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ABSTRACT: BACKGROUND: NOTCH signaling is involved in every step of metazoan development and maintenance of adult tissue homeostasis. It is frequently deregulated by mutations and overexpression in different cancer types including solid tumors such as breast cancer. Another common feature of solid tumors is hypoxia, which occurs due to defective or insufficient vascularization. Hypoxia-inducible factors (HIFs) are key regulators of the homeostatic response to low oxygen levels. HIF-1α is overexpressed in many solid tumors, including breast cancer. Hypoxia-induced stabilization of HIF transcription factors has been shown to lead to NOTCH activation in vitro in different contexts and tissues, causing differentiation arrest and induction of proliferation and migration. METHODS: Since the link between HIF-1α and NOTCH signalling has hardly been studied, we set out to closely investigate associations between the expression of HIF-1α and NOTCH pathway members in primary and metastatic human breast cancer specimens and their prognostic value. RESULTS: Co-expression of NOTCH1 intracellular domain (N1ICD) and HIF-1α was associated with a high grade and a high proliferation rate in invasive breast cancer. HIF-1α expression was low in classic, but high in pleomorphic lobular cancers, which also frequently showed stromal HIF-1α expression. NOTCH1 pathway activation was prognostically unfavorable. CONCLUSION: In breast cancer, NOTCH pathway activation appears to be associated with a poor prognosis, but NOTCH and HIF signaling do not seem to be functionally associated.
Cellular oncology (Dordrecht). 09/2012;
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ABSTRACT: Poly(ADP-ribose) polymerase 1 (PARP) is a key element of the single-base excision pathway for repair of DNA single-strand breaks. To compare the cytoplasmic and nuclear poly(ADP-ribose) expression between familial (BRCA1, BRCA2, or non BRCA1/2) and sporadic breast cancer, we investigated 39 sporadic and 39 familial breast cancer cases. The two groups were matched for hormone receptor status and human epidermal growth factor receptor 2 status. Additionally, they were matched by grading with a maximum difference of ±1 degree (e.g., G2 instead of G3). Cytoplasmic PARP (cPARP) expression was significantly higher in familial compared to sporadic breast cancer (P = 0.008, chi-squared test for trends) and a high nuclear PARP expression (nPARP) was significantly more frequently observed in familial breast cancer (64 %) compared with sporadic breast cancer (36 %) (P = 0.005, chi-squared test). The overall PARP expression was significantly higher in familial breast cancer (P = 0.042, chi-squared test). In familial breast cancer, a combination of high cPARP and high nPARP expression is the most common (33 %), whereas in sporadic breast cancer, a combination of low cPARP and intermediate nPARP expression is the most common (39 %). Our results show that the overall PARP expression in familial breast cancer is higher than in sporadic breast cancer which might suggest they might respond better to treatment with PARP inhibitors.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 09/2012; 461(4):425-31. · 2.49 Impact Factor
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ABSTRACT: Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers.
Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer.
The combination of highly tumor-specific markers glucose transporter 1 (GLUT1), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF1-R), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor receptor (MET), and carbonic anhydrase 9 (CAIX) 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6) resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status.
In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R) that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate.
BMC Cancer 06/2012; 12:240. · 3.01 Impact Factor
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ABSTRACT: p53 is a tumor suppressor that is frequently mutated in human cancers. Although alterations in p53 are common in breast cancer, few studies have specifically investigated TP53 mutations in the breast cancer subtype invasive lobular carcinoma (ILC). Recently reported conditional mouse models have indicated that functional p53 inactivation may play a role in ILC development and progression. Since reports on the detection of TP53 mutations in the relatively favorable classic and more aggressive pleomorphic variants of ILC (PILC) are rare and ambiguous, we performed a comprehensive analysis to determine the mutation status of TP53 in these breast cancer subtypes.
To increase our understanding of p53-mediated pathways and the roles they may play in the etiology of classic ILC and PILC, we investigated TP53 mutations and p53 accumulation in a cohort of 22 cases of classic and 19 cases of PILC by direct DNA sequencing and immunohistochemistry.
