Seeding of epithelial cells into circulation during surgery for breast cancer: the fate of malignant and benign mobilized cells

BACKGROUND: Surgery of malignant tumors has long been suspected to be the reason for enhancement of growth of metastases with fatal outcome. This often prevented surgeons from touching the tumor if not absolutely necessary. We have shown in lung cancer patients that surgery, itself, leads to mobilization of tumor cells into peripheral blood. Some of the mobilized cells finding an appropriate niche might grow to form early metastases. Monitoring of tumor cell release during and the fate of such cells after surgery for breast cancer may help to reveal how metastases develop after surgery. METHOD: We used the MAINTRAC(® )analysis, a new tool for online observation of circulating epithelial cells, to monitor the number of epithelial cells before, 30 min, 60 min, three and seven days after surgery and during subsequent variable follow up in breast cancer patients. RESULTS: Circulating epithelial cells were already present before surgery in all patients. During the first 30–60 min after surgery values did not change immediately. They started increasing during the following 3 to 4 days up to thousand fold in 85% of treated patients in spite of complete resection of the tumor with tumor free margins in all patients. There was a subsequent re-decrease, with cell numbers remaining above pre-surgery values in 58% of cases until onset of chemotherapy. In a few cases, where no further therapy or only hormone treatment was given due to low risk stage, cell numbers were monitored for up to three years. They remained elevated with no or a slow decrease over time. This was in contrast to the observation in a patient where surgery was performed for benign condition. She was monitored before surgery with no cells detectable. Epithelial cells increased up to more than 50 000 after surgery but followed by a complete reduction to below the threshold of detection. CONCLUSION: Frequently before but regularly during surgery of breast cancer, epithelial cells are mobilized into circulation. Part of these cells, most probably normal or apoptotic cells, are cleared from the circulation as also shown to occur in benign conditions. After resection even if complete and of small tumors, cells can remain in the circulation over long times. Such cells may remain "dormant" but might settle and grow into metastases, if they find appropriate conditions, even after years

CAMK2N1/RUNX3 methylation is an independent prognostic biomarker for progression-free and overall survival of platinum-sensitive epithelial ovarian cancer patients

Background!#!To date, no predictive or prognostic molecular biomarkers except BRCA mutations are clinically established for epithelial ovarian cancer (EOC) despite being the deadliest gynecological malignancy. Aim of this biomarker study was the analysis of DNA methylation biomarkers for their prognostic value independent from clinical variables in a heterogeneous cohort of 203 EOC patients from two university medical centers.!##!Results!#!The marker combination CAMK2N1/RUNX3 exhibited a significant prognostic value for progression-free (PFS) and overall survival (OS) of sporadic platinum-sensitive EOC (n = 188) both in univariate Kaplan-Meier (LogRank p < 0.05) and multivariate Cox regression analysis (p < 0.05; hazard ratio HR = 1.587). KRT86 methylation showed a prognostic value only in univariate analysis because of an association with FIGO staging (Fisher's exact test p < 0.01). Thus, it may represent a marker for EOC staging. Dichotomous prognostic values were observed for KATNAL2 methylation depending on BRCA aberrations. KATNAL2 methylation exhibited a negative prognostic value for PFS in sporadic EOC patients without BRCA1 methylation (HR 1.591, p = 0.012) but positive prognostic value in sporadic EOC with BRCA1 methylation (HR 0.332, p = 0.04) or BRCA-mutated EOC (HR 0.620, n.s.).!##!Conclusion!#!The retrospective analysis of 188 sporadic platinum-sensitive EOC proved an independent prognostic value of the methylation marker combination CAMK2N1/RUNX3 for PFS and OS. If validated prospectively this combination may identify EOC patients with worse prognosis after standard therapy potentially benefiting from intensive follow-up, maintenance therapies or inclusion in therapeutic studies. The dichotomous prognostic value of KATNAL2 should be validated in larger sample sets of EOC

Interactions in cancer treatment considering cancer therapy, concomitant medications, food, herbal medicine and other supplements

Purpose!#!The aim of our study was to analyse the frequency and severity of different types of potential interactions in oncological outpatients' therapy. Therefore, medications, food and substances in terms of complementary and alternative medicine (CAM) like dietary supplements, herbs and other processed ingredients were considered.!##!Methods!#!We obtained data from questionnaires and from analysing the patient records of 115 cancer outpatients treated at a German university hospital. Drug-drug interactions were identified using a drug interaction checking software. Potential CAM-drug interactions and food-drug interactions were identified based on literature research.!##!Results!#!92.2% of all patients were at risk of one or more interaction of any kind and 61.7% of at least one major drug-drug interaction. On average, physicians prescribed 10.4 drugs to each patient and 6.9 interactions were found, 2.5 of which were classified as major. The most prevalent types of drug-drug interactions were a combination of QT prolonging drugs (32.3%) and drugs with a potential for myelotoxicity (13.4%) or hepatotoxicity (10.1%). In 37.2% of all patients using CAM supplements the likelihood of interactions with medications was rated as likely. Food-drug interactions were likely in 28.7% of all patients.!##!Conclusion!#!The high amount of interactions could not be found in literature so far. We recommend running interaction checks when prescribing any new drug and capturing CAM supplements in medication lists too. If not advised explicitly in another way drugs should be taken separately from meals and by using nonmineralized water to minimize the risk for food-drug interactions

Complementary and alternative medicine (CAM) supplements in cancer outpatients: analyses of usage and of interaction risks with cancer treatment

Purpose!#!The aim of our study was to analyze the use of complementary and alternative medicine (CAM) supplements, identify possible predictors, and analyze and compile potential interactions of CAM supplements with conventional cancer therapy.!##!Methods!#!We included outpatient cancer patients treated at a German university hospital in March or April 2020. Information was obtained from questionnaires and patient records. CAM-drug interactions were identified based on literature research for each active ingredient of the supplements consumed by the patients.!##!Results!#!37.4% of a total of 115 patients consumed CAM supplements. Potential interactions with conventional cancer treatment were identified in 51.2% of these patients. All types of CAM supplements were revealed to be a potential source for interactions: vitamins, minerals, food and plant extracts, and other processed CAM substances. Younger age (< 62 years) (p = 0.020, φc = 0.229) and duration of individual cancer history of more than 1 year (p = 0.006, φc = 0.264) were associated with increased likelihood of CAM supplement use. A wide range of different CAM supplement interactions were reviewed: effects of antioxidants, cytochrome (CYP) interactions, and specific agonistic or antagonistic effects with cancer treatment.!##!Conclusion!#!The interaction risks of conventional cancer therapy with over-the-counter CAM supplements seem to be underestimated. Supplements without medical indication, as well as overdoses, should be avoided, especially in cancer patients. To increase patient safety, physicians should address the risks of interactions in physician-patient communication, document the use of CAM supplements in patient records, and check for interactions