217 results on '"Stefan Glück"'
Search Results
2. Long-Term Complete Remission with nab-Paclitaxel, Bevacizumab, and Gemcitabine Combination Therapy in a Patient with Triple-Negative Metastatic Breast Cancer
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Alberto Montero and Stefan Glück
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Triple-negative breast cancer ,Metastatic breast cancer ,HER2 negative ,nab-paclitaxel ,Long-term response ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
This is a case study of a 52-year-old female patient diagnosed in June 2007 with primary metastatic invasive ductal carcinoma of the left breast and synchronous metastases in the bone, lymph nodes, and lung. Biopsy results of the tumor tissue were negative for the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). In November 2007, she participated in a phase II study of metastatic HER2-negative breast cancer. Treatment consisted of systemic chemotherapy with gemcitabine 1,500 mg/m2, nab-paclitaxel 150 mg/m2, and bevacizumab 10 mg/kg once every other week. The patient experienced pain relief in her sternum after 5 weeks of chemotherapy, and her analgesic therapy was discontinued. After 7 months, the patient achieved a complete radiographic response, which was maintained for nearly 2 additional years. She continued receiving treatment throughout this period, requiring 1 dose reduction due to fatigue. The patient experienced no other adverse events, including neuropathy, and continued working uninterrupted throughout her treatment. The patient was discontinued from the study in May 2010 after disease progression, almost a full 3 years after diagnosis. The patient showed minimal response to subsequent therapies but had disease stabilization and died from her disease in April 2012. Median overall survival for patients with metastatic triple-negative breast cancer is between 12 and 13.3 months. This patient survived nearly 5 years following diagnosis. This case exemplifies how therapy with nab-paclitaxel, bevacizumab, and gemcitabine may prolong survival, with minimal toxicity, in select patients with triple-negative metastatic breast cancer.
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- 2012
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3. Is the Improved Efficacy of Trastuzumab and Lapatinib Combination Worth the Added Toxicity? A Discussion of Current Evidence, Recommendations, and Ethical Issues Regarding Dual HER2-Targeted Therapy
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Eugene R. Ahn, Emilie Wang, and Stefan Glück
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2012
4. Exemestane in the Adjuvant Treatment of Breast Cancer in Postmenopausal Women
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Muaiad Kittaneh and Stefan Glück
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2011
5. Gemcitabine and taxanes in metastatic breast cancer: a systematic review
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Vinay Gudena, Alberto J Montero, and Stefan Glück
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Therapeutics. Pharmacology ,RM1-950 - Abstract
Vinay Gudena, Alberto J Montero, Stefan GlückDivision of Hematology/Oncology, Braman Family Breast Cancer Institute, UMSylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL, USAAbstract: Incremental advances over the last two decades in the treatment of stage IV metastatic breast cancer (MBC) have resulted in significantly prolonging the average life expectancy. In 2008, the estimated 5-year relative survival rate for MBC is 27% which compares favorably to rates in stage IV lung (3%) and pancreatic cancers (1%). Despite these advances, MBC remains an incurable disease, often associated with many symptoms and a decreased quality of life (QoL). Therefore, therapy goals in the treatment of MBC include prolonging both progression-free survival and overall survival rates, while at the same time improving QoL by palliation of symptoms. Therefore, systemic chemotherapy ideally should not induce unnecessary toxicities. Once chemotherapy is indicated, a number of drugs and regimens are available but only a few offer both palliation of symptoms (responses to therapy) and overall survival benefit. The addition of novel biologic compounds to chemotherapy has been shown in phase III trials to improve all the above mentioned clinical outcomes in MBC. This review will discuss data supporting the use of gemcitabine/taxane combinations in the treatment of MBC.Keywords: metastatic breast cancer, gemcitabine, taxanes
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- 2008
6. XeNA: Capecitabine Plus Docetaxel, With or Without Trastuzumab, as Preoperative Therapy for Early Breast Cancer
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Stefan Glück, Edward F. McKenna Jr, Melanie Royce
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Medicine - Abstract
Combinations of capecitabine and a taxane are highly active in metastatic breast cancer, and synergy between capecitabine and docetaxel has also been demonstrated. Such combinations potentially would provide a promising non–anthracycline-based alternative for patients with early breast cancer. Non-anthracycline preoperative regimens are a particularly interesting proposition in human epidermal growth factor receptor 2 (HER2)-positive breast cancer, as they offer less cardiotoxicity and thus can be used concomitantly with preoperative trastuzumab therapy. Capecitabine plus docetaxel (XT) and trastuzumab with XT (HXT) are promising non-anthracycline regimens for the preoperative treatment of women with HER2-negative and HER2-positive breast cancer, respectively. The Xeloda in Neoadjuvant (XeNA) trial, an open-label, multicenter, phase II study, independently assesses the efficacy of preoperative XT in HER2-negative and HXT in HER2-positive breast cancer. A particularly important feature of the XeNA study is the use of pathologic complete response (pCR) plus near pCR (npCR) as the primary endpoint. pCR is associated with long-term survival, and although it is valuable as a surrogate marker, pCR has some limitations. Measurement of residual breast cancer burden (RCB) has been proposed as a more practical alternative to predict survival after preoperative chemotherapy. The combination of RCB-0 and RCB-I (npCR) expands the subset of patients shown to benefit from preoperative chemotherapy, and achievement of pCR or npCR is associated with long disease-free survival. In XeNA, the sum of pCR and npCR will facilitate correlative studies designed to identify patients most likely to benefit from XT and HXT and may expedite the clinical evaluation of these novel preoperative regimens.
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- 2008
7. Future perspectives and challenges with CDK4/6 inhibitors in hormone receptor–positive metastatic breast cancer
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Soley Bayraktar, Sameer Batoo, Sandeep Basu, Stefan Glück, Scott H. Okuno, Eyad Al-Hattab, and Tıp Fakültesi
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Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.drug_class ,Breast Neoplasms ,Ribociclib ,Palbociclib ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,medicine ,Humans ,Aromatase Inhibitor ,Molecular Targeted Therapy ,030212 general & internal medicine ,skin and connective tissue diseases ,Protein Kinase Inhibitors ,neoplasms ,Abemaciclib ,CDK4/6 Inhibitors ,Predictive biomarker ,Aromatase inhibitor ,business.industry ,Faslodex ,Disease progression ,Cyclin-Dependent Kinase 4 ,Metastatic Breast Cancer ,Cyclin-Dependent Kinase 6 ,General Medicine ,Hormone-Receptor Positive ,medicine.disease ,Metastatic breast cancer ,Treatment Outcome ,Receptors, Estrogen ,chemistry ,Hormone receptor ,030220 oncology & carcinogenesis ,Female ,Receptors, Progesterone ,business - Abstract
There are three US FDA–approved CDK4/6 inhibitors: palbociclib, ribociclib and abemaciclib for patients with HR-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (MBC). They are all equally effective, so the question becomes how to choose among these agents and how to sequence them. Other areas with active investigation include identifying predictive biomarkers for the selection of patients whom may benefit more from CDK4/6 inhibitors, deciding whether to continue CDK4/6 inhibitors after disease progression on CDK4/6 inhibitors, creating novel treatment combinations and expanding use beyond HR+/HER2- MBC. Here, we review the current use of and potential next directions for CDK4/6 inhibitors in the treatment of patients with HR+/HER2- MBC.
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- 2020
8. Prostate Cancer-Associated Trousseau´S Syndrome Versus Asymptomatic Isolated Muscular Calf Vein Thrombosis as the Origin of Acute Submassive Pulmonary Embolism: A Case Report and Review of the Literature
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Antonis Tsamaloukas, Aristoteles Giagounidis, Jan Roigas, and Stefan Glück
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medicine.medical_specialty ,business.industry ,Prostatectomy ,medicine.medical_treatment ,Cancer ,medicine.disease ,Rate ratio ,Thrombosis ,Asymptomatic ,Gastroenterology ,Pulmonary embolism ,Venous thrombosis ,Prostate cancer ,Internal medicine ,medicine ,General Earth and Planetary Sciences ,medicine.symptom ,business ,General Environmental Science - Abstract
Venous thromboembolism (VTE) is a major cause of morbidity and mortality in cancer patients. Cancer patients have a four to sevenfold increased risk of VTE compared with non-cancer patients and approximately 20% -30% of all VTE occurs in patients with cancer. Incidence of VTE varies with cancer type and is the highest among patients with metastatic-stage disease. Assessing risk of VTE in the patients with cancer and risk stratification tools as the Khorana score may predict VTE. The highest risk is associated with cancers of the pancreas, stomach, brain, and lung and some hematologic malignancies, whereas lower risks are associated with breast and prostate cancer. The incidence rate ratio (IRR) for prostate cancer is 3.25(2,56 - 4,13) and for pancreas 15.56 (10.50-23.0). We give a case report with a quite perplexing undertaking, where a submassive acute pulmonary embolism (PE) originated from an asymptomatic calf vein thrombosis or intertwined with the Trousseau´s syndrome. Essential Section: One of the authors (A.T) was unexpected faced with the diagnosis of poorly differentiated prostate cancer. There were no signs of the disease, the PSA level was normal. As a retired medical oncologist, he had to care for many patients with prostate cancer and had now to cope with this cancer. To make the matter worse he suffered after the radical prostatectomy a submassive asymptomatic pulmonary embolism. Clinically there were no signs if a deep venous thrombosis. The coincidence of both events without clinical signs of a thrombosis could be caused by the Trousseau´s syndrome. Prostasomes extracellular vesicles synthesizes by prostate cancer cells and secreted into body fluids are prothrombotic by virtue of the expression of polyphosphate-activated coagulation factor XII.
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- 2020
9. Optimal Strategies for Successful Initiation of Neratinib in Patients with HER2-Positive Breast Cancer
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Joyce O'Shaughnessy, Manuel Ruiz-Borrego, Barbara Pistilli, Jack A. Di Palma, Stefan Glück, Rupert Bartsch, Carlos H. Barcenas, Christian Jackisch, Hope S. Rugo, Guilherme Macedo, and Nadia Harbeck
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0301 basic medicine ,Oncology ,Diarrhea ,Cancer Research ,medicine.medical_specialty ,Antimetabolites, Antineoplastic ,Receptor, ErbB-2 ,Neratinib ,Breast Neoplasms ,Capecitabine ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,HER2 ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Adjuvant therapy ,Humans ,In patient ,Neoplasm Metastasis ,skin and connective tissue diseases ,Dose-Response Relationship, Drug ,business.industry ,medicine.disease ,Metastatic breast cancer ,030104 developmental biology ,Tolerability ,030220 oncology & carcinogenesis ,Quinolines ,Metastatic ,Female ,medicine.symptom ,business ,medicine.drug - Abstract
Neratinib is an irreversible, pan-human epidermal growth factor inhibitor that has shown efficacy across human epidermal growth factor receptor 2 (HER2)-positive breast cancer settings. Neratinib is indicated for use as extended adjuvant therapy for HER2-positive early-stage breast cancer or, in combination with capecitabine, in the treatment of HER2-positive metastatic breast cancer. The primary tolerability concern with neratinib is diarrhea, and severe diarrhea early in treatment can lead to a substantial proportion of patients discontinuing neratinib, which may lead to reduced or nonexistent efficacy. In order to establish a set of treatment recommendations for use of neratinib, on May 12, 2020, an expert panel of oncologists and gastroenterologists met virtually to discuss the role of neratinib in the treatment of patients with HER2-positive breast cancer. The panel reviewed the current data on neratinib, including efficacy across settings and diarrhea management strategies. Based on these data and their clinical experience, the panelists developed a set of recommendations to guide selection of patients for neratinib, implement weekly dose escalation at initiation of therapy, and prophylactically manage diarrhea.