We observed 11 potentially pathogenic TP53 mutations, of which three were detected in classic ILC (13.6%) and 8 in PILC (42.1%; p = 0.04). While p53 protein accumulation was not significantly different between classic and pleomorphic ILC, mutations that affected structure and protein function were significantly associated with p53 protein levels.
TP53 mutations occur more frequently in PILC than classic ILC.
Cellular oncology (Dordrecht). 02/2012; 35(2):111-8.
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ABSTRACT: The impact of axillary treatment in daily practice on 5-year regional recurrence rate in breast cancer patients with isolated tumor cells or micrometastases in the sentinel node (SLN).
Axillary dissection is recommended in patients with tumor-positive SLNs. But, in recent studies, regional recurrence rates seemed low if dissection was omitted.
We identified all patients in The Netherlands with invasive breast cancer who had an SLN biopsy before 2006, favorable primary tumor characteristics, and node-negative disease, isolated tumor cells or micrometastases as final nodal status. The primary endpoint was regional recurrence rate. To investigate differences in recurrence rates between patients with and without axillary treatment, a proportional hazard regression was carried out correcting for potential confounders.
In total, 857 patients with node-negative disease, 795 patients with isolated tumor cells, and 1028 patients with micrometastases in the SLN were included. Without axillary treatment, the 5-year regional recurrence rates were 2.3%, 2.0%, and 5.6%, respectively. Compared with patients who underwent axillary treatment, the adjusted hazard ratio for regional recurrence in patients who underwent an SLN procedure only was 1.08 (95% CI, 0.23-4.98) for node-negative disease, 2.39 (95% CI, 0.67-8.48) for isolated tumor cells, and 4.39 (95% CI, 1.46-13.24) for micrometastases. Doubling of tumor size, grade 3 and negative hormone receptor status were also significantly associated with recurrence.
Not performing axillary treatment in patients with SLN micrometastases is associated with an increased 5-year regional recurrence rate. Axillary treatment is recommended in patients with SLN micrometastases and unfavorable tumor characteristics.
Annals of surgery 01/2012; 255(1):116-21. · 7.90 Impact Factor
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Jeroen F Vermeulen,
Robert A H van de Ven,
Cigdem Ercan,
Petra van der Groep,
Elsken van der Wall, Peter Bult,
Matthias Christgen,
Ulrich Lehmann,
Juliet Daniel,
Paul J van Diest,
Patrick W B Derksen
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ABSTRACT: Kaiso is a BTB/POZ transcription factor that is ubiquitously expressed in multiple cell types and functions as a transcriptional repressor and activator. Little is known about Kaiso expression and localization in breast cancer. Here, we have related pathological features and molecular subtypes to Kaiso expression in 477 cases of human invasive breast cancer. Nuclear Kaiso was predominantly found in invasive ductal carcinoma (IDC) (p = 0.007), while cytoplasmic Kaiso expression was linked to invasive lobular carcinoma (ILC) (p = 0.006). Although cytoplasmic Kaiso did not correlate to clinicopathological features, we found a significant correlation between nuclear Kaiso, high histological grade (p = 0.023), ERα negativity (p = 0.001), and the HER2-driven and basal/triple-negative breast cancers (p = 0.018). Interestingly, nuclear Kaiso was also abundant in BRCA1-associated breast cancer (p<0.001) and invasive breast cancer overexpressing EGFR (p = 0.019). We observed a correlation between nuclear Kaiso and membrane-localized E-cadherin and p120-catenin (p120) (p<0.01). In contrast, cytoplasmic p120 strongly correlated with loss of E-cadherin and low nuclear Kaiso (p = 0.005). We could confirm these findings in human ILC cells and cell lines derived from conditional mouse models of ILC. Moreover, we present functional data that substantiate a mechanism whereby E-cadherin controls p120-mediated relief of Kaiso-dependent gene repression. In conclusion, our data indicate that nuclear Kaiso is common in clinically aggressive ductal breast cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent transcriptional repression characterize ILC.
