scholarly journals Metastatic Breast Cancer with Extensive Osseous Metastasis Presenting with Symptomatic Immune Thrombocytopenic Purpura and Anemia: A Case Report and Review of the Literature

2015 ◽  
Vol 8 (2) ◽  
pp. 256-263 ◽  
Author(s):  
Jiaxin Niu ◽  
Teresa Goldin ◽  
Maurie Markman ◽  
Madappa N. Kundranda
Keyword(s):  
Breast Cancer ◽  
Platelet Count ◽  
Metastatic Breast Cancer ◽  
Immune Thrombocytopenic Purpura ◽  
English Literature ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Severe Thrombocytopenia ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated

Background: Immune thrombocytopenic purpura (ITP) is a rare acquired bleeding disorder with an estimated incidence of 1 in 10,000 people in the general population. The association of ITP with breast cancer is an even rarer entity with very limited reports in the English literature. Case Presentation: We report a case of a 51-year-old female with no significant past medical history who presented with sudden onset of malaise, syncope, gingival bleed and epistaxis. She was found to have severe thrombocytopenia (platelet count 6,000/μl) and anemia (hemoglobin 7.2 g/dl). Her workup led to the diagnosis of metastatic ductal breast cancer with extensive bone metastasis. Bone marrow biopsy demonstrated myelophthisis which was initially thought to be consistent with her presentation of thrombocytopenia and anemia. Therefore, the patient was started on hormonal therapy for the treatment of her metastatic breast cancer. After 3 months of therapy, she did not improve and developed severe mucosal bleeding. Her clinical presentation was suspicious for ITP and immune-mediated anemia, and hence she was started on steroids and intravenous immunoglobulin. The patient had a dramatic response to therapy with normalization of her platelet count and hemoglobin within 2 weeks. Conclusion: To our knowledge, this is the first reported case of metastatic breast cancer presenting with symptomatic ITP and anemia, and both symptoms are postulated to be immune-mediated.

scholarly journals Impact of systemic therapy on circulating leukocyte populations in patients with metastatic breast cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna-Maria Larsson ◽  
Anna Roxå ◽  
Karin Leandersson ◽  
Caroline Bergenfelz
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Natural Killer ◽  
Endocrine Therapy ◽  
Immune Cells ◽  
Systemic Therapy ◽  
Immune Cell ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Cell Populations

Abstract Tumors affect the immune system, locally and systemically. The frequencies of specific circulating immune cell populations correlate with disease progression as well as prognosis of the patients. Although largely neglected, conventional antitumoral therapies often possess immunomodulatory properties and affect the levels of specific immune cell populations. Most information, however, derive from animal or in vitro studies. As this could impact prognosis as well as response to therapy, further studies of the effects of treatment on circulating immune cells in patients are warranted. In this pilot study, we evaluated a wide panel of circulating immune cells over time (up to six months) in ten patients with metastatic breast cancer receiving standard antitumoral regimens. Overall, endocrine therapy tends to enrich for natural killer (NK) and natural killer T (NKT) cells in the circulation, whereas both chemotherapy and endocrine therapy reduce the levels of circulating monocytic myeloid-derived suppressor cells (Mo-MDSCs). This indicates that the systemic immunosuppressive profile observed in patients tends to revert over the course of systemic therapy and holds promise for future combination treatment with standard antitumoral agents and immunotherapy.

Trastuzumab-reactive antibodies (TR-abs) in serum and trastuzumab (Tzb) benefit prediction in patients with HER2-overexpressing breast cancer.

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 77-77 ◽  
Author(s):  
Paula Raffin Pohlmann ◽  
Todd W. Miller ◽  
David L Blum ◽  
Dipti Pareh ◽  
Heping Yan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Transgenic Mice ◽  
Univariate Analysis ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Breast Cancer Cell Lines ◽  
Therapeutic Antibodies ◽  
Stage Iv Breast Cancer ◽  
Pharmacologically Active

