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Departments of 1 Obstetrics and Gynecology, 2 Pathology, 3 Urology, and 4 Biostatistics and Documentation, Innsbruck Medical University, Innsbruck, Austria
Requests for reprints: Martin Widschwendter, Department of Obstetrics and Gynecology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. Phone: 43-512-504-81055; Fax: 43-512-504-23112; E-mail: Martin.Widschwendter{at}uibk.ac.at.
Adjuvant systemic therapy (a strategy that targets potential disseminated tumor cells after complete removal of the tumor) has clearly improved survival of patients with cancer. To date, no tool is available to monitor efficacy of these therapies, unless distant metastases arise, a situation that unavoidably leads to death. We analyzed RASSF1A DNA methylation in pretherapeutic sera and serum samples collected 1 year after surgery from 148 patients with breast cancer who were receiving adjuvant tamoxifen; 19.6% and 22.3% of patients with breast cancer showed RASSF1A DNA methylation in their pretherapeutic and 1-year-after serum samples, respectively. RASSF1A methylation 1 year after primary surgery (and during adjuvant tamoxifen therapy) was an independent predictor of poor outcome, with a relative risk (95% confidence interval) for relapse of 5.1 (1.3-19.8) and for death of 6.9 (1.9-25.9). Measurement of serum DNA methylation allows adjuvant systemic treatment to be monitored for efficacy: disappearance of RASSF1A DNA methylation in serum throughout treatment with tamoxifen indicates a response, whereas persistence or new appearance means resistance to adjuvant tamoxifen treatment. It remains to be seen whether modifications made in adjuvant therapeutic strategies based on detection of circulating nucleic acids will improve survival as well as quality of life.
Key Words: Breast cancer • Tumor markers and detection of metastasis • DNA methylation/epigenetics • Clinical drug resistance • Molecular markers of metastasis and progression
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