PLoS ONE 01/2012; 7(5):e37864. · 4.09 Impact Factor
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ABSTRACT: In breast cancer, it has been shown that pN0(i+) and pN1mi have a comparable negative impact on disease-free survival, compared with pN0. However, pN0(i+) is considered to be a heterogeneous group. We determined the effect of metastatic size and microanatomic location within the pN0(i+) group on breast cancer recurrence. We included all Dutch breast cancer patients diagnosed in 1998-2005 with favorable primary tumor characteristics and a final nodal status of pN0(i+). For this analysis, only patients without adjuvant systemic therapy were eligible (n = 513). Presence of single tumor cells versus cell clusters, metastatic size and microanatomic location were recorded. Primary endpoint was disease-free survival. Analyses were adjusted for age at diagnosis, tumor size, tumor grade, axillary treatment and hormone receptor status. The 5-year disease-free survival of patients with single tumor cell(s) (n = 93) was 78.6% and with tumor cell cluster(s) (n = 404) 77.1%. The hazard ratio for disease events was 1.05 (95% CI 0.63-1.76) for cell cluster(s) compared with single cell(s). In a Cox regression model, doubling of metastatic tumor size corresponded to a hazard ratio of 1.21 (95% CI 1.02-1.43). The adjusted hazard ratio was 0.90 (95% CI 0.54-1.50) for parenchymal (n = 112) versus sinusoidal location (n = 395). Single tumor cells bear similar prognostic information as small tumor cell clusters, even though results do suggest that within the pN0(i+) group, increasing size of nodal involvement is associated with reduced survival. Microanatomic location does not seem to have prognostic relevance.
Breast Cancer Research and Treatment 09/2011; 131(2):645-51. · 4.43 Impact Factor
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Acta oncologica (Stockholm, Sweden) 04/2011; 50(3):462-5. · 2.27 Impact Factor
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ABSTRACT: The Immunodeficiency, Centromeric region instability, and Facial anomalies (ICF) syndrome (OMIM #242860) is a rare autosomal recessive disorder caused by defective DNA methylation. Hematological disease and malignancy (macrophage activation syndrome, myelodysplastic syndrome, and Hodgkin lymphoma) have been reported in three patients. To date, there have been no reports of either epithelial or mesenchymal malignancies. We present a patient with all clinical and laboratory findings of the ICF syndrome who died of a metastatic angiosarcoma of the liver. This is the first report of a non-hematological malignancy in the ICF syndrome. The young age at which our patient developed an angiosarcoma suggests an effect of the defective DNA methylation observed in the ICF syndrome. Therefore, with improvement of recognition and treatment of the ICF syndrome, malignancy could become more common in this condition.
American Journal of Medical Genetics Part A 02/2011; 155A(3):622-5. · 2.39 Impact Factor
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ABSTRACT: Intensified examination of the sentinel lymph node (SN) may result in increased detection of tumor-affected lymph nodes. The authors of this report hypothesized that the introduction of the SN procedure has led to stage migration because of the intensified workup of SNs by pathologists.
After the introduction of the SN procedure, 360 patients with operable breast cancer were included prospectively from 2 large hospitals (Hospital A and Hospital B). The prospectively included patients (the "SN era" group) were compared with 88 historic controls from the year 1994 who were diagnosed with primary breast cancer before introduction of the SN procedure.
After correcting for classic clinical and pathologic prognostic factors in a multiple logistic regression analysis, the detection frequency of lymph node involvement was significantly higher in the SN era group compared with historic controls (P = .04). However, when using the 2002 TNM classification, in which isolated tumor cells (<or=0.2 mm) were categorized as lymph node-negative disease, no stage migration was observed (P = .98). Also, when analyzing both hospitals (Hospital A vs Hospital B) separately with respect to lymph node involvement, there was no difference, between the SN era and the historic controls (P = .79 and P = .69, respectively). This remained nonsignificant after the analysis was corrected for patient and primary tumor characteristics (P = .85 and P = .66, respectively).
Introduction of the SN procedure has led to the detection of more tumor-affected lymph nodes because of the intensified workup of SNs by pathologists. However, stage migration did not occur when tumor deposits of <or=0.2 mm were categorized as lymph node-negative disease, according to the 2002 TNM classification.
