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  • 1
    In: The FEBS Journal, Wiley, Vol. 282, No. 12 ( 2015-06), p. 2327-2338
    Abstract: Recent investigations have suggested that inflammasome activation plays an important role during atherosclerosis. Upon activation, the inflammasome induces processing and release of pro‐inflammatory cytokines interleukin 1β ( IL ‐1β) and interleukin 18 ( IL ‐18) via activation of caspase‐1/11. Previously, it was shown that complete caspase‐1 deficiency is protective against atherosclerosis development. However, while macrophages are the main inflammatory cells involved in atherosclerosis, the exact role of macrophage‐specific caspase‐1/11 activation during development of cardiovascular disease has never been investigated. We hypothesized that hematopoietic caspase‐1/11 deficiency leads to reduced atherosclerosis development. To investigate the specific contribution of hematopoietic caspase‐1/11 activation to atherosclerosis development, Ldlr −/− mice received a transplant (tp) of wild‐type ( WT ) or caspase‐1/11 −/− bone marrow, to create WT ‐tp mice and caspase‐1/11 −/− ‐tp mice, and fed a high‐fat, high‐cholesterol diet for 12 weeks. Our results showed an increase in anti‐inflammatory blood leukocytes in caspase‐1/11 −/− ‐tp mice compared with WT ‐tp mice, as indicated by a decreased level of Ly6C high monocytes and an increased level of Ly6C low monocytes. In line with our hypothesis, hematopoietic deletion of caspase‐1/11 resulted in a strong reduction in atherosclerotic plaque size. Furthermore, necrotic core content was dramatically decreased in caspase‐1/11 −/− ‐tp mice. Our data indicate that hematopoietic caspase‐1/11 activation is involved in vascular inflammation and atherosclerosis, and plays an important role in cardiovascular disease progression.
    Type of Medium: Online Resource
    ISSN: 1742-464X , 1742-4658
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2172518-4
    SSG: 12
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  • 2
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 375, No. 6580 ( 2022-02-04), p. 540-545
    Abstract: A cluster of HIV-infected individuals with high viral loads, rapid CD4 + cell declines, and increased infectivity has been detected in Europe.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 3
    In: Biomarkers in Medicine, Future Medicine Ltd, Vol. 9, No. 12 ( 2015-12), p. 1301-1309
    Abstract: Aim: Nonalcoholic steatohepatitis (NASH) is a liver disease characterized by lipid accumulation and inflammation. Here, we aimed to evaluate plasma IL-1Ra as a marker for NASH and to determine whether diagnosis of NASH can be further improved by adding IL-1Ra measurements. Materials & methods: Therefore, plasma concentrations of IL-1Ra were measured from 146 subjects of a biopsy-proven NASH cohort with matched controls. Results: NASH patients had higher levels of plasma IL-1Ra compared with patients with steatosis or healthy controls. Conclusion: Our data confirm that IL-1Ra can be a useful tool in the diagnosis of hepatic inflammation and suggest that measuring plasma IL-1Ra levels in addition to ALT will improve the diagnosis for NASH at all stages of the disease.
