Search

Inflammatory breast cancer is a rare and aggressive form of cancer characterized by dermal lymphatic invasion and tumor embolization resulting in erythema and edema. In many cases, by the time of diagnosis there is already distant metastasis. Mammography, sonography, CT, and MRI are usually performed for initial staging; however, PET/CT can also be used for initial staging as it offers additional diagnostic information.

Asymptomatic (smoldering) multiple myeloma is a heterogeneous plasma cell proliferative disorder with a variable rate of progression to active multiple myeloma or related disorders. Hypercalcemia, renal insufficiency, anemia, bone lesions or recurrent bacterial infections characterize active multiple myeloma. Some patients with asymptomatic myeloma develop active disease rapidly, and others can stay asymptomatic for many years. Those who are likely to progress within the first 2 years of diagnosis have been categorized as having high-risk disease. The availability of novel agents in the treatment of active multiple myeloma and our better understanding of the heterogeneity of asymptomatic multiple myeloma have spurred interest in the early treatment of these patients. We have reviewed the current proposed definitions of high-risk asymptomatic multiple myeloma, the concerns about future therapy in view of the transient nature, remissions and toxicities of the therapies, and the eventual relapses that characterize this incurable disease.

Summary Purpose We conducted a comparative survival analysis between patients with resected pancreatic cancer who received adjuvant treatment with either gemcitabine- or 5-fluorouracil-based chemotherapy and chemoradiation regimens. Patients and methods The Surveillance, Epidemiology and End Results (SEER)-Medicare database was used to identify patients with pancreatic cancer diagnosed from 1998 to 2005 who received curative surgery and adjuvant chemotherapy with either 5-fluorouracil or gemcitabine. These groups were subdivided by treatment with radiotherapy. Patients were followed until death, study end-point or a maximum of 5 years after diagnosis. Results Three hundred and fifty-nine patients received 5-fluorouracil and 346 received gemcitabine. Compared with chemoradiation with 5-fluorouracil, outcomes for patients who received chemoradiation with gemcitabine did not differ. Patients who received gemcitabine without radiation had increased hazards (poorly differentiated tumours: HR = 1.50, p = 0.01; moderately differentiated tumours, HR = 1.28, p = 0.11). However, outcomes of patients who received 5-fluorouracil without radiation varied with tumour grade. In moderately differentiated tumours, patients had better outcomes with 5-fluorouracil when compared with chemoradiation with 5-fluorouracil (HR = 0.42, p = 0.02). In poorly differentiated tumours, the opposite was true (HR 2.10, p = 0.09). Conclusion Patients with low-grade resected pancreatic cancer may have better outcomes with 5-fluorouracil-based chemotherapy without radiation when compared with 5-fluorouracil with radiation.

The outcome of patients diagnosed with primary myelodysplastic syndromes (MDS) between 1990 and 1997 from William Beaumont Hospital (WBH) was analyzed according to the International Prognostic Scoring System (IPSS) risk categorization. A retrospective study of 195 MDS patients was performed. Seventy-nine patients with MDS, in whom a karyotype was obtained and with an adequate follow-up were included in the final analysis. Cases of proliferative CMML (WBC >12×10 9 /l) were excluded from the study. The overall median survival was 3.1 years, and median survival stratified by IPSS was 3.4, 4.1 and 0.5 years for the INT-1, INT-2 and high risk group and not yet reached for the low risk group. The overall survival by IPSS subcategorization were 6.88, 5.29, 5.30 and 2.12 years for the low, INT-1, INT-2, and high risk groups respectively. Cytogenetics were significant in predicting the overall survival. The IPSS score stratified patients into risk categories for development of AML. The risk of development into AML was 8, 8, 33 and 54% for the low, INT-1, INT-2 and high risk groups, respectively. We conclude that IPSS score can be useful in predicting survival and AML evolution in some MDS patients.

