Occult Disseminated Metastatic Breast Carcinoma Presenting as Acquired Thrombotic Thrombocytopenic Purpura

Cancer-related microangiopathic hemolytic anemia (MAHA) is a rare and life-threatening condition. We present a patient who had been treated for invasive lobular breast carcinoma in clinical remission with fever and hemolytic anemia. The peripheral blood film showed MAHA and thrombocytopenia, and a functional deficiency of ADAMTS13 activity of 23% consistent with acquired thrombotic thrombocytopenic purpura. Bone marrow aspirate and trephine biopsy confirmed metastatic carcinoma. Further evaluation revealed the involvement of multiple bone sites without recurrence of the primary tumor. The patient received a daily plasma exchange with cryosupernatant and was pulsed with corticosteroids. MAHA related to breast cancer appears to be a rare occurrence.

Metastatic Breast Carcinoma Mimicking Urothelial Carcinoma

Besides being the most frequently diagnosed cancer in women, breast cancer is the main cause of cancer-related deaths in this group of patients. Breast cancer frequently metastasizes to bone, lung, brain, and liver. Renal metastasis from the breast is extremely rare. Here we aimed to report a case of breast cancer with metastasis to bone and left renal pelvis. A 58-year old woman with a mass lesion in the left renal pelvis that mimicked urothelial carcinoma was referred to our clinic. The left nephroureterectomy procedure was performed, and the pathology revealed that a renal pelvis metastasis secondary to breast cancer.

1H -NMR Metabolomics Study of the Effect of Cisplatin and Casiopeina IIgly on MDA-MB-231 Breast Tumor Cells

The knowledge of the metabolic processes of designed metallodrugs for cancer treatment is an area that has been not profoundly studied. Casiopeina IIgly (CasIIgly), which belongs to the Casiopeínas® family, is a copper (II) coordination compound that has shown good biological activity against several cancer cells, low toxicity in normal cells, and antineoplastic activity in in vivo murine and xenografted models. In this work we employed a triple-negative highly metastatic breast carcinoma line (MDA-MB-231), which is one of the cancer types with a great mortality index, for 1H-NMR metabolomic analysis using cisplatin and CasIIgly, in order to quantify the effect of metallodrugs in the metabolic profile of this cell tumor line as a consequence of treatment at different times. Our findings indicate that cisplatin mainly contributes to phospholipid biosynthesis while CasIIgly affects processes such as carbohydrates and nucleotides metabolism. Also, we observed that CasIIgly treatment has an important and fast effect over MDA-MB-231 cell metabolism, which makes it a good alternative for treatment in this type of cancer.

945 Characterization of the immune landscape of malignant pleural effusion composition from patients with metastatic breast carcinoma: a pilot study

BackgroundBreast cancer(BC) is the second most common cause after lung cancer of malignant pleural effusions(MPEs),in approximately one third of all MPEs.Although,MPEs are relativity easy to be collated are still not well characterized in their cellular compositions. This opens new avenues to characterize the cellular milieu comprising the MPE, as it has the potential to be highly informative about mutational markers and immune response –ultimately guiding targeted therapy and predicting therapeutic outcomes with their study. The proposed study will characterize immune landscape of the cellular composition of MPE from patients with metastatic breast carcinoma and characterize their relationship with clinicopathologic features in these patients.Abstract 945 Figure 1Comparison between the cell block in H-E and mIF expression CK, CD68 and CD3Abstract 945 Figure 2Composite image in mIF expressing 8 markers. In higher magnification is possible to observe the co expression of CK+Ki67+, CK PDL1, CD3+Foxp3+ and CD3+CD8+Abstract 945 Table 1Results: cell phenotypes in percentage in the six cases analyzedAbstract 945 Table 2Clinical data of the six patients. L: left . R: right , BR : Breast cáncer, CRC: Colorrectal cáncer, NE: No evaluable , IDC : Invasive ductal carcinoma , CT: chemotherapy and BT : biotherapy* Last appointment of the patient.MethodsFive microns thickness paraffin cell pellet blocks from six cases randomly selected of breast carcinoma MPE were stained using a quantitative multiplex immunofluorescence(mIF) panel containing 8 markers against pancytokeratin(CK), PD-L1, PD-1, CD3, CD8, Foxp3, CD68, Ki67, and DAPI (figure 1). Representative regions of interest were scanned using a multispectral scanner (Vectra Polaris) in high magnification (20x) to capture different cell populations. Markers co-expression were processed and analyzed using a quantitative image analysis software (InForm). The final results were obtained as absolute number of cells from each phenotype and were characterized with clinicopathologic features.ResultsWe analyzed and stained six breast cancer MPE cases with previously optimized and validated mIF panel for formalin fixed and paraffin embedded (FFPE) tumor tissues against CK, CD3, CD68, CD8, Foxp3, Ki67, PD1 and PD-L1 (figure 2). The median cellular density was 5870.53 cells. Median for each marker: CK+ was presented in 75.9% (between malignant cells and reactive mesothelial cells) in these cells the expression of Ki67 was 8% and PD-L1+ was present in 0.2%.CD3+ was 0.72% and being the cytotoxic T-cells CD3+CD8+ was 12.13% of these cells and it expression for CD3+PD1+ was in 1.14% without concomitant expression for PD-L1. The median of the macrophages CD68+ was 8.1% of the total cells (table 2).ConclusionsmIF is a promising tool to study diverse corporal effusion from different origin. Although more studies are needed, this new perspective can help us to resolve some clues and possible prognosis in advanced stages of BC.ReferenceNicholas D T, Matthew A. S. Diagnosis and Management of Pleural Metastases and Malignant Effusion in Breast Cancer.En: Kirby I B, Edward M C, V. Suzanne K, William J. G. The Breast (Fifth Edition): Elsevier; 2018. P 934.