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- 2020
10. Trial-level prediction of long-term outcome based on pathologic complete response (pCR) after neoadjuvant chemotherapy for early-stage breast cancer (EBC)
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Andreas Schneeweiss, Stefan Glück, Valentina Nekljudova, Gunter von Minckwitz, Huiling Li, Richard Crane, Xiaolong Luo, and Sibylle Loibl
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Breast Neoplasms ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,F-test ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,p-value ,Neoplasm Staging ,Proportional Hazards Models ,business.industry ,Proportional hazards model ,Surrogate endpoint ,Hazard ratio ,Reproducibility of Results ,General Medicine ,Odds ratio ,Prognosis ,medicine.disease ,Neoadjuvant Therapy ,030104 developmental biology ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Predictive value of tests ,Female ,business - Abstract
Background The US Food and Drug Administration and European Medicines Agency have published guidance for industry on the use of pathologic complete response (pCR) as a surrogate endpoint to accelerate the regulatory approval of neoadjuvant agents in high-risk early-stage breast cancer (EBC). Three meta-analyses, the CTNeoBC consortium (Cortazar 2014), Berruti (2014), and Korn (2016), evaluated the association between the pCR odds ratio and the event hazards ratio but did not identify strong trial-level associations. Thus, uncertainties remain with respect to whether the magnitude of effect-size increase in pCR reasonably predicts long-term clinical benefit. Findings Trial-level data from CTNeoBC were used as the training data set to derive an empirical nonlinear model for predicting long-term outcomes based on pCR results. A Cox regression model was used to evaluate the relationship among treatments, event hazards, and pCR as joint covariates. The trial-level association between treatment and event hazard was derived and then linked with pCR rates. Magnitude of the patient-level association was also included in the analysis. Additional published trials were used to validate the predictive model. Numerical differences between the perfect surrogate prediction and observed effect followed normal distribution based on the Kolmogorov-Smirnov test. For event-free survival (EFS), the Student t- test P value of 0.02 suggested a statistically significant nonzero difference, with a mean value of −0.163 (SE 0.058). For overall survival (OS), the Student t- test P value of 0.0027 suggested a statistically significant nonzero difference, with a mean value of −0.153 (SE 0.038). Three studies, including GeparSixto, BOOG, and Neo-tAnGo, were used for validation. The F test suggested the model fit the test data well. Implications The observed hazard ratios fit well with the predicted hazard ratios for both EFS and OS and suggest plausible trial-level associations with the new predictor. Major findings Our model predicted the correlation between pCR and EFS as well as OS. This model could be used as a supporting tool to help interpret positive pCR results in neoadjuvant clinical studies in patients with high-risk EBC.
- Published
- 2018
11. Abstract P5-15-03: nab-paclitaxel + carboplatin or gemcitabine vs gemcitabine/carboplatin as first-line treatment for patients with triple-negative metastatic breast cancer: Results from the randomized phase 2 portion of the tnAcity trial
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Denise A. Yardley, Robert Beck, Haythem Ali, J. Eakel, L de la Cruz Merino, Robert E. Coleman, Sharon Wilks, Andreas Schneeweiss, Carmelo Bengala, Stefan Glück, J O'Shaugnessy, Mikhail Shtivelband, Nadia Harbeck, Adam Brufsky, Haocheng Li, Pierfranco Conte, Robyn R. Young, J. Cortes, and Debora Barton
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Phases of clinical research ,Context (language use) ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,Internal medicine ,medicine ,Gynecology ,Chemotherapy ,business.industry ,Cancer ,medicine.disease ,Metastatic breast cancer ,Carboplatin ,Gemcitabine ,030104 developmental biology ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
Background: nab-Paclitaxel (nab-P)–containing regimens have demonstrated efficacy and safety in triple-negative breast cancer (TNBC). In the absence of a standard of care for metastatic (m) TNBC, tnAcity evaluated the efficacy and safety of 3 common chemotherapy combination regimens: nab-P + carboplatin (nab-P/C) or gemcitabine (nab-P/G) vs G/C as first-line treatment (Tx) for patients (pts) with mTNBC based on a ranking algorithm of efficacy and safety. Results of the phase 2 portion are reported here. Methods: Pts with pathologically confirmed mTNBC, no prior cytotoxic chemotherapy for metastatic disease, and no brain metastases were enrolled. Pts received (1:1:1) nab-P 125 mg/m2 + C AUC 2, nab-P 125 mg/m2 + G 1000 mg/m2, or G 1000 mg/m2 + C AUC 2, all given on d 1 and 8 every 3 weeks. The phase 2 primary endpoint was investigator-assessed progression-free survival (PFS); secondary endpoints included overall response rate (ORR), overall survival (OS), percentage of pts initiating cycle 6 receiving doublet therapy, and safety. Results: 191 pts were included in the phase 2 portion. Median age was 55, 53, and 59 years in the nab-P/C, nab-P/G, and G/C groups, respectively. Overall, 98% of pts had an ECOG PS of 0 - 1, 83% were white, and 48% were treated in North America. Most pts (81%) had relapsed disease. Median Tx duration was 25, 18, and 20 weeks, and 47%, 33%, and 52% of pts had ≥ 1 dose reduction for both agents in the nab-P/C, nab-P/G, and G/C groups, respectively. Key efficacy and safety results are summarized in the table. PFS was significantly longer with nab-P/C vs either nab-P/G or G/C (median, 7.4 vs 5.4 mo, P = 0.03 and 7.4 vs 6.0 mo, P = 0.02). Overall, 179 pts discontinued Tx; of these, 55% discontinued due to progression and 16% due to adverse events (AEs). Grade ≥ 3 AEs in ≥ 10% of pts were mainly hematologic. The rank sum of the algorithm for 5 key weighted efficacy and safety endpoints favored nab-P/C. Table 1 nab-P/Cnab-P/GG/CEfficacyn = 64n = 61n = 66PFS, median, mo7.4a5.4b6.0ORR, %71.937.743.9OS, median, mo16.411.913.7Pts initiating cycle 6 with a doublet, %64.155.750.0Safetyn = 64n = 60n= 64Myelosuppression-related events, %c53.141.767.2Pts discontinuing all Tx due to AE, %18.820.021.9Serious TEAEs, %29.736.737.5Grade ≥ 3 AEs, %Neutropenia40.633.348.4Anemia7.88.315.6Thrombocytopenia4.73.314.1Peripheral neuropathy4.75.01.6Deaths due to TEAE, n (%)1 (2)2 (3)2 (3)a P = 0.03 vs nab-P/G; P = 0.02 vs G/C; b P = 0.85 vs G/C; c Including grade ≥ 3 neutropenia, thrombocytopenia, anemia, bleeding, febrile neutropenia, or red blood cell/platelet transfusion. Conclusions: In this phase 2 study, nab-P/C demonstrated a statistically significant longer PFS and a better risk/benefit profile vs nab-P/G or G/C as first-line Tx in pts with mTNBC. These data demonstrate nab-P/C efficacy in mTNBC and address a relevant question around a nab-P/C chemotherapy backbone for this difficult-to-treat tumor type. Further studies are warranted in the context of immunotherapies and targeted agents. NCT01881230. Citation Format: Yardley D, Coleman R, Conte P, Cortes J, Brufsky A, Shtivelband M, Young R, Bengala C, Ali H, Eakel J, Schneeweiss A, de la Cruz Merino L, Wilks S, O'Shaugnessy J, Glück S, Li H, Beck R, Barton D, Harbeck N. nab-paclitaxel + carboplatin or gemcitabine vs gemcitabine/carboplatin as first-line treatment for patients with triple-negative metastatic breast cancer: Results from the randomized phase 2 portion of the tnAcity trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-15-03.
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- 2017
12. Post-surgical depressive symptoms and long-term survival in non-metastatic breast cancer patients at 11-year follow-up
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Lisa M. Gudenkauf, Charles S. Carver, Laura C. Bouchard, Bonnie B. Blomberg, Stefan Glück, Devika R. Jutagir, Jamie M. Jacobs, Michael H. Antoni, and Suzanne C. Lechner
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Adult ,medicine.medical_specialty ,Breast Neoplasms ,Article ,Disease-Free Survival ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Randomized controlled trial ,law ,Internal medicine ,Outcome Assessment, Health Care ,medicine ,Humans ,Postoperative Period ,Depression (differential diagnoses) ,Aged ,Subclinical infection ,Depression ,Proportional hazards model ,business.industry ,Hazard ratio ,Hamilton Rating Scale for Depression ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,030220 oncology & carcinogenesis ,Physical therapy ,Female ,business ,Psychosocial ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Background Mild to moderate depressive symptoms are common during treatment for non-metastatic breast cancer. The goal of this secondary analysis was to determine if depressive symptoms predict clinical outcomes at long-term follow-up. Methods From 1998 to 2005, we interviewed 231 women with the Hamilton Rating Scale for Depression who were participating in a psychosocial study 2–10weeks post-surgery for non-metastatic breast cancer (Stage 0-IIIb). We conducted Kaplan Meier (K-M) curves and Cox proportional hazards (PH) models to examine associations between depressive symptoms, overall survival, and disease-free survival at 8–15-year follow-up. Results A total of 95 women (41.1%) scored in the mild-moderately depressed range. Non-depressed women had longer overall survival ( M =13.56years; SE =0.26) than those in the mild/moderate depressed group ( M =11.45years; SE =0.40), Log-rank χ 2 (1)=4.41, p =0.036. Cox PH models, adjusting for covariates, showed comparable results: mild/moderate depressive symptoms hazard ratio=2.56, [95% CI, 1.11 to 5.91], p =0.027. Similar results were observed in a subsample with invasive disease (n=191). Depression category did not predict disease-free survival in the overall or invasive sample. Conclusions Screening and referrals for treatment of depressive symptoms, even at subclinical levels, is important early in treatment. A randomized trial is warranted to determine effects of depressive symptoms on clinical outcomes.
- Published
- 2017
13. Recent advances and optimal management of human epidermal growth factor receptor-2-positive early-stage breast cancer
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Sameer Batoo, Scott H. Okuno, Eyad Al-Hattab, Soley Bayraktar, Sandeep Basu, and Stefan Glück
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Anthracycline ,TDM1 ,Health, Toxicology and Mutagenesis ,medicine.medical_treatment ,Review Article ,Lapatinib ,lcsh:RC254-282 ,Capecitabine ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Trastuzumab ,pertuzumab ,Internal medicine ,medicine ,skin and connective tissue diseases ,neoplasms ,Chemotherapy ,business.industry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,neratinib ,trastuzumab ,030104 developmental biology ,030220 oncology & carcinogenesis ,Neratinib ,Pertuzumab ,business ,medicine.drug - Abstract
With the introduction of anthracycline-based regimens, 5-year survival rates have significantly improved in patients with early-stage breast cancer. With the addition of trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor-2 (HER2), improvements in overall survival have been observed among patients with advanced HER2-positive disease. Subsequently, lapatinib, an orally bioavailable small molecule dual HER2- and EGFR/HER1-specific tyrosine kinase inhibitor, received Food and Drug Administration (FDA) approval in combination with capecitabine for patients with advanced HER2+ breast cancer. Then, pertuzumab in 2012 and ado-trastuzumab emtansine in 2013 were approved in the US and elsewhere based on evidence showing an improvement in survival outcomes in patients with mostly trastuzumab naïve or trastuzumab-exposed metastatic disease. The FDA also approved 1 year of extended adjuvant neratinib after chemotherapy and a year of trastuzumab for HER2-positive breast cancer on the basis of the ExteNET trial. The clinical benefit demonstrated by those drugs in advanced disease has triggered several adjuvant and neoadjuvant trials testing them in combination with chemotherapy, but also without conventional chemotherapy, using single or dual HER2-targeting drugs. In this article, we review the current data on the therapeutic management of HER2-positive early-stage breast cancer in the adjuvant and neoadjuvant setting. We also review the data the efficacy and safety of anthracycline-based and nonanthracycline-based adjuvant chemotherapy regimens combined with trastuzumab, and optimum chemotherapy regimens in small HER2-positive tumors.
- Published
- 2019
14. Update on PARP inhibitor therapy for solid tumors
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Stefan Glück, Soley Bayraktar, and HS Darling
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business.industry ,PARP inhibitor ,Cancer research ,Medicine ,business - Published
- 2019
15. Frequency and Vehicle Capacity Determination using a Dynamic Transit Assignment Model
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Oded Cats and Stefan Glück
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050210 logistics & transportation ,Service (systems architecture) ,Service quality ,021103 operations research ,Operations research ,Computer science ,Level of service ,transit assignment ,Mechanical Engineering ,Reliability (computer networking) ,05 social sciences ,0211 other engineering and technologies ,Tactical planning ,02 engineering and technology ,Frequency setting ,Phase (combat) ,Metropolitan area ,Bus network ,0502 economics and business ,Public transport ,Vehicle capacity ,Transit (satellite) ,Civil and Structural Engineering - Abstract
We integrate for the first time, to our knowledge, a dynamic transit assignment model into the tactical planning phase. The settings of service frequencies and vehicle capacities determine line capacity and have significant consequences for level-of-service and operational costs. The objective of this study is to determine frequency and vehicle capacity at the network level while accounting for the impact of service variations on users and operator costs. To this end, we propose a simulation-based optimization approach. The proposed model allows accounting for variations in service headways and crowding as well as their consequences for passenger flows distribution, all of which have not been accounted for in the tactical planning so far. Practical benefits of the model are demonstrated by an application to a bus network in the Amsterdam metropolitan area. This study contributes to the development of a new generation of methods that integrate reliability into the tactical planning phase to improve service quality.