Paraspinal muscle metastasis as initially suggested by an electromyographic pattern of isolated posterior primary ramus denervation and subsequently confirmed by magnetic resonance imaging has been reported. However, despite widespread systemic tumor dissemination, metastases to other skeletal muscle occurs infrequently. Uniquely, the paraspinal muscles are drained by the paravertebral plexus of veins. Valveless and at very low pressures, they communicate directly by collaterals with the portal system. Valsalva maneuvers with sudden increases of pressure within the intra-abdominal and intrathoracic cavities can force venous blood from the systemic circulation into the paravertebral plexus of veins. These same venous surges potentially carry tumor emboli to the vertebrae and/or from the vertebral medulla to the adjacent paravertebral muscle by the venous communicators. The inherent increased vascularity of metastatic tumor relative to the surrounding paraspinal muscle as demonstrated by magnetic venous angiography for the first time now permits earlier confirmation and biopsy of the electromyographic-suspected metastatic lesion. In this reported instance of a magnetic resonance imaging-recognized primary lung metastasis confirmed by magnetic resonance venography, there is the future promise of identifying earlier and smaller lesions by this technique.

A man in his early 40s with a history of ulcerative colitis, treated with infliximab, was diagnosed with plasmablastic multiple myeloma. He was treated with chemotherapy and stem cell transplant but developed recurrence and ultimately died from metastatic disease. Could inflammatory bowel disease or infliximab therapy have any role in development of myeloma in this young patient? The role of inflammatory bowel disease and infliximab therapy in the development of multiple myeloma is controversial but interesting and worth considering.

A 46-year-old man with a long-standing history of Crohn’s disease who was treated with multiple therapies over a period of 9 years presented with oral lesions which on biopsy demonstrated peripheral T-cell lymphoma. Initially, the development of T-cell lymphoma was presumed to be secondary to prolonged immunosuppression but it did not respond to withholding immunosuppressive therapy. On treatment with CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) chemotherapy, complete remission was achieved. Although development of malignancies in the immune-suppressed patient with Crohn9s disease has been previously described but we present a rare case of T-cell lymphoma in a similar patient, which has not been reported before.

Background: Antigens like CD20 antigen, are established targets for antibody therapy with monoclonal antibodies (mAb) like Rituximab. Mixed clinico-pathological responses to mAb have been reported either due to presence of antibodies, rapid clearance or low density of target receptor/antigens. This demands need for an assay to monitor serum mAb therapeutic levels to ensure appropriate dosage. Enzyme-linked immunosorbent assay (ELISA) is still the most widely used technique to detect mAb level in human serum which is expensive and time consuming. Understanding properties and interactions of antigens is quintessential for developing better targeted agents and overcoming resistance. Flow cytometry is still the most widely used technique to detect CD20 level in human serum which is expensive, time consuming and does not reveal any details of interaction between the molecules. We have developed a new innovative biosensor based novel technique to not only monitor levels but also study real time interaction of antigens with antibodies using QCM Piezo-immunosensor. This quantitative label free peptide based assay can be used to characterize cell surface antigen, to study antigen- antibody interactions and obtain understanding of mechanisms of resistance to therapy. Method:Mimotope was used as a substitute for the antigen like CD20 and HER2 receptor protein in QCM assays to detect mAb level. The validation samples were prepared from the standard T solution in 10% human serum at three concentrations (10, 20 and 40 ug/ml). The changes in frequencies (ΔF) of sera from 3 female patients were obtained by calculating the differences between frequency shifts in pre and post mAb infusion. mAb level was calculated by equation, (ΔF +1.0022) ÷ 0.9997 μg / ml. The real-time processes of attachment of Cells like Raji cells on the gold electrode and the subsequent binding of antibody like Rituximab to the cells were studied using QCM biosensor. The interaction between Antigen and Antibody led to the increased resonant frequency shifts (df0) in the studied antibody concentration range from 5 to 250 μg mL-1 . Control experiments using other therapeutic antibodies (i.e., Trastuzumab and Bevacizumab) and different cells (i.e., T cells and endothelial cells) proved very specific interaction between Rituximab and CD20 antigens on B cells Results: Antigen and Antibody binding was very specific. This binding decreased the electrochemical activity and stability of the cells, supporting the cell lysis mechanisms of action of Rituximab. We showed that assay sensitivity was dependent upon the amino acids used to tether and link the peptide to the sensor surface and the buffers used. QCM assay was capable of detecting mAb like Trastuzumab serum level as low as 0.038 nM (linear operating range of 0.038-0.859 nM). The time frame of assay was 20-30 minutes. These results were in concordance with previously published results using ELISA. We have shown a systematic approach for using QCM technique to quantify the apparent binding constant between antigen and antibody can reveal antigen density. Conclusion: We have established a low cost, highly sensitive, fast, synthetic peptide based QCM assay which could be used as a basis for developing a new generation of affinity-based Immunosensor assays to monitor mAb serum levels like Rituximab, Trastuzumab and other monoclonal antibodies, helping physicians to determine the clinical efficacy of these drugs and ensuring appropriate dosages. Moreover antigen density and interactions of antigens with respective monoclonal antibodies like CD20 with Rituximab will help physicians to determine the clinical efficacy and resistance mechanisms to targeted antibodies like Rituximab and Ofatumumab. This could be used as a basis for developing a new generation of affinity-based Immunosensor assays. Our study shows that peptide mimotopes have potential benefit in sensor applications as the peptide-peptide interactions in the peptide mimotopes could be manipulated by the addition of functional groups to the peptide to influence binding of the target protein as well as for surface immobilization. Disclosures No relevant conflicts of interest to declare.

