Immunotherapy of Advanced Breast Cancer With a Heterophilic Ganglioside (NeuGcGM3) Cancer Vaccine

2003 ◽  
Vol 21 (6) ◽  
pp. 1015-1021 ◽  
Author(s):  
Adriana Carr ◽  
Edmundo Rodríguez ◽  
María del Carmen Arango ◽  
Rolando Camacho ◽  
Marta Osorio ◽  
...  

Purpose: A heterophilic ganglioside cancer vaccine was developed by combining NeuGcGM3 with the outer membrane protein complex of Neisseria meningitidis to form very small size proteoliposomes (VSSP). A phase I clinical trial was performed to determine safety and immunogenicity of this vaccine. Patients and Methods: Stage III to IV breast cancer patients received up to 15 (200 μg) doses of the vaccine by intramuscular injection. The first five doses (induction phase) were given at 2-week intervals, with the remaining treatment (maintenance) administered on a monthly basis. Results: Twenty-one patients, 11 of whom had metastatic disease, were included. Main toxicities included erythema and induration at the injection site, sometimes associated with mild pain, and low-grade fever (World Health Organization grades 1 and 2). All treated patients who completed the induction phase developed anti-NeuGcGM3 antibody titers between 1:1,280 and 1:164,000 immunoglobulin G (IgG), and 1:640 and 1:164,000 IgM. Noteworthy specific IgA antibodies were induced by vaccination in all stage III patients and in three stage IV patients. Serum antibody levels were higher in the stage III patients, with the larger increases observed after week 32. The antiganglioside IgG subclasses were mainly IgG1 and IgG3. Hyperimmune sera increased complement-mediated cytotoxicity versus P3X63 myeloma cells and a marked IgG differential reactivity against human mammary ductal carcinoma samples. Conclusion: NeuGcGM3/VSSP/Montanide ISA 51 is an unusual immunogenic ganglioside vaccine and also seems to be safe in this small trial. Immunologic surrogates of activity indicate that this reagent warrants further investigation.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16513-e16513
Author(s):  
Mir Asif Alikhan ◽  
Dianne L Limesand ◽  
Mark Schmelzel ◽  
Thomas McGlone ◽  
David Powers ◽  
...  

e16513 Background: Despite the fact that chronological age alone does not determine tolerance to cancer treatment, there is a general perception that elderly cancer patients do not receive standard treatment. We sought to review breast cancer patients above 80 years in our practice. Methods: Retrospective analysis was performed ofall women with breast cancer over the age of 80 either at the time of diagnosis or at the time of relapse since July 2005 till July 2011. Results: There were total of 492 breast cancer patients seen during the study period, 207 below 65, 213 between 66-79 and 70 above 80. 59 women met the study criteria. The median age was 86 (81to 99 years). 47 had activities of independent living, 8 were in an assisted living facility and 4 in nursing homes. Median Charlson Co morbidity Index was 2 (0-5). Pathological types: DCIS 2, Invasive ductal carcinoma 50, invasive lobular carcinoma 6 and 1 had apocrine carcinoma. 50 had ER+, PR+ and Her-, 2 patients had triple negative disease and 4 Her+. 2 patients had stage 0, 22 stage I, 23 Stage II, 7 stage III and 5 stage IV. All patients stage 0-III had surgical management, 39 had breast conservative surgery with sentinel node biopsy and 15 had mastectomy. Out of 28 patients referred for adjuvant radiation therapy 17 received it. 49 patients received hormone treatment (39 aromatase inhibitors- AIs and 14 tamoxifen) Chemotherapy was offered but refused by two stage III patients. 2 Her + patients received and tolerated well trastuzumab based chemotherapy. After a median follow up of 48 months (8-120 months) there was 1 local recurrence, 1 distant relapse and 14 deaths ( 11 from other causes 3 from breast cancer). Conclusions: In ourpractice, a majority of octogenarians and nonagenarians live independently and have minimal co morbidities and tolerate standard surgical and hormonal treatment. Although radiation therapy would be considered optional in this group of women, it was offered based on predicted longevity. Mortality form other causes was higher than that from breast cancer ( 18% vs 5%).


