title: Circulating tumor-specific DNA: a marker for monitoring efficacy of adjuvant therapy in cancer patients.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Heidi
authors.initials: H
authors.lastname: Fiegl
authors.forename: Simone
authors.initials: S
authors.lastname: Millinger
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mueller-Holzner
authors.forename: Christian
authors.initials: C
authors.lastname: Marth
authors.forename: Christian
authors.initials: C
authors.lastname: Ensinger
authors.forename: Andreas
authors.initials: A
authors.lastname: Berger
authors.forename: Helmut
authors.initials: H
authors.lastname: Klocker
authors.forename: Georg
authors.initials: G
authors.lastname: Goebel
authors.forename: Martin
authors.initials: M
authors.lastname: Widschwendter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D042282:Microdissection; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D013629:Tamoxifen / Q000627:therapeutic use*; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D013629:Tamoxifen