- Published
- 2019
16. Postsurgical Depressive Symptoms and Proinflammatory Cytokine Elevations in Women Undergoing Primary Treatment for Breast Cancer
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Stefan Glück, Lisa M. Gudenkauf, Robert P. Derhagopian, Michael H. Antoni, Jamie M. Stagl, Laura C. Bouchard, Bonnie B. Blomberg, Alain Diaz, Suzanne C. Lechner, Devika R. Jutagir, and Charles S. Carver
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Adult ,medicine.medical_specialty ,Interleukin-1beta ,Breast Neoplasms ,Comorbidity ,Gastroenterology ,Article ,Body Mass Index ,Proinflammatory cytokine ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Ethnicity ,medicine ,Humans ,Lymphocyte Count ,Interleukin 6 ,Fatigue ,Mastectomy ,Applied Psychology ,Depression (differential diagnoses) ,Inflammation ,biology ,Depression ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,business.industry ,Hamilton Rating Scale for Depression ,Cancer ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Socioeconomic Factors ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Female ,business ,Body mass index ,030217 neurology & neurosurgery - Abstract
Objective Depression and inflammation may independently promote breast cancer (BCa) disease progression and poorer clinical outcomes. Depression has been associated with increased levels of inflammatory markers in medically healthy individuals and patients with cancer. However, inconsistencies in study time frames complicate interpretation of results within specific cancer types. This study examined relationships between depressive symptoms and inflammation in women with early-stage BCa before beginning adjuvant treatment. Methods Women with Stage 0-III BCa were recruited approximately 4 to 8 weeks after surgery. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression, and blood samples were collected to quantify circulating levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α) by enzyme-linked immunosorbent assay. Analyses of covariance were used to test for group differences (elevated versus low depressive symptoms) in levels of cytokines. Multiple regression analyses were used to examine relationships between continuous severity of depressive symptoms and levels of cytokines adjusting for relevant biobehavioral covariates. Results Thirty-six (40%) of 89 patients showed elevated levels of depressive symptoms and, in adjusted models, had marginally higher levels of IL-1β (mean [M] = 14.49 [95% confidence interval {CI} = 6.11-32.65] versus M = 4.68 [95% CI = 1.96-9.86] and IL-6 [M = 88.74 {95% CI = 33.28-233.96} versus M = 61.52 {95% CI = 27.44-136.40}]) significantly higher levels of TNF-α (M = 17.07 [95% CI = 8.27-34.32] versus M = 6.94 [95% CI = 3.58-12.80]) than did women with low depressive symptoms. Across the spectrum of depressive symptoms, greater magnitude of depressive symptoms was related to greater levels of IL-1β (β = 0.06, p = .006, R = 0.25) and TNF-α (β = 0.06, p = .003, R = 0.27). Conclusions Postsurgery and preadjuvant treatment for early-stage BCa, depressive symptoms covary with elevated levels of multiple proinflammatory cytokines. Findings have implications for psychosocial and biological interventions concurrently focusing on depression and inflammation. Trial registration NCT01422551.
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- 2016
17. Comparative effectiveness of early-line
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Reshma L, Mahtani, Monika, Parisi, Stefan, Glück, Quanhong, Ni, Siyeon, Park, Corey, Pelletier, Claudio, Faria, and Fadi, Braiteh
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nab-paclitaxel ,paclitaxel ,metastatic breast cancer ,hormone receptor positive ,triple negative ,Original Research - Abstract
Background Real-world analyses of treatments for patients with metastatic breast cancer are limited. We evaluated the comparative effectiveness of nab-paclitaxel vs. paclitaxel in patients with metastatic breast cancer using data from an electronic medical record database from community practices across the USA. Methods We performed a retrospective cohort study using fully de-identified data from an independent US electronic medical record platform of patients with metastatic breast cancer initiating single-agent nab-paclitaxel or paclitaxel as a first- or second-line treatment from December 1, 2010 to October 6, 2014. The clinical efficacy objectives were time to treatment discontinuation (TTD) and time to next treatment (TTNT). Subgroup analyses were performed in patients with 2 types of metastatic breast cancer as follows: 1) hormone receptor-positive and human epidermal growth factor receptor 2 negative, and 2) triple-negative disease. Results This analysis included 925 patients. Patients receiving nab-paclitaxel vs. paclitaxel had significantly longer TTD (median 4.2 vs. 2.8 months, P
- Published
- 2018
18. A randomized controlled trial of cognitive-behavioral stress management in breast cancer: survival and recurrence at 11-year follow-up
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Lisa M. Gudenkauf, Gail Ironson, Charles S. Carver, Suzanne C. Lechner, Michael H. Antoni, Jamie M. Stagl, Qilu Yu, Devika R. Jutagir, Alain Diaz, Laura C. Bouchard, Bonnie B. Blomberg, and Stefan Glück
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Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Breast Neoplasms ,Article ,law.invention ,Cognition ,Breast cancer ,Randomized controlled trial ,Risk Factors ,law ,Cause of Death ,Internal medicine ,Psychological adaptation ,Adaptation, Psychological ,Biomarkers, Tumor ,medicine ,Humans ,Neoplasm Staging ,Proportional Hazards Models ,Cause of death ,Cognitive Behavioral Therapy ,business.industry ,Proportional hazards model ,Disease Management ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Distress ,Physical therapy ,Cognitive therapy ,Female ,Neoplasm Recurrence, Local ,business ,Psychosocial ,Stress, Psychological ,Follow-Up Studies - Abstract
Non-metastatic breast cancer patients often experience psychological distress which may influence disease progression and survival. Cognitive-behavioral stress management (CBSM) improves psychological adaptation and lowers distress during breast cancer treatment and long-term follow-ups. We examined whether breast cancer patients randomized to CBSM had improved survival and recurrence 8–15 years post-enrollment. From 1998 to 2005, women (N = 240) 2–10 weeks post-surgery for non-metastatic Stage 0–IIIb breast cancer were randomized to a 10-week, group-based CBSM intervention (n = 120) or a 1-day psychoeducational seminar control (n = 120). In 2013, 8–15 years post-study enrollment (11-year median), recurrence and survival data were collected. Cox Proportional Hazards Models and Weibull Accelerated Failure Time tests were used to assess group differences in all-cause mortality, breast cancer-specific mortality, and disease-free interval, controlling for biomedical confounders. Relative to the control, the CBSM group was found to have a reduced risk of all-cause mortality (HR = 0.21; 95 % CI [0.05, 0.93]; p = .040). Restricting analyses to women with invasive disease revealed significant effects of CBSM on breast cancer-related mortality (p = .006) and disease-free interval (p = .011). CBSM intervention delivered post-surgery may provide long-term clinical benefit for non-metastatic breast cancer patients in addition to previously established psychological benefits. Results should be interpreted with caution; however, the findings contribute to the limited evidence regarding physical benefits of psychosocial intervention post-surgery for non-metastatic breast cancer. Additional research is necessary to confirm these results and investigate potential explanatory mechanisms, including physiological pathways, health behaviors, and treatment adherence changes.
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- 2015
19. Economic Evaluations of Everolimus Versus Other Hormonal Therapies in the Treatment of HR+/HER2− Advanced Breast Cancer From a US Payer Perspective
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Stefan Glück, Cynthia Z. Qi, Zheng Yi Zhou, Gourab De, Jipan Xie, and Yanni Hao
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Oncology ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,Cost-Benefit Analysis ,Antineoplastic Agents ,Disease-Free Survival ,chemistry.chemical_compound ,Indirect costs ,Breast cancer ,Exemestane ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Everolimus ,Adverse effect ,health care economics and organizations ,Aged ,Gynecology ,Fulvestrant ,business.industry ,Cost-effectiveness analysis ,Middle Aged ,medicine.disease ,United States ,Quality-adjusted life year ,Postmenopause ,Receptors, Estrogen ,chemistry ,Female ,Quality-Adjusted Life Years ,business ,medicine.drug - Abstract
Introduction The objective of the study was to assess the cost-effectiveness of EVE+EXE versus endocrine monotherapies in the treatment of postmenopausal women with HR + , HER2 − ABC after failure of treatment with nonsteroidal aromatase inhibitors from a US third-party payer perspective. Materials and Methods A Markov model was developed to evaluate the costs and effectiveness associated with EVE+EXE, exemestane (EXE), fulvestrant (FUL), and tamoxifen (TAM) over a 10-year time horizon. The model included 3 health states: responsive/stable disease, progression, or death. Monthly transition probabilities were estimated based on the BOLERO-2 (Breast cancer trials of OraL EveROlimus-2) data and network meta-analyses. Costs included drug acquisition and administration costs, medical costs associated health states, and costs for managing adverse events (AEs). Utilities for each health state and disutilities for AEs were derived from the literature. Incremental costs per quality-adjusted life year (QALY) were estimated by comparing EVE+EXE with each endocrine monotherapy. One-way and probabilistic sensitivity analyses were performed. Results In the base case, EVE+EXE was associated with 1.99 QALYs and total direct costs of $258,648 over 10 years. The incremental cost per QALY of EVE+EXE was $139,740 compared with EXE, $157,749 compared with FUL, and $115,624 compared with TAM. At a willingness-to-pay threshold of $130,000/QALY or above, EVE+EXE appeared to be the most cost-effective treatment among all drugs. Conclusions Everolimus with EXE demonstrated QALY improvements compared with 3 other endocrine monotherapies. Benchmarked by the economic value of other novel cancer therapies, EVE+EXE might be considered a cost-effective option compared with endocrine therapies for HR + /HER2 − ABC.
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- 2015
20. Ethnic differences in types of social support from multiple sources after breast cancer surgery
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Laura C. Bouchard, Bonnie B. Blomberg, Stefan Glück, Suzanne C. Lechner, Michael H. Antoni, Jamie M. Stagl, Charles S. Carver, Devika R. Jutagir, and Lisa M. Gudenkauf
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Adult ,Male ,Cultural Studies ,medicine.medical_specialty ,Emotional support ,Ethnic group ,Breast Neoplasms ,Friends ,Disease ,Cancer Care Facilities ,White People ,Article ,03 medical and health sciences ,Social support ,0302 clinical medicine ,Breast cancer ,Arts and Humanities (miscellaneous) ,Psychological adaptation ,Humans ,Medicine ,030212 general & internal medicine ,Spouses ,skin and connective tissue diseases ,Aged ,Neoplasm Staging ,Family Health ,business.industry ,Public Health, Environmental and Occupational Health ,Social Support ,Hispanic or Latino ,Middle Aged ,medicine.disease ,Acculturation ,Surgery ,Distress ,030220 oncology & carcinogenesis ,Florida ,Regression Analysis ,Female ,business - Abstract
Diagnosis of and treatment for breast cancer (BCa) may require psychological adaptation and often involve heightened distress. Several types of social support positively relate to psychological adaptation to BCa, and negative support is associated with poorer adaptation. Although Hispanic women report greater distress than non-Hispanic White (NHW) women after diagnosis of BCa, no studies have examined ethnic differences in types of social support received from varying sources after surgery for BCa.Hispanic (N = 61) and NHW (N = 150) women diagnosed with early-stage BCa self-reported emotional, informational, instrumental, and negative support from five sources. Ethnic differences in levels of social support were compared using multiple regression analysis.When controlling for age, income, days since surgery, and stage of disease in multivariable models there were no ethnic differences in levels of emotional support from any source. Hispanic women reported greater informational support from adult women family members and children and male adult family members than did NHW women. Instrumental support from adult women family members was also greater among Hispanic than NHW women. Hispanic women reported higher negative support from husbands/partners and from children and male adult family members. When the number of years in the USA was controlled, Hispanic women showed greater informational support from adult women family members, children and male adult family members, and friends. Instrumental support from adult women family members remained greater in Hispanic women, but negative support no longer differed.Family is a greater source of informational and instrumental support for Hispanic than NHW women. Hispanic women reported higher negative support from male sources than did NHW women. Level of support from different sources may also depend on time spent in the USA. Longitudinal studies are needed to determine whether patterns and sources of social support shift over the course of BCa treatment.
