biomarker for Neoadjuvant Breast Cancer Chemotherapy Clin. Cancer Res., January 15, 2007; 13(2): 443 - 450. [Abstract] [Full Text] [PDF]

				C. Shimizu, M. Ando, T. Kouno, N. Katsumata, and Y. Fujiwara Current Trends and Controversies over Pre-operative Chemotherapy for Women with Operable Breast Cancer Jpn. J. Clin. Oncol., January 3, 2007; (2007) hyl122v1. [Abstract] [Full Text] [PDF]

				I. Sachelarie, M. L. Grossbard, M. Chadha, S. Feldman, M. Ghesani, and R. H. Blum Primary Systemic Therapy of Breast Cancer Oncologist, June 1, 2006; 11(6): 574 - 589. [Abstract] [Full Text] [PDF]

				N. Tinari, R. Lattanzio, C. Natoli, E. Cianchetti, D. Angelucci, E. Ricevuto, C. Ficorella, P. Marchetti, S. Alberti, M. Piantelli, et al. Changes of Topoisomerase II{alpha} Expression in Breast Tumors after Neoadjuvant Chemotherapy Predicts Relapse-Free Survival Clin. Cancer Res., March 1, 2006; 12(5): 1501 - 1506. [Abstract] [Full Text] [PDF]

				A. B. Chakravarthy, M. C. Kelley, B. McLaren, C. I. Truica, D. Billheimer, I. A. Mayer, A. M. Grau, D. H. Johnson, J. F. Simpson, R. D. Beauchamp, et al. Neoadjuvant Concurrent Paclitaxel and Radiation in Stage II/III Breast Cancer Clin. Cancer Res., March 1, 2006; 12(5): 1570 - 1576. [Abstract] [Full Text] [PDF]

				N. Kroger, K. Milde-Langosch, S. Riethdorf, C. Schmoor, M. Schumacher, A. R. Zander, and T. Loning Prognostic and Predictive Effects of Immunohistochemical Factors in High-Risk Primary Breast Cancer Patients Clin. Cancer Res., January 1, 2006; 12(1): 159 - 168. [Abstract] [Full Text] [PDF]

				R. Rouzier, L. Pusztai, S. Delaloge, A. M. Gonzalez-Angulo, F. Andre, K. R. Hess, A. U. Buzdar, J.-R. Garbay, M. Spielmann, M.-C. Mathieu, et al. Nomograms to Predict Pathologic Complete Response and Metastasis-Free Survival After Preoperative Chemotherapy for Breast Cancer J. Clin. Oncol., November 20, 2005; 23(33): 8331 - 8339. [Abstract] [Full Text] [PDF]

				T. A. Aloia, E. Grubbs, M. Onaitis, P. J. Mosca, T.-Y. Cheng, H. Seigler, and D. S. Tyler Predictors of Outcome After Hyperthermic Isolated Limb Perfusion: Role of Tumor Response Arch Surg, November 1, 2005; 140(11): 1115 - 1120. [Abstract] [Full Text] [PDF]

				M. Colozza, E. Azambuja, F. Cardoso, C. Sotiriou, D. Larsimont, and M. J. Piccart Proliferative markers as prognostic and predictive tools in early breast cancer: where are we now? Ann. Onc., November 1, 2005; 16(11): 1723 - 1739. [Abstract] [Full Text] [PDF]

				L. Gianni, M. Zambetti, K. Clark, J. Baker, M. Cronin, J. Wu, G. Mariani, J. Rodriguez, M. Carcangiu, D. Watson, et al. Gene Expression Profiles in Paraffin-Embedded Core Biopsy Tissue Predict Response to Chemotherapy in Women With Locally Advanced Breast Cancer J. Clin. Oncol., October 10, 2005; 23(29): 7265 - 7277. [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]

				M. A. Roubidoux, G. L. LeCarpentier, J. B. Fowlkes, B. Bartz, D. Pai, S. P. Gordon, A. F. Schott, T. D. Johnson, and P. L. Carson Sonographic Evaluation of Early-Stage Breast Cancers That Undergo Neoadjuvant Chemotherapy J. Ultrasound Med., July 1, 2005; 24(7): 885 - 895. [Abstract] [Full Text] [PDF]

				H. B. Nichols, A. Trentham-Dietz, R. R. Love, J. M. Hampton, P. T. Hoang Anh, D. C. Allred, S. K. Mohsin, and P. A. Newcomb Differences in Breast Cancer Risk Factors by Tumor Marker Subtypes among Premenopausal Vietnamese and Chinese Women Cancer Epidemiol. Biomarkers Prev., January 1, 2005; 14(1): 41 - 47. [Abstract] [Full Text] [PDF]

