Filipa Lynce

Obesity in Adult Lymphoma Survivors

Abstract As a result of therapeutic advances, survivors of lymphoma are now living longer. However, their mortality is higher when compared to the general population, probably due to multiple factors. Survivors of childhood leukemia and lymphoma appear to have an increased prevalence of obesity. The objectives of this retrospective study were to analyze weight change after lymphoma treatment in an adult population and determine factors predictive of weight gain. Data were collected from 219 patients and analyzed sequentially at the initial visit and at 6, 12 and 18 months. There was a progressive increase in weight from the initial visit to 6 months (1.5% increase of initial body weight), 12 months (4.5%) and 18 months (6.4%). More than 9% of patients experienced weight gain greater than 20% during follow-up. There was a statistically significant association between the percentage of increase in weight and age, B symptoms and body mass index (BMI) at presentation. Younger patients, those with B symptoms or those with lower BMI manifested more weight gain (p = 0.0008, p = 0.0440 and p = 0.0009, respectively). Other assessed factors had no effect on weight gain including sex, race, lymphoma histology, disease outcome, radiation therapy, number of treatment regimens and use of steroids. Further studies are needed to explore long-term weight trends and their impact on the health of lymphoma survivors.

Pertuzumab for the Treatment of Breast Cancer

HER2-targeted therapies have revolutionized the outcome of patients with HER2-positive breast cancer. Pertuzumab is the first in a new class of monoclonal antibodies that target the extracellular dimerization domain of HER2 receptors, also known as HER dimerization inhibitors. The development of pertuzumab and preclinical and clinical data in breast cancer are reviewed. Regulatory affairs related to pertuzumab and the recent accelerated approval granted by the FDA for the treatment of breast cancer in the neoadjuvant setting are also covered. This process opens doors for further approvals which could considerably shorten the time between initial drug development and availability.

Post-transfusion purpura in an African-American man due to human platelet antigen-5b alloantibody: a case report

IntroductionPost-transfusion purpura is a rare immunohematological disorder characterized by severe thrombocytopenia following transfusion of blood components and induced by an alloantibody against a donor platelet antigen. It occurs primarily in women sensitized by pregnancy and is most commonly caused by anti-human platelet antigen-1a antibodies. Here, we describe what we believe to be the first documented case of an African-American man who developed post-transfusion purpura due to an anti-human platelet antigen-5b alloantibody after receiving multiple blood products.Case presentationA 68-year-old African-American man initially admitted with atrial flutter was started on anticoagulation treatment, which was complicated by severe hematemesis. On days 4 and 5 of hospitalization, he received six units of packed red blood cells, and on days 4, 13 and 14 he received plasma. His platelet count began to drop on day 25 and on day 32 reached a nadir of 7 × 109/L. His platelet count increased after receiving intravenous immune globulin. An antibody with reactivity to human platelet antigen-5b was detected by a solid-phase enzyme-linked immunoassay. Our patient was homozygous for human platelet antigen-5a.ConclusionThis case emphasizes the importance of including post-transfusion purpura in the differential diagnosis for both men and women with acute onset of thrombocytopenia following transfusion of blood products. The prompt recognition of this entity is crucial for initiation of the appropriate management.

First, do no harm.