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- 2015
21. Abstract P5-17-02: Quality of life in patients receiving first-line eribulin mesylate for HER2- locally recurrent or MBC
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David Cox, Linda T. Vahdat, Joyce O'Shaughnessy, Erhan Berrak, Stefan Glück, Kristi McIntyre, James Song, and Lee S. Schwartzberg
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Eribulin Mesylate ,Cancer Research ,medicine.medical_specialty ,Nausea ,business.industry ,Minimal clinically important difference ,Hazard ratio ,humanities ,chemistry.chemical_compound ,Oncology ,Tolerability ,chemistry ,Quality of life ,Internal medicine ,medicine ,Physical therapy ,medicine.symptom ,Adverse effect ,business ,Eribulin - Abstract
Introduction: Eribulin mesylate is a nontaxane microtubule inhibitor approved to treat MBC in patients (pts) who previously received ≥2 chemotherapeutic regimens for MBC. A phase 2 study of first-line eribulin for HER2-negative (HER2-) MBC showed an overall response rate of 29%, median 6.8 m progression-free survival, and tolerability consistent with earlier studies. We present prespecified quality of life (QoL) results for this trial. Methods: Pts (N=56) received eribulin mesylate 1.4 mg/m2 IV on days 1 and 8 of each 3-wk cycle (median: 7 cycles). QoL was assessed using the EORTC QoL assessment (QLQ-C30) and a breast-cancer specific questionnaire (QLQ-BR23) pretreatment (baseline) and on day 1 of every other cycle during treatment. Percentage of pts with at least ±10-point change from baseline was summarized descriptively. Linear mixed-effects models were used to evaluate changes over time and compare responders vs nonresponders controlling for baseline score and time effect. Time-to-event analysis was performed on time to deterioration, defined as time from 1st dose to 1st occurrence of worsening in QoL score that reached minimally clinically important difference (MID; eg, 10 points in global health status in QLQ-C30) from baseline without further improvement of at least MID. Results: For QLQ-C30 at cycle 6 (n=29), more pts had at least a 10-point improvement from baseline in role, emotional, and social functioning; fatigue, nausea/vomiting, pain, dyspnea, and insomnia item scores, than had worsening. More pts had worsening in global health status/QoL, cognitive functioning, and diarrhea (Table). Category, n (%) ImprovedStableWorsenedGlobal health status/QoL2 (7)16 (55)11 (38)Physical functioning9 (31)13 (45)7 (24)Role functioning14 (48)10 (35)5 (17)Emotional functioning9 (31)14 (48)6 (21)Cognitive functioning2 (7)13 (45)14 (48)Social functioning10 (35)13 (45)6 (21)Fatigue16 (55)5 (17)8 (28)Nausea and vomiting8 (28)16 (55)5 (17)Pain15 (52)8 (28)6 (21)Dyspnea9 (31)18 (62)2 (7)Insomnia12 (41)15 (52)2 (7)Appetite loss7 (24)16 (55)6 (21)Constipation5 (17)18 (62)6 (21)Diarrhea2 (7)21 (72)6 (21) Median time to deterioration in global health status/QoL was 5.06 m (responders, 8.54 m; nonresponders, 3.71 m; hazard ratio=0.60, P=0.22). In linear mixed models, responders (n=16) performed better than nonresponders (n=40) in role functioning (P=0.011), emotional functioning (P=0.031), fatigue (P=0.007), pain (P=0.047), insomnia (P=0.018), and appetite loss (P=0.032). Mean symptom scores were significantly correlated with corresponding adverse event rates for nausea and vomiting, dyspnea, appetite loss, constipation, and diarrhea; Spearman rank correlation coefficients ranged from 0.31 to 0.54. For QLQ-BR23 at cycle 6, symptom scores were mostly stable; more pts had worsening in body image and systemic therapy side effects than had improvement and more pts had improvement in breast and arm symptoms than had worsening. Responders also had longer time to symptom deterioration. Conclusions: In this study of first-line eribulin treatment for HER2- MBC, a majority of pts had stable or improvement in QoL scales. Responders to eribulin were more likely than nonresponders to have stable or improved QoL. Citation Format: Lee Schwartzberg, Kristi McIntyre, Joyce O'Shaughnessy, Stefan Glück, Erhan Berrak, James Song, David Cox, Linda Vahdat. Quality of life in patients receiving first-line eribulin mesylate for HER2- locally recurrent or MBC [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-17-02.
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- 2015
22. Long-term psychological benefits of cognitive-behavioral stress management for women with breast cancer: 11-year follow-up of a randomized controlled trial
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Charles S. Carver, Laura C. Bouchard, Bonnie B. Blomberg, Stefan Glück, Devika R. Jutagir, Robert P. Derhagopian, Michael H. Antoni, Suzanne C. Lechner, Jamie M. Stagl, and Lisa M. Gudenkauf
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Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Psychological intervention ,Cancer ,medicine.disease ,law.invention ,Breast cancer ,Oncology ,Randomized controlled trial ,Quality of life ,law ,Internal medicine ,Cohort ,medicine ,Cognitive therapy ,Physical therapy ,business ,Psychosocial - Abstract
BACKGROUND Breast cancer survivors experience long-term physical and psychological sequelae after their primary treatment that negatively influence their quality of life (QOL) and increase depressive symptoms. Group-based cognitive-behavioral stress management (CBSM) delivered after surgery for early-stage breast cancer was previously associated with better QOL over a 12-month follow-up and with fewer depressive symptoms up to 5 years after study enrollment. This 8- to 15-year follow-up (median, 11 years) of a previously conducted trial (NCT01422551) evaluated whether women in this cohort receiving CBSM had fewer depressive symptoms and better QOL than controls at an 8- to 15-year follow-up. METHODS Women with stage 0 to IIIb breast cancer were initially recruited 2 to 10 weeks after surgery and randomized to a 10-week CBSM intervention or a 1-day psychoeducational control group. One hundred women (51 CBSM patients and 49 controls) were recontacted 8 to 15 years after study enrollment to participate in a follow-up assessment. The Center for Epidemiologic Studies–Depression (CES-D) scale and the Functional Assessment of Cancer Therapy–Breast (FACT-B) were self-administered. Multiple regression was employed to evaluate group differences on the CES-D scale and FACT-B over and above effects of confounding variables. RESULTS Participants assigned to CBSM reported significantly lower depressive symptoms (d, 0.63; 95% confidence interval [CI], 0.56-0.70) and better QOL (d, 0.58; 95% CI, 0.52-0.65) above the effects of the covariates. CONCLUSIONS Women who received CBSM after surgery for early-stage breast cancer reported lower depressive symptoms and better QOL than the control group up to 15 years later. Early implementation of cognitive-behavioral interventions may influence long-term psychosocial functioning in breast cancer survivors. Cancer 2015;121:1873–1881. © 2015 American Cancer Society.
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- 2015
23. Improved Clinical Outcomes Associated With Vitamin D Supplementation During Adjuvant Chemotherapy in Patients With HER2+ Nonmetastatic Breast Cancer
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Eugene R. Ahn, Qingyun Liu, Nikesh N. Shah, Nathan J. Markward, Tulay Koru-Sengul, Simon B. Zeichner, Alberto J. Montero, Stefan Glück, and Orlando Silva
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Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,medicine.medical_treatment ,Breast Neoplasms ,Calcitriol receptor ,Disease-Free Survival ,Breast cancer ,Trastuzumab ,Internal medicine ,medicine ,Vitamin D and neurology ,Humans ,Neoplasm Metastasis ,Vitamin D ,skin and connective tissue diseases ,Aged ,Retrospective Studies ,Chemotherapy ,business.industry ,Hazard ratio ,Cancer ,Middle Aged ,medicine.disease ,Confidence interval ,Treatment Outcome ,Endocrinology ,Chemotherapy, Adjuvant ,Dietary Supplements ,Female ,business ,Follow-Up Studies ,medicine.drug - Abstract
Vitamin D (VD) supplementation has pleiotropic effects that extend beyond their impact on bone health, including the disruption of human epidermal growth factor receptor 2 (HER2) signaling through the ErbB2/AKT/ ERK pathway. We performed a retrospective review of patients who received VD supplementation during neoadjuvant chemotherapy (n [ 134) and those who did not (n [ 112). In our final multivariate model, VD use was associated with improved disease-free survival (DFS) (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.15-0.88); P [ .026). To the best of our knowledge, our study is the first to report a significant improvement in DFS for patients who received VD supplementation concurrently with trastuzumab-based chemotherapy for HER2-positive (HER2 D ) nonmetastatic breast cancer. Background: Vitamin D (VD) supplementation has pleiotropic effects that extend beyond their impact on bone health, including the disruption of downstream VD receptor signaling and human epidermal growth factor receptor 2 (HER2) signaling through the ErbB2/AKT/ERK pathway. In the present study, we examined our institutional experience with patients having nonmetastatic HER2-positive (HER þ ) breast cancer and hypothesized that those patients who received VD supplementation during neoadjuvant chemotherapy would have improved long-term outcomes. Patients and Methods: We performed a retrospective review of all patients (n ¼ 308) given trastuzumab-based chemotherapy between 2006 and 2012 at the University of Miami/Sylvester Comprehensive Cancer Center (UM/SCCC). We identified 2 groups of patients for comparison—those who received VD supplementation during neoadjuvant chemotherapy (n ¼ 134) and those who did not (n ¼ 112). Univariate and multivariate Cox proportional hazard regression models were fitted to overall survival (OS) and disease-free survival (DFS). Results: More than half of the patients received VD during neoadjuvant chemotherapy (54.5%), with 60% receiving a dose < 10,000 units/wk and 33.3% having aV D deficiency at the start of therapy. In our final multivariate model, VD use was associated with improved DFS (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.15-0.88; P ¼ .026], whereas larger tumor size was associated with worse DFS (HR, 3.52; 95% CI, 1.06-11.66; P ¼ .04). There were no differences in OS based on any of
- Published
- 2015
24. Comparative Effectiveness Analysis of Monotherapy With Cytotoxic Agents in Triple-negative Metastatic Breast Cancer in a Community Setting
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David Cox, Stefan Glück, Hope S. Rugo, Claudio Faria, and George Dranitsaris
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Adult ,Oncology ,medicine.medical_specialty ,Receptor, ErbB-2 ,medicine.medical_treatment ,Antineoplastic Agents ,Triple Negative Breast Neoplasms ,Vinblastine ,Vinorelbine ,Deoxycytidine ,Disease-Free Survival ,Capecitabine ,chemistry.chemical_compound ,Breast cancer ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Furans ,Aged ,Retrospective Studies ,Aged, 80 and over ,Pharmacology ,Chemotherapy ,Performance status ,Cytotoxins ,business.industry ,Ketones ,Middle Aged ,medicine.disease ,Gemcitabine ,Metastatic breast cancer ,Treatment Outcome ,chemistry ,Female ,business ,Eribulin ,medicine.drug - Abstract
There has been considerable progress in the treatment of metastatic breast cancer. However, the identification of optimal cytotoxic agents in patients with triple-negative breast cancer (TNBC) (negative for hormone receptors and human epidermal growth factor receptor 2) remains a therapeutic challenge. We conducted a comparative effectiveness analysis of 4 cytotoxic agents in patients with TNBC.We retrospectively identified patients who received single-agent chemotherapy with eribulin, capecitabine, gemcitabine, or vinorelbine from 19 community oncology clinics across the United States. Data collection included baseline patient and disease characteristics, prior therapies, performance status, duration of current therapy, growth-factor use and other supportive care, and dose-limiting toxicities and associated dose reductions or delays or skipped doses. Time to treatment failure (TTF) was measured from the first cycle of chemotherapy until disease progression, discontinuation due to toxicity, or death. TTF was estimated using the Kaplan-Meier method and Cox proportional hazards modeling adjusted for clustering on the practice site. To control for selection bias, which is inherent in observational studies, a propensity score-weighted TTF analysis was also conducted.Data from 225 patients were included in the analysis (eribulin, 47 patients; capecitabine, 69; gemcitabine, 56; and vinorelbine, 53). The median age of each group was60 years, with the exception of the gemcitabine group (63 years). The 4 groups were comparable with respect to age, performance status, duration of disease-free survival, presence of comorbidities, and hemoglobin level before the start of chemotherapy. Median lines of therapy of eribulin, capecitabine, gemcitabine, and vinorelbine and were 4th, 2nd, 3rd, and 3rd, respectively. The median durations of treatment were ~2 months with eribulin, capecitabine, and gemcitabine compared with 1.6 months with vinorelbine. Using eribulin as the reference drug, and with adjustment for line of therapy and associated prognostic factors, the propensity score-weighted Cox regression analysis did not identify significant between-treatment differences in TTF (hazard ratios [95% CI] vs eribulin: capecitabine, 1.15 [0.75-1.76]; gemcitabine, 0.62 [0.34-1.13]; and vinorelbine, 1.0 [0.67-1.67]).In this assessment of patients with TNBC treated in a community oncology setting, eribulin was utilized in later lines compared with the other agents. However, comparable drug activity was reported among the 4 agents.