CONTEXT Chronic Lymphocytic Leukemia (CLL) is a clonal proliferation of small mature B-cell lymphocytes diagnosed clinically when the peripheral blood clonal B lymphocyte count is persistently >5,000/mcL with distinctive immunological markers defined by co-expression of CD5 and CD23 with additional expression of CD19, CD20 (weak) with weak surface immunoglobulin expression, usually IgM heavy chain. Expression of CD79b and FMC7 is typically negative to weakly positive. With the recent advancement in cancer genetics and the continued understanding of the transforming events in CLL, the importance of the various somatic genomic aberrations has been well documented. Multiple studies have shown the clinical implications of these aberrations in terms of their prognostic and predictive relevance in clinical practice and these genomic aberrations are usually assessed clinically by cytogenetic analysis and FISH. OBJECTIVE We proposed this study to determine the incidence of the genomic aberrations in the CLL patients diagnosed at the Rose Cancer Treatment Center of the William Beaumont Hospital between 2010 and 2015 and to determine their impact on survival among the patients diagnosed during the study period. STUDY DESIGN A retrospective review of all the patients diagnosed with CLL between 2010 and 2015 at the Rose Cancer Treatment Center was conducted with the assistance of the staff in the William Beaumont cancer registry office. We determined the demographic variables and analyzed the incidence of CLL among the subjects diagnosed within the study period. Data analysis was performed using SPSS 21 and Kaplan-Meier curves were plotted for survival analysis and log rank (Mantel-Cox) was used to compare these curves. 12-Month and 36-Month overall survival rates were analyzed by actuarial method. The distribution of the various genomic aberrations was determined using descriptive statistical analysis. RESULTS A total of 151 patients were identified at the Rose Cancer Center of the William Beaumont Hospital during the study period. The median age at diagnosis was 74 years (range 38-101) of which 90 were male (59.6%) and 61 female (40.4%). One-hundred and twenty-four (82.1%) patients were white, six patients (4.0%) were African American, two patients (1.3%) were Asian and nineteen (12.6%) patients declined to identify their race. Analysis of cytogenetic distribution showed that, twenty patients (13.2%) had normal cytogenetic, eleven patients (7.3%) had del(13q) alone, eight (5.3%) had both del(13q) and del(11q), four patients (2.6%) had del(13q) plus trisomy 12 aberrations, ten (6.6%) patients had del(13q) and other karyotypes (TP53, RB1, trisomy 1q, del(6q23), unmutated IGHV). Thirteen patients (8.6%) had trisomy 12 abnormality, five patients (3.3%) had del(11q), three patients (2.0%) had del(17p), twenty-five patients (16.6%) had complex cytogenetic abnormalities and fifty-two (34.4%) patients cytogenetic were not checked (see Fig.1). The median follow-up duration for the cohort was 22.5 months (range 0 to 70 months). The survival rates at 12 months and 36 months for the cohorts based on cytogenetic are described in table 1 and fig.2. CONCLUSION Our study showed that majority of our patients (34.4%) did not have their cytogenetics checked at diagnosis, patients with del(13q) abnormality alone had the most favorable 36-Month overall survival rate and those with del(17p) fared worst with the most unfavorable outcome followed by patients with complex cytogenetic abnormalities. Presence of del(13q) with either del(11q) or trisomy 12 abnormalities appeared to ameliorate their poor and intermediate adverse prognostic effects, respectively. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

e18522Background: Despite the development of prognostic factors for stratification models in AML patients, treatment response in individual patient has not been predicted accurately. Early assessme...

