Correspondence

Case 24-2005: A Woman with Estrogen-Receptor–Positive Breast Cancer

N Engl J Med 2005; 353:2304-2305November 24, 2005

Article

To the Editor:

In her discussion of Case 24-2005 (Aug. 11 issue),1 Dr. Ryan recommended adjuvant therapy with anastrozole (Arimidex) for a postmenopausal woman with hormone-receptor–positive breast cancer. Although the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial showed a disease-free survival advantage of 2.4 percent favoring anastrozole, there was no benefit in overall survival, and the risk of fracture with anastrozole was 7.1 percent, as compared with 4.4 percent with tamoxifen (hazard ratio, 1.61; P<0.001).2

The patient's medical problems included osteopenia, which was being treated with calcium and vitamin D. Therapy with anastrozole for five years will probably place her at increased risk for fracture, and perhaps an alternative approach of administering tamoxifen alone or tamoxifen for two to three years followed by an aromatase inhibitor might have been preferable.

Alex E. Denes, M.D.
Washington University, St. Louis, MO 63110
alex@denesmd.com

2 References

1. 1

   Case Records of the Massachusetts General Hospital (Case 24-2005). N Engl J Med 2005;353:617-622
   Full Text | Web of Science | Medline

2. 2

   Baum M, Buzdar A, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer 2003;98:1802-1810
   CrossRef | Web of Science | Medline

Author/Editor Response

The balance of benefits and risks is an important issue when advising patients on adjuvant treatment for early-stage breast cancer. The patient in this case did have a history of osteopenia, and despite the fact that the potential risk of further loss of bone density with aromatase-inhibitor therapy was discussed with her, she opted for anastrozole therapy with careful monitoring of bone density. As pointed out by Dr. Denes, the ATAC trial did demonstrate a higher fracture rate in the anastrozole-treatment group. Aromatase inhibitors were also associated with more fractures than tamoxifen or placebo in the Intergroup Exemestane Study (3.1 percent with exemestane, vs. 2.3 percent with tamoxifen; P=0.08)1 and in the National Cancer Institute of Canada Clinical Trial Group MA-17 study, although not statistically significantly (5.3 percent with letrozole, vs. 4.6 percent with placebo; P=0.25).2 It is important to mention, however, that aromatase-inhibitor–associated bone loss can be monitored and treated; details of management strategies are outlined in the American Society of Clinical Oncology bisphosphonate and bone health guideline.3

Paula D. Ryan, M.D., Ph.D.
Massachusetts General Hospital, Boston, MA 02114

3 References

1. 1

   Coombes RC, Hall E, Gibson LJ, et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 2004;350:1081-1092[Erratum, N Engl J Med 2004;351:2461.]
   Full Text | Web of Science | Medline

2. 2

   Goss PE, Ingle JN, Martino S, et al. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst 2005;97:1262-1271
   CrossRef | Web of Science | Medline

3. 3

   Hillner BE, Ingle JN, Chlebowski RT, et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 2003;21:4042-4057[Erratum, J Clin Oncol 2004;22:1351.]
   CrossRef | Web of Science | Medline