Cancer 09/2009; 115(23):5589-95. · 4.77 Impact Factor
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Maaike de Boer,
Carolien H M van Deurzen,
Jos A A M van Dijck,
George F Borm,
Paul J van Diest,
Eddy M M Adang,
Johan W R Nortier,
Emiel J T Rutgers,
Caroline Seynaeve,
Marian B E Menke-Pluymers, Peter Bult,
Vivianne C G Tjan-Heijnen
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ABSTRACT: The association of isolated tumor cells and micrometastases in regional lymph nodes with the clinical outcome of breast cancer is unclear.
We identified all patients in The Netherlands who underwent a sentinel-node biopsy for breast cancer before 2006 and had breast cancer with favorable primary-tumor characteristics and isolated tumor cells or micrometastases in the regional lymph nodes. Patients with node-negative disease were randomly selected from the years 2000 and 2001. The primary end point was disease-free survival.
We identified 856 patients with node-negative disease who had not received systemic adjuvant therapy (the node-negative, no-adjuvant-therapy cohort), 856 patients with isolated tumor cells or micrometastases who had not received systemic adjuvant therapy (the node-positive, no-adjuvant-therapy cohort), and 995 patients with isolated tumor cells or micrometastases who had received such treatment (the node-positive, adjuvant-therapy cohort). The median follow-up was 5.1 years. The adjusted hazard ratio for disease events among patients with isolated tumor cells who did not receive systemic therapy, as compared with women with node-negative disease, was 1.50 (95% confidence interval [CI], 1.15 to 1.94); among patients with micrometastases, the adjusted hazard ratio was 1.56 (95% CI, 1.15 to 2.13). Among patients with isolated tumor cells or micrometastases, the adjusted hazard ratio was 0.57 (95% CI, 0.45 to 0.73) in the node-positive, adjuvant-therapy cohort, as compared with the node-positive, no-adjuvant-therapy cohort.
Isolated tumor cells or micrometastases in regional lymph nodes were associated with a reduced 5-year rate of disease-free survival among women with favorable early-stage breast cancer who did not receive adjuvant therapy. In patients with isolated tumor cells or micrometastases who received adjuvant therapy, disease-free survival was improved.
New England Journal of Medicine 09/2009; 361(7):653-63. · 53.30 Impact Factor
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ABSTRACT: Breast-conserving treatment of invasive breast carcinoma with an extensive intraductal component (EIC) is associated with DCIS-involved surgical margins and therefore it has an increased recurrence rate. EIC is a non-palpable lesion of which the size is frequently underestimated on mammography. This study was undertaken to evaluate the accuracy of MRI in size assessment of breast cancer with EIC.
23 patients were identified and the mammographic (n = 21) and MR (n = 23) images were re-reviewed by a senior radiologist. Size on MR images was compared with histopathological tumour extent.
The correlation of radiological size with histopathological size was r = 0.20 in mammography (p = 0.39) compared to r = 0.65 in MRI (p < 0.01). Mammography underestimated histopathological tumour size in 62%. MR images over- or underestimated tumour size in 22% and 30% of the cases, respectively. In poorly differentiated EIC, MRI adequately estimated the extent more often compared to moderately differentiated EIC (60% versus 25%, respectively).
Size assessment of MRI imaging was more accurate compared to mammography. This was predominantly true for poorly differentiated EIC.