e18206Background: Rasburicase is a recombinant urate-oxidase used in prevention and treatment of tumor lysis syndrome (TLS.) Since conversion of uric acid to allantoin leads to the production of hy...

e13007Background: BRCA mutations are associated with an increased risk of breast and ovarian cancers in women. The cancer characteristics of men with BRCA 1 and 2 mutations are less well studied. We reviewed data on male patients diagnosed with BRCA 1 or 2 mutations in our clinical database and described their unique cancer characteristics. Methods: After IRB approval, we performed a retrospective chart review on male patients seen at the Nancy and James Grosfeld Cancer Genetics Center from January 2004 to December 2014, who tested positive for a BRCA 1 or 2 mutation. Results: A total of 103 male patients were identified who tested positive for a BRCA1 or 2 deleterious mutation. Of these 103 patients, 32 (31%) had a diagnosis of cancer either prior to testing (12 pts) or after genetic testing was performed (20 pts). Of these 32 patients with cancer, the majority (18 pts) were found to carry a BRCA 2 mutation. Median age of cancer diagnosis was 65 years (range 35-75 years). Of the 32 patients diagnosed wit...

PURPOSE The mechanisms of antitumor activity, clinical pharmacology, toxicity, and efficacy of tamoxifen in women with early and advanced breast cancer and the drug's potential role in prevention of breast cancer were reviewed. DESIGN A comprehensive review of the literature from 1966 to 1994 was conducted; reports were identified using the Cancerline and Medline data bases. RESULTS The cellular actions of tamoxifen are not completely understood, but it appears that the drug's antiproliferative effects are mediated primarily by inhibition of the activities of estrogen through binding to estrogen receptors (ERs). Disease-free and overall survival rates have been increased in postmenopausal women with ER-positive tumors when tamoxifen has been used as adjuvant therapy (irrespective of nodal status). In premenopausal women, adjuvant therapy with tamoxifen has been associated with prolongation of disease-free survival, but its impact on survival remains to be defined. Tamoxifen is the initial hormonal treatment of choice in both premenopausal and postmenopausal women with ER-positive metastatic disease. Retrospective review of adjuvant therapy studies showed an approximately 39% reduction in the incidence of contralateral primary breast carcinoma in tamoxifen-treated women, which indicates that tamoxifen could have a role in breast cancer prevention. CONCLUSION The use of tamoxifen has resulted in a substantial modification of breast cancer's natural history, particularly in postmenopausal women. Ongoing clinical trials will examine the effects of tamoxifen therapy on lipids, coagulation proteins, bone, and endometrium, and its effectiveness as an agent in the prevention of breast cancer.

OBJECTIVES We analyzed differences in disease presentation, outcomes, and toxicities between African American (AA) and White (W) men treated with definitive radiation therapy for their prostate cancer. METHODS Three thousand one hundred eighty cases of prostate cancer treated with various radiation modalities at a single institution were reviewed. The cohort consisted of 92% W patients and 8% AA patients. Clinical and pathologic characteristics at presentation, treatment outcomes, and related toxicities were analyzed between the 2 groups. The median follow-up was 6.6 years (0.6 to 22.4 y). RESULTS At presentation, AA men were younger (P

Tumor lysis syndrome (TLS) is an oncology emergency that occurs as a result of rapid tumor cell breakdown and the consequent release of massive amounts of intracellular contents, including potassium, phosphate, and uric acid, into the systemic circulation. These metabolic disturbances lead to life-threatening conditions and may cause sudden death if not treated. TLS commonly occurs following initiation of cytotoxic treatment in patients with high-grade lymphomas or acute lymphoblastic leukemia. Spontaneous cases involving both solid and hematologic tumors have also been reported. Rarely, TLS occurs following treatment with irradiation, corticosteroids, hormonal therapy, or biologic therapy. It is necessary to identify patients at risk for TLS early in order to initiate preventive measures. In the event that preventive measures fail, the clinical parameters and signs of TLS must be understood and recognized so that treatment can begin as soon as possible, as this condition is a significant cause of morbidity and mortality.