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- 2015
25. EGF receptor inhibitors: patient selection and clinical outcomes
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Kiran Avancha, Alberto J. Montero, Stefan Glück, Gabriel Tinoco, and Sean Warsch
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business.industry ,Medicine ,Bioinformatics ,Receptor ,business ,Selection (genetic algorithm) - Published
- 2014
26. Paraneoplastic neurological syndromes in breast cancer
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Damien Mikael Hansra and Stefan Glück
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Oncology ,medicine.medical_specialty ,Pathology ,business.industry ,Paraneoplastic Neurologic Syndromes ,Cancer therapy ,medicine.disease ,Breast cancer ,Quality of life ,Internal medicine ,medicine ,Treatment strategy ,Radiology, Nuclear Medicine and imaging ,In patient ,business ,Organ system - Abstract
SUMMARY There is an increased understanding and recognition of paraneoplastic syndromes in patients with a variety of malignancies. Paraneoplastic syndromes are associated with many tumor types and can potentially affect most organ systems. Breast cancer is one of the most common cancers worldwide, including in the USA, and can be associated with a variety of paraneoplastic syndromes affecting many systems, including the endocrine, neurologic, dermatologic, rheumatologic, hematologic and psychiatric systems. These syndromes can cause significant morbidity; therefore, effective diagnostic and treatment strategies need to be applied to improve quality of life, enhance delivery of cancer therapy and potentially prolong survival. This review focuses on the diagnosis and treatment of major paraneoplastic neurologic syndromes associated with breast cancer.
- Published
- 2014
27. Herausforderungen der mechatronischen Produktentwicklung mittels Systems Engineering meistern am Beispiel sensorisierter Lager
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Andreas Schiffler, Ralf Weippert, Stefan Glück, Thomas Drescher, and Carolin Böckler
- Published
- 2016
28. Immunotherapy in breast cancer
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Scott H. Okuno, Stefan Glück, Sameer Batoo, Soley Bayraktar, and Tıp Fakültesi
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Cytotoxic T Lymphocyte Associated Antigen 4 ,Programmed Cell Death 1 ,Health, Toxicology and Mutagenesis ,medicine.medical_treatment ,Review Article ,programmed cell death-1 ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Breast cancer ,Internal medicine ,medicine ,programmed cell death ligand-1 ,Triple-negative breast cancer ,business.industry ,Cancer ,Programmed Cell Death Ligand 1 ,Immunotherapy ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Chimeric antigen receptor ,cytotoxic T-lymphocyte-associated antigen-4 ,Clinical trial ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer vaccine ,immunotherapy ,business ,checkpoint inhibitors - Abstract
The idea of using the immune system to fight cancer is over 100 years old. A new molecular approach led to a better understanding of the immune system. Checkpoint regulation, understanding the roles of Tregs, Th1, and Th2, development of Chimeric antigen receptor (CAR) T cells, as well as regulation of dendritic cells and macrophages, are just a few examples of our understating that has also led to the discovery of immune checkpoint inhibitors (ICIs) and modulators. This led the Nobel Prize committee in 2018, to award Dr. James P. Allison the Nobel Prize in medicine for the discovery of Cytotoxic T lymphocyte associated antigen 4, and Dr. Tasuku Honjo for the discovery of programmed cell death 1 (PD 1)/PD 1 ligand (PDL 1). Several ICIs are already approved by the regulatory authorities, and many more are currently used in studies of several solid tumors and hematologic malignancies. Positive studies have led to the US Food and Drug Administration (FDA) and European Medicines Agency approval of a number of these compounds, but none to date are approved in breast cancer (BC). Moreover, PD 1/PDL 1, MSI high (and dMMR), and tumor mutational burden are the currently “best” predictive markers for benefit from immunotherapy. BCs have some of these markers positive only in subsets but less frequently expressed than most other solid tumors, for example, malignant melanoma or non small cell lung cancer. To improve the potential efficacy of ICI in BC, the addition of chemotherapy was one of the strategies. Many early and large clinical trials in all phases are underway in BC. We will discuss the role of immune system in BC editing, and the potential impact of immunotherapy in BC outcomes.
- Published
- 2019
29. Abstract P6-09-03: Improved clinical outcomes associated with statin use during adjuvant chemotherapy in patients with HER2+ non-metastatic breast cancer
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E Ahn, SB Zeichner, Stefan Glück, NN Shah, and Alberto J. Montero
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Gynecology ,Oncology ,Cancer Research ,Chemotherapy ,medicine.medical_specialty ,Univariate analysis ,Statin ,business.industry ,medicine.drug_class ,medicine.medical_treatment ,Cancer ,medicine.disease ,Breast cancer ,Trastuzumab ,Internal medicine ,Epidemiology of cancer ,medicine ,Adjuvant therapy ,skin and connective tissue diseases ,business ,medicine.drug - Abstract
Background Statins are established as first line therapy in patients with hypercholesterolemia and are thought to have pleiotropic effects including inhibition of signaling pathways known to drive cell proliferation and survival responses. Numerous preclinical and observational studies have demonstrated activity and improved outcomes in breast cancer patients who received statins, particularly lipophilic statins, as part of their adjuvant therapy. In the Life After Cancer Epidemiology (LACE) Study, 1,945 early-stage breast cancer survivors were shown to have a 33% decreased risk of breast cancer recurrence with post-diagnosis statin use, an effect that was magnified with increasing duration of statin use. We hypothesized that statin use concurrent with trastuzumab based chemotherapy in patients treated for non-metastatic HER2 positive breast cancer would be associated with improved outcomes. Methods We performed a retrospective review of all patients (n = 300) with HER2+ breast cancer who received trastuzumab from 2006-2012 at UM/SCCC. We identified two groups of patients for comparison - those who received statins (ST) during adjuvant chemotherapy (n = 45) or no statins during chemotherapy (NST) during adjuvant chemotherapy (n = 200). Patients with unclear documentation of concurrent statin use, men, patients with de-novo-metastatic breast cancer or prior primary cancer, bilateral breast cancers, and patients without follow-up were excluded. 5-year disease free (DFS) and overall survival (OS) were calculated. A univariate analysis was performed. Multivariate analysis for time-to-event data, using the Cox and extended Cox regression model will be performed and reported. Results The median age at diagnosis was 58 and 48, in the ST and NST groups, respectively. The most commonly used statin was lipophilic simvastatin (34.1%). The average baseline and post chemotherapy total cholesterol level in the ST group was 200.8 and 218.1mg/dL, respectively. Descriptive characteristics of the ST and NST groups respectively are as follows: postmenopausal (77.8% vs. 43.5%) tumor size 30 (40.0% vs. 27.0%), and concomitant metformin (28.9% vs. 11.5%). The NST group was more likely to have a reduction of greater than 10% in their EF (9.0% vs. 6.7%). At a median follow-up of 32 and 26 months, the estimated 5-year DFS was significantly improved in the ST group (81.8% vs. 51.5%, p = 0.046). Meanwhile, the estimated 5-year OS was not significantly different between both groups (93.4% vs. 91.6%, p = 0.121). Metformin was not associated with a significant improvement in DFS or OS. Conclusion Our study demonstrated that statin use concurrent with trastuzumab-based chemotherapy for non-metastatic HER2 breast cancer was associated with improved estimated 5-year DFS, but not OS. The retrospective nature of our study does not allow for a definitive answer but further research needs to be done to define the role of statins in HER2+ breast cancer treatment. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-09-03.
- Published
- 2013
30. Abstract P3-13-05: Eribulin mesylate as first-line therapy for locally recurrent or metastatic HER2-negative breast cancer: Results of a phase 2, multicenter, single-arm study
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David Cox, James Song, Kristi McIntyre, Stefan Glück, J Rege, Lee S. Schwartzberg, Erhan Berrak, Linda T. Vahdat, and Joyce A. O'Shaughnessy
- Subjects
Eribulin Mesylate ,Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Neutropenia ,medicine.disease ,Metastatic breast cancer ,Surgery ,chemistry.chemical_compound ,Breast cancer ,chemistry ,Internal medicine ,medicine ,Adjuvant therapy ,business ,Febrile neutropenia ,Progressive disease ,Eribulin - Abstract
Background: Eribulin mesylate is a novel nontaxane microtubule dynamics inhibitor that is approved for treatment of metastatic breast cancer (MBC) in patients who have previously received at least two chemotherapeutic regimens for MBC. We present final data from a phase 2 study that evaluated the efficacy and safety of eribulin as first-line therapy for HER2-negative (HER2-) MBC. Methods: Patients with measureable HER2- locally recurrent or MBC with ≥12 months since prior neoadjuvant or adjuvant chemotherapy received eribulin mesylate 1.4 mg/m2 IV on days 1 and 8 of each 3-week cycle. Endpoints included objective response rate (ORR) (primary), safety, progression-free survival (PFS), time to response (TTR), and duration of response (DOR). Tumor assessments were conducted every 6 weeks for the first 6 cycles and every 6-12 weeks thereafter per RECIST 1.1. Results: Fifty-six patients enrolled and received eribulin. Patients had a median age of 56 years (range 31-85); 32 (57%) had an ECOG status of 0; 17 (30%) had de novo stage IV; 33 (59%) had prior (neo)adjuvant therapy, including anthracycline and/or taxane (A/T) chemotherapy. Thirty-nine patients (70%) had visceral disease (45% liver, 32% lung); 41(73%) had estrogen receptor-positive (ER+) disease and 12 (21%) had triple negative (TN) disease. Thirty-two patients (57%) completed at least 6 cycles of treatment; among the 24 patients who completed fewer than 6 cycles, reasons for not completing were progressive disease (PD; n = 18), adverse events (AEs; n = 3) and patient choice (n = 3). The median number of cycles delivered was 7 (range 1-39); 6 patients (11%) received treatment for ≥12 months. Overall ORR was 27%, with median TTR of 1.4 months and median DOR of 7.4 months; stable disease (SD) rate was 48% (Table 1). Median PFS was 6.8 months. Thirty-five patients (63%) had grade 3/4 treatment-related AEs (Table 2). Treatment-related serious AEs occurred in 5 (9%) patients: neutropenia (5%), febrile neutropenia (5%), and leukopenia (2%). Conclusions: The results of this study suggest that first-line eribulin has antitumor activity in ER+/HER2- and TN MBC with safety consistent with the known profile. Further exploration of this treatment as part of earlier lines of breast cancer therapy, including neo/adjuvant, is warranted. Table 1. Summary of EfficacyEfficacyEribulin-treated patients N = 56ORR, n (%)15 (27)CR0PR15 (27)SD27 (48)PD12 (21)Clinical benefit rate (ORR + ≥6 mo SD)27 (48)Median months (95% CI) TTR1.4 (1.2, 2.7)DOR7.4 (4.7, NE)PFS6.8 (4.4, 7.4)NE, not estimable Table 2. Treatment-Related AEsAE (N = 56)All events (%)Grade 3/4 (%)Leading to study drug withdrawal1111Leading to dose reduction3427Common AEs (≥25%) Alopecia820Neutropenia7050Fatigue572Peripheral neuropathy5420Nausea460Anemia364Leukopenia3018Constipation270 Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-13-05.
