Analysis of and prognostic information from disseminated tumour cells in bone marrow in primary breast cancer: a prospective observational study

Background Disseminated tumour cells (DTCs) in the bone marrow of patients with breast cancer have been identified as an independent predictor of poor prognosis in patients with non-metastatic disease. This prospective study aimed to evaluate the presence and prognostic value of DTCs in the bone marrow of female patients with primary breast cancer. Methods Between 1999 and 2003, bone marrow aspirates were obtained from patients at the time of surgery for primary invasive breast cancer. DTCs in bone marrow were identified using monoclonal antibodies against cytokeratins for detection of epithelial cells. The detection of DTCs was related to clinical follow-up with distant disease-free survival (DDFS) and breast cancer-specific survival as endpoints. Bone marrow aspirates from adult healthy bone marrow donors were analysed separately. Results DTCs were analysed in 401 patients, and cytokeratin-positive cells were found in 152 of these (38%). An immunofluorescence (IF) staining procedure was used in 327 patients, and immunocytochemistry (IC) was performed in 74 patients. The IF-based method resulted in 40% DTC-positive cases, whereas 30% were positive using IC (p = 0.11). The presence of DTCs in bone marrow was not significantly related to patient or tumour characteristics. The presence of DTCs was not a prognostic factor for DDFS (IF: hazards ratio [HR], 2.2; 95% confidence interval [CI], 0.63–2.2; p = 0.60; IC: HR, 0.84; 95% CI, 0.09–8.1; p = 0.88). Significant prognostic factors were lymph node metastases, oestrogen receptor positivity, Nottingham histological grade, and tumour size using Cox univariate analysis. The analyses were positive for epithelial cells in bone marrow from adult healthy donors in 19 (25%) samples. Conclusions The detection of DTCs in bone marrow in primary breast cancer was previously shown to be a predictor of poor prognosis. We were not able to confirm these results in a prospective cohort including unselected patients before the standard procedure was established. Future studies with a standardised patient protocol and improved technique for isolating and detecting DTCs may reveal the clinical applications of DTC detection in patients with micrometastases in the bone marrow.BioMed Central open acces

Sentinel lymph node biopsy in operations for recurrent breast cancer

Background: In a pilot prospective consecutive series on 50 patients with recurrent breast cancer, results of sentinel lymph node biopsy (SLNB) are reported. The interval between primary operation and recurrence was 8 years (range 1-18 years). Only three patients had not undergone dissection of the axilla (ALND). Results: In 51% of patients scintigraphy disclosed sentinel nodes (SN). At operation SN was identified in 45% of patients corresponding to 83% of the SN's visualized by the scintigraphy. SN contained metastases in seven cases (16%), and the treatment plan was changed as a consequence of the SN examination. Conclusion: SLNB can identify SN at a high rate, and the findings may influence further planning of treatment. SLNB should be a future standard procedure in operations for recurrent breast cancer. Next step should be a randomized study

Decreased angiogenic activity in breast cancer in ever-users of oral contraceptive therapy--preliminary report

BACKGROUND: Angiogenic activity defined by microvessel density or measurement of vascular endothelial growth factor is a key process under physiological and malignant conditions in steroid hormone responding organs. The aim of this study was to relate microvessel density (MVD) in primary breast cancer to reproductive data and use of exogenous hormones. MATERIAL AND METHODS: MVD was calculated retrospectively in forty-two consecutive tumours and related to clinical, histopathological and gynecological data. RESULTS: Tumours in ever-users of oral contraceptive therapy (OC) had lower MVD (p = 0.002), a finding not explained by smaller tumour size or lower histological grade. There was no influence on MVD by other reproductive data. CONCLUSION: These preliminary data on a supposed interaction between the use of OC and angiogenesis in breast cancer indicate that biological properties in breast tumours may be altered by ever-use of OC, but have to be further explored in an extended number of patients

Hospital stay related to TNM-stage and the surgical procedure in primary breast cancer

In Sweden from 1980 to 1995 there was an overall decrease of 56% in mean length of stay (MLOS) for surgical curative breast cancer treatment. The objective of this study was to separate the possible impact of tumour size and lymph node dissemination and changes in surgical procedures. All women diagnosed (n=13 290) with breast cancer between 1982 and 1995 were selected from the Southern Swedish Tumour Register. Data on LOS, diagnoses, and surgical procedures were obtained from the Swedish Hospital Discharge Register. A multifactorial model was fitted to the data. Discharges where patients were treated with breast conserving surgery had more than two days shorter MLOS (-2.49, 95% CI -1.66) compared with mastectomy. Although TNM data imply a shift from T2 to smaller T1 among operated women the effect on MLOS is negligible when controlled for age, type of operation etc. Changes in clinical practice such as changes in operation technique can explain approximately 13% of the total decrease in MLOS

Determination of sentinel lymph node (SLN) status in primary breast cancer by prospective use of immunohistochemistry increases the rate of micrometastases and isolated tumour cells: Analysis of 174 patients after SLN biopsy.