We studied the feasibility of implementing a community-based participatory process (CBPP) that addressed cancer education, prevention, and screening in 2 ethnic minority populations by evaluating the improvement in rates of cancer screening compared with historical benchmarks.From 2003 to 2009, 2281 community members participated in CBPPs conducted by the Beaumont Cancer Institute in cooperation with the Arab American and Chaldean (AAC) Council, the National Cancer Institute, and the American Cancer Society. The study population consisted of 1067 individuals who completed a postcancer forum survey: 642 from the African American (AA) and 425 from the AAC forums. Data were collected on participants' screening history and participation in subsequent screening tests after the previous year's CBPP.Following attendance of at least one cancer forum the previous year, 329 (30.8%) of the 1067 participant respondents underwent some type of cancer screening, 32% in the AA forums and 28.9% in the AAC forums. Compared with published controls, the CBPPs led to a 38.6% increase in mammographic screening and a 28.7% increase in prostate-specific antigen screening; the AA cohort had 39.7% and 28.4% increases whereas the AAC cohort had 36.3% and 28.9% increases in mammographic and prostate-specific antigen screening, respectively.The results of this study suggest that implementing CBPPs are feasible in underscreened ethnic minority populations. Further studies need to be performed to determine the absolute benefit of CBPPs compared with baseline levels of screening within these ethnic minority populations.

Background. Hairy cell leukemia (HCL) is a chronic B-cell malignancy, typically seen in middle-aged men, characterized by pancytopenia, splenomegaly, immunologic abnormalities, and morphologically typical neoplastic mononuclear cells in the blood, bone marrow, liver, spleen, and other tissues. Diagnosis is confirmed by demonstration of hairy cells in biopsy specimens from the bone marrow or spleen or in peripheral blood. The natural history of this lymphoproliferative disorder varies. Patients may die early during the initial phase of therapy; others may require no therapy; and for some, splenectomy alone, without further treatment, may suffice for many years. Recently, the nucleosides pentostatin (2′-deoxycoformycin) (DCF) and 2′-chlorodeoxyadenosine (2-CdA) have been shown to produce greater numbers of durable complete remissions with curative potential in patients with HCL. The treatment options, with emphasis on major therapeutic advances with alpha-interferon, DCF, and 2-CdA, are reviewed in this article. Methods. Studies on HCL published from 1958 to 1992 were reviewed using the Cancerline and Medline retrieval systems and other bibliographies. Results. Management of HCL has changed in the last decade as a result of three new effective agents: alpha-interferon, DCF, and 2-CdA. DCF has produced an overall response rate of 86% and a complete remission rate of 62%. 2-CdA has yielded an overall response rate of 95% and a complete remission rate of 82%. Alpha-interferon has given an overall response rate of 82% and a complete remission rate of 8%. Other agents with limited activities include chlorambucil, cyclophosphamide, cytarabine, vincristine, doxorubicin, and zorubicin hydrochloride. The effects of lithium carbonate, immunotherapy, splenic irradiation, androgens, and leukaphoresis are minimal and transient. Conclusions. Modern management of HCL with 2-CdA and DCF is now potentially curative rather than palliative in some patients; however, the optimal therapeutic approach remains uncertain. Alpha-interferon has been approved by the Food and Drug Administration as the first-line drug therapy, followed by DCF in non-responding patients. 2-CdA remains an experimental therapy, but its higher response rate and ease of administration may make it the first-line treatment of choice. Additional research into the biology of HCL and further clinical trials are needed to determine the optimal treatment strategy for this disorder. Therefore, the best therapeutic approach at the current time is to include patients with HCL in ongoing clinical trials.Cancer 1993; 72:5–16.