2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
Author(s):  
Aejaz Nasir ◽  
Dung-Tsa Chen ◽  
Mike Gruidl ◽  
Evita B. Henderson-Jackson ◽  
Chinnambally Venkataramu ◽  
...  

To detect the molecular changes of malignancy in histologically normal breast (HNB) tissues, we recently developed a novel 117-gene-malignancy-signature. Here we report validation of our leading malignancy-risk-genes, topoisomerase-2-alpha (TOP2A), minichromosome-maintenance-protein-2 (MCM2) and “budding-uninhibited-by-benzimidazoles-1-homolog-beta” (BUB1B) at the protein level. Using our 117-gene malignancy-signature, we classified 18 fresh-frozen HNB tissues from 18 adult female breast cancer patients into HNB-tissues with low-grade (HNB-LGMA; ) and high-grade molecular abnormality (HNB-HGMA; ). Archival sections of additional HNB tissues from these patients, and invasive ductal carcinoma (IDC) tissues from six other patients were immunostained for these biomarkers. TOP2A/MCM2 expression was assessed as staining index (%) and BUB1B expression as H-scores (0–300). Increasing TOP2A, MCM2, and BUB1B protein expression from HNB-LGMA to HNB-HGMA tissues to IDCs validated our microarray-based molecular classification of HNB tissues by immunohistochemistry. We also demonstrated an increasing expression of TOP2A protein on an independent test set of HNB/benign/reductionmammoplasties, atypical-ductal-hyperplasia with and without synchronous breast cancer, DCIS and IDC tissues using a custom tissue microarray (TMA). In conclusion, TOP2A, MCM2, and BUB1B proteins are potential molecular biomarkers of malignancy in histologically normal and benign breast tissues. Larger-scale clinical validation studies are needed to further evaluate the clinical utility of these molecular biomarkers.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tarek Hashem ◽  
Ahmed Abdelmoez ◽  
Ahmed Mohamed Rozeka ◽  
Hazem Abdelazeem

Abstract Background Due to the high variability of incidence and prevalence of intra-mammary lymph nodes (IMLNs), they might be overlooked during clinical and radiological examinations. Properly characterizing pathological IMLNs and detecting the factors that might influence their prevalence in different stages of breast cancer might aid in proper therapeutic decision-making and could be of possible prognostic value. Methods Medical records were reviewed for all breast cancer patients treated at the National Cancer Institute of Cairo University between 2013 and 2019. Radiological, pathological, and surgical data were studied. Results Intra-mammary lymph nodes were described in the final pathology reports of 100 patients. Five cases had benign breast lesion. Three cases had phyllodes tumors and two cases had ductal carcinoma in situ (DCIS). All ten cases were excluded. The remaining 90 cases all had invasive breast cancer and were divided into two groups: one group for patients with malignant IMLNs (48) and another for patients with benign IMLNs (42). Pathological features of the malignant IMLN group included larger mean tumor size in pathology (4.7 cm), larger mean size of the IMLN in pathology (1.7 cm), higher incidence of lympho-vascular invasion (65.9%), and higher rate of extracapsular extension in axillary lymph nodes (57.4%). In addition, the pathological N stage was significantly higher in the malignant IMLN group. Conclusion Clinicians frequently overlook intra-mammary lymph nodes. More effort should be performed to detect them during preoperative imaging and during pathological processing of specimens. A suspicious IMLN should undergo a percutaneous biopsy. Malignant IMLNs are associated with advanced pathological features and should be removed during surgery.


