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1. Strong CD8+ lymphocyte infiltration in combination with expression of HLA class I is associated with better tumor control in breast cancer patients treated with neoadjuvant chemotherapy

Author

de Groot, A. F., Blok, E. J., Charehbili, A., Engels, C. C., Smit, V. T. H. B. M., Dekker-Ensink, N. G., Putter, H., Meershoek-Klein Kranenbarg, E., van de Velde, C. J. H., Liefers, G. J., Nortier, J. W. R., Kuppen, P. J. K., van der Burg, S. H., and Kroep, J. R.

Published
2019
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3. 89 Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy: A Feasibility Study.

Author

Linders, D. G. J., Deken, M. M., van Dam, M. A., Wasser, M. N. J. M., Voormolen, E. M. C., Kroep, J. R., van Dongen, G. A. M. S., Vugts, D., Oosterkamp, H. M., Straver, M. E., van de Velde, C. J. H., Cohen, D., Dibbets-Schneider, P., van Velden, F. H. P., Pereira Arias-Bouda, L. M., Vahrmeijer, A. L., Liefers, G. J., de Geus-Oei, L. F., and Hilling, D. E.

Subjects
BREAST tumor diagnosis, PILOT projects, TRASTUZUMAB, EPIDERMAL growth factor receptors, POSITRON emission tomography computed tomography, LYMPH nodes, TREATMENT effectiveness, DUCTAL carcinoma, BREAST cancer, QUALITATIVE research, CANCER patients, RESEARCH funding, COMBINED modality therapy, BREAST tumors
Abstract

Simple Summary: In breast cancer patients in whom tumor cells overexpress the protein human epidermal growth factor receptor 2 (HER2), HER2-targeted therapy is the mainstay of neoadjuvant therapy (NAT). Two thirds of these patients respond so well to HER2-targeted therapy that during microscopic analysis of the surgically resected tissue, it becomes apparent there are no vital tumor cells left, classified as complete responders. These patients might not have needed surgery. However, with current imaging techniques such as MRI, it remains difficult to preoperatively assess whether there is residual tumor after NAT or not, so all patients still undergo surgery. This study investigated if a HER2-targeted PET/CT scan can reliably assess the response to NAT. In six patients, a HER2-targeted PET/CT scan was acquired before and after NAT. Two out of six patients had residual tumor at microscopic analysis. Visual assessment of the PET/CT scans correctly predicted the response in 66.7% of cases. When the PET/CT signal in both the scan before and after NAT was quantified and (percentual) changes were calculated, there was a difference in the change of signal between patients with and without residual tumor. This difference, although not statistically significant due to the limited patient number in this study, suggests that quantitative assessment of HER2-targeted PET/CT can be used for accurate response evaluation after NAT. Background: Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 (89Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation. Methods: HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a 89Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed. Results: Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUVR on PET/CT-1 and PET/CT-2 (ΔSUVR) in patients with a pPR and pCR of −48% and −90% (p = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was −79% and −94% (p = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI. Conclusions: NAT response evaluation using 89Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer. [ABSTRACT FROM AUTHOR]

Published
2023
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17. Aromatase inhibitors versus tamoxifen in early breast cancer

Author

Dowsett, M, Forbes, JF, Bradley, R, Ingle, J, Aihara, T, Bliss, J, Boccardo, F, Coates, A, Coombes, RC, Cuzick, J, Dubsky, P, Gnant, M, Kaufmann, M, Kilburn, L, Perrone, F, Rea, D, Thuerlimann, B, Van de Velde, C, Pan, H, Peto, R, Davies, C, Gray, R, Baum, M, Buzdar, A, Sestak, I, Markopoulos, C, Fesl, C, Jakesz, R, Colleoni, M, Gelber, R, Regan, M, Von Minckwitz, G, Snowdon, C, Goss, P, Pritchard, K, Anderson, S, Costantino, J, Mamounas, E, Ohashi, Y, Watanabe, T, Bastiaannet, E, Interne Geneeskunde, Other departments, CCA -Cancer Center Amsterdam, Radiotherapy, Dowsett, M, Forbes, J. F, Bradley, R, Ingle, J, Aihara, T, Bliss, J, Boccardo, F, Coates, A, Coombes, R. C, Cuzick, J, Dubsky, P, Gnant, M, Kaufmann, M, Kilburn, L, Perrone, F, Rea, D, Thürlimann, B, van de Velde, C, Pan, H, Peto, R, Davies, C, Gray, R, DE LAURENTIIS, Michelino, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Oncology, chemistry.chemical_compound, Exemestane, Aromatase, skin and connective tissue diseases, Randomized Controlled Trials as Topic, AUSTRIAN BREAST, biology, Aromatase Inhibitors, Medicine (all), Incidence (epidemiology), Letrozole, PHASE-III TRIAL, 11 Medical And Health Sciences, General Medicine, POSTMENOPAUSAL WOMEN, Female, BONE-MINERAL DENSITY, Life Sciences & Biomedicine, Breast Neoplasm, Human, medicine.drug, medicine.medical_specialty, Antineoplastic Agents, Hormonal, EXEMESTANE, medicine.drug_class, Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Anastrozole, Breast Neoplasms, LETROZOLE, Drug Administration Schedule, ANASTROZOLE, Medicine, General & Internal, Breast cancer, SDG 3 - Good Health and Well-being, General & Internal Medicine, Internal medicine, medicine, Aromatase Inhibitor, Humans, CONTINUED TAMOXIFEN, Gynecology, Science & Technology, Aromatase inhibitor, BIG 1-98, business.industry, medicine.disease, LONG, Tamoxifen, chemistry, biology.protein, ADJUVANT ENDOCRINE THERAPY, business
Abstract

Background The optimal ways of using aromatase inhibitors or tamoxifen as endocrine treatment for early breast cancer remains uncertain.Methods We undertook meta-analyses of individual data on 31 920 postmenopausal women with oestrogen-receptor-positive early breast cancer in the randomised trials of 5 years of aromatase inhibitor versus 5 years of tamoxifen; of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5; and of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen. Primary outcomes were any recurrence of breast cancer, breast cancer mortality, death without recurrence, and all-cause mortality. Intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded aromatase inhibitor versus tamoxifen first-event rate ratios (RRs).Findings In the comparison of 5 years of aromatase inhibitor versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors significantly during years 0-1 (RR 0.64, 95% CI 0.52-0.78) and 2-4 (RR 0.80, 0.68-0.93), and non-significantly thereafter. 10-year breast cancer mortality was lower with aromatase inhibitors than tamoxifen (12.1% vs 14.2%; RR 0.85, 0.75-0.96; 2p=0.009). In the comparison of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5, recurrence RRs favoured aromatase inhibitors significantly during years 0-1 (RR 0.74, 0.62-0.89) but not while both groups received aromatase inhibitors during years 2-4, or thereafter; overall in these trials, there were fewer recurrences with 5 years of aromatase inhibitors than with tamoxifen then aromatase inhibitors (RR 0.90, 0.81-0.99; 2p=0.045), though the breast cancer mortality reduction was not significant (RR 0.89, 0.78-1.03; 2p=0.11). In the comparison of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors significantly during years 2-4 (RR 0.56, 0.46-0.67) but not subsequently, and 10-year breast cancer mortality was lower with switching to aromatase inhibitors than with remaining on tamoxifen (8.7% vs 10.1%; 2p=0.015). Aggregating all three types of comparison, recurrence RRs favoured aromatase inhibitors during periods when treatments differed (RR 0.70, 0.64-0.77), but not significantly thereafter (RR 0.93, 0.86-1.01; 2p=0.08). Breast cancer mortality was reduced both while treatments differed (RR 0.79, 0.67-0.92), and subsequently (RR 0.89, 0.81-0.99), and for all periods combined (RR 0.86, 0.80-0.94; 2p=0.0005). All-cause mortality was also reduced (RR 0.88, 0.82-0.94; 2p=0.0003). RRs differed little by age, body-mass index, stage, grade, progesterone receptor status, or HER2 status. There were fewer endometrial cancers with aromatase inhibitors than tamoxifen (10-year incidence 0.4% vs 1.2%; RR 0.33, 0.21-0.51) but more bone fractures (5-year risk 8.2% vs 5.5%; RR 1.42, 1.28-1.57); non-breast-cancer mortality was similar.Interpretation Aromatase inhibitors reduce recurrence rates by about 30% (proportionately) compared with tamoxifen while treatments diff er, but not thereafter. 5 years of an aromatase inhibitor reduces 10-year breast cancer mortality rates by about 15% compared with 5 years of tamoxifen, hence by about 40% (proportionately) compared with no endocrine treatment. Copyright (C) Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Open Access article distributed under the terms of CC BY.