Accessible online at: www.karger.com/onk Fax +49 761 4 52 07 14 Information@Karger.de www.karger.com vational study, Pinder et al. report a 26% increased risk of CHF in older women treated with adjuvant anthracyclines for breast cancer, compared with non-anthracycline regimens [8]. Cardiac troponins are regulatory proteins that control the calcium-mediated interaction of actin and myosin. The troponin complex consists of 3 subunits: troponin C (TnC), troponin I (TnI) and troponin T (TnT), each performing specific functions. TnC is a calcium-binding protein. TnI binds to actin and inhibits actin-myosin interactions. TnT provides proper fixation of TnC and TnI on the actin-tropomyosin filament. Although both TnT and TnI are present in cardiac and skeletal muscle, their amino acid sequences encode tissue-specific isoforms detected by monoclonal antibody-based assays. TnC is not used clinically because both cardiac and skeletal muscles share the same isoforms [9]. The notion that troponin is increased only after irreversible myocardial necrosis has already been challenged [10]. Cardiac troponin elevation is common in many diseases and does not necessarily indicate the presence of a thrombotic acute coronary syndrome. In this issue of ONKOLOGIE, Horacek et al. [11] report a study of the cardiac function of 23 patients with acute leukemia treated with anthracycline-containing chemotherapy. Patients had cardiac function evaluated during chemotherapy and 6 months after treatment with conventional imaging (echocardiography with systolic and diastolic left ventricular parameters) and cardiac troponin I (cTnI) and T (cTnT) measurements. The authors report that monitoring cTnI during anthracycline treatment, but not cTnT, identifies patients at risk of developing drug-related cardiotoxicity. Previous studies have shown the benefit of cTnI [12] and cTnT [13] in the early identification of patients at risk of cardiac events. In a study with more than 700 patients treated with different antineoplastic agents, it was demonstrated that cTnI elevation predicted late cardiac dysfunction and major adverse cardiac events in the subsequent 3 years [14]. Both cTnI and cTnT have been conThe progress made over the last years has turned cancer into a potentially curable, or at least, chronic disease [1]. Thus, our concern moves towards toxicity. While some years ago cardiotoxicity was an issue mainly in children with leukemia treated with anthracyclines, today it has become a significant problem for many others. Moreover, a prolonged survival allows more time for the use of different potentially cardiotoxic agents as well as radiotherapy. The agents most commonly associated with cardiac toxicity are anthracyclines and trastuzumab. Anthracycline-induced cardiotoxicity is progressive and dose-dependent. It can range from asymptomatic cardiac dysfunction to overt congestive heart failure (CHF). Asymptomatic systolic dysfunction, evaluated by decrease of left ventricular ejection fraction (LVEF), was 6% higher in patients treated with adjuvant doxorubicin compared to CMF [2]. A retrospective analysis showed that 5–48% of patients who had received anthracyclines presented with symptomatic CHF, depending on the cumulative dose [3]. Trastuzumab-associated cardiotoxicity has a different mechanism and has been classified as type II chemotherapy-related cardiac dysfunction [4]. It is not dose-related and is mostly reversible. However, the short period of follow up in trastuzu mab adjuvant trials offers us a limited picture of the potential risks [5]. Furthermore, direct comparison of toxicity between trials is difficult due to different definitions of cardiac endpoints, eligibility criteria and treatments regimens. Since we do not routinely screen asymptomatic people in the general population for subclinical cardiac disease why, many may think, worry about cancer survivors? Cardiac dysfunction is a progressive condition that can lead to CHF. The 5-year survival of women with CHF (38%) is higher than that of women with metastatic breast cancer (26.1%), but much lower than of women with regional (81.3%) or localized breast cancer (98%) [6, 7]. It is important to balance the risk/benefit ratio. Recent data seem to confirm our concerns. In an obserFirst, Do no Harm

Bone-Modifying Agents in Early-Stage and Advanced Breast Cancer

Purpose of ReviewBone-modifying agents have an important role in the treatment of patients with bone mineral density loss, early-stage breast cancer to reduce risk of recurrence, and metastatic breast cancer with bone involvement. Here we review mechanisms of action of these agents and clinical indications for their use.Recent FindingsThe meta-analysis undertaken by the Early Breast Cancer Trialists’ Collaborative Group showed that the use of bisphosphonates was associated with a decreased risk of breast cancer recurrence.SummaryThe effect of bisphosphonates and receptor activator of nuclear factor kappa-B ligand inhibitors on bone health provides an opportunity to decrease the incidence of skeletal-related events and improve cancer outcomes in certain subsets of patients.

Video intervention increases participation of black breast cancer patients in therapeutic trials

There is a striking racial and ethnic disparity in incidence and mortality of cancer yet minorities remain markedly underrepresented in clinical trials. This pilot study set out to determine the impact of a 15-min culturally tailored educational video on three outcomes relating to clinical trials: likely participation, attitudes (assessed based on six barriers), and actual enrollment. Breast cancer patients with Stage I-III, if diagnosed within previous 6 months, or metastatic disease who self-identified as black or African American were invited to participate. The primary outcome measure was the decision to participate in a therapeutic clinical trial after the intervention. Patients’ intention to enroll on a therapeutic clinical trial and the change in attitudes toward clinical trials were measured by the previously developed Attitudes and Intention to Enroll in Therapeutic Clinical Trials (AIET) questionnaire. Of the 200 patients that participated, 39 (19.5%) patients signed consent to participate in a therapeutic clinical trial; 27 (13.5%) patients enrolled, resulting in a 7.5% increase from our baseline comparison of 6% clinical trial enrollment rate in black cancer patients (p < .001). Pre-test versus post-test assessment demonstrated the proportion of patients expressing likelihood to enroll in a therapeutic trial following the intervention increased by 14% (p < .001). Among 31 AIET items, 25 (81%) showed statistically significant and positive change post-intervention. The findings suggest the promising utility of a culturally tailored video intervention for improving black patients’ attitudes regarding clinical trial participation and resultant enrollment. Future efforts should continue to target facilitators of population-specific recruitment, enrollment, and retention in therapeutic and non-therapeutic clinical trials.Educational video boosts trial enrollment among black patients with breast cancerA culturally tailored educational video can boost participation among black patients in clinical trials of new breast cancer treatments. A US team led by Sandra Swain from Georgetown University Medical Center in Washington, DC, created a 15-min video designed to address six of the concerns commonly cited by blacks about human subjects research. The researchers showed the video to 200 black patients, and saw a large bump in the number of women willing to sign up for a therapeutic trial. On average, only 6% of black cancer patients typically enroll in clinical trials. But in the video intervention study, 19.5% agreed to participate and then 13.5% went ahead with a trial. Video watchers also reported a positive change in their attitude toward clinical research. The study points to the need for population-specific recruitment efforts.

