Circulating breast-derived DNA allows universal detection and monitoring of localized breast cancer.

BACKGROUND: Tumor-derived circulating cell-free DNA (cfDNA) is present in the plasma of individuals with cancer. Assays aimed at detecting common cancer mutations in cfDNA are being developed for the detection of several cancer types. In breast cancer, however, such assays have failed to detect the disease at a sensitivity relevant for clinical use, in part due to the absence of multiple common mutations that can be co-detected in plasma. Unlike individual mutations that exist only in a subset of tumors, unique DNA methylation patterns are universally present in cells of a common type and therefore may be ideal biomarkers. Here we describe the detection and quantification of breast-derived cfDNA using a breast-specific DNA methylation signature. PATIENTS AND METHODS: We collected plasma from patients with localized breast cancer before and throughout treatment with neoadjuvant chemotherapy and surgery (N = 235 samples). RESULTS: Pretreatment breast cfDNA was detected in patients with localized disease with a sensitivity of 80% at 97% specificity. High breast cfDNA levels were associated with aggressive molecular tumor profiles and metabolic activity of the disease. During neoadjuvant chemotherapy, breast cfDNA levels decreased dramatically. Importantly, the presence of breast cfDNA towards the end of the chemotherapy regimen reflected the existence of residual disease. CONCLUSION: We propose that breast-specific cfDNA is a universal and powerful marker for the detection and monitoring of breast cancer.

Relaxation and assertive training as automated adjunct behaviour therapy administered in a self-control orientation with psychiatric patients.

The present study evaluated the efficacy of two automated behavioural treatment modalities used as a self-control strategy (deep muscle relaxation and assertive training) as compared to two control groups (attention/placebo and no behavioural treatment) in a psychiatric out-patient population. Results indicate that, as compared to the other groups, the relaxation group achieved a clinically substantial and statistically significant change. Furthermore, the efficacy of automated relaxation used as a self-control strategy is sufficient to warrant its introduction as an adjunct psychiatric therapy in out-patient psychiatric settings. More research is needed before automated assertive training as a self-control strategy can be introduced to the clinic as an adjunct therapy.