Published
2015
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18. Effect of peri-operative chemotherapy on the quality of life of patients with early breast cancer

Author

Kiebert, G. M., Hanneke, J., de Haes, J. Hanneke C. J. M., Kievit, J., van de Velde, C. J., and Other departments

Subjects
Adult, medicine.medical_specialty, medicine.medical_treatment, Mammary gland, Breast Neoplasms, Drug Administration Schedule, Breast cancer, Quality of life, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Stage (cooking), Chemotherapy, Intraoperative Care, business.industry, Perioperative, Middle Aged, medicine.disease, Social relation, Surgery, medicine.anatomical_structure, Hair loss, Oncology, Quality of Life, Female, business
Abstract

Since chemotherapy is assumed to have a negative impact on quality of life, the impact of peri-operative chemotherapy on physical, psychological and social well-being and on the activity level of patients with early stage breast cancer was investigated. 24 women received peri-operative chemotherapy and 29 did not. They were interviewed 2 months and at a mean of 12 months post-surgery. Although the treated group reported more fatigue and considered hair loss a severe side-effect, no differences were found in overall physical and psychological well-being, perceived social interaction and activity level at 2 months. 1 year after surgery no differences were found between the two groups. Although no substantial effects of peri-operative chemotherapy on quality of life were demonstrated, patients almost unanimously considered peri-operative chemotherapy the most burdensome aspect of the treatment because of alopecia.

Published
1990
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19. Clinical evidence supporting genomic tests in early breast cancer: Do all genomic tests provide the same information?

Author

Markopoulos, C., van de Velde, C., Zarca, D., Ozmen, V., and Masetti, R.

Subjects
GENETICS of breast cancer, EARLY detection of cancer, BREAST cancer treatment, BREAST cancer patients, GENE expression
Abstract

Breast cancer (BC) has historically been treated as a single disease entity; however, in the last decade, insights into its molecular heterogeneity have underpinned the development/commercialisation of several genomic tools whose goal is to guide patient management in early BC. These include the Oncotype DX ® Breast Recurrence Score™ assay, MammaPrint ® , Prosigna ® , and EndoPredict ® . Although these assays are similar in that they are all multigene assays reflecting risk of recurrence, they differ substantially in the technological platform used to measure gene expression; the number and identity of genes assessed; the patient populations used for development and validation; and the level of evidence supporting clinical utility. They also differ in the amount of evidence demonstrating their impact on treatment decisions and cost effectiveness in different countries. This review discusses these 4 assays, highlighting the clinical evidence that supports each of them, while focussing on the Recurrence Score assay. This assay has the greatest body of evidence supporting its clinical utility and decision impact/effectiveness, and currently is the only one validated as a predictor of response to adjuvant chemotherapy in hormone-receptor positive early BC patients treated with endocrine therapy and to be included as such in international/national BC treatment guidelines. The review also discusses ongoing prospective trials investigating the 4 assays, recent outcome studies, as well as analyses comparing different assays on the same tumour blocks. [ABSTRACT FROM AUTHOR]

Published
2017
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20. P156 - Impact of endocrine therapy on quality of life in early stage breast cancer patients: prospective patient reported outcomes from the international registry INSPIRE.

Author

Esgueva, A., Noordhoek, I., Meershoek-Klein Kranenbarg, E., Siso Raber, C., Mátrai, Z., Zhygulin, A., Irmesj, A., Mavioso, C., Meani, F., González, E., Özdemir, M., Allweis, T., Rogowski, K., Rodrigues dos Santos, C., Mora, H., Ponzone, R., Samorani, D., van de Velde, C., Audisio, R.A., and Rubio, I.T.

Subjects
QUALITY of life, HORMONE therapy, BREAST cancer, CANCER patients, TUMOR classification
Published
2021
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21. Quantitative assessment of lymph vascular space invasion (LVSI) provides important prognostic information in node-negative breast cancer.

Author

Dekker, T. J. A., van de Velde, C. J. H., van Bruggen, D., Mesker, W. E., van der Hoeven, J. J. M., Kroep, J. R., Tollenaar, R. A. E. M., and Smit, V. T. H. B. M.

Subjects
*BREAST cancer prognosis, *BREAST cancer patients, *PERIMENOPAUSE, *CANCER relapse, *LYMPH nodes, *CLINICAL trials, *CANCER risk factors
Abstract

Background Some studies investigating the prognostic value of lymph vascular space invasion (LVSI) have shown an association between LVSI and disease-free survival. Definitive criteria and optimal determination of this parameter remain unclear, however, especially regarding the clinical relevance of LVSI quantification. Patients and methods A subset of node-negative breast carcinomas from premenopausal patients from the European Organization for the Research and Treatment of Cancer trial 10854 (assessing efficacy of perioperative chemotherapy patients with T1–T3, N0–2, and M0 breast cancer (BC) was selected and scored for LVSI. In 358 evaluable breast carcinomas, the number of LVSI foci and tumor cells was determined in the largest tumor embolus within the lymph vessels. These two parameters were multiplied to calculate the LVSI tumor burden (LVSI TB). The optimal cutoff for this parameter was calculated in a test set (N = 120), tested in a validation set (N = 238), and compared with simple quantitation of the number of LVSI foci. Results Tumors with a single LVSI focus are not associated with increased risk for relapse [hazard ratio (HR) 1.423, 95% confidence interval (CI) 0.762–2.656]. The LVSI TB had higher sensitivity and specificity compared with simple determination of the number of LVSI foci. LVSI TB was independently associated with disease-free survival in the validation set (HR 2.366, 95% CI 1.369–4.090, P = 0.002) in multivariate analysis and provided prognostic information in both the low- and high-risk node-negative BC groups (P < 0.001 and P = 0.007, respectively). Conclusion The determination of the number of LVSI foci multiplied by the number of tumor cells gives the most reliable quantitative assessment of this parameter, which can provide prognostic information in node-negative BC. [ABSTRACT FROM PUBLISHER]

Published
2013
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22. Do type 1 receptor tyrosine kinases inform treatment choice? A prospectively planned analysis of the TEAM trial.

Author

Bartlett, J M S, Brookes, C L, Piper, T, van de Velde, C J H, Stocken, D, Lyttle, N, Hasenburg, A, Quintayo, M A, Kieback, D G, Putter, H, Markopoulos, C, Kranenbarg, E M-K, Mallon, E A, Dirix, L Y, Seynaeve, C, and Rea, D W

Subjects
PROTEIN-tyrosine kinases, EPIDERMAL growth factor receptors, BREAST cancer, DISEASE relapse, MICROARRAY technology, LONGITUDINAL method
Abstract

Background:Epidermal growth factor receptors contribute to breast cancer relapse during endocrine therapy. Substitution of aromatase inhibitors (AIs) may improve outcomes in HER-positive cancers.Methods:Tissue microarrays were constructed. Quantitative analysis of HER1, HER2, and HER3 was performed. Data were analysed relative to disease-free survival and treatment using outcomes at 2.75 and 6.5 years.Results:Among 4541 eligible samples, 4225 (93%) had complete HER1-3 data. Overall, 5% were HER1-positive, 13% HER2-positive, and 21% HER3-positive; 32% (n=1351) overexpressed at least one HER receptor. In the HER1-3-negative subgroup, the hazard ratio (HR) for upfront exemestane vs tamoxifen at 2.75 years was 0.67 (95% confidence interval (CI), 0.52-0.87), in the HER1-3-positive subgroup, the HR was 1.15 (95% CI, 0.85-1.56). A prospectively planned treatment-by-marker analysis demonstrated a significant interaction between HER1-3 and treatment at 2.75 years (HR=0.58; 95% CI, 0.39-0.87; P=0.008), as confirmed by multivariate regression analysis adjusting for prognostic factors (HR=0.55; 95% CI, 0.36-0.85; P=0.005). This effect was time dependent.Conclusion:In the 2.75 years prior to switching patients initially treated with tamoxifen to exemestane, a significant treatment-by-marker effect exists between AI/tamoxifen treatment and HER1-3 expression, suggesting HER expression could be used to select appropriate endocrine treatment at diagnosis to prevent or delay early relapses. [ABSTRACT FROM AUTHOR]

Published
2013
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23. Self-reported cognitive functioning in postmenopausal breast cancer patients before and during endocrine treatment: findings from the neuropsychological TEAM side-study.

Author

Schilder, C. M. T., Seynaeve, C., Linn, S. C., Boogerd, W., Beex, L. V. A. M., Gundy, C. M., Nortier, J. W. R., van de Velde, C. J. H., van Dam, F. S. A. M., and Schagen, S. B.