BMC Medical Imaging 04/2009; 9:5. · 1.09 Impact Factor
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ABSTRACT: There are many reports on the frequency of non-sentinel lymph node involvement when isolated tumor cells are found in the sentinel node, but results and recommendations for the use of an axillary lymph node dissection differ among studies. This systematic review was conducted to give an overview of this issue and to provide recommendations for the use of an axillary lymph node dissection in these patients. We searched Medline, Embase, and Cochrane databases from January 1, 2002, through November 27, 2007, for articles on patients with invasive breast cancer who had isolated tumor cells in the sentinel lymph node (according to the sixth edition of the Cancer Staging Manual of the American Joint Committee on Cancer) and who also underwent axillary lymph node dissection. Of 411 selected articles, 29 (including 836 patients) were included in this review. These 29 studies were heterogeneous, reporting a wide range of non-sentinel lymph node involvement (defined as the presence of isolated tumor cells or micro- or macrometastases) associated with isolated tumor cells in the sentinel lymph node, with an overall pooled risk for such involvement of 12.3% (95% confidence interval = 9.5% to 15.7%). This pooled risk estimate was marginally higher than the risk of a false-negative sentinel lymph node biopsy examination (ie, 7%-8%) but marginally lower than the risk of non-sentinel lymph node metastases in patients with micrometastases (ie, approximately 20%) who are currently eligible for an axillary lymph node dissection. Because 36 (64%) of the 56 patients with isolated tumor cells in their sentinel lymph node also had non-sentinel lymph node macrometastases, those patients with isolated tumor cells in the sentinel lymph node without other indications for adjuvant systemic therapy might be candidates for axillary lymph node dissection.
CancerSpectrum Knowledge Environment 12/2008; 100(22):1574-80. · 14.07 Impact Factor
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ABSTRACT: Iatrogenic displacement and mechanical transport of epithelial cells to the sentinel node (SN) has been suggested to result in false-positive findings in breast cancer patients, but little biologic evidence has yet been presented for this hypothesis. As malignant nuclei are larger than benign ones, nuclear morphometry of SN isolated tumor cells (ITC) could provide relevant information with regard to the malignant origin-or-not of epithelial cells in the SN. In patients with primary invasive breast cancer and SN ITC with (N=16) or without (N=45) non-SN involvement, nuclear morphometry was performed on the primary tumor as well as on the ITC in the SN. Nuclear size in the primary tumor was compared with that in the corresponding ITC. Patients with SN micrometastases (N=30) and SN macrometastases (N=30) served as controls. Nuclear size of ITC was significantly smaller compared with nuclear size of the corresponding primary tumor (P<0.0001). In contrast, there were no differences in nuclear size between SN micrometastases and macrometastases on the one hand and their corresponding primary tumors on the other. In addition, a subgroup of cases (10/61, 16%) with benign morphometric features of SN ITC nuclei (small and isomorph) could be discerned that had no non-SN metastases. In conclusion, nuclei of SN ITC are significantly smaller compared with the corresponding primary tumor and are often not associated with non-SN involvement. This supports the hypothesis that some of these deposits could represent benign epithelium or degenerated malignant cells lacking outgrowth potential.
The American journal of surgical pathology 10/2008; 33(1):106-10. · 4.06 Impact Factor
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ABSTRACT: To assess the effect of time on finding residual breast cancer in re-excision specimens after non-radical breast-conserving surgery for both DCIS and invasive breast carcinoma.
315 breast-conserving surgical procedures with tumour-positive margins were retrospectively reviewed. The significance of association between the presence of finding residual tumour in the re-excision specimen and mean time interval was calculated with Student's t-test. A multivariate logistic regression model was used to assess the independent relative risk of time on presence of residual tumour.
Residual tumour was found in 240 (76.2%) of the re-excision specimens. For primary invasive carcinomas time was a risk-reducing factor for finding residual disease (OR 0.89, 95% CI 0.82-0.98, P = 0.01). If invasive carcinoma was transected, the absence of residual disease was significantly related with a longer mean time interval (OR 0.98, 95% CI 0.95-0.99, P = 0.04).
An increased time interval between primary surgery and re-excision for tumour-positive surgical margins for invasive carcinoma is associated with a decreased incidence of finding residual tumour. This could be explained by inflammatory responses after surgical trauma. For DCIS there was no influence of time on finding residual tumour, which could be explained by a more protective microenvironment of DCIS or re-growth of surviving malignant cells.
Journal of Surgical Oncology 01/2008; 96(7):569-74. · 2.10 Impact Factor
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Marieke J Bolster,
Petronella G M Peer, Peter Bult,
Frederik B J M Thunnissen,
René F M Schapers,
Jos W R Meijer,
Luc J A Strobbe,
Charles L H van Berlo,
Jean H G Klinkenbijl,
Louk V A M Beex,
Theo Wobbes,
Vivianne C G Tjan-Heijnen
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ABSTRACT: In this multi-institutional prospective study, we evaluated whether we could identify risk factors predictive for non-sentinel lymph node (non-SN) metastases in breast cancer patients with a positive sentinel lymph node (SN).