- Published
- 2013
31. Treatment effect of capecitabine and docetaxel or docetaxel alone by oestrogen receptor status in patients with metastatic breast cancer: Results of an exploratory analysis
- Author
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Joanne L. Blum, Joyce O'Shaughnessy, S Hu, EF McKenna, Stefan Glück, C. Russell, and Dawn Odom
- Subjects
Adult ,Oncology ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Breast Neoplasms ,Docetaxel ,Kaplan-Meier Estimate ,Deoxycytidine ,Disease-Free Survival ,Capecitabine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,In patient ,Oestrogen receptor ,Aged ,Proportional Hazards Models ,Retrospective Studies ,business.industry ,Hazard ratio ,General Medicine ,Middle Aged ,medicine.disease ,Metastatic breast cancer ,Confidence interval ,Receptors, Estrogen ,Disease Progression ,Female ,Taxoids ,Surgery ,Fluorouracil ,Receptors, Progesterone ,business ,Adjuvant ,medicine.drug - Abstract
We investigated treatment effects by oestrogen receptor (ER) status among women with metastatic breast cancer (MBC) receiving capecitabine (C) plus docetaxel (D) or D alone in a randomised phase III trial. Data were retrospectively analysed from patients whose disease had recurred following (neo) adjuvant anthracyclines. ER status was identified in 356/506 patients. In patients with ER-positive tumours, median overall survival from enrolment was 17.7 months with CD versus 12.5 months with D (hazard ratio [HR] 0.65, 95% confidence interval [CI]: 0.47e0.89; P ¼ 0.007) and median time to progression (TTP) was 6.8 and 5.4 months, respectively (HR 0.62, 95% CI: 0.46e0.84; P ¼ 0.002). For patients with ER-negative tumours, significantly longer TTP was seen with CD (5.2 versus 3.5 months; HR 0.73, 95% CI: 0.53e0.98; P ¼ 0.038). Whether there is an additional C to D treatment benefit in ER-positive versus ER-negative MBC requires further evaluation.
- Published
- 2013
32. Nonsteroidal Anti-inflammatory Drug Induced Thrombotic Thrombocytopenic Purpura
- Author
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Jeremy Ramdial, Stefan Glück, and Karlos Z. Oregel
- Subjects
medicine.medical_specialty ,TTP ,NSAIDs ,medicine.medical_treatment ,Thrombotic thrombocytopenic purpura ,Renal function ,Case Report ,Ibuprofen ,Hematocrit ,Gastroenterology ,drug-induced TTP ,White blood cell ,Internal medicine ,hemic and lymphatic diseases ,medicine ,thrombotic thrombocytopenic purpura ,Blood urea nitrogen ,medicine.diagnostic_test ,business.industry ,lcsh:RC633-647.5 ,Acute kidney injury ,Hematology ,lcsh:Diseases of the blood and blood-forming organs ,medicine.disease ,ADAMTS13 ,medicine.anatomical_structure ,Hemodialysis ,business ,Biomedical engineering - Abstract
A 21-year-old male presented to the emergency department after a 5-day history of recurrent vomiting and decreased urine output. History revealed ingestion of ibuprofen. During the diagnostic workup, the following was identified: white blood cell count 13.4 (x10(3)/mcL), hemoglobin 11.9 (x10(6)/mcL) with an MCV of 73 fL, hematocrit 34% and platelets were 31,000/mcL, sodium of 130 mmol/L, potassium of 5.1 mmol/L, chloride of 83 mmol/L, bicarbonate of 21 mmol/L, blood urea nitrogen of 184 mg/dL and creatinine of 19.1 mg/dL. He was later diagnosed with thrombotic thrombocytopenic purpura (TTP) based on the fact that he presented with most components of the TTP pentad (except for fever), which included altered mental status, acute kidney injury, thrombocytopenia, and evidence of red cell fragmentation and his ADAMTS13 level was found to be less than 10% prior to therapy. The patient then received plasma exchange, oral corticosteroids, and hemodialysis, which led to a full recovery of platelet count and renal function.
- Published
- 2013
33. Ductal carcinoma in situ: how should we treat it?
- Author
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Soley Bayraktar, Banu Arun, and Stefan Glück
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Precursor lesion ,Lumpectomy ,Clinical course ,Ductal carcinoma ,medicine.disease ,law.invention ,Natural history ,Breast cancer ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,In patient ,skin and connective tissue diseases ,business - Abstract
SUMMARY The observed incidence of ductal carcinoma in situ (DCIS) has increased because of the increasing use of sensitive imaging modalities. While the clinical course of DCIS is quite variable, it is considered a precursor lesion to invasive breast cancer. The current focus of DCIS treatment is on the prevention of progression to invasive disease. However, at present, validated diagnostic tests to predict progression accurately are lacking. Additionally, important clinical questions arise during DCIS management. For example, optimal margins of excision or axillary lymph node sampling have not been addressed in randomized clinical trials. May whole-breast radiation after lumpectomy be omitted in selected patients? What is the role of adjuvant tamoxifen if it does not impact overall survival rates? This review aims to describe the natural history of DCIS and highlights the current therapeutic options and challenges in patient management.
- Published
- 2013
34. Aromatase inhibitors in the treatment of elderly women with metastatic breast cancer
- Author
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Michael Untch, Stefan Glück, and Gunter von Minckwitz
- Subjects
Oncology ,medicine.medical_specialty ,Health Status ,Population ,Antineoplastic Agents ,Breast Neoplasms ,Comorbidity ,Anastrozole ,chemistry.chemical_compound ,Life Expectancy ,Breast cancer ,Exemestane ,Internal medicine ,Nitriles ,medicine ,Humans ,education ,Geriatric Assessment ,Aged, 80 and over ,education.field_of_study ,Aromatase Inhibitors ,business.industry ,Standard treatment ,Disease Management ,General Medicine ,Triazoles ,Prognosis ,medicine.disease ,Metastatic breast cancer ,Androstadienes ,Clinical trial ,Regimen ,Treatment Outcome ,chemistry ,Letrozole ,Disease Progression ,Quality of Life ,Drug Therapy, Combination ,Female ,Surgery ,business ,Tamoxifen ,medicine.drug - Abstract
The proportion of elderly women in the population is rising, and in tandem, the incidence of breast cancer rises with age. Because of health and tolerability concerns, as well as life expectancy, physicians may be reluctant to advise a standard treatment regimen for elderly patients with metastatic breast cancer. To elucidate this issue, we performed a literature review of clinical studies that included women with metastatic breast cancer who were over the age of 65. Our results show that although little clinical evidence exists, what is available suggests that standard treatment is tolerated and beneficial for patients meeting certain criteria. A geriatric assessment may identify specific patient groups (independent, dependent, or frail) and thereby guide treatment. Treatment recommendations for elderly patients with metastatic breast cancer are sparse, although first-line endocrine treatment, usually aromatase inhibitors or tamoxifen, is recommended for hormone-sensitive disease. In general, the evidence from clinical studies suggests that aromatase inhibitors are more effective than either tamoxifen or megestrol acetate as first- or second-line treatment in postmenopausal women with metastatic breast cancer. Ultimately, quality of life, treatment effects, and comorbidities are important aspects in this population and may guide treatment choice. To provide evidence-based treatment guidance, future clinical trials should include more patients over the age of 65 years.
- Published
- 2013
35. Molecularly targeted therapies for metastatic triple-negative breast cancer
- Author
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Stefan Glück and Soley Bayraktar
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,medicine.drug_class ,Angiogenesis ,medicine.medical_treatment ,Antineoplastic Agents ,Breast Neoplasms ,Targeted therapy ,Breast cancer ,Trastuzumab ,Internal medicine ,medicine ,Humans ,Molecular Targeted Therapy ,Epidermal growth factor receptor ,Neoplasm Metastasis ,Triple-negative breast cancer ,Chemotherapy ,biology ,business.industry ,medicine.disease ,Receptors, Estrogen ,Estrogen ,biology.protein ,Female ,Receptors, Progesterone ,business ,medicine.drug - Abstract
Triple-negative breast cancer (TNBC) refers to a heterogeneous group of tumors that do not express the estrogen/progesterone-receptor (ER/PR), and human epidermal growth factor receptor-2 (HER2). TNBC is an aggressive histological subtype with limited treatment options and very poor prognosis following progression after standard chemotherapy regimens. There have been significant improvements in the outcome of other subtypes of breast cancer, including ER-positive/HER2 overexpressed tumors, attributed to the addition of targeted therapy, including hormonal agents and trastuzumab. However, no specific targeted agents are currently available for the treatment of TNBC. This review aims to collate and describe the most recent data on targeted therapies that have demonstrated efficacy in the management of metastatic TNBC. Targeted agents that have been investigated in the treatment of metastatic TNBC include inhibitors of poly(ADP-ribose) polymerase, angiogenesis, mammalian target of rapamycin, epidermal growth factor receptor, HDAC, Jak2, and Src. Several of these agents have shown considerable promise.
- Published
- 2013
36. Treating Breast Cancer in the 21st Century: Emerging Biological Therapies
- Author
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Sean Warsch, Stefan Glück, Alberto J. Montero, Kiran Avancha, and Gabriel Tinoco
- Subjects
PARP inhibitors ,business.industry ,medicine.drug_class ,novel therapeutics ,BRCA mutation ,Review ,Pharmacology ,chemotherapy ,medicine.disease ,Lapatinib ,Tyrosine-kinase inhibitor ,breast cancer ,Breast cancer ,Oncology ,Trastuzumab ,HER2 ,Cancer research ,medicine ,biologics ,Pertuzumab ,skin and connective tissue diseases ,business ,PI3K/AKT/mTOR pathway ,Triple-negative breast cancer ,medicine.drug - Abstract
For many years, the medical treatment of breast cancer was reliant solely on cytotoxic chemotherapy. However, over the past twenty years, treatment has evolved to a more target-directed approach. We now employ tailored therapy based on the presence or absence of receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER2). We expect this trend to continue, as agents that use novel approaches to target HER2, as well as targeting different portions of the HER signaling pathway, are in various stages of development. Notably, pertuzumab, a humanized monoclonal antibody that binds to a different domain of the extracellular portion of the HER2 receptor than trastuzumab, was recently approved for use, as was lapatinib, a small-molecule tyrosine kinase inhibitor. Patients with triple negative breast cancer, particularly those with the BRCA mutation, have more limited treatment options and carry a worse prognosis than those who are hormone receptor positive. However, recent data has shown that PARP inhibitors may have significant anti-tumor effect in those with this subtype of breast cancer. Novel agents that inhibit mTOR, PI3K, the insulin-like growth factor, heat shock protein 90, and histone deacetylase have shown promise in phase I-III trials and offer exciting new possibilities for the treatment of this often fatal disease. As we are presented with an ever increasing number of treatment options, the timing and combinations of therapeutic agents used becomes ever more complex in the age of personalized care, but we are hopeful that ultimately this will lead to improved patient outcomes.
- Published
- 2013
37. Treating Breast Cancer in the 21st Century: Emerging Biological Therapies
- Author
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Gabriel Tinoco, Sean Warsch, Stefan Glück, Kiran Avancha, Alberto J. Montero
- Subjects
skin and connective tissue diseases ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 - Abstract
For many years, the medical treatment of breast cancer was reliant solely on cytotoxic chemotherapy. However, over the past twenty years, treatment has evolved to a more target-directed approach. We now employ tailored therapy based on the presence or absence of receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER2). We expect this trend to continue, as agents that use novel approaches to target HER2, as well as targeting different portions of the HER signaling pathway, are in various stages of development. Notably, pertuzumab, a humanized monoclonal antibody that binds to a different domain of the extracellular portion of the HER2 receptor than trastuzumab, was recently approved for use, as was lapatinib, a small-molecule tyrosine kinase inhibitor. Patients with triple negative breast cancer, particularly those with the BRCA mutation, have more limited treatment options and carry a worse prognosis than those who are hormone receptor positive. However, recent data has shown that PARP inhibitors may have significant anti-tumor effect in those with this subtype of breast cancer. Novel agents that inhibit mTOR, PI3K, the insulin-like growth factor, heat shock protein 90, and histone deacetylase have shown promise in phase I-III trials and offer exciting new possibilities for the treatment of this often fatal disease. As we are presented with an ever increasing number of treatment options, the timing and combinations of therapeutic agents used becomes ever more complex in the age of personalized care, but we are hopeful that ultimately this will lead to improved patient outcomes.
