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Black Cohosh Increases Metastatic Mammary Cancer in Transgenic Mice Expressing c-erbB2

¹ Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania; ² Tengion Laboratories, Winston-Salem, North Carolina; ³ Cedars-Sinai Medical Center and ⁴ Simms/Mann-UCLA Center for Integrative Oncology, Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, California; ⁵ Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada; and ⁶ Medical and Scientific Services, Quintiles, Research Triangle Park, North Carolina

Requests for reprints: Vicki L. Davis, Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA 15282. Phone: 412-396-1168; Fax: 412-396-4660; E-mail: davisv{at}duq.edu.

Key Words: Breast cancer • metastasis • HER2/neu • tumor development and progression • transgenic mice

Black cohosh is an herbal extract that is often used as an alternative to estrogen-based replacement therapies to treat hot flushes that frequently accompany the transition to menopause. Although cancer-free women as well as breast cancer patients and survivors use black cohosh to relieve vasomotor symptoms, there is limited information on its potential to influence breast cancer development or progression. Therefore, in this study, the effects of black cohosh on mammary tumorigenesis were investigated in the MMTV-neu mouse model due to its similarities to HER2⁺ breast cancer, including stochastic development of mammary tumors, which frequently progress to metastatic disease. Using an adjusted dose for the mice to correlate to the recommended dose in women (40 mg/d), no differences were detected in the incidence or onset of mammary tumors in black cohosh–treated versus control females. The lack of effect on mammary tumor development suggests that black cohosh would not influence breast cancer risk if given to women before tumor formation. In contrast, black cohosh significantly increased the incidence of lung metastases in tumor-bearing animals compared with mice fed the isoflavone-free control diet. Additional studies will be needed to correlate these findings to women taking different black cohosh products at various times during breast cancer development; however, these results suggest caution for women using black cohosh, especially for extended periods of time. As metastatic progression is linked to patient survival, these data stress the importance of investigating how women's therapies influence all stages of mammary tumorigenesis, particularly for assessing their safety. [Cancer Res 2008;68(20):8377–83]