    Type of Medium: Online Resource
    ISSN: 1752-0363 , 1752-0371
    Language: English
    Publisher: Future Medicine Ltd
    Publication Date: 2015
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  • 4
    In: American Journal of Gastroenterology, Ovid Technologies (Wolters Kluwer Health), Vol. 110, No. 3 ( 2015-03), p. 462-470
    Type of Medium: Online Resource
    ISSN: 0002-9270
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    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
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  • 5
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. P5-06-08-P5-06-08
    Abstract: Purpose: Extended adjuvant hormone therapy improves estrogen receptor (ER)-positive breast cancer outcome. The total duration of endocrine therapy is still a subject for debate. The CTS5 score, developed by Dowsett et al1., predicts late distant recurrence (LDR) between years 5 and 10 after diagnosis in ER-positive invasive breast cancers in postmenopausal women. This LDR risk might be used to select patients for extended endocrine therapy. The CTS5 score is calculated using age at the start of endocrine therapy, tumor size, grade, and lymph node status. The aim of this study is the validation of this tool in a series of women from the UZ Leuven. Methods: This retrospective cohort study included 1125 postmenopausal women consecutively diagnosed with invasive estrogen receptor (ER) positive breast cancer who stopped endocrine therapy after 4.5 to 5.5 years. Tissue was tested for ER positivity and considered positive if & gt;1% of tumor nuclei were stained. HER2 status was defined according to ASCO guidelines. Statistical analysis was performed by Cox proportional hazards models which determined the prognostic performance of the CTS5 score for LDR. Results: A total of 1125 patients were included in this analysis, of which 1097 had a known HER2 status and 1023 were negative. 62 of 1125 (5.5%) developed an LDR between years 5 and 10. The continuous CTS5 was a significant predictor for LDR (HR =2.69 (1.99-3.60), p & lt;0.001). The tool was not significant in the HER2 positive population (n=74), but numbers were small with only 5 LDR recorded (HR=0.92 (0.32-2.66), p=0.88). Further analysis was performed in a strictly HER2-negative cohort. In this cohort, 8 of the 401 patients (2.0%) with a CTS5 predicted low risk ( & lt;5% LDR risk) developed LDR, in the intermediate risk group (5-10% LDR risk) 16 out of 336 (4.8%) and in the high risk group (≥10% LDR risk) 32 out of 286 (11.2%) developed LDR. Conclusion: In our series of postmenopausal women, CTS5 accurately predicts late distant recurrence in ER-positive, HER2-negative early invasive breast cancers. The CTS5-score, identifying a patient group with LDR risk of ≥5%, might be used to discuss the benefits of extended endocrine therapy for individual patients. However, the exact predictive value for the benefit of prolonged therapy can only be based on a randomized controlled trial (RCT) using the LDR risk as a stratification factor. It would be of great value to expand the study population, especially HER2-positive tumors, and define the prognostic performance of the CTS5 score in premenopausal women. Further research is needed. 1. Dowsett, M. et al. Integration of Clinical Variables for the Prediction of Late Distant Recurrence in Patients With Estrogen Receptor-Positive Breast Cancer Treated With 5 Years of Endocrine Therapy: CTS5. J. Clin. Oncol. 36, 1941-1948 (2018). Citation Format: Josephine Van Cauwenberge, Ivana Sestak, Kevin Punie, Hans Wildiers, Giuseppe Floris, Ignace Vergote, Patrick Berteloot, Toon Van Gorp, Ann Smeets, Els Van Nieuwenhuysen, Sileny Han, Ines Nevelsteen, Caroline Weltens, Hilde Janssen, Patrick Neven. Predicting distant recurrence of ER+ HER2- breast cancer after 5 years of endocrine therapy: The CTS5-tool validation in real life [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-08.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 6
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. P3-08-26-P3-08-26
    Abstract: Purpose: Metaplastic Breast Cancer (mBC) is uncommon and often behaves aggressive with a high incidence of recurrence. Prognostic factors are poorly understood. We analyzed prognostic factors in a single center series of triple negative mBC and compared those to a patients with ductal TNBC of no special type (dTNBC-NST), treated during the same time period; Materials and methods: We retrospectively analyzed prognostic factors (demographic and clinical pathological features) and distant recurrence of all ER-negative mBC’s (primary operated and neoadjuvant chemotherapy (NAC-)) treated in the University Hospitals Leuven (UHL) between 1/1/2000 and 31/12/2016. TNBC was defined as IHC-ER & lt;1%, IHC-PR & lt;1% and