Introduction Patients with visceral metastatic breast cancer (MBC) generally have a poor prognosis. 1 Treatment options for patients who have progressed after tamoxifen therapy include cytotoxic chemotherapy or a trial of a new hormonal therapy. 2 However, with the develop- ment of visceral metastases, chemotherapy is the more traditional option because visceral disease is generally considered to be rapidly progressive and possibly resistant to endocrine therapy. The aromatase inhibitors (AIs) anastrozole and exemestane are approved in much of the world for first-line (anastrozole) treatment of postmenopausal women with advanced estrogen receptor–positive and/or progesterone receptor–positive breast cancer and for second-line (exemestane and anastrozole) treatment, in particular, after progression on tamoxifen (exemestane). 3,4 Both anastrozole and exemestane have demonstrated efficacy in the treatment of advanced, tamoxifen-refrac- tory breast cancer with visceral metastases in preliminary analyses. 5-9 Patients with visceral metastases treated with the reversible AI anastrozole have reported objective response rates (ORRs) of 7% 10 to 14%, 7 whereas similar patients receiving the irreversible AI Abstract Purpose: Patients developing visceral breast cancer metastases generally receive chemotherapy rather than endocrine therapy. Recent aromatase inhibitor studies have reported activity in such patients; therefore, this study formally evaluated anastrozole and exemestane in postmenopausal patients in this setting. Patients and Methods: Postmenopausal women with advanced breast cancer and q 1 visceral (liver or lung) lesion were randomized to anastrozole (1 mg/day orally) or exemestane (25 mg/day orally) for q 8 weeks. The primary endpoint was objective response in visceral lesions based on modified Response Evaluation Criteria in Solid Tumors. Secondary endpoints included clinical benefit (objective response plus stable dis- ease q 180 days), overall survival, and adverse events. Results: A total of 130 patients were enrolled, and 128 patients (64 anastrozole, 64 exemestane) were included in the intent-to-treat analysis. Accrual delays caused study closure before the target enrollment (N = 200) was reached, limiting the statistical power of the study. Objective response in visceral sites was approximately 15% in both groups. Clinical benefit in vis- ceral sites was 32% of the patients treated with anastrozole and 38% of the patients treated with exemestane. Median survival was 33.3 months and 30.5 months in the anastrozole and exemestane groups, respectively. Toxicities were similar to those previously reported; however, treatment-related adverse events were more frequent with anastrozole (41%) than with exemestane (31%). Both treatments were generally well tolerated in patients with postmenopausal breast cancer with visceral metastases. Conclusion: Efficacy was similar in both treatment groups for all endpoints. Aromatase inhibitors can be considered as a treatment option in postmenopausal patients with hormone receptor–positive visceral breast cancer metastases. Clinical Breast Cancer, Vol. 9, No. 1, 39-44, 2009; DOI: 10.3816/CBC.2009.n.007 Keywords: Aromatase inhibitor, Hormone receptor–positive disease; National Cancer Institute Common Toxicity Criteria original contribution A Comparative Study of Exemestane Versus Anastrozole in Patients with Postmenopausal Breast Cancer with Visceral Metastases Susana M. Campos, 1 Jean Paul Guastalla, 2 Milayna Subar, 3 Paula Abreu, 3 Eric P. Winer, 1* David A. Cameron 4* 1 Dana-Farber Cancer Institute, Boston, MA 2 Centre Léon Bérard, Lyon, France 3 Pfizer Inc, New York, NY 4 Western General Hospital, Edinburgh, UK Submitted: Jul 21, 2008; Revised: Oct 14, 2008; Accepted: Nov 3, 2008 Address for correspondence: Susana M. Campos, MD, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115 Fax: 617-632-1930; e-mail: susana_campos@dfci.harvard.edu *Senior authors were co-principal investigators on the study and contributed equally to this manuscript. This article might include the discussion of investigational and/or unlabeled uses of drugs and/or devices that might not be approved by the FDA. Electronic forwarding or copying is a violation of US and international copyright laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1526-8209, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA. www.copyright.com 978-750-8400. Clinical Breast Cancer February 2009 | 39