BackgroundMultiple myeloma (MM) is the second most common malignancy in the United States and has a higher incidence in the black and Afro-Caribbean population. There remain limited data on disease presentation and clinical characteristics in this patient group in the United States. The clinical profile of MM in this underrepresented patient group is described here.MethodsThis retrospective study was conducted at Kings County Hospital, an urban New York City hospital in a majority Afro-Caribbean neighborhood. Data from patients diagnosed with MM from 2000 through 2013 were collected from the institution’s tumor registry. Clinical and demographic characteristics of these patients were then analyzed.ResultsPatients with a diagnosis of MM were identified (N = 287). Data were available for 231 patients and of these, 97% self-identified as black. 55% were female, and there was a male-to-female ratio of 1:1.2. The mean age of female patients was 64 years; that of male patients was 63 years. Of the 231 patients, 81% had anemia, 68% had bone lesions, 47% had renal impairment, and 29% had hypercalcemia. Low levels of monoclonal protein were present in 27% of patients and 57% had disease of International Staging System stages I and II. Women had higher BMI than men.ConclusionThe mean age of presentation of MM in Afro-Caribbean patients is similar to that in the standard population; however, unlike the general US population, there was a higher incidence in women; mean BMI of women also was higher than that of male patients. A sizeable percentage of Afro-Caribbean patients with MM presented with low levels of monoclonal protein in the presence of multiorgan involvement and damage, suggesting the need for early and aggressive diagnostic testing.

The optimal management of cancer in patients with severe heart failure is not defined. This issue is particularly challenging when a diagnosis of limited-stage small cell lung cancer (SCLC) is made incidentally in the context of evaluating patient for candidacy for cardiac transplantation. Limited-stage SCLC is typically managed on a curative therapeutic paradigm with combined modality approach involving chemotherapy and radiation. Even with excellent performance status and good organ function, the presence of severe cardiomyopathy poses significant challenges to the delivery of even single modality approach with chemotherapy or radiotherapy, let alone the typical curative combined modality approach. With mechanical left ventricular devices to provide cardiac support, treatment options for cancer in the setting of advanced heart failure may be improved. Here we discuss the therapeutic dilemma involving a patient with severe cardiomyopathy and left ventricular assistant device (LVAD) who was found to have limited-stage SCLC during the evaluation process for cardiac transplantation.

Introduction Monoclonal gammopathy of undetermined significance (MGUS) is defined as the presence of monoclonal immunoglobulin (Ig), without the diagnosis of multiple myeloma (MM), while the diagnosis of MM requires the presence of a monoclonal immunoglobulin (Ig) ≥ 3g/dl or Bence-Jones protein (BJP) ≥ 500mg/24h, with bone marrow involvement of greater than 10% clonal plasma cells. Kings County Hospital (KCH) is an institution that serves a large population of Afro-Caribbean population. In our institution, an increased number of patients were observed to present with MM with monoclonal Ig <3g/dl but yet have end organ damage. The clinical characteristics of Afro-Caribbean population have not been well studied and further characterization may have diagnostic implications. Methods This is a retrospective study conducted at KCH. Data regarding the clinical profile of patients diagnosed with MM from 2000- 2013 was collected from the institution's tumor registry. Patients with monoclonal Ig < 3g/dl and BJP <500mg/24h were analyzed and compared to standard MM patients with monoclonal Ig ≥ 3g/dl or BJP ≥ 500mg/24h. Data was collected for lab parameters which included quantity and type of monoclonal Ig, serum free light chains and ratio, monoclonal plasma cell percentage in the bone marrow, International staging system (ISS) stage, cytogenetics, presence of anemia, hypercalcemia, renal failure and lytic lesions. Epidemiologic parameters age and gender were also collected. Results were analyzed by a Chi-square test to calculate a mid-P exact. Results A total of 287 patients with MM were screened, of which 56 patients with incomplete electronic records were excluded. Of the remaining 231 patients, 63 (27%) had monoclonal Ig <3 g/dl without the presence of BJP ≥ 500mg/24h. These patients were labeled hyposecretory MM. 168 (73%) patients had standard MM, with monoclonal Ig ≥ 3g/dl or BJP ≥ 500mg/24h. In the hyposecretory MM group, 35% of patients presented with International staging system (ISS) stage I vs. 13% in the standard MM group (P= 0.0001). IgG monoclonal Ig was present in 75% of patients with hyposecretory MM compared to 62% in the standard MM group (P=0.04). Mean plasma cell percentage in the bone marrow was similar in both groups, 40% in the hyposecretory MM group compared to 51% in standard MM. Average age of presentation was 64 yrs in the hyposecretory MM group as compared to 63 yrs in the standard MM group. There were more females than males in both groups, 61% females in hyposecretory MM and 53% in standard MM group. The most common presenting symptom was anemia in both groups and there were no statistically significant differences noted in gender, presence of hypercalcemia, presence of bone lesions, and renal dysfunction. Cytogenetic data was insufficient. Conclusion In our study, a substantial number of Afro-Caribbean patients with low levels of serum monoclonal Ig without the presence of Bence-Jones protein were diagnosed with active multiple myeloma. The results of our study underline the importance of an aggressive diagnostic approach with a bone marrow biopsy at initial presentation with MGUS in Afro-Caribbean population. This may prevent disease progression and end organ damage. Unlike the general population with MM, there were more females. Disclosures No relevant conflicts of interest to declare.