Background: Breast Cancer is one of the leading causes of death worldwide. Pakistan alone has the highest rate of Breast Cancer than any other Asian country as approximately 90000 new cases are diagnosed every year out of which 40000 dies. Obesity is also a critical public health problem growing with every passing year in Pakistan and worldwide. Research studies are being conducted worldwide regarding the relation between the two problems. Objective: The objective of this study is to determine the prevalence of obesity in breast cancer patients in a tertiary care hospital in Karachi, Pakistan. Methods: BMI is used as a screening tool for overweight and obesity. According to World Health Organization, a body mass index (BMI) over 25 is considered overweight, and over 30 is obese. A retrospective analysis of 262 patients diagnosed with Breast Cancer during 2019 and 2020 was performed. Patients’ hospital records in Oncology were reviewed. The weight in kilograms and height in centimeters of patients were reviewed. Their BMI was calculated and recorded using the SPSS system. Results: The median BMI was 28.25 kg/m2 with an interquartile range of 25.15 - 31.99 kg/m2. Nearly 80% of the study participants had body mass index higher than normal levels (n=203, 77.5%) and out of them approximately half were overweight (n=104, 51.2%) and the remaining were obese (n=99, 48.7%). Conclusion: We conclude from our study that body mass index is positively correlated with breast cancer occurrence and thus the proportion of females having BMI >= 25 was significantly higher among patients.


2021 ◽  
Author(s):  
Bronte Morse ◽  
Kobi Decker

We have compared the global profiles of 100 tumors in Stage I, II and III with two independently releasedmicroarray datasets in order to understand their transcriptional behaviors accompanying a progression in breastcancer (1, 2). The olfactive receptor, family 56, subfamily A, member 4 OR56A4, was discovered to have beenone of the genes with the most varied expression when comparing initial tumors in stage I, stage II, and stageIII of breast cancer patients. In the stage III tumors, OR56A4 expression in comparison to the stage I tumorswas lower.


2019 ◽  
Vol 7 (1) ◽  
pp. 210
Author(s):  
Abhishek Jina ◽  
U. C. Singh

Background: Various factors have been identified as influencing factors of breast cancer. The free radicals can cause increased oxidative stress by negatively affecting the body’s nucleic acids, lipids and proteins leading to various illnesses including cancer. Therefore, this study was aimed at discovering the progress of treatment of breast carcinoma by exploring the connections of the disease with free radical injury.Methods: The present study was conducted among 30 breast carcinoma patients received in the surgery department of BRD Medical College Gorakhpur. Determination of the levels superoxide dismutase (SOD) (the procedure of photoluminescence), catalase (method of Cavarochi) and the lipid peroxidise was done. The results were presented as mean and standard error (SE). P value of <0.05 was considered as statistically significant.Results: Among the total participants, 73% patients had infiltrating ductal carcinoma and 27% patients had intraductal carcinoma. The dismutase levels showed an increase in the post-operative patients for both the groups. The catalase levels and the lipid peroxide levels showed a reduction in the postoperative patients (p<0.05).Conclusions: The present study result showed that the low amounts of SOD and catalase may not be sufficient to detoxify high amounts of free radicals. The administration of catalase could help in reducing the symptoms. Though, low amounts of SOD and catalase may not be sufficient to detoxify high amounts of free radicals. The administration of enzymes could help in the treatment of breast cancer patients.


2020 ◽  
Vol 1 (2) ◽  
pp. 23
Author(s):  
Satyam Tripathi ◽  
Megha Panchal ◽  
Nooraini Binti Aliyas

This is a case study for invasive ductal carcinoma diagnosed in a patient aged 60 years in 2015. She went through chemotherapy and radiotherapy and was on remission in 2016. Bone density degeneration was the side effect from the breast cancer treatment. After trying the conventional treatment, she was not satisfied, she came to Union Yoga Ayurveda (UYA), Singapore. She came to clinic looking for alternative therapy to help her increase her bone density, cope up with weakness and overall mental and physical wellbeing. The patient was given holistic treatment of yoga and Ayurveda, involving patra pinda sweda (herbal compress) and picchu (herbal soaked gauze pieces). The yoga therapy involved asanas practise to increase strength, breathing and meditation for overall wellbeing. The patient was not on any other treatment/medication during the entire treatment. After uninterrupted therapy for six months there was an increase in her bone density along with increase in energy level. The patient case study is an attempt to provide yoga and Ayurveda as an alternative/supportive treatment for remission management osteoporosis from breast cancer patients.


2019 ◽  
Vol 70 (7) ◽  
pp. 2671-2676
Author(s):  
Adriana Andreea Jitariu ◽  
Amalia Raluca Ceausu ◽  
Adriana Meche ◽  
Cristian Nica ◽  
Amelia Burlea ◽  
...  

