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71.
M.J. Bolster M.J. Pepels C.A.P. Wauters R.F.M. Schapers J.W.R. Meijer L.J.A. Strobbe C.L.H. van Berlo J.H.G. Klinkenbijl T. Wobbes A.C. Voogd P. Bult V.C.G. Tjan-Heijnen 《European journal of surgical oncology》2013
Background
Internationally, there is no consensus on the pathology protocol to be used to examine the sentinel lymph node (SN) in breast cancer patients. Previously, we reported that ultra-staging led to more axillary lymph node dissections (ALND). The question was, whether ultra-staging is effective in reducing the risk of regional relapse.Methods
From January 2002 to July 2003, 541 patients from 4 hospitals were prospectively registered when they underwent a SN biopsy. In hospitals A, B, and C, 3 levels of the SN were examined pathologically, whereas in hospital D at least 7 additional levels were examined. Patients with a positive SN, including isolated tumor cells, underwent an ALND. This analysis focuses on the 341 patients with a negative SN. Primary endpoint was 5-year regional recurrence rate.Results
In hospital D 34% of the patients had a negative SN as compared to 71% in hospitals A, B, and C combined (p < 0.001). At 5 years follow-up, 9 (2.6%) patients had developed a regional lymph node relapse. In hospital D none of the patients had a regional recurrence, as compared to 9 (2.9%) cases of recurrence in hospitals A, B, and C.Conclusion
The less intensified SN pathology protocol appeared to be associated with a slightly increased risk of regional recurrence. The absolute risk was still less than 3%, and does not seem to justify the intensified SN pathology protocol of hospital D. 相似文献72.
Patricia M. M. B. Soetekouw Johanna N. H. Timmer-Bonte Miep A. van der Drift Frank van Leeuwen Michiel Wagenaar Lya van Die Jan Bussink Vivianne C. G. Tjan-Heijnen 《International journal of clinical oncology / Japan Society of Clinical Oncology》2013,18(6):988-996
Background
Improving survival in non-small cell lung cancer (NSCLC) will require new strategies or new drugs. Sequential administration of conventional non-cross-resistant cytotoxic drugs offers an opportunity to increase drug diversity while maintaining dose intensity. This Phase II trial was designed to assess the efficacy and feasibility of such a regimen in advanced NSCLC.Methods
Patients with NSCLC stage IIIB or IV received as first-line treatment four cycles of carboplatin (AUC 5) (day 1) plus gemcitabine 1000 mg/m2 (days 1 and 8) every 3 weeks. Thereafter, treatment continued with 12 weekly cycles of paclitaxel 80 mg/m2.Results
In total, 46 patients were included. Median age was 59.6 years (range 41.3–74.3 years) and 93.5 % (n = 43) had Eastern Cooperative Oncology Group performance score of 0 or 1. All but 6 had stage IV disease, and 13 (28.3 %) had squamous cell carcinomas. Thirty-six (78 %) patients completed 4 cycles of carboplatin–gemcitabine and 35 patients received at least 1 cycle of paclitaxel, of whom 16 (46 % of total) patients completed 12 cycles of paclitaxel. The overall objective response rate was 49 %. Sixteen (37 %) patients had a response to carboplatin–gemcitabine, increasing to 21 (49 %) patients after administration of paclitaxel. Of the 13 assessable patients who showed a partial response (PR) on carboplatin–gemcitabine, 12 (92 %) patients showed also a PR on paclitaxel. Of 19 assessable patients with stable disease (SD) on carboplatin–gemcitabine, 4 (21 %) had a PR and 13 (68 %) SD on paclitaxel. Toxicity was moderate: 24 % stopped because of toxicity.Conclusion
Sequential chemotherapy with carboplatin–gemcitabine and weekly paclitaxel is active and feasible in advanced NSCLC patients. 相似文献73.