- Published
- 2013
38. Clinical Utility of Aromatase Inhibitors as Adjuvant Treatment in Postmenopausal Early Breast Cancer
- Author
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Francisco Socola, Arturo Loaiza-Bonilla, and Stefan Glück
- Subjects
Oncology ,medicine.medical_specialty ,medicine.drug_class ,Estrogen receptor ,Review ,Malignancy ,aromatase inhibitors ,breast cancer ,Breast cancer ,adjuvant ,Internal medicine ,medicine ,Aromatase ,skin and connective tissue diseases ,lcsh:R5-920 ,hormonal therapy ,postmenopausal ,Aromatase inhibitor ,biology ,business.industry ,General Medicine ,medicine.disease ,Estrogen ,biology.protein ,Hormonal therapy ,business ,lcsh:Medicine (General) ,Tamoxifen ,Biomedical engineering ,medicine.drug - Abstract
Breast cancer is the most frequently diagnosed malignancy in women, with over 200,000 new cases diagnosed each year. Adjuvant systemic endocrine therapy has demonstrated its benefits in reducing the risk of occult micro metastatic infiltration by preventing breast cancer cells from receiving endogenous estrogen stimulation. Initial adjuvant treatment with an aromatase inhibitor (AI) is considered the standard of care for most postmenopausal women with node-positive and high-risk node-negative estrogen receptor (ER)-positive breast cancer. Aromatase inhibitors (AIs) are generally preferred over tamoxifen due to their effectiveness in preventing breast cancer recurrence post surgery and when tamoxifen side effects are to be avoided. When compared with tamoxifen, AIs are associated with significantly improved disease-free survival, however no OS advantage has been noted. Potential toxicities such as bone loss, dyslipidemia, musculoskeletal and cardiovascular health issues should be taken into consideration when AIs are to be used.
- Published
- 2013
39. Abstract P1-12-02: Results of a phase 2, multicenter, single-arm study of eribulin mesylate as first-line therapy for locally recurrent or metastatic HER2-negative breast cancer
- Author
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J Rege, Stefan Glück, Lee S. Schwartzberg, David Cox, Linda T. Vahdat, J Liao, and Joyce A. O'Shaughnessy
- Subjects
Oncology ,Eribulin Mesylate ,Cancer Research ,medicine.medical_specialty ,business.industry ,Phases of clinical research ,medicine.disease ,Metastatic breast cancer ,Surgery ,chemistry.chemical_compound ,Breast cancer ,chemistry ,Internal medicine ,Adjuvant therapy ,Medicine ,Progression-free survival ,business ,Febrile neutropenia ,Eribulin - Abstract
Background: Eribulin mesylate is a novel nontaxane microtubule dynamics inhibitor that is approved in patients (pts) with metastatic breast cancer (MBC) who have previously received at least two chemotherapeutic regimens for MBC. We are reporting a preliminary planned analysis (first 6 cycles of treatment) of a phase 2 study that evaluates efficacy and safety of eribulin as first-line therapy for HER2-negative MBC. Methods: Pts with measureable HER2-negative locally recurrent or MBC with at least 12 months since prior neoadjuvant or adjuvant chemotherapy received eribulin mesylate at 1.4 mg/m2 IV on days 1 and 8 of each 3-week cycle. Endpoints include objective response rate (ORR) (primary), safety, progression free survival (PFS), time to response (TTR), and duration of response (DOR). Tumor assessments were evaluated every 6 weeks for the first 6 cycles and every 6–12 weeks thereafter per RECIST 1.1. Results: 54 of 56 enrolled pts had at least 1 post-baseline assessment. The median number of cycles delivered was 7 (range 1,21). Pt characteristics: median age, 56 yrs (range 31–85); ECOG of 0, 32 (57%); 29% had de novo stage IV; 38/56 (68%) had prior neo/adjuvant (45% had anthracycline and 45% taxane, the majority of which were given together). Seventy percent have visceral disease (45% liver, 38% lung); 41 (73%) have estrogen receptor-positive (ER) disease and 12 (21%) have triple negative (TN) (ER−/PR−/HER2−) disease. Objective response data are found in Table 1. The most common treatment-related AEs are reported in Table 2. Treatment-related serious AEs occurred in 5 (9%) pts, neutropenia (4%), and febrile neutropenia (5%). Five pts stopped study therapy due to adverse events. Fourteen pts remain on study treatment. Conclusions: The preliminary results of this first-line study suggest that eribulin has antitumor activity in ER+/HER2− and TN MBC with an acceptable safety profile. Further exploration of this treatment as part of neo/adjuvant therapy is warranted. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-12-02.
- Published
- 2012
40. Long-Term Complete Remission with nab-Paclitaxel, Bevacizumab, and Gemcitabine Combination Therapy in a Patient with Triple-Negative Metastatic Breast Cancer
- Author
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Stefan Glück and Alberto J. Montero
- Subjects
Oncology ,medicine.medical_specialty ,Bevacizumab ,Combination therapy ,medicine.medical_treatment ,Phases of clinical research ,Published online: December, 2012 ,lcsh:RC254-282 ,nab-paclitaxel ,Breast cancer ,Triple-negative breast cancer ,Internal medicine ,medicine ,Chemotherapy ,business.industry ,HER2 negative ,medicine.disease ,Metastatic breast cancer ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Gemcitabine ,Long-term response ,business ,medicine.drug - Abstract
This is a case study of a 52-year-old female patient diagnosed in June 2007 with primary metastatic invasive ductal carcinoma of the left breast and synchronous metastases in the bone, lymph nodes, and lung. Biopsy results of the tumor tissue were negative for the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). In November 2007, she participated in a phase II study of metastatic HER2-negative breast cancer. Treatment consisted of systemic chemotherapy with gemcitabine 1,500 mg/m 2 , nab-paclitaxel 150 mg/m 2 , and bevacizumab 10 mg/kg once every other week. The patient experienced pain relief in her sternum after 5 weeks of chemotherapy, and her analgesic therapy was discontinued. After 7 months, the patient achieved a complete radiographic response, which was maintained for nearly 2 additional years. She continued receiving treatment throughout this period, requiring 1 dose reduction due to fatigue. The patient experienced no other adverse events, including neuropathy, and continued working uninterrupted throughout her treatment. The patient was discontinued from the study in May 2010 after disease progression, almost a full 3 years after diagnosis. The patient showed minimal response to subsequent therapies but had disease stabilization and died from her disease in April 2012. Median overall survival for patients with metastatic triple-negative breast cancer is between 12 and 13.3 months. This patient survived nearly 5 years following diagnosis. This case exemplifies how therapy with nab-paclitaxel, bevacizumab, and gemcitabine may prolong survival, with minimal toxicity, in select patients with triplenegative metastatic breast cancer.
- Published
- 2012
41. Abstract P3-06-11: Response and long-term outcomes after neo-adjuvant chemotherapy: Pooled dataset of patients stratified by molecular subtyping using MammaPrint and BluePrint
- Author
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Lisette Stork-Sloots, F de Snoo, Justine K. Peeters, Stefan Glück, G. Somlo, and Veer L van't
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Cancer ,Bioinformatics ,medicine.disease ,Subtyping ,Breast cancer ,MammaPrint ,Internal medicine ,Cohort ,medicine ,Long term outcomes ,Neo adjuvant chemotherapy ,business - Abstract
Background: Classification into molecular subtypes may increasingly be important for the selection of therapy for patients with early-stage breast cancer. Previous analyses had shown that breast cancer subtypes have distinct clinical outcome [Sorlie et al. PNAS 2001; Esserman et al. BCRT 2011]. In our study, we analyzed the response to neo-adjuvant chemotherapy and long-term outcomes using the 70-gene profile (MammaPrint) together with an 80-gene molecular subtyping profile (BluePrint). Methods: This analysis was performed on data from 421 patients: 141 patients from the I-SPY I trial; 230 patients from the biomarker discovery program at MD Anderson (131 and 99 respectively; Hess et al. JCO 2006; Iwamoto et al. BCRT 2011]; and 50 patients from the City of Hope [Somlo et al. ASCO 2010]. All patients were treated in the neo-adjuvant setting with chemotherapy. MammaPrint and BluePrint outcomes were determined from either 44K Agilent arrays run at Agendia or available through the I-SPY I data portal, or from Affymetrix U133A arrays. The combination of MammaPrint and BluePrint resulted in four distinct molecular groups: Luminal A (MammaPrint Low Risk/Luminal-type), Luminal B (MammaPrint High Risk/ Luminal-type), Basal-type and HER2-type. Results: The overall pCR of this patient cohort was 22% but differed substantially among the defined BluePrint molecular subgroups. pCR was observed in 3% of the Luminal A and 12% of Luminal B, in 38% of the HER2-type and in 42% of the Basal-type samples. 42% of patients with clinical HER2-positive phenotype are classified as Luminal-type by BluePrint: eight patients as Luminal A and 34 patients as Luminal B. 5-year distant metastases-free survival (DMFS) of patients with HER2-type by BluePrint who achieve pCR is 87%, compared with 78% for clinical HER2+ patients with pCR. These data are in line with a recent retrospective analysis of a large cohort of patients, which showed that pCR rate is not a suitable surrogate for clinical HER2+/Hormone Receptor-positive patients and is not associated with outcome [von Minckwitz et al. JCO 2012]. BluePrint classifies more patients as Basal-type (n = 120) with higher pCR rate (42%), compared with clinical subtyping (triple negative, n=93) with a pCR rate of 31%. Despite including eight clinical HER2+ and 11 triple-negative patients, those with BluePrint Luminal A subtype (n = 88) have excellent 5-year DMFS of 94% and appear to have no benefit from chemotherapy (low pCR rate). Conclusions: Molecular subtyping using BluePrint with MammaPrint can help to improve outcomes of patients in the neo-adjuvant setting over clinical subtyping. We observed differences in pCR and DMFS following neo-adjuvant treatment in groups stratified by MammaPrint and BluePrint; for example, patients with Luminal A breast cancer (assessed with MammaPrint and BluePrint) have a good baseline prognosis with excellent survival and may not benefit from chemotherapy. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-11.
- Published
- 2012
42. Toxicity profile differences of adjuvant docetaxel/cyclophosphamide (TC) between Asian and Caucasian breast cancer patients
- Author
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Chiun-Sheng Huang, L. Zhu, Masakazu Toi, C.Y.C. Chow, Laura Biganzoli, Katsumasa Kuroi, H. S. Han, L.W.C. Chow, Y.S. Lu, J. Patel, Angelo Di Leo, W.T.Y. Loo, and Stefan Glück
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Cyclophosphamide ,medicine.medical_treatment ,Population ,Breast Neoplasms ,Docetaxel ,Neutropenia ,Gastroenterology ,White People ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Asian People ,Internal medicine ,medicine ,Humans ,education ,Retrospective Studies ,education.field_of_study ,business.industry ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,Taxoids ,business ,Adjuvant ,Febrile neutropenia ,medicine.drug - Abstract
AIM For early-stage breast cancer, four cycles of docetaxel and cyclophosphamide (TC) was proven superior to doxorubicin plus cyclophosphamide in the US Oncology 9375 trial. Given primary prophylactic antibiotics, 5% febrile neutropenia was recorded in a population comprising 75.5% Caucasians. Smaller trials and retrospective studies reviewing TC use in Asian patients did not produce similar incidence rates. This study aims to discover the variable hematological toxicities with TC use in Caucasian and Asian patients. METHODS Breast cancer data was retrospectively reviewed for patients receiving adjuvant docetaxel 60-75 mg/m2 plus cyclophosphamide 600 mg/m2 from six countries (China, Hong Kong, Japan, Taiwan, Italy, and United States). Similar number of patients with relatively balanced baseline characteristics were chosen for analysis of hematological and nonhematological toxicities and survival data. RESULTS From March 2004 to July 2013, data of 227 patients (127 Asians and 100 Caucasian) patients were analyzed for treatment-related toxicities. During the four cycles of TC, Asians had a significantly higher rate of grade ≥2 neutropenia than Caucasians (45.7% vs 6.0%; P
- Published
- 2016
43. Breast cancers from black women exhibit higher numbers of immunosuppressive macrophages with proliferative activity and of crown-like structures associated with lower survival compared to non-black Latinas and Caucasians
- Author
-
Manuel L. Penichet, Tan A. Ince, Zhibin Chen, Merce Jorda, Ana M. Santander, Tulay Koru-Sengul, Margot P. Cleary, Mehrad Nadji, Feng Miao, Lidia G. Sanchez, Stefan Glück, and Marta Torroella-Kouri
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Adipose tissue ,Antigens, Differentiation, Myelomonocytic ,Inflammation ,Breast Neoplasms ,Receptors, Cell Surface ,Article ,Disease-Free Survival ,White People ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Antigens, CD ,Internal medicine ,medicine ,Humans ,Crown-Like Structure ,Lectins, C-Type ,skin and connective tissue diseases ,Cell Proliferation ,business.industry ,Incidence (epidemiology) ,Macrophages ,Hispanic or Latino ,medicine.disease ,Prognosis ,Survival Analysis ,Black or African American ,030104 developmental biology ,Mannose-Binding Lectins ,Tumor progression ,030220 oncology & carcinogenesis ,Immunology ,Female ,medicine.symptom ,business ,Macrophage proliferation ,CD163 ,Mannose Receptor - Abstract
Racial disparities in breast cancer incidence and outcome are a major health care challenge. Patients in the black race group more likely present with an early onset and more aggressive disease. The occurrence of high numbers of macrophages is associated with tumor progression and poor prognosis in solid malignancies. Macrophages are observed in adipose tissues surrounding dead adipocytes in "crown-like structures" (CLS). Here we investigated whether the numbers of CD163+ tumor-associated macrophages (TAMs) and/or CD163+ CLS are associated with patient survival and whether there are significant differences across blacks, non-black Latinas, and Caucasians. Our findings confirm that race is statistically significantly associated with the numbers of TAMs and CLS in breast cancer, and demonstrate that the highest numbers of CD163+ TAM/CLS are found in black breast cancer patients. Our results reveal that the density of CD206 (M2) macrophages is a significant predictor of progression-free survival univariately and is also significant after adjusting for race and for HER2, respectively. We examined whether the high numbers of TAMs detected in tumors from black women were associated with macrophage proliferation, using the Ki-67 nuclear proliferation marker. Our results reveal that TAMs actively divide when in contact with tumor cells. There is a higher ratio of proliferating macrophages in tumors from black patients. These findings suggest that interventions based on targeting TAMs may not only benefit breast cancer patients in general but also serve as an approach to remedy racial disparity resulting in better prognosis patients from minority racial groups.