Increased microvessel density (MVD) values in breast cancer correlate with tumor growth and progression while mammaglobin (MGB) expression in tumor cells is associated with a favorable prognosis. We aim to evaluate and correlate MVD values with MGB expression in molecular types of breast cancer specimens and to determine their utility as prognostic biological markers. A number of 52 breast cancer specimens were included in the study. Specimens were processed for routine histopathological diagnosis followed by the molecular classification by means of estrogen (ER), progesterone (PR) and HER2 immunohistochemical reactions. After performing immunohistochemistry for CD34 and MGB, MVD evaluation was made using the �hot spot� method for each case and MGB was scored between 0 (negative) and +3 (strong positive) depending on the intensity and distribution of the staining. MGB expression in tumor cells and MVD mean values were extremely variable. The greatest MVD mean values were obtained in luminal B followed by HER2, luminal A and triple negative breast cancer (TNBC) (95.33, 69, 62, and 40, respectively). MGB expression in the tumor cells generally ranged from mild to weak and was strong only in a few invasive ductal carcinoma cases. In cases with TNBCs the expression of MGB in tumor cells was weak and focal or negative. This variability was noticed between the molecular types of breast cancers and even within the same molecular type. In a restricted number of cases, MGB positive tumors were associated with low MVD values while the negative cases were characterized by increased MVD mean values. The variable results we obtained regarding the correlation between MVD and MGB in breast cancer specimens may indicate a rather restricted use of MVD/MGB in estimating breast cancer patients� prognosis.


2021 ◽  
Author(s):  
Parth Sharma ◽  
Josh Thomas Georgy ◽  
Anand George Andrews ◽  
Ajoy Oommen John ◽  
Anjana Joel ◽  
...  

Abstract Purpose: Dose dense chemotherapy improves survival but also increases toxicity and treatment related cost. Here we report the prevalence of anemia, understand the risk factors of chemotherapy related anemia and determine the cost and time-delay associated with transfusion requirement in Indian non-metastatic breast cancer patients on dose dense preoperative chemotherapy.Methods: In this study, 116 triple negative breast cancer (TNBC) patients were treated preoperatively with Docetaxel and Cyclophosphamide alternating with Epirubicin and Cisplatin every 2-weekly. Patients were evaluated for anemia pre- and post-chemotherapy. We examined trends in the cell counts, transfusion requirement, time to transfusion as well as risk factors associated with transfusion during treatment, along with delay in treatment due to anemia and the additional cost incurred.Results: One hundred and sixteen women with high-risk non-metastatic TNBC were treated. Median age was 44.5 years. 56.1% had stage III disease. Delivery of 6/8 planned doses was achieved in 98.3% of patients, and all 8 doses in 86% patients. Anemia was detected at baseline in 54(46.5%) patients with mild(10-12g/dl) anemia in 42(36.2%) patients and moderate(8-10g/dl) in 12(10.3%) patients. Forty-four patients (37.9%) required transfusion during chemotherapy with 55(47.4%) patients having grade 1-2 anemia and 40(34.5%) patients having grade 3 anemia. The factors associated with transfusion were low grade of tumor (OR 2.48 (95% CI 1.08 - 5.68), p = 0.025), hemoglobin post 2 cycles of chemotherapy (OR 1.74 (95% CI 1.21- 2.51), p = 0.003), thrombocytopenia grade 3 or 4 (OR 4.35 (95% CI 1.062-17.827), p = 0.034) and drop in hemoglobin after 2 cycles (OR 1.65 (95% CI 1.09-2.48), p = 0.017). Nearly one fourth of the study population had a delay between two cycles of chemotherapy due to anemia. A median additional cost of Rs 7000 (IQR-Rs 7000 – Rs 14000) was incurred on transfusion.Conclusion: Anemia is a common toxicity associated with dose dense chemotherapy during curative breast cancer treatment leading to delay in treatment and increased cost. Low grade tumor, grade 3 or 4 thrombocytopenia and Grade 2 or higher anemia after 2 cycles of chemotherapy are risk factors for blood transfusions during treatment.


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