Subjects
COGNITIVE ability, SELF-evaluation, POSTMENOPAUSE, BREAST cancer, ANXIETY in women
Abstract

Objective: This study aimed to evaluate self-reported cognitive functioning of postmenopausal breast cancer patients before and during endocrine treatment compared with healthy female controls, and to investigate associations between self-reported cognitive functioning, cognitive test performance and anxiety/depression, fatigue, and menopausal complaints. Methods: Self-reported cognitive functioning, anxiety/depression, fatigue, menopausal complaints, and cognitive tests performance were assessed before (T1) and after 1 year (T2) of adjuvant endocrine treatment in postmenopausal chemotherapy-naïve breast cancer patients. Self-reported cognitive functioning was assessed by the cognitive failures questionnaire and interview questions concerning cognitive complaints. Patients participated in the TEAM-trial, a prospective randomized study investigating tamoxifen versus exemestane as adjuvant therapy for hormone-sensitive breast cancer. Identical information was obtained from healthy postmenopausal volunteers. Results: Two measures for self-reported cognitive functioning provided the distinctive results. At T1 and T2, healthy controls reported a higher frequency of cognitive failures than patients; change over time did not differ between groups. The prevalence of cognitive complaints did not differ between the groups at T1, but change over time regarding attention/concentration complaints differed between groups, due to an increased prevalence in tamoxifen users. Self-reported cognitive functioning showed moderate associations with anxiety/depression, fatigue, and menopausal complaints. Cognitive test performance was not associated with self-reported cognitive functioning, but weakly with anxiety/depression and fatigue. Conclusion: Adjuvant therapy with tamoxifen and exemestane did not influence the self-reported frequency of cognitive failures. Increased attention/concentration complaints were observed in tamoxifen users, but not in exemestane users. This latter finding should be confirmed with better validated instruments. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Published
2012
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24. Specific activity of cyclin-dependent kinase I is a new potential predictor of tumour recurrence in stage II colon cancer.

Author

Zeestraten, E C M, Maak, M, Shibayama, M, Schuster, T, Nitsche, U, Matsushima, T, Nakayama, S, Gohda, K, Friess, H, van de Velde, C J H, Ishihara, H, Rosenberg, R, Kuppen, P J K, and Janssen, K-P

Subjects
BIOMARKERS, TUMORS, BREAST cancer, METASTASIS, COLON cancer, COHORT analysis
Abstract

Background:There are no established biomarkers to identify tumour recurrence in stage II colon cancer. As shown previously, the enzymatic activity of the cyclin-dependent kinases 1 and 2 (CDK1 and CDK2) predicts outcome in breast cancer. Therefore, we investigated whether CDK activity identifies tumour recurrence in colon cancer.Methods:In all, 254 patients with completely resected (R0) UICC stage II colon cancer were analysed retrospectively from two independent cohorts from Munich (Germany) and Leiden (Netherlands). None of the patients received adjuvant treatment. Development of distant metastasis was observed in 27 patients (median follow-up: 86 months). Protein expression and activity of CDKs were measured on fresh-frozen tumour samples.Results:Specific activity (SA) of CDK1 (CDK1SA), but not CDK2, significantly predicted distant metastasis (concordance index=0.69, 95% confidence interval (CI): 0.55-0.79, P=0.036). Cutoff derivation by maximum log-rank statistics yielded a threshold of CDK1SA at 11 (SA units, P=0.029). Accordingly, 59% of patients were classified as high-risk (CDK1SA 11). Cox proportional hazard analysis revealed CDK1SA as independent prognostic variable (hazard ratio=6.2, 95% CI: 1.44-26.9, P=0.012). Moreover, CKD1SA was significantly elevated in microsatellite-stable tumours.Conclusion:Specific activity of CDK1 is a promising biomarker for metastasis risk in stage II colon cancer. [ABSTRACT FROM AUTHOR]

Published
2012
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25. Which factors should be taken into account in perimenopausal women with early breast cancer who may become eligible for an aromatase inhibitor? Recommendations of an expert panel.

Author

Ortmann, O., Pagani, O., Jones, A., Maass, N., Noss, D., Rugo, H., van de Velde, C., Aapro, Matti, and Coleman, R.

Abstract

Summary: Menopausal status is a major consideration in adjuvant breast cancer therapy. The variable onset and duration of the menopausal transition and the poor predictive value of bleeding patterns and hormone levels mean many women fall naturally into a “perimenopausal” category. Women becoming amenorrhoeic during cytotoxic or endocrine treatment are also of uncertain status since ovarian function may resume even in older patients after several months without menses. The recent St. Gallen panel acknowledged that aromatase inhibitors (AIs) should form part of standard endocrine therapy for postmenopausal women with receptor-positive tumours. Among perimenopausal women at sufficiently high risk of recurrence, there may also be a case for adjuvant AIs either up-front or after tamoxifen. Such treatment should be initiated only after careful consideration of the patient’s age, menstrual history and the effects of tamoxifen (which may make hormone levels an unreliable guide to ovarian function). In treatment-naïve women whose postmenopausal status cannot be confirmed by reliable, serial hormone measurements, treatment should start with tamoxifen. Serial monitoring of hormone levels may enable an AI to be started if postmenopausal status is confirmed. In women with treatment-induced amenorrhoea, any decision to start an AI requires baseline hormone levels consistent with postmenopausal status; and continuation of treatment requires that hormone levels remain postmenopausal during regular monitoring. [ABSTRACT FROM AUTHOR]

Published
2011
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26. Localization of non-palpable breast cancer using a radiolabelled titanium seed.

Author

van Riet, Y. E. A., Jansen, F. H., van Beek, M., van de Velde, C. J. H., Ruttent, H. J. T., and Nieuwenhuijzen, G. A. P.

Subjects
THERAPEUTIC use of iodine, BREAST cancer, LUMPECTOMY, MEDICAL screening, CANCER treatment
Abstract

The article presents a study which investigates the effectiveness of using iodine-125-radiolabelled (I-125) titanium seed in the localization of non-palpable breast cancer. The results show that the use of I-125 is safe in the localization of palpable breast cancer. It was concluded that theses results indicate that I-125 can lead to a high proportion of radical lumpectomies.

Published
2010
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27. Validation study of the prognostic value of cyclin-dependent kinase (CDK)-based risk in Caucasian breast cancer patients.

Author

van Nes, J. G. H., Smit, V. T. H. B. M., Putter, H., Kuppen, P. J., Kim, S. J., Daito, M., Ding, J., Shibayama, M., Numada, S., Gohda, K., Matsushima, T., Ishihara, H., Noguchi, S., and van de Velde, C. J. H.

Subjects
CYCLIN-dependent kinases, PROTEIN kinases, BREAST cancer, CANCER risk factors, CANCER patients
Abstract

In a Japanese study, cyclin-dependent kinase (CDK) based risk determined by CDK 1 and 2 activities was associated with risk of distance recurrence in early breast cancer patients. The aim of our study was to validate this risk categorization in European early breast cancer patients. We retrospectively analyzed frozen breast cancer specimens of 352 Dutch patients with histologically confirmed primary invasive early breast cancer. CDK-based risk was determined in tumour tissues by calculating a risk score (RS) according to kinases activity and protein mass concentration assay without the knowledge of outcome. Determination of CDK-based risk was feasible in 184 out of 352 (52%) tumours. Median follow-up of these patients was 15 years. In patients not receiving systemic treatment, the proportions of risk categories were 44% low, 16% intermediate, and 40% high CDK-based risk. These groups remained significant after univariate and multivariate Cox-regression analysis. Factors associated with a shorter distant recurrence-free period were positive lymph nodes, mastectomy with radiotherapy, and high CDK-based risk. There was no significant correlation with overall survival (OS). CDK-based risk is a prognostic marker of distance recurrence of patients with early breast cancer. More validation would be warranted to use of CDK-based risk into clinical practice. [ABSTRACT FROM AUTHOR]

Published
2009
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28. Stability of preferences with regard to adjuvant chemotherapy: impact of treatment decision, experience and the passing of time.

Author

JANSEN, S. J. T., OTTEN, W., BAAS-THIJSSEN, M. C. M., VAN DE VELDE, C. J. H., NORTIER, H. W. R., and STIGGELBOUT, A. M.

Subjects
DRUG therapy, DECISION making, COLON cancer, BREAST cancer, EXPERIENCE
Abstract

Research has shown that patients' preferences for adjuvant chemotherapy do not change as a result of experience. However, the preferences of experienced patients are usually more favourable than those of inexperienced patients. These results indicate a shift in preferences after the decision to proceed with adjuvant chemotherapy has been made, but before actual experience. We tested this assumption in early-stage breast and colorectal cancer patients. We asked patients to provide their preferences for chemotherapy before surgery and thus before they knew whether chemotherapy would be advised (T1), after surgery but before the start of chemotherapy (T2) and about 1 month after chemotherapy (T3). Patients who did not undergo chemotherapy co-operated at similar points in time. Preferences were measured on a nine-point scale, ranging from (1) ‘very strong preference for no chemotherapy’ to (9) ‘very strong preference for chemotherapy’. As hypothesized, the preferences of patients who would be treated with chemotherapy became more favourable after the treatment decision had been made ( n = 7, P = 0.06). The preferences of patients for whom chemotherapy was not part of the treatment plan showed the opposite effect ( n = 38, P = 0.03). We did not find any effect of experiencing treatment ( n = 22, P = 0.62) or the passing of time ( n = 81, P = 0.25) on the stability of preferences. We conclude that the frequently observed discrepancy in treatment preferences between experienced and inexperienced patients seems to be an effect of the treatment decision and not of experience of the treatment. [ABSTRACT FROM AUTHOR]

Published
2008
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29. Neoadjuvant chemotherapy for operable breast cancer.

