Prognostic Relevance of Circulating Tumor Cells in Molecular Subtypes of Breast Cancer.

Circulating tumor cells (CTCs) can be detected in the peripheral blood of breast cancer patients with early and metastatic disease. Recent data suggest that immune pathologic characteristics between the primary tumor, metastatic colonies and CTCs are discordant and that CTCs possess an independent phenotype that is associated with prognosis and treatment efficacy. Large scale gene expression analysis has provided the possibility to stratify breast cancer according to the gene expression fingerprint of primary tumor tissue into five intrinsic molecular subtypes which can be associated with different clinical outcome. As a consequence of the different prognostic power of primary tumors' characteristics and CTCs several groups have started to investigate if CTCs might be disseminated differentially within these breast cancer subtypes. They determined the CTC number in immunohistochemical subtypes to validate if CTCs may provide differential and more specific prognostic information within each subtype. This review provides an overview of the outcome of some recently published data gathered from early and metastatic breast cancer.

Potential interactions of complementary and alternative medicine with cancer therapy in outpatients with gynecological cancer in a comprehensive cancer center.

PURPOSE: About 40-50 % of cancer patients use complementary and alternative medicine (CAM). Women, and especially those with gynecological cancers, are more active in this field than men. The goal of our study was to estimate the likelihood of CAM use and the likelihood of interactions of CAM with cancer therapy in the setting of a gynecological outpatient clinic at a German Comprehensive Cancer Center (CCC). METHODS: One hundred consecutive gynecological outdoor patients of the CCC in Frankfurt am Main in Germany were interviewed with a standardized questionnaire on CAM use. An investigation on potential interactions was done by matching a scientific database systematically. RESULTS: Sixty-nine of the interviewed 100 women received chemotherapy, 23 endocrine therapy and 41 monoclonal antibodies. In total, 64 % used CAM, 48 % used at least one substance-bound CAM. In 17 out of those 48 cases (35 %), interactions were unlikely, whereas they were probable in 14 patients (29 %). Thus, a third of all patients in this study were in danger of interactions. More than half of all CAM users and three quarters of users of substance-bound CAM are at risk of interactions. This number is independent of whether the patient is taking chemotherapy, endocrine therapy or antibodies. CONCLUSIONS: The frequency of CAM use we found is in line with international data from CCCs in the USA. To our knowledge, this is the first study publishing data on the frequency of potential interactions. Thus, an initiative to protect women from the dangers of uncontrolled CAM use is urgently needed. In the discussion, we propose a concept of how to achieve this aim.

First-line therapy with moderate dose capecitabine in metastatic breast cancer is safe and active: results of the MONICA trial.

BACKGROUND: To determine activity and safety of capecitabine at a moderate dose of 2000 mg/m(2) as first-line therapy for metastatic breast cancer. METHODS: In this prospective phase II trial, patients with HER2-negative metastatic breast cancer received first-line capecitabine 2000 mg/m(2) on days 1-14 every 3 weeks. The primary aim was to exclude a time to progression (TTP) <6 months. Secondary end-points were overall response rate, overall survival (OS), toxicity and quality of life. RESULTS: Median age of the 161 included patients was 65 years. Median TTP and OS were 7.3 months [95% (confidence interval) CI: 6.2-8.4] and 17.1 months (95% CI: 14.0-20.3), respectively. An overall response rate of 26.1%, including 13 complete remissions was observed. Patients developing grade I-III hand-foot syndrome had a significantly longer TTP and OS and patients >65 years also achieved a significantly longer TTP. Haematological grade I-IV toxicities were leucopenia (64.0%), anaemia (50.9%) and thrombocytopenia (28.0%). Relevant non-haematological toxicities were hand-food-syndrome (37.3%), fatigue (34.2%), nausea (29.8%) and diarrhoea (20.5%). Quality of life assessment revealed an improved emotional function, but worsening of nausea and vomiting from cycle 1-10. CONCLUSIONS: Capecitabine at a dose of 2000 mg/m(2) is active and safe as first-line treatment of patients with metastatic breast cancer.

Clinical relevance of the putative stem cell marker p63 in breast cancer.

P63 is a member of the p53 family. This protein is crucial for the maintenance of a stem cell population in the human epithelium and necessary for the normal development of all epithelial tissues including mammary glands. In normal breast tissue, the p63 seems to be a specific myoepithelial cell marker. P63 expression has been described in highly aggressive ER negative basal-like breast tumors. The value of p63 expression in ER positive disease is less clear. The expression levels of p63 mRNA by Affymetrix microarray analysis in a combined cohort of 2,158 ER positive breast cancers and its prognostic and predictive impact were analyzed. Tumor samples containing large amounts of benign breast tissue, which will interfere with p63 measurement, were excluded prior to the analysis. Survival analysis revealed a better prognosis of ER positive breast cancer expressing p63 (n = 410; P < 0.036). No correlation of p63 with standard parameters was observed. In a subgroup analysis, endocrine-treated patients with high p63 expression showed a better prognosis than low p63 expression (P = 0.06; n = 186). In untreated patients, this effect was less clear (n = 148; P = 0.5). P63 is a positive prognostic factor in endocrine-treated ER positive breast cancer and might influence responsiveness to endocrine treatment. Thus, p63 could be helpful as a predictive factor for endocrine therapy.

Differentially expressed genes of reprogrammed human pluripotent stem cells in breast cancer.

Reprogramming of human somatic cells into pluripotent cell types gives insight in the pathophysiology of diseases. We analysed genes recently shown to be differentially expressed in induced pluripotent stem cells (iPS) in 95 breast cancer samples. This analysis reveals two breast cancer subgroups with stem cell-like features, differing in ER-status and proliferation as well as in their clinical course of disease.