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The MKSAP Challenge

From the July-August ACP Observer, copyright 2005 by the American College of Physicians.

Answer: D

Educational objective: Treat metastatic breast cancer.

A recently reported prospective randomized clinical trial in patients with metastatic breast cancer has demonstrated that the combination of trastuzumab and paclitaxel are at least additive, if not synergistic, in women with HER2-positive disease. Patients treated with this combination had significantly longer survival than those treated initially with chemotherapy alone.

Few if any patients are cured of metastatic breast cancer. For many patients, however, systemic therapy probably does result in modest survival prolongation of several months to a few years compared with best supportive care, and the palliative benefits are well recognized. Therefore, this patient should receive treatment. The key to effective palliation is balancing the potential benefits with the expected side effects of specific therapies.

In this regard, endocrine therapy is almost always less toxic than chemotherapy. The steroid hormone receptors in her tumor, however, have been consistently negative. Therefore, she is very unlikely (less than 10%) to respond to endocrine therapy of any sort. Given that she has symptomatic visceral disease, she should be treated with therapy that has a higher chance of working, even though she will suffer more side effects from it.

Preclinical studies and some preliminary clinical data suggest that aromatase inhibitors are not likely to be effective and may be dangerous in premenopausal women.

References:

1. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20:719-26. PMID: 11821453.

2. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783-92. PMID: 11248153.

The above feature contains questions and answers from MKSAP 13, the latest version of the College's popular self-assessment program. More information on MKSAP 13 is online. To order MKSAP 13, contact ACP Customer Service at 800-523-1546, ext. 2600, or call 215-351-2600.

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