77 Background: Trastuzumab (Tzb) is a humanized monoclonal antibody (MAb) approved for treatment of HER2-overexpressing breast cancer. Unfortunately not all patients benefit from it and lack of response cannot be predicted. We detected TR-abs in serum of mice and patients treated with Tzb. We hypothesized that TR-abs would associate with response to therapy. Methods: Direct/competition ELISA, dot blot, and mass spectrometry were used to detect and characterize TR-abs in sera from Tzb treated FVBMMTV/HER2transgenic mice, from hybridoma MAbs stemming from transgenic mice responding favorably to Tzb (992-18 mMAb), and in sera of 22 patients with metastatic breast cancer enrolled in a phase I clinical trial. WST-1 viability assay was used to assess biological activity of 992-18 on SKBR3 or BT474 human breast cancer cell lines. Results: From 12 mice bearing HER2-overexpressing tumors and treated with Tzb, 5 responded to therapy and 7 exhibited progressive disease (PD). All 5 responders had elevated TR-abs, whereas TR-abs were low/undetectable with PD (p=0.002; Mann-Whitney two-tailed). This was confirmed in a second cohort of 16 mice, in which TR-abs were undetectable prior to treatment, but gradually detected with Tzb therapy and tumor regression. TR-MAb 992-18 directly targeted also SKBR3 and BT474 in cell-based ELISAs and immunofluorescence assays. Treatment with 992-18 reduced BT474 and SKBR3 cell viability in comparison to isotype-matched control Ab (p<0.0001). In sera from patients with metastatic breast cancer, higher concentrations of TR-abs were significantly associated with lower risk of disease progression (p=0.023, Cox regression, univariate analysis). Conclusions: Low serum TR-abs are associated with poor response to Tzb in mice and with shorter progression free survival in women with HER2 overexpressing stage IV breast cancer. In addition, TR-abs (e.g. 992-18) produced in response to therapy may be pharmacologically active. Results support prospective evaluation of patients undergoing treatment with therapeutic antibodies to determine if this non-invasive immunoassay detecting anti-therapeutic antibodies would predict benefit to therapy.

scholarly journals Gene Expression Signatures in Circulating Tumor Cells Correlate with Response to Therapy in Metastatic Breast Cancer

2017 ◽  
Vol 63 (10) ◽  
pp. 1585-1593 ◽  
Author(s):  
Maren Bredemeier ◽  
Philippos Edimiris ◽  
Pawel Mach ◽  
Mikael Kubista ◽  
Robert Sjöback ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Clinical Staging ◽  
Significant Differential Expression

Abstract BACKGROUND Circulating tumor cells (CTCs) are thought to be an ideal surrogate marker to monitor disease progression in metastatic breast cancer (MBC). We investigated the prediction of treatment response in CTCs of MBC patients on the basis of the expression of 46 genes. METHODS From 45 MBC patients and 20 healthy donors (HD), 2 × 5 mL of blood was collected at the time of disease progression (TP0) and at 2 consecutive clinical staging time points (TP1 and TP2) to proceed with the AdnaTest EMT-2/StemCellSelectTM (QIAGEN). Patients were grouped into (a) responder (R) and non-responder (NR) at TP1 and (b) overall responder (OR) and overall non-responder (ONR) at TP2. A 46-gene PCR assay was used for preamplification and high-throughput gene expression profiling. Data were analyzed by use of GenEx (MultiD) and SAS. RESULTS The CTC positivity was defined by the four-gene signature (EPCAM, KRT19, MUC1, ERBB2 positivity). Fourteen genes were identified as significantly differentially expressed between CTC+ and CTC− patients (KRT19, FLT1, EGFR, EPCAM, GZMM, PGR, CD24, KIT, PLAU, ALDH1A1, CTSD, MKI67, TWIST1, and ERBB2). KRT19 was highly expressed in CTC+ patients and ADAM17 in the NR at TP1. A significant differential expression of 4 genes (KRT19, EPCAM, CDH1, and SCGB2A2) was observed between OR and ONR when stratifying the samples into CTC+ or CTC−. CONCLUSIONS ADAM17 could be a key marker in distinguishing R from NR, and KRT19 was powerful in identifying CTCs.

scholarly journals PIK3CA and MAP3K1 alterations imply luminal A status and are associated with clinical benefit from pan-PI3K inhibitor buparlisib and letrozole in ER+ metastatic breast cancer

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Mellissa J. Nixon ◽  
Luigi Formisano ◽  
Ingrid A. Mayer ◽  
M. Valeria Estrada ◽  
Paula I. González-Ericsson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Benefit ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Pi3k Inhibitor ◽  
Breast Cancer Cell Lines ◽  
Luminal A ◽  
Pik3ca Mutations ◽  
Pi3k Inhibitors

