Detection and prognostic significance of circulating tumour cells in patients with metastatic breast cancer according to immunohistochemical subtypes.

BACKGROUND: The enumeration of circulating tumour cells (CTCs) with the EpCAM-based CellSearch system has prognostic significance in patients with metastatic breast cancer (MBC). The aim of this study was to explore potential differences in the detection and prognostic significance of CTCs in MBC according to immunohistochemical subtypes of breast cancer. METHODS: CellSearch CTC counts were obtained from 154 MBC patients before first-line systemic treatment between November 2007 and August 2012. Patients were categorised in five subgroups according to immunohistochemical surrogate definitions of intrinsic subtypes in breast cancer based on hormone receptor status, HER2/neu status and histological grade. Differences in progression-free (PFS) and overall survival (OS) were assessed relative to the cut-off value of ≥5 CTCs per 7.5 ml blood. RESULTS: No significant differences were observed in the absolute CTC counts (P=0.120) or in CTC positivity rates according to ≥1 and ≥5 CTCs per 7.5 ml blood detection thresholds (P=0.165 and P=0.651, respectively) between immunohistochemical subtypes. However, very high CTC counts, defined as ≥80 CTCs per 7.5 ml, were observed more frequently in patients with Luminal A and triple negative (TN) breast cancer (P=0.024). In the total study population, the presence of ≥5 CTCs was the single most significant prognostic factor for both PFS and OS in multivariate analysis (P<0.001). A more limited prognostic impact, not reaching statistical significance, was observed in patients with HER2-positive disease as opposed to patients with Luminal A, Luminal B-HER2-negative and TN disease. CONCLUSION: The detection of EpCAM+CTCs was not clearly associated with any of the immunohistochemical subtypes of breast cancer in patients with MBC before first-line treatment. Potentially clinically relevant differences were however observed at very high CTC counts. Furthermore, our data suggest a lower prognostic significance of CTC evaluation in HER2-positive patients with MBC.

Longitudinal humoral response after SARS-CoV-2 vaccination in ocrelizumab treated MS patients: To wait and repopulate?

OBJECTIVE: The objective of this study was to measure humoral responses after SARS-CoV-2 vaccination in MS patients treated with ocrelizumab (OCR) compared to MS patients without disease modifying therapies (DMTs) in relation to timing of vaccination and B-cell count. METHODS: OCR treated patients were divided into an early and a late group (cut-off time 12 weeks between infusion and first vaccination). Patients were vaccinated with mRNA-1273 (Moderna). B-cells were measured at baseline (time of first vaccination) and SARS-CoV-2 antibodies were measured at baseline, day 28, 42, 52 and 70. RESULTS: 87 patients were included (62 OCR patients, 29 patients without DMTs). At day 70, seroconversion occurred in 39.3% of OCR patients compared to 100% of MS patients without DMTs. In OCR patients, seroconversion varied between 26% (early group) to 50% (late group) and between 27% (low B-cells) to 56% (at least 1 detectable B-cell/µL). CONCLUSIONS: Low B-cell counts prior to vaccination and shorter time between OCR infusion and vaccination may negatively influence humoral response but does not preclude seroconversion. We advise OCR treated patients to get their first vaccination as soon as possible. In case of an additional booster vaccination, timing of vaccination based on B-cell count and time after last infusion may be considered.

Circulating tumour cells in the central and the peripheral venous compartment in patients with metastatic breast cancer.

BACKGROUND: The enumeration of circulating tumour cells (CTC) has prognostic significance in patients with metastatic breast cancer (MBC) and monitoring of CTC levels over time has considerable potential to guide treatment decisions. However, little is known on CTC kinetics in the human bloodstream. METHODS: In this study, we compared the number of CTC in both 7.5 ml central venous blood (CVB) and 7.5 ml peripheral venous blood (PVB) from 30 patients with MBC starting with a new line of chemotherapy. RESULTS: The number of CTC was found to be significantly higher in CVB (median: 43.5; range: 0-4036) than in PVB (median: 33; range: 0-4013) (P=0.001). When analysing samples pairwise, CTC counts were found to be significantly higher in CVB than in PVB in 12 out of 26 patients with detectable CTC. In contrast, only 2 out of 26 patients had higher CTC counts in PVB as compared with CVB, whereas in 12 remaining patients no significant difference was seen. The pattern of CTC distribution was independent of the sites of metastatic involvement. CONCLUSION: A substantial difference in the number of CTC was observed between CVB and PVB of patients with MBC. Registration of the site of blood collection is warranted in studies evaluating the role of CTC assessment in these patients.