IHC-HER2 0-1+ and FISH negative if HER2 IHC 2/3+. For comparison, only ductal TNBC of no special type were included (dTNBC-NST). Demographic features included age, Body Mass Index (BMI, kg/m²) and detection method. Clinical pathological features included grading, size, lymphovascular invasion (LVI) and nodal involvement. Outcome included distant recurrence rate. The Cox proportional hazards model was used to analyze prognostic factors on distant recurrence rate. A multivariate model was used to correct for possible confounders (grade, nodal stage, tumor size). The clinical pathological variables were compared using Fisher exact test or Mann-Withney U test. All tests are two-sided and a 5% significance level is assumed for all tests. Results on distant recurrent rates are presented as hazard ratios (HR) with 95% confidence intervals (CI). Results: 49 mBC patients were identified; 11 treated with NAC and 38 primary operated. The dTNBC-NST group contained 662 patients; 194 treated with NAC and 468 primary operated. Median follow up was 8.35yrs [5.33 - 12.16] in the mBC and 9.48yrs [5.23-13.44] in the dTNBC-NST group. Median age was 52yr in the mBC and 53yr in the dTNBC-NST (p=0.482). There was a tendency for a higher BMI in the mBC group: median BMI was 26.4kg/m² in mBC and 24.7kg/m² in the dTNBC-NST group (p=0.09, univariate analysis). Tumors were significantly larger in the mBC group with the median size (mm) of 29.5 in mBC and 25.0 in dTNBC-NST (p=0.008). Nodal involvement was 17/49 (34.7%) in the mBC group and 205/662 (31.0%) in dTNBC-NST (p=0.345). LVI was significantly less present in mBC (7.9%) than in dTNBC-NST (24.4%) (p=0.026). A similar proportion in either group received adjuvant chemotherapy (76.3% in mBC and 80.8% in dTNBC-NST) but mBC received more often adjuvant radiotherapy (85.7% in mBC and 60.1% in dTNBC-NST, p & lt;0.01) despite having a similar mastectomy rate (51.0% in mBC and 47.6% in dTNBC-NST, p=0.659). pCR in NAC treated mBC was achieved in 4/11 (36.4%) and in 86/194 (43.9%) of dTNBC-NST (p=0.785). There is a tendency to a higher distant relapse rate in mBC with 28.9% (95% CI: 16.5;42.5) having distant relapse within 5 years compared to 16.6% (95% CI: 13.8;19.7) in dTNBC-NST) [HR 1.722, 95% CI (0.970 - 3.057), p=0.064)]. However, when corrected in a multivariate model (corrected for grade, nodal stage and size) this trend becomes irrelevant [HR 1.189, 95% CI (0.659 - 2.144)] . Conclusion: mBC is larger at diagnosis and less often LVI-pos compared to dTNBC-NST. Adjuvant radiotherapy was more often given to mBC patients. The trend we observed of more distant relapse in mBC disappeared when corrected for tumor characteristics. Citation Format: Jan Ardui, Kevin Punie, Giuseppe Floris, Hava Izci, Hans Wildiers, Ignace Vergote, Patrick Berteloot, Toon Van Gorp, Annouschka Laenen, Ann Smeets, Caroline Weltens, Patrick Neven. Clinico-pathological characteristics of metaplastic breast cancer as compared to normal TNBC: A single center analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-26.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. P3-08-18-P3-08-18
    Abstract: Background: Breast cancer is a disease that can recur even after 20 years of diagnosis. At the moment it remains difficult to predict which women will have a late relapse as most scientific research is conducted for relapse within 10 years following diagnosis. A recent meta-analysis by Pan et al was the first to look at risk factors for relapse in the second decade after diagnosis. However this paper mostly included patients that were treated before the year 2000, which makes the results less applicable to patients nowadays. Objective: We retrospectively explored known early relapse risk factors for late relapse in a population that was diagnosed between year 2000 and 2008, 10-year disease-free and treated in one center. Patients and methods: We included all patients, diagnosed with invasive breast cancer who remained disease-free for 10 years. We selected these from a prospectively managed database of consecutive treated patients in the University Hospitals Leuven for early breast cancer, diagnosed between 01-01-2000 and 01-08-2008. We analyzed the association of patient and tumor characteristics for relapse during the second decade after diagnosis. A disease-free survival event (invasive or in situ) was defined as local (ipsi- and contralateral breast), loco-regional (ipsi- and contralateral axillary, internal mammary and subclavian lymph nodes) or metastatic. For the statistical analysis we used Cox proportional hazard models, with time to recurrence as response variable. Furthermore, a multivariable model of independent predictors was constructed using backward selection. Results: 2757 patients were included with a median follow-up of 13.78 years since