Purpose To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer. Methods and Materials Patients with unresected pancreatic cancer (Zubrod performance status 0–2) were eligible for the present study. Gemcitabine was given weekly for 7 weeks (1,000 mg/m 2 ) with erlotinib daily for 8 weeks (100 mg). A final toxicity assessment was performed in Week 9. Radiotherapy (starting at 30 Gy in 2-Gy fractions, 5 d/wk) was given to the gross tumor plus a 1-cm margin starting with the first dose of gemcitabine. A standard 3 plus 3 dose escalation (an additional 4 Gy within 2 days for each dose level) was used, except for the starting dose level, which was scheduled to contain 6 patients. In general, Grade 3 or greater gastrointestinal toxicity was considered a dose-limiting toxicity, except for Grade 3 anorexia or Grade 3 fatigue alone. Results A total of 20 patients were treated (10 men and 10 women). Nausea, vomiting, and infection were significantly associated with the radiation dose ( p = .01, p = .03, and p = .03, respectively). Of the 20 patients, 5 did not complete treatment and were not evaluable for dose-escalation purposes (3 who developed progressive disease during treatment and 2 who electively discontinued it). Dose-limiting toxicity occurred in none of 6 patients at 30 Gy, 2 of 6 at 34 Gy, and 1 of 3 patients at 38 Gy. Conclusion The results of the present study have indicated that the recommended Phase II dose is 30 Gy in 15 fractions.

Monoclonal gammopathy of undetermined significance (MGUS) is defined by the presence of a serum M-protein at a concentration of 3 g/dL or less, with less than 10% plasma cells in the bone marrow, and the absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the plasma cell proliferative process. The annual risk of MGUS progressing to a symptomatic plasma cell proliferation or other related malignancy is approximately 1%. The association between malignancy and venous thromboembolism (VTE) is well recognized. In this retrospective study of MGUS patients, VTE was seen in 8% (9/112) of patients, a rate that is 22.8-fold higher than that in the general population (P is less than .001). Although many studies have identified VTE as a marker for subsequent malignancy, we did not find a significant difference in the incidence of VTE as a function of the risk factor group.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the John Cunningham (JC) virus, a DNA papovavirus. It is usually associated with conditions causing profound immunodeficiency, classically seen in patients with HIV/AIDS. Since its first description in 1958, PML has also been associated with various lymphoproliferative malignancies, including chronic lymphocytic leukemia (CLL). With the use of newer chemotherapeutic agents such as the purine analogue fludarabine and various monoclonal antibodies in the treatment of CLL, more cases of PML are being described. In this article, we describe 3 patients encountered in our clinical practice having CLL and PML infection. All three patients had received fludarabine and rituximab at some point during the course of their chemotherapy. We provide these cases with a review of the literature.

Aromatase inhibitors (AIs) are an effective treatment for postmenopausal women with hormone receptor-positive breast cancer. However, patients receiving AIs report a higher incidence of musculoskeletal symptoms and bone fractures; the mechanism and risk factors for this correlation are not well studied. The aim of this study was to correlate these musculoskeletal symptoms and bone fractures in patients receiving AIs with bone mineral density (BMD), previous tamoxifen use, and administration of calcium/bisphosphonate (Ca/Bis).We reviewed charts of 856 patients with hormone receptor-positive nonmetastatic breast cancer seen at our institution between January 1999 and October 2007. A total of 316 patients met the inclusion criteria of treatment with one of the AIs foror = 3 months and availability of a dualenergy X-ray absorptiometry (DEXA) during this treatment. Arthralgia, generalized bone pain and/or myalgia, bone fracture after beginning AIs, any tamoxifen treatment, and Ca/Bis therapy were recorded.Our study demonstrates a significant association between symptoms and DEXA-BMD results (P.001). Similarly, the group receiving tamoxifen before AIs had fewer patients with arthralgia or generalized bone pain/myalgia or bone fracture (P.001). Furthermore, the group receiving AIs plus Ca/Bis had more patients without musculoskeletal symptoms and had fewer fractures. Finally, the group receiving steroidal AIs compared with nonsteroidal AIs had more patients with arthralgia or generalized bone pain and/or myalgia, and bone fractures (P.001).Patients on AIs who develop osteoporosis are at increased risk of musculoskeletal symptoms and bone fracture. Comedication with Ca/Bis reduces the likelihood for osteoporosis and musculoskeletal symptoms. Patients who received tamoxifen before AIs were less likely to develop AI-related musculoskeletal symptoms. We recommend that patients on AIs should be offered Ca/Bis to reduce the incidence of musculoskeletal symptoms and fracture, especially if patients are receiving steroidal AI and/or did not receive tamoxifen before AIs.

