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In Reply

Cross Cancer Institute and University of Alberta, Edmonton, Alberta, Canada

We thank Buyukhatipoglu et al for their interest in our study of the relationship between human epidermal growth factor receptor 2 (HER-2) positivity in newly diagnosed nonmetastatic breast cancer and the risk of eventually developing CNS metastases.¹ As expected in a population-based study, treatment was not uniform across the population, and several standard adjuvant chemotherapy regimens were used in these patients. However, patients with HER-2–positive breast cancer presented with a higher frequency of other adverse prognostic factors, and consequently received more aggressive systemic and locoregional therapy. Nonetheless, we showed that women with newly diagnosed HER-2–positive breast cancer had a higher incidence of brain metastases compared to the cohort with HER-2–negative disease (9% v 1.9%).¹ We agree that the incidence of brain metastasis in the entire population is relatively low and would not warrant screening or prophylactic treatment strategies. However, in the HER-2–positive cohort who ultimately developed metastatic breast cancer, the incidence of brain metastasis was 40%, a figure consistent with other published series.^2-5 Because most brain metastases occur after the development of systemic disease, we suggested that clinical trials are warranted to look at screening or prophylactic treatment strategies in the HER-2–positive metastasic breast cancer (MBC) population. While the role of prophylactic cranial irradiation has not been examined in patients with MBC, prophylactic cranial irradiation has been shown to reduce the incidence of brain metastases and to improve quality of life⁶ and survival⁷ in limited-stage small-cell lung cancer. Such a study in HER-2–positive MBC would be designed to evaluate whether reduction in the risk of brain metastases could be achieved with acceptable quality of life and preservation of neurocognitive function.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The authors indicated no potential conflicts of interest.

REFERENCES

1. Gabos Z, Sinha R, Hanson J, et al: Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer. J Clin Oncol 24:5658-5663, 2006[Abstract/Free Full Text]

2. Clayton AJ, Danson S, Jolly S, et al: Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer. Br J Cancer 91:639-643, 2004[Medline]

3. Bendell JC, Domchek SM, Burstein HJ, et al: Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 97:2972-2977, 2003[CrossRef][Medline]

4. Eitzen R, Zach L, Kaufman B, et al: High incidence of brain metastasis in patients on trastuzumab for advanced breast cancer. Proc Am Soc Clin Oncol 21:31b, 2002 (abstr 1936)

5. Wardely AM, Danson S, Clayton AJ, et al: High incidence of brain metastasis in patients treated with Trastuzumab for metastatic breast cancer at a large cancer center. Proc Am Soc Clin Oncol 21:61a, 2002 (abstr 241)

6. Lee JJ, Bekele BN, Zhou X: Decision analysis for prophylactic cranial irradiation for patients with small-cell lung cancer. J Clin Oncol 2006;24: 3597-3603[Abstract/Free Full Text]

7. Auperin A, Arriagada R, Pignon JP, et al: Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission: Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 341:476-484, 1999[Abstract/Free Full Text]

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Related Correspondence

• Is Prophylactic Cranial Irradiation a Possible Option for Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer?
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