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 Singletary, E. Articles by Lippman, S. M. Search for Related Content PubMed PubMed Citation Articles by Singletary, E. Articles by Lippman, S. M.

Novel Translational Model for Breast Cancer Chemoprevention Study: Accrual to a Presurgical Intervention with Tamoxifen and N-[4-Hydroxyphenyl] Retinamide¹

The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [E. S., N. A., N. S., A. S., S. T., M. C., T. B., C. S., B. F., H. F., W. H., S. M. L.], and National Cancer Institute, Chemoprevention Branch, Bethesda, Maryland 20852 [R. L., G. K.]

Surrogate end point biomarkers for risk assessment and efficacy of potential chemopreventive agents are needed to improve the efficiency and reduce the cost of chemoprevention trials. It is imperative to develop the best clinical breast model for translational surrogate end point biomarker studies, especially with respect to accrual feasibility. We have initiated a prospective study to develop biomarkers for tamoxifen and N-[4-hydroxyphenyl] retinamide by administering either a placebo or both drugs for 2–4 weeks to women with ductal carcinoma in situ or early invasive cancers in the interval between the initial diagnostic core biopsy and definitive surgery. The principle end point is pretreatment versus posttreatment tumor levels of Ki-67; a number of other exploratory markers will also be examined. The planned target sample size is 100 patients. Between February 1997 and February 2000, 4514 women who had either an abnormal mammogram or a diagnosed breast cancer were screened for the study. Of these 4514 screened patients, 52 (1%) were registered on the study. Major factors of nonparticipation in the remaining 4462 women were as follows: (a) no evidence of malignancy (2081 patients; 46%); (b) ineligible per protocol criteria (575 patients; 13%); (c) preoperative chemotherapy/tamoxifen (520 patients; 11%); (d) surgery scheduling conflict (360 patients; 8%); (e) outside needle biopsy (221 patients; 5%); (f) no residual disease after excisional biopsy (345 patients; 8%); and (g) second opinion only (123 patients; 3%). Other nonparticipation factors included fine needle aspiration only, refusal, tumor size > 2 cm, and estrogen replacement therapy (35 patients each; 2% each). The protocol was amended in midstudy to allow outside needle biopsy, tumor > 2 cm, and estrogen replacement therapy. Accrual to biomarker (nontherapeutic) protocols with delay in definitive cancer surgery is challenging but feasible. Although some accrual problems remain, we have nonetheless succeeded in recruiting 50% of our target sample size in a 3-year period.

This article has been cited by other articles:

				A. C. Wolff, D. Berry, L. A. Carey, M. Colleoni, M. Dowsett, M. Ellis, J. E. Garber, D. Mankoff, S. Paik, L. Pusztai, et al. Research Issues Affecting Preoperative Systemic Therapy for Operable Breast Cancer J. Clin. Oncol., February 10, 2008; 26(5): 806 - 813. [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]

				V. Stearns, A. Gallagher, C. G. Kleer, B. Singh, M. Freedman, B. R. Haddad, C. Isaacs, R. Warren, M. Brown, J. Cullen, et al. A Pilot Study to Establish a Clinical Model to Perform Phase II Studies of Breast Cancer Chemopreventive Agents in Women at High Risk with Biomarkers as Surrogate Endpoints for Activity Clin. Cancer Res., December 15, 2004; 10(24): 8332 - 8340. [Abstract] [Full Text] [PDF]

				V. Stearns, A. Coop, B. Singh, A. Gallagher, H. Yamauchi, R. Lieberman, M. Pennanen, B. Trock, D. F. Hayes, and M. J. Ellis A Pilot Surrogate End Point Biomarker Trial of Perillyl Alcohol in Breast Neoplasia Clin. Cancer Res., November 15, 2004; 10(22): 7583 - 7591. [Abstract] [Full Text] [PDF]

				A. L. Sabichi, M. R. Modiano, J. J. Lee, Y.-M. Peng, M.-J. Xu, H. Villar, W. S. Dalton, and S. M. Lippman Breast Tissue Accumulation of Retinamides in a Randomized Short-term Study of Fenretinide Clin. Cancer Res., July 1, 2003; 9(7): 2400 - 2405. [Abstract] [Full Text] [PDF]

				M. Dowsett Preoperative Models to Evaluate Endocrine Strategies for Breast Cancer Clin. Cancer Res., January 1, 2003; 9(1): 502S - 510S. [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]

				R. T. Chlebowski, N. Col, E. P. Winer, D. E. Collyar, S. R. Cummings, V. G. Vogel III, H. J. Burstein, A. Eisen, I. Lipkus, and D. G. Pfister American Society of Clinical Oncology Technology Assessment of Pharmacologic Interventions for Breast Cancer Risk Reduction Including Tamoxifen, Raloxifene, and Aromatase Inhibition J. Clin. Oncol., August 1, 2002; 20(15): 3328 - 3343. [Abstract] [Full Text] [PDF]

				P. Greenwald Science, medicine, and the future: Cancer chemoprevention BMJ, March 23, 2002; 324(7339): 714 - 718. [Full Text] [PDF]

				B. A. Stoll Oestrogen/insulin-like growth factor-I receptor interaction in early breast cancer: clinical implications Ann. Onc., February 20, 2002; 13(2): 191 - 196. [Abstract] [Full Text] [PDF]

				A. Hoque, D. G. Menter, A. A. Sahin, N. Sneige, and S. M. Lippman No Increased Ki67 Expression in Ductal Carcinoma in Situ Associated with Invasive Breast Cancer Cancer Epidemiol. Biomarkers Prev., February 1, 2001; 10(2): 153 - 154. [Full Text]