Author

Mieog, J. S. D., Van Der Hage, J. A., and Van De Velde, C. J. H.

Subjects
DRUG therapy, BREAST cancer, MASTECTOMY, CLINICAL trials, META-analysis
Abstract

Background: Neoadjuvant chemotherapy for early breast cancer can avoid mastectomy by shrinkage of tumour volume. This review assesses the effectiveness of neoadjuvant chemotherapy on clinical outcome. Methods: All randomized trials comparing neoadjuvant and adjuvant chemotherapy for early breast cancer were reviewed systematically and meta-analyses were performed. Results: Fourteen studies randomizing 5500 women were eligible for analysis. Overall survival was equivalent in both groups. In the neoadjuvant group, the mastectomy rate was lower (relative risk 0.71 (95 per cent confidence interval (c.i.) 0.67 to 0.75)) without hampering local control (hazard ratio 1.12 (95 per cent c.i. 0.92 to 1.37)). Neoadjuvant chemotherapy was associated fewer adverse effects. Conclusion: Neoadjuvant chemotherapy is an established treatment option for early breast cancer. [ABSTRACT FROM AUTHOR]

Published
2007
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30. Overexpression of P70 S6 kinase protein is associated with increased risk of locoregional recurrence in node-negative premenopausal early breast cancer patients.

Author

van der Hage, J. A., van den Broek, L. J. C. M., Legrand, C., Clahsen, P. C., Bosch, C. J. A., Robanus-Maandag, E. C., van de Velde, C. J. H., and van de Vijver, M. J.

Subjects
BREAST cancer, IMMUNOHISTOCHEMISTRY, MULTIVARIATE analysis, DIAGNOSTIC use of tumor markers, CANCER treatment
Abstract

The RPS6KB1 gene is amplified and overexpressed in approximately 10% of breast carcinomas and has been found associated with poor prognosis. We studied the prognostic significance of P70 S6 kinase protein (PS6K) overexpression in a series of 452 node-negative premenopausal early-stage breast cancer patients (median follow-up: 10.8 years). Immunohistochemistry was used to assess PS6K expression in the primary tumour, which had previously been analysed for a panel of established prognostic factors in breast cancer. In a univariate analysis, PS6K overexpression was associated with worse distant disease-free survival as well as impaired locoregional control (HR 1.80, P 0.025 and HR 2.50, P 0.006, respectively). In a multivariate analysis including other prognostic factors, PS6K overexpression remained an independent predictor for poor locoregional control (RR 2.67, P 0.003). To our knowledge, P70 S6 kinase protein is the first oncogenic marker that has prognostic impact on locoregional control and therefore may have clinical implications in determining the local treatment strategy in early-stage breast cancer patients.British Journal of Cancer (2004) 90, 1543-1550. doi:10.1038/sj.bjc.6601741 www.bjcancer.com Published online 30 March 2004 [ABSTRACT FROM AUTHOR]

Published
2004
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31. Patient's needs and preferences in routine follow-up after treatment for breast cancer.

Author

de Bock, G. H., Bonnema, J., Zwaan, R. E., van de Velde, C. J. H., Kievit, J., and Stiggelbout, A. M.

Subjects
BREAST cancer, CANCER education, GENETIC disorders, CANCER patients, INFORMATION resources, PATIENT satisfaction, WOMEN'S health
Abstract

The purpose of the study was to analyse the needs of women who participated in a routine follow-up programme after treatment for primary breast cancer. A cross-sectional survey was conducted using a postal questionnaire among women without any sign of relapse during the routine follow-up period. The questionnaire was sent 2-4 years after primary surgical treatment. Most important to patients was information on long-term effects of treatment and prognosis, discussion of prevention of breast cancer and hereditary factors and changes in the untreated breast. Patients preferred additional investigations (such as X-ray and blood tests) to be part of routine follow-up visits. Less satisfaction with interpersonal aspects and higher scores on the Hospital Anxiety and Depression Scale (HADS) scale were related to stronger preferences for additional investigation. Receiving adjuvant hormonal or radiotherapy was related to a preference for a more intensive follow-up schedule. There were no significant differences between patients treated with mastectomy compared to treated with breast-conserving therapy. During routine follow-up after a diagnosis of breast cancer, not all patients needed all types of information. When introducing alternative follow-up schedules, individual patients’ information needs and preferences should be identified early and incorporated into the follow-up routine care, to target resources and maximise the likelihood that positive patient outcomes will result.British Journal of Cancer (2004) 90, 1144-1150. doi:10.1038/sj.bjc.6601655 www.bjcancer.com Published online 24 February 2004 [ABSTRACT FROM AUTHOR]

Published
2004
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32. Surgical Treatment of Early Stage Breast Cancer in Elderly: An International Comparison

Author

Kiderlen, M., Bastiaannet, E., Schrodi, S., Engel, J., van de Water, W., Ess, S. M., van Eycken, L., Miranda, A., de Munck, L., van de Velde, C. J. H., de Craen, A. J. M., Liefers, G. J., Walsh, P.M., and Keating, Nancy Lynn

Subjects
breast cancer, elderly, surgery, treatment, survival, population-based
Abstract

Over 40% of breast cancer patients are diagnosed above the age of 65. Treatment of these elderly patients will probably vary over countries. The aim of this study was to make an international comparison (several European countries and the US) of surgical and radiation treatment for elderly women with early stage breast cancer. Survival comparisons were also made. Data were obtained from national or regional population-based registries in the Netherlands, Switzerland, Ireland, Belgium, Germany, and Portugal. For the US patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Early stage breast cancer patients aged ≥65 diagnosed between 1995 and 2005 were included. An international comparison was made for breast and axillary surgery, radiotherapy after breast conserving surgery (BCS), and relative or cause-specific survival. Overall, 204.885 patients were included. The proportion of patients not receiving any surgery increased with age in many countries; however, differences between countries were large. In most countries more than half of all elderly patients received breast conserving surgery (BCS), with the highest percentage in Switzerland. The proportion of elderly patients that received radiotherapy after BCS decreased with age in all countries. Moreover, in all countries the proportion of patients who do not receive axillary surgery increased with age. No large differences in survival between countries were recorded. International comparisons of surgical treatment for elderly women with early stage breast cancer are scarce. This study showed large international differences in treatment of elderly early stage breast cancer patients, with the most striking result the large proportion of elderly who did not undergo surgery at all. Despite large treatment differences, survival does not seem to be affected in a major way.

Published
2011
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33. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials

Author

Abe, O., Abe, R., Enomoto, K., Kikuchi, K., Koyama, H., Masuda, H., Nomura, Y., Sakai, K., Sugimachi, K., Tominaga, T., Uchino, J., Yoshida, M., Haybittle, J. L., Davies, C., Harvey, V. J., Holdaway, T. M., Kay, R. G., Mason, B. H., Forbes, J. F., Wilcken, N., Gnant, M., Jakesz, R., Ploner, M., Yosef, H. M. A., Focan, C., Lobelle, J. P., Peek, U., Oates, G. D., Powell, J., Durand, M., Mauriac, L., Di Leo, A., Dolci, S., Piccart, M. J., Masood, M. B., Parker, D., Price, J. J., Hupperets, P. S. G. J., Jackson, S., Ragaz, J., Berry, D., Broadwater, G., Cirrincione, C., Muss, H., Norton, L., Weiss, R. B., Abu-Zahra, H. T., Portnoj, S. M., Baum, M., Cuzick, J., Houghton, J., Riley, D., Mansel, R. E., Gordon, N. H., Davis, H. L., Beatrice, A., Mihura, J., Naja, A., Lehingue, Y., Romestaing, P., Dubois, J. B., Delozier, T., Mace Lesec'h, J., Rambert, P., Petruzelka, L., Pribylova, O., Owen, J. R., Harbeck, N., Jänicke, F., Meisner, C., Meier, P., Howell, A., Ribeiro, G. C., Swindell, R., Burrett, J., Clarke, M., Collins, R., Darby, S., Elphinstone, P., Evans, V., Godwin, J., Gray, R., Harwood, C., Hicks, C., Jackson, D., James, S., Mackinnon, E., Mcgale, P., Mchugh, T., Mead, G., Morris, P., Oulds, J., Peto, R., Taylor, C., Wang, Y., Albano, J., De Oliveira, C. F., Gervásio, H., Gordilho, J., Johansen, H., Mouridsen, H. T., Gelman, R. S., Harris, J. R., Henderson, I. C., Shapiro, C. L., Christiansen, P., Ejlertsen, B., Møller, S., Overgaard, M., Carstensen, B., Palshof, T., Trampisch, H. J., Dalesio, O., De Vries, E. G. E., Rodenhuis, S., Van Tinteren, H., Comis, R. L., Davidson, N. E., Robert, N., Sledge, G., Tormey, D. C., Wood, W., Cameron, D., Chetty, U., Forrest, P., Jack, W., Rossbach, J., Klijn, J. G. M., Treurniet-Donker, A. D., Van Putten, W. L. J., Costa, A., Veronesi, U., Bartelink, H., Duchateau, L., Legrand, C., Sylvester, R., Van Der Hage, J. A., Van De Velde, C. J. H., Cunningham, M. P., Catalano, R., Creech, R. H., Bonneterre, J., Fargeot, P., Fumoleau, P., Kerbrat, P., Namer, M., Jonat, W., Kaufmann, M., Schumacher, M., Von Minckwitz, G., Bastert, G., Rauschecker, H., Sauer, R., Sauerbrei, W., Schauer, A., De Schryver, A., Vakaet, L., Belfiglio, M., Nicolucci, A., Pellegrini, F., Sacco, M., Valentini, M., Mcardle, C. S., Smith, D. C., Galligioni, E., Boccardo, F., Rubagotti, A., Dent, D. M., Gudgeon, C. A., Hacking, A., Erazo, A., Medina, J. Y., Izuo, M., Morishita, Y., Takei, H., Fentiman, I. S., Hayward, J. L., Rubens, R. D., Skilton, D., Scheurlen, H., Von Fournier, D., Dafni, U., Fountzilas, G., Klefstrom, P., Blomqvist, C., Saarto, T., Margreiter, R., Asselain, B., Salmon, R. J., Vilcoq, J. R., Arriagada, R., Hill, C., Laplanche, A., M. G., Lê, Spielmann, M., Bruzzi, P., Montanaro, E., Rosso, R., Sertoli, M. R., Venturini, M., Amadori, D., Benraadt, J., Kooi, M., Van De Velde, A. O., Van Dongen, J. A., Vermorken, J. B., Castiglione, M., Cavalli, F., Coates, A., Collins, J., Forbes, J., Gelber, R. D., Goldhirsch, A., Lindtner, J., Price, K. N., Rudenstam, C. M., Senn, H. J., Bliss, J. M., Chilvers, C. E. D., Coombes, R. C., Hall, E., Marty, M., Borovik, R., Brufman, G., Hayat, H., Robinson, E., Wigler, N., Bonadonna, G., Camerini, T., De Palo, G., Del Vecchio, M., Formelli, F., Valagussa, P., Martoni, A., Pannuti, F., Cocconi, G., Colozza, A., Camisa, R., Aogi, K., Takashima, S., Ikeda, T., Inokuchi, K., Sawa, K., Sonoo, H., Korzeniowski, S., Skolyszewski, J., Ogawa, M., Yamashita, J., Bonte, J., Christiaens, R., Paridaens, R., Van Den Bogaert, W., Martin, P., Geniez, ROMAIN SYLVAIN JEAN, Hakes, T., Hudis, C. A., Wittes, R., Giokas, G., Kondylis, D., Lissaios, B., De La Huerta, R., Sainz, M. G., Altemus, R., Cowan, K., Danforth, D., Lichter, A., Lippman, M., O'Shaughnessy, J., Pierce, L. J., Steinberg, S., Venzon, D., Zujewski, J. A., Paradiso, A., De Lena, M., Schittulli, F., Myles, J. D., Pater, J. L., Pritchard, K. I., Whelan, T., Anderson, S., Bass, G., Brown, A., Bryant, J., Costantino, J., Dignam, J., Fisher, B., Redmond, C., Wieand, S., Wolmark, N., Jackson, I. M., Palmer, M. K., Ingle, J. N., Suman, V. J., Bengtsson, N. O., Jonsson, H., Larsson, L. G., Lythgoe, J. P., Kissin, M., Erikstein, B., Hannisdal, E., Jacobsen, A. B., Varhaug, J. E., Gundersen, S., Hauer-Jensen, M., Høst, H., Nissen-Meyer, R., Blamey, R. W., Mitchell, A. K., Morgan, D. A. L., Robertson, J. F. R., Di Palma, M., Mathé, G., Misset, J. L., Clark, R. M., Levine, M., Morimoto, K., Takatsuka, Y., Crossley, E., Harris, A., Talbot, D., Taylor, M., Di Blasio, B., Ivanov, V., Semiglazov, V., Brockschmidt, J., Cooper, M. R., Ueo, H., Falkson, C. I., A'Hern, R., Ashley, S., Powles, T. J., Smith, I. E., Yarnold, J. R., Gazet, J. C., Corcoran, N., Deshpande, N., Di Martino, L., Douglas, P., Lindtner, A., Notter, G., Bryant, A. J. S., Ewing, G. H., Firth, L. A., Krushen-Kosloski, J. L., Foster, L., George, W. D., Stewart, H. J., Stroner, P., Malmström, P., Möller, T. R., Rydén, S., Tengrup, I., Tennvall-Nittby, L., Carstenssen, J., Dufmats, M., Hatschek, T., Nordenskjöld, B., Söderberg, M., Carpenter, J. T., Albain, K., Crowley, J., Green, S., Martino, S., Osborne, C. K., Ravdin, P. M., Glas, U., Johansson, U., Rutqvist, L. E., Singnomklao, T., Wallgren, A., Maibach, R., Thürlimann, B., Brenner, H., Hercbergs, A., Yoshimoto, M., Deboer, G., Paterson, A. H. G., Meakin, J. W., Panzarella, T., Shan, Y., Shao, Y. F., Wang, X., Zhao, D. B., Chen, Z. M., Pan, H. C., Bahi, J., Reid, M., Spittle, M., Deutsch, G. P., Senanayake, F., Kwong, D. L. W., Bianco, A. R., Carlomagno, C., De Laurentiis, M., De Placido, S., Buzdar, A. U., Smith, T., Bergh, J., Holmberg, L., Liljegren, G., Nilsson, J., Seifert, M., Sevelda, P., Zielinsky, C. C., Buchanan, R. B., Cross, M., Royle, G. T., Dunn, J. A., Hills, R. K., Lee, M., Morrison, J. M., Spooner, D., Litton, A., Chlebowski, R. T., Caffier, H., Clarke, M, Collins, R, Darby, S, Davies, C, Elphinstone, P, Evans, E, Godwin, J, Gray, R, Hicks, C, James, S, MacKinnon, E, McGale, P, McHugh, T, Peto, R, Taylor, C, and Wang, Y

Subjects
medicine.medical_specialty, Time Factors, medicine.medical_treatment, Breast Neoplasms, Rate ratio, Breast Conservation Treatment, Disease-Free Survival, Breast cancer, Cause of Death, Breast-conserving surgery, Medicine, Humans, Lung cancer, Aged, Probability, Randomized Controlled Trials as Topic, business.industry, Female, Middle Aged, Neoplasm Recurrence, Local, Medicine (all), General Medicine, medicine.disease, Surgery, Radiation therapy, Unilateral Breast Neoplasms, Neoplasm Recurrence, Local, business, Mastectomy
Abstract