In this multi-institutional study, 541 eligible breast cancer patients were included prospectively.
The occurrence of non-SN metastases was related to the size of the SN metastasis (P = .02), primary tumor size (P = .001), and lymphovascular invasion (P = .07). The adjusted odds ratio was 3.1 for SN micro-metastasis compared with SN isolated tumor cells, 4.0 for SN macro-metastasis versus SN isolated tumor cells, 3.1 for tumor size (>3.0 cm compared with </=3.0 cm), and 2.0 for lymphovascular invasion (yes versus no). There were no positive non-SNs when the primary tumor size was </=1.0 cm (n = 24) [95% confidence interval (95% CI) 0%-14.0%]. The proportion of positive non-SNs ranged in a prognostic logistic regression model from 9.7% (95% CI 4.0%-23.0%) for patients with SN isolated tumor cells, tumor size of 1.1-3.0 cm, and without vessel invasion, to 72.6% (95% CI 47.0%-89.0%) for patients with SN macro-metastasis, tumor size >3.0 cm, and with vessel invasion.
We identified three predictive factors for non-SN metastases in breast cancer patients with a positive SN: size of the SN metastasis; primary tumor size; and vessel invasion. We were not able to identify a specific group of patients with a positive SN in whom the risk for non-SN metastases was less than 5%.
Annals of Surgical Oncology 01/2007; 14(1):181-9. · 4.17 Impact Factor
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ABSTRACT: Internationally, there is no consensus on the pathology protocol to be used to examine the sentinel lymph node (SN). At present, therefore, various hospitals use different SN pathology protocols of which the effect has not been fully elucidated. We hypothesized that differences between hospitals in SN pathology protocols affect subsequent surgical treatment strategies.
Patients from four hospitals (A-D) were prospectively registered when they underwent an SN biopsy. In hospitals A, B, and C, three levels of the SN were examined pathologically, whereas in hospital D, at least seven additional levels were examined. In the absence of apparent metastases with hematoxylin and eosin examination, immunohistochemical examination was performed in all four hospitals.
In total, 541 eligible patients were included. In hospital D, more patients were diagnosed with a positive SN (P < .001) as compared with hospitals A, B, and C, mainly because of increased detection of isolated tumor cells. This led to more completion axillary lymph node dissections in hospital D (66.3% of patients (P < .0001), compared with 29.0% in hospitals A, B, and C combined). Positive non-SNs were detected in 13.9% of patients in hospital D, compared with 9.7% in hospitals A, B, and C (P = .70). That is, in 52.4% of patients in hospital D, a negative completion axillary lymph node dissection was performed, compared with 19.3% of patients in hospitals A, B, and C combined.
Differences in SN pathology protocols between hospitals do have a substantial effect on SN findings and subsequent surgical treatment strategies. Whether ultrastaging and, thus, additional surgery can offer better survival remains to be determined.
Annals of Surgical Oncology 11/2006; 13(11):1466-73. · 4.17 Impact Factor
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ABSTRACT: The value of magnetic resonance imaging (MRI) in diagnosis and size assessment of ductal carcinoma-in-situ (DCIS) and DCIS with small (<10 mm) invasive carcinoma was evaluated.
Fifty-four patients with DCIS and 12 patients with DCIS and small invasive carcinoma were included. Mammographic (N = 64) and MRI (N = 22) images were retrospectively reviewed. Correlation coefficients were calculated to assess differences in size between imaging and histopathologic examination.
Mammographic rate of detection for DCIS was 48/52 (92%) and for DCIS with small invasive carcinoma, 10/12 (83%). MRI revealed 1 false negative case and the rate of detection for DCIS was 16/17 (94%). Correlation of mammographic size with histopathologic size was r = .44 (P < .01) and r = 0.49 (P = .03) for MRI. Mammography underestimated lesion size by 5 mm or more in 47%, whereas with MRI size was adequately assessed in 43% and overestimated in 38%.