Abstract P1-03-01: Cardiac function in BRCA1/2 mutation carriers with a history of breast cancer (BC) treated with anthracyclines (anthra)

Introduction: Animal data suggest that cardiac-specific loss of BRCA1/2 genes leads to increased cardiac dysfunction in the setting of stressors such as ischemia or anthra chemotherapy (CT). Women with BRCA1/2 mutations who develop BC may receive anthra-based CT. It is not known whether BRCA1/2 mutation carriers treated for early stage BC with anthra-based CT are at higher risk for anthra-induced cardiac toxicity than similarly treated women with sporadic BC. This study investigates left ventricular ejection fraction (LVEF) and myocardial global longitudinal strain (GLS), a novel echocardiographic measure of cardiac contractility, in women with and without BRCA1/2 mutations who were treated with anthra-based CT. Methods: We identified 41 women with a history of BRCA1/2 mutation-associated BC and 52 women with a history of sporadic BC, all of whom received anthra-based adjuvant or neoadjuvant CT. We excluded women who received HER2 therapy or who had stage IV disease. BC CT was completed at least 6 months prior to study enrollment. All participants completed a cardiac questionnaire and underwent a comprehensive 2D and 3D echocardiographic exam with assessment of myocardial GLS using speckle-tracking software (QLAB10, Philips, Andover, MA). Abnormal LVEF was defined as less than 55% (50-54.9% borderline reduced and 40-49% mildly reduced) and abnormal GLS was defined as absolute value of less than 18.9%. Patients with history of hypertension (HTN) were excluded from this analysis to avoid confounding effects of HTN on GLS. Results: We present data on 57 normotensive participants, 34 BRCA1/2 mutation-carriers and 23 non-mutation carriers. Mean age was 49.5 +/- 8.7 years in the BRCA mutation-carrier group and 51.1 +/- 8.7 years in the non-mutation carrier group (p=0.496). Women with BRCA1/2 mutations were more likely to be Caucasian (p=0.026) and have undergone oophorectomy (p Conclusions: In this population, reduced LVEF and myocardial GLS were present in a small percentage of women treated with anthra-based CT for early stage BC. However, reduction in LVEF and myocardial GLS did not differ between the BRCA1/2 mutation carriers and the women with a history of sporadic BC. Larger studies are needed to definitively rule out a difference in cardiac toxicity by BRCA mutation status in BC survivors treated with anthra. This project is supported by Fisher Center for Familial Cancer Research Award at Lombardi Comprehensive Cancer Center. AB is supported by Georgetown-Howard Universities Center for Clinical & Translational Science (GHUCCTS) post-doctoral KL2 Award (5KL2TR000102-04). Citation Format: Filipa Lynce, Ana Barac, Karen L Smith, Mihriye Mete, Lynette Wray, Madeline Nardacci, Pia Herbolsheimer, Raquel Nunes, Sandra M Swain, Robert Warren, Claudine Isaacs. Cardiac function in BRCA1/2 mutation carriers with a history of breast cancer (BC) treated with anthracyclines (anthra) [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 P1-03-01.

Avastin withdrawal symptoms

Angiogenesis is an essential requirement for the growth of solid tumors and the inhibition of the angiogenic pathway has become an important therapeutic target. Bevacizumab (Avastin , Genentech), a monoclonal antibody against vascular endothelial growth factor (VEGF), was the first antiangiogenic drug to demonstrate a survival benefit in cancer patients. Initially approved by the Food and Drug Administration (FDA) in 2004 as first-line treatment for metastatic colon cancer, bevacizumab was then designated as ‘the fourth modality for cancer treatment’ [1].