Background In early breast cancer, variations in local treatment that substantially affect the risk of locoregional recurrence could also affect long-term breast cancer mortality. To examine this relationship, collaborative meta-analyses were undertaken, based on individual patient data, of the relevant randomised trials that began by 1995. Methods Information was available on 42 000 women in 78 randomised treatment comparisons (radiotherapy vs no radiotherapy, 23 500; more vs less surgery, 9300; more surgery vs radiotherapy, 9300). 24 types of local treatment comparison were identified. To help relate the effect on local (ie, locoregional) recurrence to that on breast cancer mortality, these were grouped according to whether or not the 5-year local recurrence risk exceeded 10% (10%, 25 000 women). Findings About three-quarters of the eventual local recurrence risk occurred during the first 5 years. In the comparisons that involved little (10%) differences, however, 5-year local recurrence risks were 7% active versus 26% control (absolute reduction 19%), and 15-year breast cancer mortality risks were 44·6% versus 49·5% (absolute reduction 5·0%, SE 0·8, 2p These 25 000 women included 7300 with breast-conserving surgery (BCS) in trials of radiotherapy (generally just to the conserved breast), with 5-year local recurrence risks (mainly in the conserved breast, as most had axillary clearance and node-negative disease) 7% versus 26% (reduction 19%), and 15-year breast cancer mortality risks 30·5% versus 35·9% (reduction 5·4%, SE 1·7, 2p=0·0002; overall mortality reduction 5·3%, SE 1·8, 2p=0·005). They also included 8500 with mastectomy, axillary clearance, and node-positive disease in trials of radiotherapy (generally to the chest wall and regional lymph nodes), with similar absolute gains from radiotherapy; 5-year local recurrence risks (mainly at these sites) 6% versus 23% (reduction 17%), and 15-year breast cancer mortality risks 54·7% versus 60·1% (reduction 5·4%, SE 1·3, 2p=0·0002; overall mortality reduction 4·4%, SE 1·2, 2p=0·0009). Radiotherapy produced similar proportional reductions in local recurrence in all women (irrespective of age or tumour characteristics) and in all major trials of radiotherapy versus not (recent or older; with or without systemic therapy), so large absolute reductions in local recurrence were seen only if the control risk was large. To help assess the life-threatening side-effects of radiotherapy, the trials of radiotherapy versus not were combined with those of radiotherapy versus more surgery. There was, at least with some of the older radiotherapy regimens, a significant excess incidence of contralateral breast cancer (rate ratio 1·18, SE 0·06, 2p=0·002) and a significant excess of non-breast-cancer mortality in irradiated women (rate ratio 1·12, SE 0·04, 2p=0·001). Both were slight during the first 5 years, but continued after year 15. The excess mortality was mainly from heart disease (rate ratio 1·27, SE 0·07, 2p=0·0001) and lung cancer (rate ratio 1·78, SE 0·22, 2p=0·0004). Interpretation In these trials, avoidance of a local recurrence in the conserved breast after BCS and avoidance of a local recurrence elsewhere (eg, the chest wall or regional nodes) after mastectomy were of comparable relevance to 15-year breast cancer mortality. Differences in local treatment that substantially affect local recurrence rates would, in the hypothetical absence of any other causes of death, avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.

34. A patient-centred instrument for assessment of quality of breast cancer care: results of a pilot questionnaire.

Author

de Kok, M, Sixma, H J M, van der Weijden, T, Kessels, A G H, Dirksen, C D, Spijkers, K F J, van de Velde, C J H, Roukema, J A, van der Ent, F W C, Finaly-Marais, C, and von Meyenfeldt, M F

Abstract

Background In several breast cancer research environments, there was a need to develop a questionnaire that would (1) provide data on how breast cancer patients experience healthcare services, (2) address issues corresponding with patients' needs and expectations and (3) produce useful data for quality assessment and improvement projects aimed at breast cancer care. This article describes the first part of the quantitative process of item selection, instrument construction and optimisation based on the results of a pilot questionnaire. Methods Based on qualitative research, a pilot questionnaire with items formulated as “performance” and “importance” statements was developed and sent to all breast cancer patients operated on in the previous 3–15 months in five participating hospitals. Reduction criteria, exploratory factor analysis and reliability analysis were used as part of the process of instrument optimisation. Results Of the 637 questionnaires sent out, 299 (47%) were returned and 276 (43%) were used for analyses. Out of the 72 quality items included in the pilot questionnaire, 42 items did not meet the inclusion criteria for the revised version. The remaining items refer to the factors patient education regarding aspects related to postoperative treatment, services by the breast nurse, services by the surgeon, patient education regarding activities at home and patient education regarding aspects related to preoperative treatment (Cronbach α=0.70–0.89). Conclusions In this study, the number of items to be included in the self-administered questionnaire was reduced. The resulting set of items that determines patients' perceptions on quality of breast cancer care is easy to complete and enables anonymous responses. Further research can be aimed at establishing the reliability of the current questionnaire. [ABSTRACT FROM PUBLISHER]

Published
2010
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35. Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials

Author

Richard Gray, Rosie Bradley, Jeremy Braybrooke, Zulian Liu, Richard Peto, Lucy Davies, David Dodwell, Paul McGale, Hongchao Pan, Carolyn Taylor, William Barlow, Judith Bliss, Paolo Bruzzi, David Cameron, George Fountzilas, Sibylle Loibl, John Mackey, Miguel Martin, Lucia Del Mastro, Volker Möbus, Valentina Nekljudova, Sabino De Placido, Sandra Swain, Michael Untch, Kathleen I Pritchard, Jonas Bergh, Larry Norton, Clare Boddington, Julie Burrett, Mike Clarke, Christina Davies, Fran Duane, Vaughan Evans, Lucy Gettins, Jon Godwin, Robert Hills, Sam James, Hui Liu, Elizabeth MacKinnon, Gurdeep Mannu, Theresa McHugh, Philip Morris, Simon Read, Yaochen Wang, Zhe Wang, Peter Fasching, Nadia Harbeck, Pascal Piedbois, Michael Gnant, Guenther Steger, Angelo Di Leo, Stella Dolci, Prue Francis, Denis Larsimont, Jean Marie Nogaret, Catherine Philippson, Martine Piccart, Sabine Linn, Petronella Peer, Vivianne Tjan-Heijnen, Sonja Vliek, Dennis Slamon, John Bartlett, Vivien H Bramwell, Bingshu Chen, Stephen Chia, Karen Gelmon, Paul Goss, Mark Levine, Wendy Parulekar, Joseph Pater, Eileen Rakovitch, Lois Shepherd, Dongsheng Tu, Tim Whelan, Don Berry, Gloria Broadwater, Constance Cirrincione, Hyman Muss, Raymond Weiss, Yi Shan, Yong Fu Shao, Xiang Wang, Binghe Xu, Dong-Bing Zhao, Harry Bartelink, Nina Bijker, Jan Bogaerts, Fatima Cardoso, Tanja Cufer, Jean-Pierre Julien, Philip Poortmans, Emiel Rutgers, Cornelis van de Velde, Eva Carrasco, Miguel Angel Segui, Jens Uwe Blohmer, Serban Costa, Bernd Gerber, Christian Jackisch, Gunter von Minckwitz, Mario Giuliano, Michele De Laurentiis, Christina Bamia, Georgia-Angeliki Koliou, Dimitris Mavroudis, Roger A'Hern, Paul Ellis, Lucy Kilburn, James Morden, John Yarnold, Mohammad Sadoon, Augustinus H Tulusan, Stewart Anderson, Gordon Bass, Joe Costantino, James Dignam, Bernard Fisher, Charles Geyer, Eleftherios P Mamounas, Soon Paik, Carol Redmond, D Lawrence Wickerham, Marco Venturini, Claudia Bighin, Simona Pastorino, Paolo Pronzato, Mario Roberto Sertoli, Theodorus Foukakis, Kathy Albain, Rodrigo Arriagada, Elizabeth Bergsten Nordström, Francesco Boccardo, Etienne Brain, Lisa Carey, Alan Coates, Robert Coleman, Candace Correa, Jack Cuzick, Nancy Davidson, Mitch Dowsett, Marianne Ewertz, John Forbes, Richard Gelber, Aron Goldhirsch, Pamela Goodwin, Daniel Hayes, Catherine Hill, James Ingle, Reshma Jagsi, Wolfgang Janni, Hirofumi Mukai, Yasuo Ohashi, Lori Pierce, Vinod Raina, Peter Ravdin, Daniel Rea, Meredith Regan, John Robertson, Joseph Sparano, Andrew Tutt, Giuseppe Viale, Nicholas Wilcken, Norman Wolmark, Wiliam Wood, Milvia Zambetti, Gray, R., Bradley, R., Braybrooke, J., Liu, Z., Peto, R., Davies, L., Dodwell, D., Mcgale, P., Pan, H., Taylor, C., Barlow, W., Bliss, J., Bruzzi, P., Cameron, D., Fountzilas, G., Loibl, S., Mackey, J., Martin, M., Del Mastro, L., Mobus, V., Nekljudova, V., De Placido, S., Swain, S., Untch, M., Pritchard, K. I., Bergh, J., Norton, L., Boddington, C., Burrett, J., Clarke, M., Davies, C., Duane, F., Evans, V., Gettins, L., Godwin, J., Hills, R., James, S., Liu, H., Mackinnon, E., Mannu, G., Mchugh, T., Morris, P., Read, S., Wang, Y., Wang, Z., Fasching, P., Harbeck, N., Piedbois, P., Gnant, M., Steger, G., Di Leo, A., Dolci, S., Francis, P., Larsimont, D., Nogaret, J. M., Philippson, C., Piccart, M., Linn, S., Peer, P., Tjan-Heijnen, V., Vliek, S., Slamon, D., Bartlett, J., Bramwell, V. H., Chen, B., Chia, S., Gelmon, K., Goss, P., Levine, M., Parulekar, W., Pater, J., Rakovitch, E., Shepherd, L., Tu, D., Whelan, T., Berry, D., Broadwater, G., Cirrincione, C., Muss, H., Weiss, R., Shan, Y., Shao, Y. F., Wang, X., Xu, B., Zhao, D. -B., Bartelink, H., Bijker, N., Bogaerts, J., Cardoso, F., Cufer, T., Julien, J. -P., Poortmans, P., Rutgers, E., van de Velde, C., Carrasco, E., Segui, M. A., Blohmer, J. U., Costa, S., Gerber, B., Jackisch, C., von Minckwitz, G., Giuliano, M., De Laurentiis, M., Bamia, C., Koliou, G. -A., Mavroudis, D., A'Hern, R., Ellis, P., Kilburn, L., Morden, J., Yarnold, J., Sadoon, M., Tulusan, A. H., Anderson, S., Bass, G., Costantino, J., Dignam, J., Fisher, B., Geyer, C., Mamounas, E. P., Paik, S., Redmond, C., Wickerham, D. L., Venturini, M., Bighin, C., Pastorino, S., Pronzato, P., Sertoli, M. R., Foukakis, T., Albain, K., Arriagada, R., Bergsten Nordstrom, E., Boccardo, F., Brain, E., Carey, L., Coates, A., Coleman, R., Correa, C., Cuzick, J., Davidson, N., Dowsett, M., Ewertz, M., Forbes, J., Gelber, R., Goldhirsch, A., Goodwin, P., Hayes, D., Hill, C., Ingle, J., Jagsi, R., Janni, W., Mukai, H., Ohashi, Y., Pierce, L., Raina, V., Ravdin, P., Rea, D., Regan, M., Robertson, J., Sparano, J., Tutt, A., Viale, G., Wilcken, N., Wolmark, N., Wood, W., and Zambetti, M.