Recombinant human granulocyte colony-stimulating factor (G-CSF) has been in clinical use for approximately 2 decades. In healthy donors, it has been used to mobilize peripheral blood progenitor cells for hematopoietic stem cell transplantation and granulocytes for apheresis collection. In patients, it has been used to decrease the duration of neutropenia after chemotherapy and to offset the neutropenia due to myelodysplasia, acquired immunodeficiency syndrome, and genetic disorders of granulocyte production. As the number of uses of G-CSF in clinical practice grows, more side effects of this generally safe pharmaceutical agent are being recognized. Our objective in this article is to provide an in-depth review of the reported adverse events associated with the use of G-CSF.

heterogeneous, chromosome 3 abnormalities involving non-3q26 loci (groups D and E) also conferred a worse prognosis compared with changes involving other chromosomes. Conclusion: The emergence of 3q26 rearrangements in CML is a sign of TKIs resistance and dismal prognosis. Investigational therapy should be explored to target this subtype of CML.

e14583 Background: Colorectal cancer (CRC) is a common and lethal disease. Age is a major risk factor for developing sporadic CRC. CRC is uncommon before 50 years of age, and it is often discovered...

Objective To describe the time between treatment for choroidal melanoma and first diagnosis of metastatic disease, sites of metastasis, treatments for metastasis, and time between diagnosis of metastasis and death. Design Prospective, longitudinal follow-up of patients diagnosed with choroidal melanoma who were enrolled in 2 randomized trials conducted by the Collaborative Ocular Melanoma Study Group. Methods Systemic and laboratory evaluations were performed during follow-up according to a standard protocol for 2320 patients enrolled in the Collaborative Ocular Melanoma Study trials without evidence of melanoma metastasis or other primary cancer at baseline. Results Seven hundred thirty-nine patients were diagnosed with at least 1 site of metastasis during follow-up after treatment for choroidal melanoma. Five- and 10-year cumulative metastasis rates were 25% (95% confidence interval, 23%-27%) and 34% (95% confidence interval, 32%-37%), respectively. Liver was the most common site (89%). The death rate following the report of melanoma metastasis was 80% at 1 year (95% confidence interval, 77%-83%) and 92% at 2 years (95% confidence interval, 89%-94%). Overall survival after metastasis did not vary by baseline size of primary tumor nor treatment for metastasis (when known). Long-term survival after diagnosis of metastasis was uncommon; only 8 patients survived 5 or more years. Conclusion Metastasis rate increased significantly with increasing primary tumor dimensions at time of patient enrollment. Prognosis after metastatic disease remains poor. Effective methods are needed to prevent, diagnose, and treat metastasis from choroidal melanoma.

A 76-year-old man presented with leukostasis syndrome, including oculodynia, blurred vision, and visual field defects, due to mantle cell lymphoma, prolymphocytoid variant, with marked leukocytosis, 1227 x 10(9)/l. He had splenomegaly but no lymphadenopathy or hepatomegaly. The tumor cells were CD5+, CD19+, CD20+, FMC-7+, and kappa light chain restricted. Immunohistochemistry showed expression of p53 and of cyclin D1. Fluorescent in situ hybridization demonstrated t(11;14) with translocation between CYCLIN D1 and the immunoglobulin heavy-chain genes. The patient received leukapheresis and aggressive chemotherapy, but the leukocyte count remained above 100 x 10(9)/l. The patient's condition rapidly deteriorated with lymphomatous infiltration of his lungs and soft tissues, and he expired 6 months after diagnosis. While it is known that mantle cell lymphoma may have a leukemic phase, the degree of leukocytosis in this case exceeds that previously reported in the literature and resulted in a clinical syndrome of leukostasis.