initial diagnosis (range=10.01-18.65). Out of this group, 179 patients (6,5%) had a disease-free survival event (6 were in situ carcinoma). The multivariate analysis showed a higher risk of relapse in patients with a younger age (HR=1.044, p=0.0002), higher BMI (HR=1.036, p=0.0243) and postmenopausal status at diagnosis (HR=2.266, p=0.0012), higher tumor grade (HR=1.943, p=0.0151), more lymph node involvement (HR=1.626, p & lt;0.0001) and HER-2 negativity (HR=0.378, p=0.0087). Tumor size, hormone sensitivity and ductal versus lobular carcinoma showed no significant results. Conclusion: Several patient and tumor related factors proved to be significant independent risk factors for late relapse ( & gt;10 years after diagnosis). Our findings may help to differentiate between patients with high and low risk of relapse beyond 10 years of treatment and in this way, provide them with a more personalized form of follow-up. Citation Format: Anne-Sophie Vertongen, Hans Wildiers, Kevin Punie, Floris Giuseppe, Vergote Ignace, Patrick Berteloot, Toon Van Gorp, Ann Smeets, Els Van Nieuwenhuysen, Han Sileny, Ines Nevelsteen, Annouschka Laenen, Caroline Weltens, Hilde Janssens, Patrick Neven. Risk of breast-cancer recurrence after a 10-year disease-free interval [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-18.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 8
    In: International Journal of Gynecologic Cancer, BMJ, Vol. 19, No. 9 ( 2009-11), p. 1501-1504
    Abstract: In a group of 6 BRCA -related ovarian cancer patients presenting with clinical relapse, paclitaxel-carboplatin (TC) in a dose-dense regimen was administered to evaluate the response and tolerability compared with those of the sporadic group and of the patients using a regimen administered every 3 weeks. All patients were carboplatin sensitive at the time of first relapse: 4 patients showed intermediate sensitivity (6-12 months), and 2 patients were truly carboplatin sensitive ( 〉 12 months) at first relapse and first administration of a TC dose-dense regimen. A total of 14 dose-dense regimens were administered in a median 5th line (range, 2nd-10th line). A median of 2 dose-dense regimens (range, 1-4) was given per patient. After first administration of the TC dose-dense regimen (median, 3rd line), this resulted in response in all patients: complete remission in 33% and partial remission in the remaining 67%. Furthermore, after another consecutive line of TC dose-dense regimen, 100% response (75% with partial remission and 25% with complete remission) was reached. The results are encouraging and support the observation of extreme carboplatin sensitivity of BRCA -related ovarian cancer. The use of a TC dose-dense regimen might be even more effective.
    Type of Medium: Online Resource
    ISSN: 1048-891X , 1525-1438
    Language: English
    Publisher: BMJ
    Publication Date: 2009
    detail.hit.zdb_id: 2009072-9
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  • 9
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2008
    In:  The Oncologist Vol. 13, No. 4 ( 2008-04-01), p. 410-414
    In: The Oncologist, Oxford University Press (OUP), Vol. 13, No. 4 ( 2008-04-01), p. 410-414
    Abstract: After completing this course, the reader will be able to: Assess the rationale behind using i.p. chemotherapy for epithelial ovarian cancer patients and critically evaluate the data supporting its use.Interpret the argument that i.p. chemotherapy cannot be accepted as standard of care for first-line systemic treatment of advanced ovarian carcinoma.Determine which epithelial ovarian cancer patients may be appropriate for i.p. chemotherapy.Avoid and/or manage the toxicities observed with i.p. chemotherapy. CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com The CME activity for this article consists of material from both “Intraperitoneal Chemotherapy in Patients with Advanced Ovarian Cancer: The Con View” (Vergote et al.) and “Intraperitoneal Chemotherapy for Women with Epithelial Ovarian Cancer” (Trimble et al.). Objectives. In this paper we wish to present the reasons why i.p. chemotherapy cannot be accepted as standard of care for first-line systemic treatment of advanced ovarian carcinoma. Methods. The recent literature on i.p. chemotherapy is critically reviewed. All possible arguments against i.p. chemotherapy are reviewed. Conclusions. Intraperitoneal chemotherapy is associated with a higher toxicity rate than i.v. chemotherapy. For this reason, none of the regimens investigated in the three Gynecologic Oncology Group (GOG) studies can be used as standard treatment outside clinical protocols. The trials on i.p. chemotherapy have suggested a survival difference. However, in the two most recent trials, i.p. chemotherapy or not was not the only research question because different schedules and dosages were used. In addition, the significance of the most recent GOG 172 study was only weak (p = .03), and the result was nonsignificant for progression-free survival. Intraperitoneal chemotherapy should be used only in the context of properly designed clinical trials. These trials must either assess i.p. therapy in comparison with the standard treatment or address the issue of route of administration for equivalent dosages and schedules of the same drugs, and not a mosaic of these questions. In addition, these trials should investigate i.p. regimens that are less toxic than the regimens used in the three GOG trials, and which can be combined with molecular targeted therapies.