Aim: The objective of the present study was to evaluate the prospective use of immunohistochemistry (IHC) for histopathological diagnosis of sentinel lymph node(s) (SLN) in primary breast cancer using stage migration and non-SLN metastases as endpoints in relation to metastatic involvement. Method: Serial sectioning and prospective use of IHC were applied to SLN examination in addition to routine haematoxylin-eosin staining in 174 consecutive patients with unifocal T1-T2 breast cancer included in a National Sentinel Node Study. Axillary lymph node dissection (ALND) was performed in all cases with macrometastases, micrometastases and isolated tumour cells (ITC). Results: The SLN was found in 173/174 patients and a metastatic foci was found in 50 patients including 28/50 with macrometastases, 16/ 50 with micrometastases and 6/50 with ITC. IHC detected 3/16 of the micrometastases and 4/6 of ITC. Stage migration from NO to N1mi was encountered in 3/132 patients by use of IHC. Non-SLN metastases were noted in 15/28 of patients with macrometastases and in 3/16 of patients with micrometastases, whereas no patient with ITC had additional metastases (p = 0.007). Conclusion: The prospective use of lHC and serial sectioning for histopathological diagnosis of SLNs increased the detection rate of N1mi and ITC, but only 3/132 patients were stage-migrated by use of IHC. Patients with ITC did not have any risk of non-SLN metastases, supporting that ALND can safely be omitted in this group of patients. (C) 2006 Elsevier Ltd. All fights reserved

Natural remedy use in a prospective cohort of breast cancer patients in southern Sweden.

Abstract Background. Complementary and alternative medicine (CAM) use is common among breast cancer patients. Several CAM therapies may have negative side effects or interact with conventional therapies. We studied biologically based CAM use with and without vitamins/minerals in relation to patient and tumor characteristics as well as treatment in an ongoing prospective cohort of 855 primary breast cancer patients. Methods. Patients from two hospitals in southern Sweden were included. Pre-operative and follow-up questionnaires containing questions on food intake, lifestyle, and concomitant medications, including natural remedies, were completed up to five years postoperatively. Clinical information was obtained from clinical records and tumor characteristics from pathology reports. Results. CAM and/or vitamins/minerals were used by 34.2% pre-operatively and by 57.9% during at least one visit. Over 100 different preparations were reported. At least eight of the commonly used preparations may interact with conventional breast cancer therapies. CAM users more often had a BMI <25 kg/m(2) (OR 1.76; 95%CI 1.33-2.33), were more often nulliparous (OR 1.59; 1.08-2.34), alcohol (OR 2.13; 1.44-3.14), antidepressants (OR 1.48; 1.02-2.15), and hormone therapy users (OR 1.57; 1.18-2.07), less often smokers (OR 0.71; 0.50-0.99), and consumed less coffee (OR 0.88; 0.82-0.95) than non CAM users. Tumor characteristics were not associated with CAM use. CAM use was more common among tamoxifen (OR 1.32; 1.00-1.75) and less common among chemotherapy (OR 0.63; 0.42-0.92) treated patients. Vitamins/minerals use was more common in aromatase inhibitor treated patients (OR 1.84; 1.33-2.53). There was no significant association between short-term disease-free survival and CAM use. Conclusion. CAM use was common and associated with certain patient characteristics. CAM use may cause clinically significant drug interactions and it is therefore of clinical interest to identify potential CAM users

Evidence for tissue factor phosphorylation and its correlation with protease activated receptor expression and the prognosis of primary breast cancer.

Tissue factor (TF)-mediated protease activated receptor (PAR)-2 signaling is associated with a pro-migratory, invasive and pro-angiogenic phenotype in experimental models of breast cancer, and has been mechanistically coupled to phosphorylation of the TF cytoplasmic domain (pTF). However, the clinical relevance of these findings are unknown. Here, we provide first in vivo evidence of TF phosphorylation in experimental as well as clinical breast cancer tumors. pTF was demonstrated in MDA-MB-231 xenografts and in tumors from the MMTV-PyMT transgene model of spontaneous murine breast adenocarcinoma. Tumors from PAR-2-deficient transgenic mice were negative for pTF, thus linking pTF to PAR-2 signaling. The clinical correlation between TF, pTF, PAR-1, PAR-2, and VEGF-A was determined by IHC on tumors from a cohort of 172 consecutive primary breast cancer patients with a median follow-up time of 50 months. In 160 evaluable patient tumors, pTF was associated with TF (p=0.01) and cancer cell expression of PAR-1 (p=0.001), PAR-2 (p=0.014) and VEGF-A (p=0.003) using chi(2) test. PAR-2 and VEGF-A were co-expressed (p=0.013) and associated with a more aggressive phenotype. Interestingly, all patients experiencing recurrences had tumors expressing pTF and PAR-2, and pTF alone as well as co-expression of pTF and PAR-2 were significantly correlated with shorter recurrence-free survival (log rank test, p=0.04 and p=0.02, respectively). This study provides first evidence to link PAR-2 expression and TF phosphorylation to clinical data in human breast cancer. In conjunction with experimental tumor models, these data support an important role of TF-PAR-2 signaling in breast cancer recurrence. (c) 2009 UICC