Subjects
Oncology, treatment schedule, medicine.medical_specialty, Anthracycline, medicine.medical_treatment, novotvorbe dojk, Antineoplastic Agents, Breast Neoplasms, režim zdravljenja, Disease, randomized trials, 030204 cardiovascular system & hematology, chemotherapy, meta-analiza, klinični protokoli, Drug Administration Schedule, randomizirane raziskave, Antineoplastic Agent, 03 medical and health sciences, breast cancer, 0302 clinical medicine, Breast cancer, Internal medicine, breast neoplasms, medicine, Humans, clinical protocols, terapija z zdravili, 030212 general & internal medicine, Early breast cancer, Chemotherapy, Taxane, business.industry, rak dojk, kemoterapija, General Medicine, medicine.disease, Dose intensity, udc:618.19-006, drug therapy, meta-analysis, Meta-analysis, Female, women, ženske, business, Breast Neoplasm
Abstract

Background Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p Interpretation Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes.

Published
2019
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36. Prognostic and predictive value of ERβ1 and ERβ2 in the Intergroup Exemestane Study (IES)--first results from PathIES.

Author

Speirs, V., Viale, G., Mousa, K., Palmieri, C., Reed, S. N., Nicholas, H., Cheang, M., Jassem, J., Lønning, P. E., Kalaitzaki, E., van de Velde, C. J. H., Rasmussen, B. B., Verhoeven, D. M., Shaaban, A. M., Bartlett, J. M. S., Bliss, J. M., and Coombes, R. C.

Subjects
*BREAST cancer prognosis, *BREAST cancer patients, *TAMOXIFEN, *ESTROGEN receptors, *RANDOMIZED controlled trials, *HORMONE therapy
Abstract

Background: Intergroup Exemestane Study (IES) was a randomised study that showed a survival benefit of switching adjuvant endocrine therapy after 2-3 years from tamoxifen to exemestane. PathIES aimed to assess the potential prognostic and predictive value of ERβ1 and ERβ2 expression in primary tumours in order to determine benefit in the two treatment arms. Patients and methods: Primary tumour samples were available for 1256 patients (27% IES population). ERβ1 and ERβ2 expression was dichotomised at the median IHC score (high if ERβ1 ≥ 191, ERβ2 ≥ 164). Hazard ratios (HRs) were estimated by multivariable Cox proportional hazards models adjusting for clinicopathological factors. Treatment effects with biomarker expressions were determined by interaction tests. Analysis explored effects of markers both as a continuous variable and with dichotomised cut-offs. Results: Neither ERβ1 nor ERβ2 were associated with disease-free survival (DFS) or overall survival (OS) in the whole cohort. In patients treated with continued tamoxifen, high ERβ1 expression compared with low was associated with better DFS [HR = 0.38:95% confidence interval (CI) 0.21-0.68, P = 0.001]. DFS benefit of exemestane over tamoxifen (HR = 0.40:95% CI 0.22-0.70) was found in the low ERβ1 subgroup (interaction P = 0.01). No significant difference with treatment was observed for ERβ2 expression in either DFS or OS. Conclusion: In the PathIES population, exemestane appeared to be superior to tamoxifen among patients with low ERβ1 expression but not in those with high ERβ1 expression. This is the first trial of its kind to report a parameter potentially predicting benefit of an aromatase inhibitor when compared with tamoxifen and an independent validation is warranted. [ABSTRACT FROM AUTHOR]

Published
2015
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37. Dynamic prediction in breast cancer: proving feasibility in clinical practice using the TEAM trial.

Author

Fontein, D. B. Y., Grand, M. Klinten, Nortier, J. W. R., Seynaeve, C., Kranenbarg, E. Meershoek-Klein, Dirix, L. Y., van de Velde, C. J. H., and Putter, H.

Subjects
*BREAST cancer prognosis, *POSTMENOPAUSE, *HORMONE receptors, *CANCER relapse, *PREDICTION models, *FOLLOW-up studies (Medicine)
Abstract

Background: Predictive models are an integral part of current clinical practice and help determine optimal treatment strategies for individual patients. A drawback is that covariates are assumed to have constant effects on overall survival (OS), when in fact, these effects may change during follow-up (FU). Furthermore, breast cancer (BC) patients may experience events that alter their prognosis from that time onwards. We investigated the 'dynamic' effects of different covariates on OS and developed a nomogram to calculate 5-year dynamic OS (DOS) probability at different prediction timepoints (tP) during FU. Methods: Dutch and Belgian postmenopausal, endocrine-sensitive, early BC patients enrolled in the TEAM trial were included. We assessed time-varying effects of specific covariates and obtained 5-year DOS predictions using a proportional baselines landmark supermodel. Covariates included age, histological grade, hormone receptor and HER2 status, T- and N-stage, locoregional recurrence (LRR), distant recurrence, and treatment compliance. A nomogram was designed to calculate 5-year DOS based on individual characteristics. Results: A total of 2602 patients were included (mean FU 6.2 years). N-stage, LRR, and HER2 status demonstrated time-varying effects on 5-year DOS. Hazard ratio (HR) functions for LRR, high-risk N-stage (N2/3), and HER2 positivity were HR = (8.427 × 0.583tP Þ, HR = (3.621 × 0.816tP Þ, and HR = (1.235 × 0.851tP Þ, respectively. Treatment discontinuation was associated with a higher mortality risk, but without a time-varying effect [HR 1.263 (0.867-1.841)]. All other covariates were time-constant. Discussion: The current nomogram accounts for elapsed time since starting adjuvant endocrine treatment and optimizes prediction of individual 5-year DOS during FU for postmenopausal, endocrine-sensitive BC patients. The nomogram can facilitate in determining whether further therapy will benefit an individual patient, although validation in an independent dataset is still needed. [ABSTRACT FROM AUTHOR]

Published
2015
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39. Addition of zoledronic acid to neoadjuvant chemotherapy does not enhance tumor response in patients with HER2-negative stage II/III breast cancer: the NEOZOTAC trial (BOOG 2010-01).

Author

Charehbili, A., van de Ven, S., Smit, V. T. H. B. M., Meershoek-Klein Kranenbarg, E., Hamdy, N. A. T., Putter, H., Heijns, J. B., van Warmerdam, L. J. C., Kessels, L., Dercksen, M., Pepels, M. J., Maartense, E., van Laarhoven, H. W. M., Vriens, B., Wasser, M. N., van Leeuwen-Stok, A. E., Liefers, G. J., van de Velde, C. J. H., Nortier, J. W. R., and Kroep, J. R.