- Published
- 2016
44. Erratum to: ‘Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tnAcity study): study protocol for a randomized controlled trial
- Author
-
J.-M. Nabholtz, Markus F. Renschler, Javier Cortes, Debora Barton, Amy Ko, Stefan Glück, Joyce O'Shaughnessy, Denise A. Yardley, Robert E. Coleman, Robert Beck, Pierfranco Conte, Nadia Harbeck, and Adam Brufsky
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Medicine (miscellaneous) ,Carboplatin ,Gemcitabine ,law.invention ,First line treatment ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Randomized controlled trial ,law ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Pharmacology (medical) ,030212 general & internal medicine ,business ,Triple-negative breast cancer ,medicine.drug ,Nab-paclitaxel - Published
- 2016
45. HER2-positive metastatic breast cancer: a double-edged sword
- Author
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Reshma Mahtani, Jose D. Sandoval-Sus, and Stefan Glück
- Subjects
Oncology ,medicine.medical_specialty ,Breast cancer ,business.industry ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,SWORD ,medicine.disease ,business ,Metastatic breast cancer - Published
- 2012
46. Systemic therapy options in BRCA mutation-associated breast cancer
- Author
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Stefan Glück and Soley Bayraktar
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,DNA Repair ,endocrine system diseases ,DNA repair ,medicine.medical_treatment ,Genes, BRCA2 ,Genes, BRCA1 ,Antineoplastic Agents ,medicine.disease_cause ,Breast cancer ,Internal medicine ,medicine ,Humans ,Molecular Targeted Therapy ,skin and connective tissue diseases ,Triple-negative breast cancer ,Cisplatin ,Clinical Trials as Topic ,Mutation ,Chemotherapy ,business.industry ,Cell Cycle ,BRCA mutation ,medicine.disease ,Chemotherapy regimen ,Hereditary Breast and Ovarian Cancer Syndrome ,Female ,business ,medicine.drug - Abstract
BRCA mutation-associated breast cancers are characterized by deficient homologous recombination of DNA, and 80 % of BRCA1-associated breast cancers dis- play the basal-like molecular subtype. Traditionally, BRCA carriers have received conventional systemic chemotherapy based on their baseline tumor characteristics, and it is gen- erally accepted that after the appropriate treatment the prognosis of a mutation carrier is equivalent to that of a patient with sporadic breast cancer. However, with the growing understanding of the functions of BRCA1/2 pro- teins in homologous DNA repair, it is recognized that BRCA-associated breast cancer tumors may have distinct biochemical characteristics and thus require tailored treat- ment strategies. Tumors arising in patients with BRCA mutations were shown to be particularly sensitive to plati- num compounds or inhibitors of poly(ADP-ribose) poly- merase. In addition, BRCA1-mutation carriers seem to benefit from anthracycline-taxane-containing regimens as much as sporadic triple-negative breast cancers do. In this article, we review the functions of the BRCA1 and BRCA2 genes, and their differential chemosensitivity in both the preclinical and clinical settings. The optimal chemotherapy regimen for this subset of patients still remains to be determined.
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- 2012
47. Management of women with BRCA1/2 mutation-associated breast cancer
- Author
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Stefan Glück and Soley Bayraktar
- Subjects
Oncology ,medicine.medical_specialty ,animal structures ,endocrine system diseases ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,BRCA mutation ,Cancer ,medicine.disease ,female genital diseases and pregnancy complications ,Breast cancer ,Internal medicine ,Mutation (genetic algorithm) ,medicine ,Radiology, Nuclear Medicine and imaging ,Family history ,skin and connective tissue diseases ,Ovarian cancer ,business ,Mastectomy ,Genetic testing - Abstract
SUMMARY BRCA mutation-associated breast cancer differs from sporadic breast cancer as studies show that mutation carriers have a higher risk of breast and ovarian cancer, and also have differential sensitivity to chemotherapeutic agents. With the more readily available BRCA genetic testing, BRCA mutation status should be considered in high-risk women, including women who are diagnosed with breast cancer at an early age, have a strong family history or have tumors with triple-negative status. This article reviews the risk-reducing surgeries, including the prophylactic contralateral mastectomy and bilateral salpingo-oophorectomy, in women diagnosed with BRCA-associated breast cancer. Additionally, the sensitivity of BRCA-defective breast cancer cell lines to platinum cytotoxic compounds, PARP and endocrine therapy is reviewed.
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- 2012
48. Using modern molecular markers to tailor breast cancer treatment: a new era for personalized medicine
- Author
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Stefan Glück and Arturo Loaiza-Bonilla
- Subjects
medicine.diagnostic_test ,Proliferation index ,business.industry ,Translational research ,Computational biology ,Disease ,Omics ,medicine.disease ,Breast cancer ,Oncology ,Gene duplication ,medicine ,Radiology, Nuclear Medicine and imaging ,Personalized medicine ,Oncotype DX ,business - Abstract
Breast cancer is well known as a heterogeneous disease; the traditional morphological and pathologic anatomical classification cannot accurately predict its biological and clinical behavior, prognosis or response to treatment. Defining and understanding the ‘omics’ (the term used to characterize sets of biologic molecules, e.g., DNA, RNA, proteins and metabolites) and pathway changes associated with individual tumors and their treatment can identify patient subsets and be used to tailor treatment regimens. Since the advent of such multidisciplinary initiatives, it has been a tremendously exciting time for oncology, and an opportunity for transforming clinical and translational research to deliver more effective and personalized cancer therapies faster has emerged. Personalized medicine is the new term for the 21st century approach: but what does it mean for breast cancer? Nowadays, it is not only important to identify the clinical stage, but also to use biologic or molecular markers that determine outcome (i.e., prognosis) and therapy (i.e., prediction); customarily, we determine the receptor status, including Ki67 proliferation index, p53 proto-oncogene, uPA/PAI-1 invasion factor and other selected markers that can partially help to determine prognosis and identify prediction for systemic therapy. The biomarkers are examined for their presence or absence and whether gene amplification has occured; occasionally, mutation is also checked for (e.g., p53) [1]. One of the most remarkable, fast-paced advances in breast cancer research has been the development of techniques for sequencing, identifying and profiling molecular and gene expression signatures [2]. Serial analyses of gene expression, as well as oligonucleotide and cDNA arrays, have been applied by several groups such as The Cancer Genome Atlas and the International Cancer Genome Consortium, and have led to the active sequencing and identification of thousands of cancer-related genes, transcriptomes and critical pathways that have subsequently been validated as prognostic and therapeutic targets and are in clinical use [3]. The first and most widely used test using these techniques is the 21-gene recurrence score (OncoType Dx), which was developed from an original database of the 250 most widely described genes related
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- 2012
49. Eribulin mesylate, a novel microtubule inhibitor in the treatment of breast cancer
- Author
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Stefan Glück, Javier Cortes, and Alberto J. Montero
- Subjects
Eribulin Mesylate ,Oncology ,medicine.medical_specialty ,Breast Neoplasms ,Pharmacology ,chemistry.chemical_compound ,Breast cancer ,Internal medicine ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Furans ,Adverse effect ,Vinflunine ,business.industry ,Cancer ,General Medicine ,Ketones ,medicine.disease ,Metastatic breast cancer ,Tubulin Modulators ,Clinical trial ,chemistry ,Female ,business ,Eribulin - Abstract
Summary Background Microtubule-targeted agents are one of the most common classes of chemotherapeutic drug for the treatment of breast cancer. Limitations of current microtubule-targeted agents such as primary or secondary resistance of cancer cells and side effects like neuropathy prompted the discovery and introduction of newer more effective drugs. This review aims to provide a summary of the novel halichondrin B analog eribulin mesylate (E7389) and illustrate where it is placed in the treatment arena versus other agents that are approved or are currently in various stages of clinical development. Methods Preclinical and clinical trial (phases I–III) data for eribulin were obtained from scientific journals and meeting abstracts, posters, and oral presentations. The use of current and other emerging microtubule inhibiting agents in breast cancer was also surveyed and briefly reviewed. Results Eribulin mesylate at a dose of 1.4mg/m 2 given on days 1 and 8 of a 21-day cycle increased overall survival in patients with metastatic breast cancer (MBC). Neutropenia, fatigue, alopecia, nausea and anemia were common adverse events (AEs) associated with eribulin in clinical studies. A low incidence of peripheral neuropathy was also associated with eribulin in clinical studies (21–26%). Other emerging microtubule targeted agents, such as vinflunine and larotaxel, also reported efficacy in patients with MBC who had received prior chemotherapy, with grade 3/4 neutropenia being the most common AEs for both agents. Conclusions Eribulin mesylate offers clinical activity in advanced breast cancer through improved overall survival, its favorable side-effect profile and convenience of preparation and administration.
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- 2012
50. Can we replace the microscope with microarrays for diagnosis, prognosis and treatment of early breast cancer?
- Author
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Elizabeth L Y Ng, Stefan Glück, and Adrian Y S Yip
- Subjects
Oncology ,medicine.medical_specialty ,Receptor, ErbB-2 ,Cost-Benefit Analysis ,Clinical Biochemistry ,Treatment outcome ,Breast Neoplasms ,Prospective evaluation ,Breast cancer ,Internal medicine ,Drug Discovery ,Clinical information ,medicine ,Humans ,Early Detection of Cancer ,Oligonucleotide Array Sequence Analysis ,Early breast cancer ,Pharmacology ,Microscopy ,business.industry ,Endocrine therapy ,Prognosis ,medicine.disease ,Surgery ,Tamoxifen ,Receptors, Estrogen ,Molecular Medicine ,Female ,DNA microarray ,Receptors, Progesterone ,business ,medicine.drug - Abstract
In recent years, molecular research has translated into remarkable changes for breast cancer diagnostics and therapeutics. Molecular tests such as Oncotype DX® and MammaPrint® have revolutionized the predictive and prognostic tools in the clinic. By stratifying the risk of recurrence for patients, the tests are able to provide clinicians with more information on the treatment outcomes of using chemotherapy, endocrine therapy or combination therapies for patients with genetic expression patterns. However, it is still questionable for clinical applications as some areas remain unclear; the true benefit still needs prospective evaluation. In this paper, the limitation and the possibility to replace traditional histopathologic features of molecular tests are discussed. At the moment, it seems there are still limitations that prevent microarrays from replacing the microscope for diagnosis, prognosis and treatment of early breast cancer. However, additional important clinical information is added to traditional histology and IHC determination of ER, PR and HER2 in terms of prognostic and predictive power.
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- 2012
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