Purpose of StudyOver 240,000 individuals are diagnosed with breast cancer each year in the USA. Outcomes depend on DNA deregulations in tumors. Carriers of deleterious BRCA1 and BRCA2 mutations are predisposed to 30 fold higher lifetime risks of breast and ovarian cancer.Aims:1. To check for differences in SNPs of genomic DNA obtained in BRCA+/− with and without BrCa.2. Analyze correlates of molecular mechanisms occurring in BRCA mutant patients.Methods UsedWe analyzed 94 subjects (41 BRCA positive) with or without BrCa to detect SNPs whose expression is significantly differentially expressed between breast cancer and controls. DNA samples were extracted from PBMCs. Samples were measured for DNA concentration using an Invitrogen QuBit Fluorometer, and diluted to 50 ng/µL.All samples were collected between 2010 and 2014 and survival data was known in all cancer patients. Processed samples were sequenced using an Illumina MiSeq Sequencer with a 300 cycle kit to detect SNPs. Variant Call Files were analyzed in Microsoft Excel using Fisher's Exact Test.Summary of ResultsALK SNPs were commonly found in cancer relative to control. Significant associations of ALK SNPs were seen in BRCA mutation subjects. ALK protein was overexpressed in 47% of BRCA mutations cases, which was significantly higher than in non-BRCA cases. Our results show that the ALK signaling pathway possibly is more common in early onset of breast cancer as seen with BRCA mutations. Coremine analysis showed SNPs identified in cancer were most commonly associated with deregulation of Transforming Growth Factor-Beta Superfamily protein synthesis and binding function.ConclusionsDifferences in the associations of the modifying polymorphisms with BrCarisk for BRCA1 and BRCA2 mutation carriers are likely to reflect differences in the biology of tumor development in these two groups of women at high risk of breast cancer. The identification of modifying polymorphisms could therefore lead to a better understanding of the etiology of tumors in mutation carriers and also to the development of effective and more specific therapies for BrCa in mutation carriers.

Purpose of StudyBlack women with triple negative breast cancer have 46% lower survival rates attributed to differences in tumor biology. We analyzed presurgical plasma microRNA of white (W) and black (B) women with TNBC enrolled in our breast ovarian tissue bank between 2004 and 2014.AimsDetect microRNA patterns in pre-surgical plasma of TNBC W or B Analyze differences by integrated approach to detect pathways differentially activated in the two groups.Methods UsedBetween 2004 and 2014 we investigated patterns of plasma miRNAs collected before, after surgery, during and after chemotherapy in 67 patients presenting for surgery for breast cancer (W=44 & B=44) and 25 age and race matched normal controls. Two-sample t-test was used for all 2-sample comparison and ANOVA followed by Benjamin Hochberg post-hoc test to compare the mean response between subject factors of interest. All tests were 2-tailed and results with a p<0.05 were considered statistically significant. Coremine was used to identify datasets in breast cancer microarray with emphasis on our differentially expressed circulating miRs.Summary of ResultsMean age cancer 48 (range 35–78), control 44 (range 35–67): B patients did not express over 70% of pre-surgical plasma miRs over-expressed in the W pre-surgical plasma. Black patients had lower expression of MiRs: −16-5p, −484, −126, −150-5p, −142-3p; −30c-5p, −186-5p, 139-5p. Samples from white patients overexpressed miRs−126, −150-5p, −142-3p; −30c-5p, −186-5p, 139-5p compared to healthy controls. These miRs significantly suppressed in blacks p<0.05.Coremine text mining suggests differentially regulated microRNA are involved in mitochondrial quality control and biogenesis.ConclusionsDeregulation in circulating miRs between B and W patients point to pathways involved in mitochondrial fission and fusion. Aberrant mitochondria biogenesis was reported as mechanism for cancer stem cell survival and detrimental to innate immunity. Such pathways could explain the lower survival seen in black breast cancer patients.

Purpose of StudyMore than 100,000 pelvic surgeries to remove ovarian masses (BOM) are performed yearly in the USA only 8% of those remove ovarian cancer. Circulating microRNA are biomarkers for disease detection. Purpose of study:1. To analyze patterns of microRNAs in women with BOM vs. OvCa2. Discover pathway involved malignant transformation.Methods UsedPlasma from 32 women OvCa, 24 controls 32 (BOM) was analyzed using ABI Taqman OpenArray MicroRNA pools A and B to measure the expression of 754 known miRNAs .Real-time PCR was performed on the Taqman Open Array MicroRNA arrays using the Applied Biosystem Open Array Real-Time PCR system. Data were processed using the OpenArray Real-Time qPCR Analysis software and exported for analysis using the Applied Biosystems DataAssist Software Data analysis was done with the R programming language. A cutoff for Ct values at 30 was used. MiRNAs with Ct values higher than 30 were considered not detected. Data was normalized using a mean-centering restricted (MCR), a modification of the traditional delta Ct method and uses miRNAs which are expressed in all samples for data normalization. Statistical analysis was performed via custom scripts based on the R/Bioconductor package LIMMA (Linear Models for Microarray).Summary of ResultsBOM had higher expression (2–14 fold higher) of miRs −195, −126, −139-5p, −27b, −127, −152, −28, −106b, −17, −363, −181a, −192 relative to OvCa (p<0.0006). OvCa over-expressed of miRs −1274a, −720 and −625-3p (p<0.0007). Reactome pathway analysis detected involvement of miRs into pathways of activation of BAD, PI3/AKT signaling in CD28 and activation of BH3 in BOM these pathways were not detected in OvCa (p<0.000596).ConclusionsBOM patients have immune recognition and pro-apoptotic protective circulating microRNAs. It is unknown whether miRs originate in ovary or another tissue. Recent work shows that BH3 mimetics are very effective in inducing cancer cell death.

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