Subjects
*ZOLEDRONIC acid, *CANCER chemotherapy, *ADJUVANT treatment of cancer, *HER2 gene, *BREAST cancer, *CLINICAL trials, *CYCLOPHOSPHAMIDE
Abstract

The phase III randomized NEOZOTAC trial investigated whether the addition of zoledronic acid to neoadjuvant chemotherapy for breast cancer patients results in better pathological response. Our data do not confirm this hypothesis based on data from our total study population. However, our data do suggest that more research investigating a potential benefit in postmenopausal women is warranted.Background The role of zoledronic acid (ZA) when added to the neoadjuvant treatment of breast cancer (BC) in enhancing the clinical and pathological response of tumors is unclear. The effect of ZA on the antitumor effect of neoadjuvant chemotherapy has not prospectively been studied before. Patients and methods NEOZOTAC is a national, multicenter, randomized study comparing the efficacy of TAC (docetaxel, adriamycin and cyclophosphamide i.v.) followed by granulocyte colony-stimulating factor on day 2 with or without ZA 4 mg i.v. q 3 weeks inpatients withstage II/III, HER2-negative BC. We present data on the pathological complete response (pCR in breast and axilla), on clinical response using MRI, and toxicity. Post hoc subgroup analyses were undertaken to address the predictive value of menopausal status. Results Addition of ZA to chemotherapy did not improve pCR rates (13.2% for TAC+ZA versus 13.3% for TAC). Postmenopausal women (N = 96) had a numerical benefit from ZA treatment (pCR 14.0% for TAC+ZA versus 8.7% for TAC, P = 0.42). Clinical objective response did not differ between treatment arms (72.9% versus 73.7%). There was no difference in grade III/IV toxicity between treatment arms. Conclusions Addition of ZA to neoadjuvant chemotherapy did not improve pathological or clinical response to chemotherapy. Further investigations are warranted in postmenopausal women with BC, since this subgroup might benefit from ZA treatment. [ABSTRACT FROM PUBLISHER]

Published
2014

40. Diabetes in relation to breast cancer relapse and all-cause mortality in elderly breast cancer patients: a FOCUS study analysis.

Author

Kiderlen, M., de Glas, N. A., Bastiaannet, E., Engels, C. C., van de Water, W., de Craen, A. J. M., Portielje, J. E. A., van de Velde, C. J. H., and Liefers, G. J.

Subjects
*BREAST cancer treatment, *AGE factors in disease, *CANCER-related mortality, *DIABETES, *HEALTH risk assessment, *COMORBIDITY, *CANCER relapse
Abstract

Background In developed countries, 40% of breast cancer patients are >65 years of age at diagnosis, of whom 16% additionally suffer from diabetes. The aim of this study was to assess the impact of diabetes on relapse-free period (RFP) and overall mortality in elderly breast cancer patients. Patients and Methods Patients were selected from the retrospective FOCUS cohort, which contains detailed information of elderly breast cancer patients. RFP was calculated using Fine and Gray competing risk regression models for patients with diabetes versus patients without diabetes. Overall survival was calculated by Cox regression models, in which patients were divided into four groups: no comorbidity, diabetes only, diabetes and other comorbidity or other comorbidity without diabetes. Results Overall, 3124 patients with non-metastasized breast cancer were included. RFP was better for patients with diabetes compared with patients without diabetes (multivariable HR 0.77, 95% CI 0.59–1.01), irrespective of other comorbidity and most evident in patients aged ≥75 years (HR 0.67, 95% CI 0.45–0.98). The overall survival was similar for patients with diabetes only compared with patients without comorbidity (HR 0.86, 95% CI 0.45-0.98), while patients with diabetes and additional comorbidity had the worst overall survival (HR 1.70, 95% CI 1.44–2.01). Conclusion When taking competing mortality into account, RFP was better in elderly breast cancer patients with diabetes compared with patients without diabetes. Moreover, patients with diabetes without other comorbidity had a similar overall survival as patients without any comorbidity. Possibly, unfavourable effects of (complications of) diabetes on overall survival are counterbalanced by beneficial effects of metformin on the occurrence of breast cancer recurrences. [ABSTRACT FROM PUBLISHER]

Published
2013
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41. The prognostic role of TGF-β signaling pathway in breast cancer patients.

Author

de Kruijf, E. M., Dekker, T. J. A., Hawinkels, L. J. A. C., Putter, H., Smit, V. T. H. B. M., Kroep, J. R., Kuppen, P. J. K., van de Velde, C. J. H., ten Dijke, P., Tollenaar, R. A. E. M., and Mesker, W. E.

Subjects
*TRANSFORMING growth factors, *CELLULAR signal transduction, *BREAST cancer patients, *MEDICAL informatics, *GENE expression, *CANCER prognosis
Abstract

Background The transforming growth factor-β (TGF-β) pathway has dual effects on tumor growth. Seemingly, discordant results have been published on the relation between TGF-β signaling markers and prognosis in breast cancer. Improved prognostic information for breast cancer patients might be obtained by assessing interactions among TGF-β signaling biomarkers. Patients and methods The expression of nuclear Smad4, nuclear phosphorylated-Smad2 (p-Smad2), and the membranous expression of TGF-β receptors I and II (TβRI and TβRII) was determined on a tissue microarray of 574 breast carcinomas. Tumors were stratified according to the Smad4 expression in combination with p-Smad2 expression or Smad4 in combination with the expression of both TGF-β receptors. Results Tumors with high expression of TβRII, TβRI and TβRII, and p-Smad2 (P = 0.018, 0.005, and 0.022, respectively), and low expression of Smad4 (P = 0.005) had an unfavorable prognosis concerning progression-free survival. Low Smad4 expression combined with high p-Smad2 expression or low expression of Smad4 combined with high expression of both TGF-β receptors displayed an increased hazard ratio of 3.04 [95% confidence interval (CI) 1.390–6.658] and 2.20 (95% CI 1.464–3.307), respectively, for disease relapse. Conclusions Combining TGF-β biomarkers provides prognostic information for patients with stage I–III breast cancer. This can identify patients at increased risk for disease recurrence that might therefore be candidates for additional treatment. [ABSTRACT FROM PUBLISHER]

Published
2013
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42. Relationship between specific adverse events and efficacy of exemestane therapy in early postmenopausal breast cancer patients.

Author

Fontein, D. B. Y., Houtsma, D., Hille, E. T. M., Seynaeve, C., Putter, H., Meershoek-Klein Kranenbarg, E., Guchelaar, H. J., Gelderblom, H., Dirix, L. Y., Paridaens, R., Bartlett, J. M. S., Nortier, J. W. R., and van de Velde, C. J. H.

Subjects
*EXEMESTANE, *DRUG side effects, *DRUG efficacy, *BREAST cancer treatment, *POSTMENOPAUSE, *AROMATASE inhibitors, *SYMPTOMS, *ESTROGEN receptors
Abstract

Background Many adverse events (AEs) associated with aromatase inhibitors (AIs) involve symptoms related to the depletion of circulating estrogens, and may be related to efficacy. We assessed the relationship between specific AEs [hot flashes (HF) and musculoskeletal AEs (MSAE)] and survival outcomes in Dutch and Belgian patients treated with exemestane (EXE) in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Additionally, the relationship between hormone receptor expression and AEs was assessed. Methods Efficacy end points were relapse-free survival (RFS), overall survival (OS) and breast cancer-specific mortality (BCSM), starting at 6 months after starting EXE treatment. AEs reported in the first 6 months of treatment were included. Specific AEs comprised HF and/or MSAE. Landmark analyses and Cox proportional hazards models assessed survival differences up to 5 years. Results A total of 1485 EXE patients were included. Patients with HF had a better RFS than patients without HF [multivariate hazard ratio (HR) 0.393, 95% confidence interval (CI) 0.19–0.813; P = 0.012]. The occurrence of MSAE versus no MSAE did not relate to better RFS (multivariate HR 0.677, 95% CI 0.392–1.169; P = 0.162). Trends were maintained for OS and BCSM. Quantitative hormone receptor expression was not associated with specific AEs. Conclusions Some AEs associated with estrogen depletion are related to better outcomes and may be valuable biomarkers in AI treatment. [ABSTRACT FROM PUBLISHER]

Published
2012

43. Patterns of care in Dutch postmenopausal patients with hormone-sensitive early breast cancer participating in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial.

Author

van Nes, J. G. H., Seynaeve, C., Maartense, E., Roumen, R. M. H., de Jong, R. S., Beex, L. V. A. M., Meershoek-Klein Kranenbarg, W. M., Putter, H., Nortier, J. W. R., and van de Velde, C. J. H.

Subjects
*POSTMENOPAUSE, *ESTROGEN antagonists, *CANCER patients, *ANTINEOPLASTIC agents, *TAMOXIFEN
Abstract

Background: The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial investigates the efficacy and safety of adjuvant exemestane alone and in sequence after tamoxifen in postmenopausal women with hormone-sensitive early breast cancer. As there was a nationwide participation in The Netherlands, we studied the variations in patterns of care in the Comprehensive Cancer Centre Regions (CCCRs) and compliance with national guidelines. [ABSTRACT FROM PUBLISHER]

Published
2010
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