RADI-16. Efficacy of WBRT among the Sub-types of Metastatic Breast Cancer

Objectives To understand the effect of Whole Brain Radiation (WBRT) in terms of Age, Neurological performance, Radiological Improvement and the Overall Survival. Methods 34 Patients [Median Age: 45 years (31- 65)] with Metastatic Breast Carcinoma who presented with Brain metastasis to the Department of Radiation Oncology at Kidwai Memorial Institute of Oncology and subjected to Whole Brain Radiotherapy/ Focal RT were taken into the study. The efficacy of WBRT was assessed among the four subtypes of MBC. Results 39% of the patients belonged to Luminal A, 25%, 22% and 14% belonged to Luminal B, Her2 amplified and Basal respectively. Patients under Luminal A, presented with brain metastases by 25 months after the diagnosis of the primary. 60% presented with single lesion, amenable to resection and 58% underwent surgery followed by WBRT and OS fared better as compared to patients with WBRT alone with no distant recurrences on imaging and improvement in KPS. Patients with Luminal B/ HER2 amplified subgroup had predominantly oligometastatic lesions (65%), presented with brain metastases at 15 months after diagnosis of Carcinoma Breast,18% received Herceptin and Lapatinib and 33% and 22% received Herceptin and Lapatinib alone. OS was superior over WBRT alone with exaggerated radiation necrosis in those who took concurrent biological therapy and RT.In patients with Basal subtype,75%had multiple metastatic brain lesions, presented with symptoms by 10 months of diagnosis of the primary with poor KPS and OS remained poor despite WBRT. Conclusions Lesions being amenable for surgery, focal RT to post op cavity alone may be considered in patients with Luminal A. WBRT plus boost for those unfit for surgery. Addition of TKI +/- oral chemo for all patients with Luminal B and HER 2 amplified to Focal RT or WBRT. Triple Negative patients present with poor KPS can be considered for BSC/WBRT on case basis.

TRPV1 modulation of immune response in metastatic breast carcinoma: Enhanced inflammatory response may hinder therapeutic potentials of TRPV1 agonists

Background and Purpose: The transient receptor potential vanilloid 1 (TRPV1) ion channels enhance cytotoxic immune response and may have therapeutic potential in cancer treatment. Hence, we here determined how activation of TRPV1 alters immune response of tumor-bearing mice.Experimental Approach: Three different metastatic subset of 4T1 breast carcinoma cells were used to induce tumors in Balb-c mice. Mix leukocyte cultures (MLCs) using spleens and draining lymph nodes were prepared and stimulated with various challenges. Effects of four different TRPV1 agonists, antagonist (AMG9810) and Gambogic Amide (GA), a TrkA agonist that sensitizes TRPV1, on secreted levels of cytokines were determined.Results: MLCs of tumor-bearing mice secreted markedly higher levels of IL-6 and lower levels of IFN-γ compared to control mice. We observed differential effects of TRPV1 agonists, antagonist and GA in control and mice bearing different subset of metastatic cells. TRPV1 and TrkA agonists increased IFN--γ and IL-17 secretion in control mice while they markedly increased IL-6 secretion and suppressed IFN--γ secretion in tumor-bearing mice. Unexpectedly, AMG9810 acted as an inverse agonist and did not antagonize the effects of TRPV1 agonists and GA did not sensitize TRPV1 channels. Conclusions: Our results demonstrate constitutive activity of TRPV1 in immune cells, suggesting cross activation. Excessive chronic activation of TRPV1 in immune cells in the presence of metastatic breast carcinoma may have detrimental effects. Unexpected findings further document that a drug can have multiple intrinsic activities and depending on surrounding factors can act on the same receptor as an agonist, antagonist or inverse agonist.