Abstract Clinical trials have demonstrated the efficacy of combining phosphoinositide 3-kinase (PI3K) inhibitors with endocrine therapies in hormone therapy-refractory breast cancer. However, biomarkers of PI3K pathway dependence in ER+ breast cancer have not been fully established. Hotspot mutations in the alpha isoform of PI3K (PIK3CA) are frequent in ER+ disease and may identify tumors that respond to PI3K inhibitors. It is unclear whether PIK3CA mutations are the only biomarker to suggest pathway dependence and response to therapy. We performed correlative molecular characterization of primary and metastatic tissue from patients enrolled in a phase Ib study combining buparlisib (NVP-BKM-120), a pan-PI3K inhibitor, with letrozole in ER+, human epidermal growth factor-2 (HER2)-negative, metastatic breast cancer. Activating mutations in PIK3CA and inactivating MAP3K1 mutations marked tumors from patients with clinical benefit (≥6 months of stable disease). Patients harboring mutations in both genes exhibited the greatest likelihood of clinical benefit. In ER+ breast cancer cell lines, siRNA-mediated knockdown of MAP3K1 did not affect the response to buparlisib. In a subset of patients treated with buparlisib or the PI3Kα inhibitor alpelisib each with letrozole where PAM50 analysis was performed, nearly all tumors from patients with clinical benefit had a luminal A subtype. Mutations in MAP3K1 in ER+ breast cancer may be associated with clinical benefit from combined inhibition of PI3K and ER, but we could not ascribe direct biological function therein, suggesting they may be a surrogate for luminal A status. We posit that luminal A tumors may be a target population for this therapeutic combination.

Serum glycan analysis in metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11504-11504
Author(s):  
H. K. Chew ◽  
S. Miyamoto ◽  
H. An ◽  
D. Rocke ◽  
C. Lebrilla
Keyword(s):  
Breast Cancer ◽  
Mass Spectrometry ◽  
Metastatic Breast Cancer ◽  
High Resolution Mass Spectrometry ◽  
Immune Surveillance ◽  
Metastatic Breast ◽  
Cancer Biomarker ◽  
Response To Therapy ◽  
Ion Cyclotron Resonance ◽  
New Paradigm

11504 Background: There is a need for a reliable breast cancer biomarker that can predict a patient’s response to therapy. Serum glycans, or oligosaccharides, are of particular interest as over half of all proteins are glycosylated and alterations in glycosylation influence growth, adhesion, metastasis and immune surveillance of tumor, among other important functions. Serum glycans can be analyzed by high resolution mass spectrometry. Methods: Sera from patients with known metastatic breast cancer and age-matched healthy controls without medical problems were prospectively analyzed by mass spectroscopy. Women over the age of 18, who were not pregnant or breastfeeding, and who were without other active cancers were eligible. Samples were de-identified for laboratory personnel who analyzed sera by matrix-assisted laser desoprtion/ionization (MALDI) and Fourier transform ion-cyclotron resonance mass sepctrometry (FT ICR MS). Glycans were also profiled by chromatographic separation using a microchip nanoLC (Agilent) with a time-of-flight (TOF) mass analyzers. Results: Sera from 25 patients with metastatic breast cancer and 25 controls were evaluated. The mass profiles were obtained corresponding to both N-linked oligosaccharides (N-glycans) and O-linked oligosaccharides (O-glycans). Distinct variations in glycosylation were observed among sera analyzed from patients with metastatic breast cancer compared to controls. Specific glycan masses were analyzed and found to correspond to N-glycans. The chromatographic glycan profile showed individual glycans that were distinct for the cancer patients. Conclusions: Analysis of serum gylcans by mass spectrometry represents a new paradigm of cancer biomarker studies, focusing on post-translational modifications of proteins, rather than protein expression. Further refinement of this technology may be clinically useful in monitoring response to therapy in metastatic breast cancer. No significant financial relationships to disclose.

Combination trastuzumab and chemotherapy to induce immunity to multiple tumor antigens in patients with HER2-positive metastatic breast cancer: NCCTG (Alliance) studies N0337 and N98-32-52.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 521-521 ◽  
Author(s):  
Raphael Clynes ◽  
Keith L. Knutson ◽  
Karla V. Ballman ◽  
Courtney L. Erskine ◽  
Nadine Norton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Combination Therapy ◽  
Tumor Antigens ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Multiple Tumor ◽  
Her2 Breast Cancer

521 Background: The addition of trastuzumab to chemotherapy improves responses to therapy and extends survival among patients with metastatic HER2 breast cancer. Several mechanisms have been proposed for the activity of this combination therapy. Trastuzumab, specifically, is thought to activate NK cells and blunt HER2 signaling. Prior work from us has shown that combination trastuzumab and chemotherapy induces HER2-specific antibodies which correlate with response to therapy. Despite that, it remains unclear whether the immunity that was induced was due to complexing of non-tumor derived HER2 or antigen derived from the tumor site. In the present work, we addressed this question by assessing if combination therapy induced epitope spreading to tumor antigens other than HER2. Methods: Pre-and post-treatment sera were obtained from 56 women enrolled in 2 NCCTG clinical trials, N0337 and 98-32-52. IgG antibodies to HER2 intracellular domain (HER2), p53, IGFBP2, CEA and tetanus toxoid (TT) were examined using ELISAs. Sera from an age-matched group (N=56) of controls and 12 patients treated in the adjuvant setting were also examined. Results: Prior to therapy, metastatic patients had higher IgG levels (≥ 2-fold) to p53 and HER2 but not CEA, IGFBP2 and TT, relative to the controls. Similarly, adjuvant patients had elevated IgGs to multiple tumor antigens prior to therapy, relative to controls. Following therapy, levels of IgG to IGFBP2, HER2, and p53 increased in 81% of metastatic patients, with mean increases of 3.2 (±0.6 sem), 6.2 (±2.7) and 2.7 (±0.7) fold, respectively (p<0.05). Levels of antibodies to TT and CEA were not elevated by treatment. In contrast, IgGs were not increased in adjuvant patients; consistent with the idea that immunity depends on the presence of threshold levels of antigens. Conclusions: These results show that combination treatment induces adaptive immunity to antigens released by tumor and that metastatic patients remain capable of responding immunologically to their cancer. Thus, in metastatic breast cancer patients, combination trastuzumab and chemotherapy may behave as a vaccine.