Jacky D. Luiten Bram Korte Adri C. Voogd Willem Vreuls Ernest J.T. Luiten Luc J. Strobbe Matthieu J.C.M. Rutten Menno L. Plaisier Paul N. Lohle Marianne J.H. Hooijen Vivianne C.G. Tjan-Heijnen Lucien E.M. Duijm 《International journal of cancer. Journal international du cancer》2019,145(10):2720-2727
Between January 1, 2011, and December 31, 2016, we studied the incidence, management and outcome of high-risk breast lesions in a consecutive series of 376,519 screens of women who received biennial screening mammography. During the 6-year period covered by the study, the proportion of women who underwent core needle biopsy (CNB) after recall remained fairly stable, ranging from 39.2% to 48.1% (mean: 44.2%, 5,212/11,783), whereas the proportion of high-risk lesions at CNB (i.e., flat epithelial atypia, atypical ductal hyperplasia, lobular carcinoma in situ and papillary lesions) gradually increased from 3.2% (25/775) in 2011 to 9.5% (86/901) in 2016 (p < 0.001). The mean proportion of high-risk lesions at CNB that were subsequently treated with diagnostic surgical excision was 51.4% (169/329) and varied between 41.0% and 64.3% through the years, but the excision rate for high-risk lesions per 1,000 screens and per 100 recalls increased from 0.25 (2011) to 0.70 (2016; p < 0.001) and from 0.81 (2011) to 2.50 (2016; p < 0.001), respectively. The proportion of all diagnostic surgical excisions showing in situ or invasive breast cancer was 29.0% (49/169) and varied from 22.2% (8/36) in 2014 to 38.5% (5/13) in 2011. In conclusion, the proportion of high-risk lesions at CNB tripled in a 6-year period, with a concomitant increased excision rate for these lesions. As the proportion of surgical excisions showing in situ or invasive breast cancer did not increase, a rising number of screened women underwent invasive surgical excision with benign outcome. 相似文献
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76.
With the introduction of the sentinel node (SN) procedure, the detection frequency of nodal isolated tumor cells and micrometastases has increased. We reviewed the literature on prognostic significance of these small nodal metastases. All studies before the SN era and all studies using the SN procedure that reported outcome in relation to presence of isolated tumor cells and/or micrometastases were included. Studies before the SN era were divided in 'cohort' and 'occult metastases' studies. The SN studies were divided in single-centre studies and in one multicentre cohort study. In the pre-SN cohort studies, axillary lymph node metastases of 2 mm or less were associated with reduced overall survival with an adjusted pooled hazard ratio of 1.44 (95%CI 1.29-1.62). In the pre-SN occult metastases studies, occult nodal metastases were associated with a pooled relative risk of deaths after 5 years of 1.45 (95%CI 1.11-1.88). In single-centre SN studies, using multivariate analyses, the presence of micrometastases was associated with a hazard ratio for disease events of 1.43 to 1.89 as compared to node-negative disease. The largest SN study, including nearly 2000 patients with isolated tumor cells or micrometastases, reported an adjusted hazard ratio for disease-events of 1.50 (95%CI 1.15-1.94) and 1.56 (95%CI 1.15-2.13), respectively, in patients who had not received systemic therapy. We conclude that isolated tumor cells and micrometastases are associated with increased risk of disease-events of about 1.5 compared to node-negative disease. Therefore, we recommend to consider the use of adjuvant systemic therapy in these patients. 相似文献
77.
Vestjens JH Pepels MJ de Boer M Borm GF van Deurzen CH van Diest PJ van Dijck JA Adang EM Nortier JW Rutgers EJ Seynaeve C Menke-Pluymers MB Bult P Tjan-Heijnen VC 《Annals of oncology》2012,23(10):2561-2566
BackgroundIn the MIRROR study, pN0(i + ) and pN1mi were associated with reduced 5-year disease-free survival (DFS) compared with pN0. Nodal status (N-status) was assessed after central pathology review and restaging according to the sixth AJCC classification. We addressed the impact of pathology review.Patients and methodsEarly favorable primary breast cancer patients, classified pN0, pN0(i + ), or pN1(mi) by local pathologists after sentinel node procedure, were included. We assessed the impact of pathology review on N-status (n = 2842) and 5-year DFS for those without adjuvant therapy (n = 1712).ResultsIn all, 22% of the 1082 original pN0 patients was upstaged. Of the 623 original pN0(i + ) patients, 1% was downstaged, 26% was upstaged. Of 1137 patients staged pN1mi, 15% was downstaged, 11% upstaged. Originally, 5-year DFS was 85% for pN0, 74% for pN0(i + ), and 73% for pN1mi; HR 1.70 [95% confidence interval (CI) 1.27–2.27] and HR 1.57 (95% CI 1.16–2.13), respectively, compared with pN0. By review staging, 5-year DFS was 86% for pN0, 77% for pN0(i + ), 77% for pN1mi, and 74% for pN1 + .ConclusionPathology review changed the N-classification in 24%, mainly upstaging, with potentially clinical relevance for individual patients. The association of isolated tumor cells and micrometastases with outcome remained unchanged. Quality control should include nodal breast cancer staging. 相似文献
78.