				O. Modlich, H.-B. Prisack, M. Munnes, W. Audretsch, and H. Bojar Immediate Gene Expression Changes After the First Course of Neoadjuvant Chemotherapy in Patients with Primary Breast Cancer Disease Clin. Cancer Res., October 1, 2004; 10(19): 6418 - 6431. [Abstract] [Full Text] [PDF]

				R. Korah, M. Boots, and R. Wieder Integrin {alpha}5{beta}1 Promotes Survival of Growth-Arrested Breast Cancer Cells: An in Vitro Paradigm for Breast Cancer Dormancy in Bone Marrow Cancer Res., July 1, 2004; 64(13): 4514 - 4522. [Abstract] [Full Text] [PDF]

				L. G. Estevez and W. J. Gradishar Evidence-Based Use of Neoadjuvant Taxane in Operable and Inoperable Breast Cancer Clin. Cancer Res., May 15, 2004; 10(10): 3249 - 3261. [Abstract] [Full Text] [PDF]

				R. R. Love, N. B. Duc, T. C. Havighurst, S. K. Mohsin, Q. Zhang, D. L. DeMets, and D. C. Allred HER-2/neu Overexpression and Response to Oophorectomy Plus Tamoxifen Adjuvant Therapy in Estrogen Receptor-Positive Premenopausal Women With Operable Breast Cancer J. Clin. Oncol., February 1, 2003; 21(3): 453 - 457. [Abstract] [Full Text] [PDF]

				L. G. Estevez, J. M. Cuevas, A. Anton, J. Florian, J. M. Lopez-Vega, A. Velasco, F. Lobo, A. Herrero, and J. Fortes Weekly Docetaxel as Neoadjuvant Chemotherapy for Stage II and III Breast Cancer: Efficacy and Correlation with Biological Markers in a Phase II, Multicenter Study Clin. Cancer Res., February 1, 2003; 9(2): 686 - 692. [Abstract] [Full Text] [PDF]

				V. Stearns, B. Singh, T. Tsangaris, J. G. Crawford, A. Novielli, M. J. Ellis, C. Isaacs, M. Pennanen, C. Tibery, A. Farhad, et al. A Prospective Randomized Pilot Study to Evaluate Predictors of Response in Serial Core Biopsies to Single Agent Neoadjuvant Doxorubicin or Paclitaxel for Patients with Locally Advanced Breast Cancer Clin. Cancer Res., January 1, 2003; 9(1): 124 - 133. [Abstract] [Full Text] [PDF]

				P O Chappuis, J Goffin, N Wong, C Perret, P Ghadirian, P N Tonin, and W D Foulkes A significant response to neoadjuvant chemotherapy in BRCA1/2 related breast cancer J. Med. Genet., August 1, 2002; 39(8): 608 - 610. [Full Text] [PDF]

				F. Bertucci, V. Nasser, S. Granjeaud, F. Eisinger, J. Adelaide, R. Tagett, B. Loriod, A. Giaconia, A. Benziane, E. Devilard, et al. Gene expression profiles of poor-prognosis primary breast cancer correlate with survival Hum. Mol. Genet., April 15, 2002; 11(8): 863 - 872. [Abstract] [Full Text] [PDF]

				R. Rouzier, J.-M. Extra, J. Klijanienko, M.-C. Falcou, B. Asselain, A. Vincent-Salomon, P. Vielh, and E. Bourstyn Incidence and Prognostic Significance of Complete Axillary Downstaging After Primary Chemotherapy in Breast Cancer Patients With T1 to T3 Tumors and Cytologically Proven Axillary Metastatic Lymph Nodes J. Clin. Oncol., March 1, 2002; 20(5): 1304 - 1310. [Abstract] [Full Text] [PDF]

				L. Assersohn, L. Gangi, Y. Zhao, M. Dowsett, R. Simon, T. J. Powles, and E. T. Liu The Feasibility of Using Fine Needle Aspiration from Primary Breast Cancers for cDNA Microarray Analyses Clin. Cancer Res., March 1, 2002; 8(3): 794 - 801. [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]

				K. Mokbel, A. C. A. Leris, J. Chang, T. J. Powles, D. C. Allred, S. E. Ashley, G. M. Clark, and M. Dowsett Predictors of Response to Chemotherapy J. Clin. Oncol., April 7, 2000; 18(7): 1601 - 1602. [Full Text] [PDF]