Mycoplasma Pneumonia Infection - a Possible unrecognized Cause for Immune Thrombocytopenic Purpura

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4555-4555
Author(s):  
Shraga Aviner ◽  
Daniel London ◽  
Shulamith Horowitz ◽  
Menachem Schlesinger ◽  
Gilles Lugassy
Keyword(s):  
Platelet Count ◽  
Clinical Diagnosis ◽  
Intracranial Hemorrhage ◽  
Immune Thrombocytopenic Purpura ◽  
Complete Blood Count ◽  
Case Reports ◽  
English Literature ◽  
Severe Bleeding ◽  
Thrombocytopenic Purpura ◽  
Mycoplasma Pneumonia

Abstract Mycoplasma pneumonia (M. pneumonia) is usually not considered among the several pathogens that induce immune thrombocytopenic purpura (ITP). We report a case of a child with a clinical diagnosis of severe ITP (as defined by the American Society of Hematology panel guidelines of 1994), that was associated with M. pneumonia pneumonia, and reviewed the few cases described in the English literature. A 7-year-old girl was admitted to the pediatric department with 1 day history of fever, purpura and petechiae on her legs, buttocks, arms, face, hard palate, oral mucous membranes and lips. Crepitations were heard over both lungs’ lower fields. Complete blood count revealed WBC of 22.3×103/ μL, Hemoglobin of 11.1 gr/dL, and platelet count of 2×103/μL. Red cells appeared normal on blood film with no features of microangiopathy. A chest X-ray demonstrated right middle lobe infiltrate. Presumptive diagnoses of ITP and RML pneumonia were made and treatment was initiated with one dose of IVIG 0.8 g/kg and daily IV Ceftriaxon at 50 mg/kg. Twelve hours after the IVIG administration, platelet count was 1.2×103/μL. Bone marrow examination revealed normal cellularity with young megakaryocytes, compatible with the diagnosis of ITP. Since there was no response to IVIG, Methylprednisolone 4 mg/ kg for 4 days was started. An extensive search of the literature for ITP or thrombocytopenia and pneumonia retrieved only 7 case reports. In all cases M. pneumonia was the only identified pathogen. Therefore, clarithromycin 15 mg/kg/d was added to the treatment regimen, prior to obtaining the serology results. Thereafter severe hemoptysis developed; the patient was admitted to the PICU and received 4 units of platelets and a second dose of IVIG. Hemoptysis resolved after another day, when the platelet count started to increase gradually, only to drop after the cessation of steroids. A second course of steroids at the same dose was begun and tapered off gradually over 21 days, while the platelet count steadily increased, exceeding 150×103/μL at 4 weeks from presentation. A positive Mycoplasma IgM titer at diagnosis and a 1:160 titer at 2 months confirmed the clinical diagnosis. The child is by now 20 months after the event with normal CBC. Several features of the 8 cases described (including our case) distinguish them from “classic” ITP: Thrombocytopenia occurred concomitantly with the infection as opposed to a few days to a few weeks interval between infection and ITP. Severe bleeding in 4 out of 8 patients including 2 with fatal intracranial hemorrhage in contrast to around 3% severe bleeding and around 1‰ fatal intracranial hemorrhage in “classic” ITP. Three of the authors who looked for specific anti-platelet antibodies were unable to demonstrate it, whereas such antibodies are found in many patients with ITP. Several mechanisms are suggested to explain these differences; though it remains unclear whether Mycoplasma associated thrombocytopenia represents a subset of ITP or constitutes a separate entity. We conclude that M. pneumonia should be looked for in any case of pneumonia and thrombocytopenia or ITP, and early specific anti-Mycoplasma therapy should be initiated to rapidly eliminate the causative agent. This may enhance recovery of the platelet count and decrease the rate of complications.

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