DCIS can be visualised on MRI with high sensitivity, although tumor size can be overestimated.
The American Journal of Surgery 08/2006; 192(2):172-8. · 2.78 Impact Factor
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ABSTRACT: To determine the value of MR imaging in the detection and measurement of tumor size in patients with invasive lobular carcinoma (ILC) compared to mammography and ultrasound.
From 36 cases of ILC in 34 patients who were surgically treated, the pre-operative imaging measurements, being mammography, ultrasound and contrast enhanced MR, were retrospectively re-evaluated for tumor detection and size. Findings were compared with pathology. Two radiologists were used for evaluation of the mammograms, the other imaging modalities were only evaluated by one radiologist. The Pearsons correlation test was used to determine the correlation between histopathological and imaging measurements for each imaging modality.
For mammography, ultrasound and MRI the false negative scores were respectively 14%, 3% and 0%. The percentage for underestimated, correctly estimated and overestimated measurements on imaging were 56%, 33% and 11% for radiologist 1 and 50%, 33% and 17% for radiologist 2 on mammography. For ultrasound and MRI these percentages were respectively 53%, 47%, 0% and 14%, 75%, 11%. The correlation coefficients for mammography were respectively r = 0.34 (p < 0.05) and r = 0.27 (p > 0.05) for both radiologists, for Ultrasound r = 0.24 (p > 0.05) and for MRI r = 0.81 (p < 0.01).
Of the three imaging modalities contrast enhanced MR has the lowest false negative rate in detecting ILC and has the highest accuracy in measuring the size of the ILC. MR could play a key role in the pre-operative work-up for accurate tumor size determination.
Breast Cancer Research and Treatment 07/2004; 86(1):31-7. · 4.43 Impact Factor
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ABSTRACT: Sentinel lymph node biopsy has replaced the axillary lymph node dissection (ALND) in primary surgery for breast cancer in many hospitals and is expected to become the standard of care in due time. Since the sentinel lymph node is subjected to more extensive pathologic examination than the lymph nodes in the axillary dissection specimen, more patients are found to be node positive (N+); however many of them contain micro-metastases (<or=2mm). The consequence may be an overshoot of therapy: additional surgery for non-metastatic lymph nodes or systemic adjuvant therapy.
We examined 34 (out of a series of 38) clinically T1 (cT1) patients who had a SLN biopsy with or without ALND and compared them to a matched historical control group.
Twenty-one of 34 (62%) patients showed tumour cells in their SLN's. From these 21 patients in 13 (62%) the SLNs contained isolated tumour cells, of which 10 (77%) were detected only by immunohistochemistry (IHC), in four (19%) the SLNs contained micrometastases, and in four (19%) macrometastases. From 16 patients with isolated tumour cells or micrometastases in the SLN who underwent a regular ALND one had an H&E detected isolated tumour cell in a non-SLN and one patient with isolated tumour cells in the SLN who did not get a regular ALND developed an axillary recurrence 11 months after the primary treatment. On the other hand, three of four (75%) patients with macrometastases in the SLN had pathologically involved non-SLNs. In the majority (70%) of patients of the historical control group no lymph node involvement was seen. The percentage of macrometastases staged as lymph node positive in the control group was the same as in the studied group.
Most patients with cT1 breast cancer with isolated tumour cells or micrometastases in the SLN will not benefit from additional axillary dissection; 88% had a negative ALND. Since we cannot select the group that will benefit from ALND, this is still indicated in case of isolated tumour cells or micrometastases in the SLN. Since most of the affected SLNs show isolated tumour cells and are classified as pN0(i+), stage migration due to more meticulous pathologic examination does not occur according to the TNM classification. However some patients do not benefit from the introduction of the SLN, due to the high incidence of isolated tumour cells or micrometastases in the SLN. Many more patients than expected still end up with an ALND.
European Journal of Surgical Oncology 04/2003; 29(3):216-20. · 2.50 Impact Factor
