Recent translational research: circulating tumor cells in breast cancer patients

In breast cancer patients, hematogenous tumor cell dissemination can be detected, even at the single cell level, by applying immunocytochemical and molecular assays. Various methods for the detection of circulating tumor cells in the peripheral blood have been described. Results from recently reported studies suggest that circulating tumor cell levels may serve as a prognostic marker and for the early assessment of therapeutic response in patients with metastatic breast cancer. However, in early-stage breast cancer, the impact of circulating tumor cells is less well established than the presence of disseminated tumor cells in bone marrow; several clinical studies have demonstrated that cells of the latter type are an independent prognostic factor at primary diagnosis. In this article we briefly summarize recent studies examining the presence of circulating tumor cells in the blood and discuss further clinical applications

Final results of a phase I/II pilot study of capecitabine with or without vinorelbine after sequential dose-dense epirubicin and paclitaxel in high-risk early breast cancer

Background: The integration of the non-cross-resistant chemotherapeutic agents capecitabine and vinorelbine into an intensified dose-dense sequential anthracycline- and taxane-containing regimen in high-risk early breast cancer (EBC) could improve efficacy, but this combination was not examined in this context so far. Methods: Patients with stage II/IIIA EBC (four or more positive lymph nodes) received post-operative intensified dose-dense sequential epirubicin (150mg/m2 every 2 weeks) and paclitaxel (225mg/m2 every 2 weeks) with filgrastim and darbepoetin alfa, followed by capecitabine alone (dose levels 1 and 3) or with vinorelbine (dose levels 2 and 4). Capecitabine was given on days 1-14 every 21 days at 1000 or 1250 mg/m2 twice daily (dose levels 1/2 and 3/4, respectively). Vinorelbine 25 mg/m2 was given on days 1 and 8 of each 21-day course (dose levels 2 and 4). Results: Fifty-one patients were treated. There was one dose-limiting toxicity (DLT) at dose level 1. At dose level 2 (capecitabine and vinorelbine), five of 10 patients experienced DLTs. Therefore evaluation of vinorelbine was abandoned and dose level 3 (capecitabine monotherapy) was expanded. Hand-foot syndrome and diarrhoea were dose limiting with capecitabine 1250 mg/m2 twice daily. At 35.2 months' median follow-up, the estimated 3-year relapse-free and overall survival rates were 82% and 91%, respectively. Administration of capecitabine monotherapy after sequential dose-dense epirubicin and paclitaxel is feasible in node-positive EBC, while the combination of capecitabine and vinorelbine as used here caused more DLTs. Trial registration: Current Controlled Trials ISRCTN38983527

Patients' preferences for subcutaneous trastuzumab versus conventional intravenous infusion for the adjuvant treatment of HER2-positive early breast cancer: final analysis of 488 patients in the international, randomized, two-cohort PrefHer study

PrefHer revealed compelling and consistent patient preference for subcutaneous (s.c.) trastuzumab, regardless of delivery by single-use injection device or hand-held syringe. s.c. trastuzumab was well-tolerated and safety data, including immunogenicity, were consistent with previous reports. No new safety signals were identified compared with the known intravenous trastuzumab profile in early breast cance

Impact of preoperative atrial fibrillation on thromboembolic events and pump thrombosis in long-term left ventricular assist device therapy

ISSN:1010-7940ISSN:1873-734

Development of tricuspid regurgitation and right ventricular performance after implantation of centrifugal left ventricular assist devices

Background: Tricuspid regurgitation (TR) after left ventricular assist device (LVAD) implantation is associated with a poor prognosis. This study evaluates the development of TR and right ventricular (RV) performance after LVAD implantation. Methods: Retrospective analysis of patients who underwent LVAD implantation between March 2018 and June 2019. Patients who underwent concomitant tricuspid valve surgery and patients with congenital heart disease were excluded. Results: A total of 155 patients underwent LVAD implantation. Fourteen patients were excluded. Of the remaining patients, thirty-one died during the first six months, six were lost to follow-up and two underwent transplantation. 102 patients presented at 6.3 months (5.8 to 7.0). Patients were supported with HeartWare HVAD (74%) or HeartMate 3 (26%). 50.4% were rated as INTERMACS profile 1 or 2. At six months, systolic pulmonary artery pressure dropped from 36 to 21 mmHg (P<0.001). Tricuspid annular plane systolic excursion decreased from 17.3 to 14.3 mm (P<0.001), RV fractional area change did not change (P=0.839). Twenty-two patients (22%) presented with moderate-to-severe or severe (ms-s) TR pre-operatively. Of these, eighteen (81%) showed improvement to ≤ moderate TR. At follow-up twelve patients presented with ms-s TR. Of these, only four patients (33%) had been diagnosed with ms-s TR pre-operatively. There were no differences in pre-operative echocardiographic or clinical parameters between the twelve patients with ms-s late TR and the other ninety patients in the cohort. Conclusions: TR can show an impressive improvement with LVAD support. Longitudinal RV function decreases; this appears to be compensated by transverse shortening. Late TR can develop independently from pre-operative parameters including TR.ISSN:2304-1021ISSN:2225-319

Prognosis of women with primary breast cancer diagnosed during pregnancy: Results from an international collaborative study

Purpose: We aimed to determine the prognosis of patients with breast cancer diagnosed during pregnancy (BCP). Patients and Methods: In this cohort study, a multicentric registry of patients with BCP (from Cancer in Pregnancy, Leuven, Belgium, and GBG 29/BIG 02-03) compiled pro- and retrospectively between 2003 and 2011 was compared with patients who did not have associated pregnancies, using an age limit of 45 years. Patients with a diagnosis postpartum were excluded. The main analysis was performed using Cox proportional hazards regression of disease-free survival (DFS) and overall survival (OS) on exposure (pregnant or not), adjusting for age, stage, grade, hormone receptor status, human epidermal growth factor 2 status, histology, type of chemotherapy, use of trastuzumab, radiotherapy, and hormone therapy. Results: The registry contained 447 women with BCP, mainly originating from Germany and Belgium, of whom 311 (69.6%) were eligible for analysis. The nonpregnant group consisted of 865 women. Median age was 33 years for the pregnant and 41 years for the nonpregnant patients. Median follow-up was 61 months. The hazard ratio of pregnancy was 1.34 (95% CI, 0.93 to 1.91; P = .14) for DFS and 1.19 (95% CI, 0.73 to 1.93; P = .51) for OS. Cox regression estimated that the 5-year DFS rate for pregnant patients would have increased from 65% to 71% if these patients had not been pregnant. Likewise, the 5-year OS rate would have increased from 78% to 81%. Conclusion: The results show similar OS for patients diagnosed with BCP compared with nonpregnant patients. This information is important when patients are counseled and supports the option to start treatment with continuation of pregnancy