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2008
    detail.hit.zdb_id: 2023829-0
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  • 10
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. P1-10-07-P1-10-07
    Abstract: Purpose Predictors for pathological Complete Response (pCR) in TNBC are very important given pCR is considered a surrogate marker for breast cancer-related survival. Associated DCIS in TNBC (accom-DCIS) as well as presence of microcalcifications on initial mammography (micro-MG) have been correlated with Androgen Receptor positive TNBC, known to achieve lower pCR rates. We aim to investigate the predictive impact of accom-DCIS and micro-MG on pCR. We also validated known clinico-pathological predictors for pCR. Long term outcome was analyzed for pCR and accom-DCIS. Methods A retrospective cohort study (diagnosed 1/1/2000 - 31/12/2017) of prospectively registered consecutively treated TNBC patients was performed. TNBC was defined as IHC-ER & lt;1%, IHC-PR & lt;1% and IHC-HER2 0-1+ and FISH negative if HER2 IHC 2/3+. All patients had standard of care neoadjuvant chemotherapy (NAC) in our hospital. Patients with at least 2 years of documented follow up and only TNBC of no special type on core needle biopsy (CNB) were included. We evaluated the predictive value of patient factors (age, BMI, symptomatic/screening-detected), imaging (micro-MG) and tumor related factors as reported in the pathology-report (grade, cT, focality, cN, lymphovascular invasion, accom-DCIS) for pCR (defined as pT0-TisN0). We used distant relapse rate and death to evaluate outcome. The Cox proportional hazards model was used to analyze the effect of pCR and accom-DCIS on distant relapse rate as well as overall survival (OS) in a multivariate model (corrected for size, nodal state, grading). Results are presented as hazard ratios (HR) with 95% confidence intervals (CI). Results The study contains 219 patients; accom-DCIS was reported in 53/219 (24.2%) CNB’s; pCR was achieved in 90/219 (41,1%). Patient related factors were comparable in patients who achieved pCR and those who had residual disease. Unifocal, smaller clinical size tumors and high tumor grade were significant predictors for pCR in our series. Analysis of 194 available mammographies showed micro-MG in 63/194 (32.5%). Micro-MG predicted for residual disease after NAC [HR = 3.350; 95% CI (1.708 - 6.569), p=0.005]. Accom-DCIS was a strong negative predictor of pCR [HR = 3.333; 95% CI (1.558 - 7.143), p=0.002)] and was associated with more distant relapse and worse survival [HR = 2.664; 95% CI (1.575 - 4.505), p=0.003]. pCR was strongly associated with a lower distant relapse rate and a better OS [HR = 2.210; 95% CI (1.282 - n3.811), p=0.004] . In the 129 cases without pCR, remaining tumor size [HR = 1.019; 95% CI (1.012 - 1.025), p= & lt; 0,001), ypN [HR = 1.917; 95% CI (1.539 - 2.388), p= & lt; 0,001) and presence of LVI [HR = 3.720; 95% CI (2.057 - 6.728), p= & lt; 0,001] significantly predicted for secondary metastasis. There was only a trend towards more distant relapses if accom-DCIS was found in the resection specimen in those who had residual disease [HR = 1.347; 95% CI (0.780 - 2.325), p=0.2855] . Conclusion Presence of accom-DCIS in CNB as well as micro-MG predicts for less pCR in TNBC. Accom-DCIS in CNB is associated with more distant relapse and worse OS. For accom-DCIS on resection specimen, there was only a tendency towards more distant relapses. Citation Format: Jan Ardui, Sophie Vandamme, Chantal Van Ongeval, Giuseppe Floris, Hava Izci, Hans Wildiers, Kevin Punie, Tatjana Geukens, Ignace Vergote, Patrick Berteloot, Toon Van Gorp, Ann Smeets, Els Van Nieuwenhuysen, Sileny Han, Annouschka Laenen, Caroline Weltens, Hilde Janssens, Patrick Neven. The presence of ductal carcinoma in situ in core needle biopsy and microcalcifications on mammography in TNBC is associated with a lower pCR and worse long term outcome [abstract] . In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-07.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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