Time trends (2006-2015) of quality indicators in EUSOMA-certified breast centres.

AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast centres to establish minimum standards and ensure specialist multidisciplinary care. Prospectively collected anonymous information on primary breast cancer cases diagnosed and treated in the units is transferred annually to a central EUSOMA data warehouse for continuous monitoring of quality indicators (QIs) to improve quality of care. Units have to comply with the EUSOMA Breast Centre guidelines and are audited by peers. The database was started in 2006 and includes over 110,000 cancers from breast centres located in Germany, Switzerland, Belgium, Austria, The Netherlands, Spain, Portugal and Italy. The aim of the present study is assessing time trends of QIs in EUSOMA-certified breast centres over the decade 2006-2015. MATERIALS AND METHODS: Previously defined QIs were calculated for 22 EUSOMA-certified breast centres (46122 patients) during 2006-2015. RESULTS: On the average of all units, the minimum standard of care was achieved in 8 of 13 main EUSOMA QIs in 2006 and in all in 2015. All QIs, except removal of at least 10 lymph nodes at axillary clearance and oestrogen receptor-negative tumours (T > 1 cm or N+) receiving adjuvant chemotherapy, improved significantly in this period. The desirable target was reached for two QIs in 2006 and for 7 of 13 QIs in 2015. CONCLUSION: The EUSOMA model of audit and monitoring QIs functions well in different European health systems and results in better performance of QIs over the last decade. QIs should be evaluated and adapted on a regular basis, as guidelines change over time.

Identification of a putative histidine base and of a non-protein nitrogen ligand in the active site of Fe-hydrogenases by one-dimensional and two-dimensional electron spin-echo envelope-modulation spectroscopy.

The active H-cluster of the Fe-hydrogenases from Megasphaera elsdenii and Desulfovibrio vulgaris (strain Hildenborough) has been investigated with one- and two-dimensional pulsed EPR spectroscopy. In both complexes the coordination of a nitrogen-containing ligand was found. The unusual quadrupole interaction parameters (D. vulgaris: quadrupole coupling constant, K = 1.20 MHz, asymmetry parameter eta = 0.32, M. elsdenii: K = 1.23 MHz, eta = 0.25) indicate a non-protein type of nitrogen and are consistent with cyanide as ligand to the H-cluster. The additional interactions measured on the EPR signal of the inactivated H-cluster in D. vulgaris hydrogenase are consistent with an imidazole interaction similar to that found in Rieske-type iron-sulfur clusters. Since a His residue near the putative H-cluster binding motif of Cys residues, His371, is the only conserved His in Fe-hydrogenases, it is a likely candidate for the base that accepts the proton in the heterolytic cleavage of molecular hydrogen. The inactivation of the enzyme is accompanied by direct binding of the imidazole ring to the H-cluster.

Sentinel node detection in a patient with recurrent endometrial cancer initially treated by hysterectomy and radiotherapy.

This is the first article reporting sentinel node identification in a patient with endometrial cancer recurring in the vagina. A 79-year-old woman presented with a midvaginal recurrence of a stage IB, grade II endometroid carcinoma that had been treated 3 years earlier by a total abdominal hysterectomy, bilateral salpingoophorectomy, and pelvic lymph node sampling, followed by adjuvant brachytherapy to the vaginal vault. A staging examination under anesthetic was performed. Preoperatively, 60-MBq technetium-labeled nannocolloid was injected in the mucosa at 3, 6, 9, and 12 o'clock just adjacent to the tumor recurrence. Three sentinel nodes were detected, respectively, in the left obturator fossa (two) and the right external iliac region, using a laparoscopic probe (Navigator) and removed for pathological assessment. As they proved to be negative, the patient underwent a total vaginectomy, parametrectomy with pelvic lymphadenectomy. The tumor was completely removed, and all lymph nodes proved to be negative. The accuracy of sentinel node identification in patients with recurrent gynecological tumors needs further evaluation. This unique case shows that sentinel node detection is possible after previous radiotherapy and surgery and hopes to stimulate further research in this field.