Irene E.G. van Hellemond Ingeborg J.H. Vriens Petronella G.M. Peer Astrid C.P. Swinkels Carolien H. Smorenburg Caroline M. Seynaeve Maurice J.C. van der Sangen Judith R. Kroep Hiltje de Graaf Aafke H. Honkoop Frans L.G. Erdkamp Franchette W.P.J. van den Berkmortel Maaike de Boer Wilfred K. de Roos Sabine C. Linn Alexander L.T. Imholz Vivianne C.G. Tjan-Heijnen 《International journal of cancer. Journal international du cancer》2019,145(1):274-283
The DATA study (NCT00301457) compared 6 and 3 years of anastrozole in postmenopausal women with hormone receptor-positive early breast cancer after 2–3 years of tamoxifen. Patients with chemotherapy-induced ovarian function failure (CIOFF) were also eligible, but could be at risk of ovarian function recovery (OFR). The current analysis compared the survival of women with CIOFF with definitely postmenopausal women and examined the influence of OFR on survival. Therefore, we selected patients from the DATA study aged 45–57 years at randomization who had received (neo)adjuvant chemotherapy. They were classified by reversibility of postmenopausal status: possibly reversible in case of CIOFF (n = 395) versus definitely postmenopausal (n = 261). The former were monitored by E2 measurements for OFR. The occurrence of OFR was incorporated as a time-dependent covariate in a Cox-regression model for calculating the hazard ratio (HR). We used the landmark method to calculate residual 5-year survival rates. When comparing CIOFF women with definitely postmenopausal women, the survival was not different. Among CIOFF women with available E2 follow-up values (n = 329), experiencing OFR (n = 39) had an unfavorable impact on distant recurrence-free survival (HR 2.27 [95% confidence interval [CI] 0.98–5.25; p = 0.05] and overall survival (HR 2.61 [95% CI 1.11–6.13; p = 0.03]). After adjusting for tumor features, the HRs became 2.11 (95% CI 0.89–5.02; p = 0.09) and 2.24 (95% CI 0.92–5.45; p = 0.07), respectively. The residual 5-year rate for distant recurrence-free survival was 76.9% for women with OFR and 92.1% for women without OFR, and for 5-year overall survival 80.8% and 94.4%, respectively. Women with CIOFF receiving anastrozole may be at increased risk of disease recurrence if experiencing OFR. 相似文献
79.
Kotzsch M Farthmann J Meye A Fuessel S Baretton G Tjan-Heijnen VC Schmitt M Luther T Sweep FC Magdolen V Span PN 《European journal of cancer (Oxford, England : 1990)》2005,41(17):2760-2768
Recently, two components of important protease systems in cancer, i.e., the urokinase plasminogen activator receptor (uPAR) mRNA splice variant uPAR-del4/5 and the tissue inhibitor of matrix metalloproteinase-3 (TIMP-3), were independently reported to be of prognostic value in breast cancer. In the present study, we have evaluated the impact of both these factors on disease-free survival (DFS) in 205 breast cancer patients by assessing mRNA expression in tumour tissue by quantitative PCR. High uPAR-del4/5 mRNA expression was associated with shorter DFS in breast cancer patients (P=0.0363), whereas high TIMP-3 mRNA levels were associated with a good prognosis (P=0.0049). Furthermore, by combining uPAR-del4/5 with TIMP-3 values, we demonstrate that breast cancer patients with high uPAR-del4/5 and low TIMP-3 mRNA levels had a highly significantly shorter DFS in comparison to those patients with low uPAR-del4/5 and high TIMP-3 mRNA expression (P<0.0001). These patients had a more than 6-fold higher risk for disease recurrence or death in multivariate analysis. Therefore, considering the prognostic impact of two proteolytic factors stemming from complementary protease systems may improve the prediction of disease recurrence in breast cancer. 相似文献
80.
Manders P Beex LV Tjan-Heijnen VC Span PN Sweep CG 《International journal of oncology》2004,25(2):511-517
The vascular endothelial growth factor (VEGF) is a mediator of angiogenesis and has proven to be of prognostic value in patients with primary breast cancer. In this study we investigated whether VEGF is of predictive value with regard to the efficacy of adjuvant systemic therapy in primary invasive breast cancer. In 1127 tumors of patients with invasive breast cancer the cytosolic levels of VEGF were measured using a quantitative enzyme-linked immunosorbent assay. These patients were followed for a median follow-up time of 59 months (range 2-268 months) after primary surgery. Correlations with well-known prognostic factors, and univariate and multivariate survival analyses were performed. The VEGF levels showed a positive correlation with age, menopausal status and tumor size. In addition, VEGF levels were inversely correlated with estrogen and progesterone receptor levels. A high VEGF level predicted an early relapse in the univariate relapse-free survival (RFS) analysis for all patients (P=0.010), but not in the multivariate analysis. Furthermore, there were no statistically significant interactions between the levels of VEGF and the use of adjuvant endocrine therapy or chemotherapy in the RFS analysis. We conclude that tumor levels of VEGF do not predict the efficacy of adjuvant endocrine therapy or chemotherapy in patients with primary breast cancer. 相似文献