Background: CD20 antigen, expressed on greater than 90% of B-cell lymphomas, is an established target for antibody therapy with monoclonal antibodies like Rituximab, which can selectively deplete CD20-expressing cells in peripheral blood and lymphoid tissues. Understanding properties and interactions of CD20 antigens is quintessential for developing better targeted agents and overcoming resistance. It has not been clearly established yet whether CD20 antigen density corresponds with response to Rituximab. Flow cytometry is still the most widely used technique to detect CD20 level in human serum which is expensive, time consuming and does not reveal any details of interaction between the molecules. We have developed a new innovative biosensor based novel technique to study real time interaction of CD20 antigens with Rituximab using QCM Piezo-immunosensor. This quantitative label free peptide based assay can be used to characterize cell surface antigen, to study antigen- antibody interactions and obtain understanding of mechanisms of resistance to therapy. Method: The immobilization of Raji cells on the QCM gold electrode surface using RGD tripeptide was electrochemically confirmed (Figure 1). The real-time processes of attachment of Raji cells on the gold electrode and the subsequent binding of Rituximab to the cells were studied using QCM biosensor. The interaction between Rituximab and Raji cells led to the increased resonant frequency shifts (df0) in the studied antibody concentration range from 5 to 250 μg mL-1 following the Langmuir adsorption model (Figure 2). From these observations, the apparent binding constant between a single-layer of Rituximab and Raji cells was calculated to be 1.6×106 M-1 (Figure 3). Control experiments using other therapeutic antibodies (i.e., Trastuzumab and Bevacizumab) and different cells (i.e., T cells and endothelial cells) proved very specific interaction between Rituximab and CD20 antigens on B cells. Calcium and Manganese ions were added to the cell culture and corresponding responses by QCM were monitored. Results: CD20 binding with Rituximab was very specific. This binding decreased the electrochemical activity and stability of the cells, supporting the cell lysis mechanisms of action of Rituximab. We have shown a systematic approach for using QCM technique to quantify the apparent binding constant between Raji cells and Rituximab which can reveal CD20 antigen density. Moreover, increased QCM responses were found in the presence of Ca2+ ions and high concentration Mn2+ ions, supporting the function of CD20 as a calcium ion channel. Microscopic inspection proved that increased Ca2+ ions could promote the Rituximab binding and cell lysis induced by Rituximab, which was not seen with Manganese. Conclusion: CD20 antigen density and interactions of CD20 antigens with respective monoclonal antibodies will help physicians to determine the clinical efficacy and resistance mechanisms to targeted antibodies like Rituximab and Ofatumumab. For the first time, we have established a low cost, highly sensitive, fast, synthetic, QCM assay which could be used as a basis for developing a new generation of affinity-based Immunosensor assays. This real time capability of QCM and its simplicity of operation are highly suitable for multipurpose studies on living cells including cell immobilization, cytotoxicity of drugs, and the cell action mechanisms. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

Introduction Chronic Myeloid Leukemia (CML) represents 3% of pediatric leukemias. The natural history and molecular biology of pediatric CML is the same as those of older patients with CML. 95% of pediatric CML presents in asymptomatic chronic phase and the rest diagnosed in accelerated or in blast crisis stage. It is reported that patients with pediatric CML have higher white blood cell (WBC) counts and thereby have higher incidence of symptomatic leukostasis compared to adults. Sparse literature exists on particular triggers for treatment with leukapheresis (LA). We present a case of asymptomatic hyperleukocytosis (HL) secondary to pediatric CML and a brief discussion of treatment in this emergency. Objective To report a rare case of asymptomatic pediatric CML with HL. Case Summary A 9-year-old Caucasian male presented to his pediatrician on the outpatient basis for well child care and was found to have a WBC of > 200,000 and then was admitted to the Pediatric Intensive Care Unit for further management. Upon arrival in the PICU, pt was found to have splenomegaly (down 4-5 cm from the costal margin) and hepatomegaly (2 cm down from costal margin). CBC revealed hemoglobin of 7.4 g/dL, platelet of 883 bil/L and a total white blood cell count (WBC) of 302.7 bil/L. A differential on the WBC revealed 43.9 basophils, 24.2 blasts, and 6.1 promyelocytes. Flow cytometry showed prominent myeloid population with 5% CD34 positive myeloblasts and a prominent basophil population, consistent with morphological expression of CML. The cytogenetic analysis revealed a t(9,22)(q34;q11) translocation consistent with a Philadelphia chromosome. Pediatric Leukaphresis (LA) for cytoreduction was not available at our facility, thus he was transferred. Discussion The HL in this patient is a direct result of his pediatric CML. The decision regarding need for cytoreduction with LA has been described in the literature for symptomatic children, but no case has been reported of when to perform LA when no symptoms of leukostasis are present. Conclusions In this case, it was discovered that the trigger(s) to perform LA is vague in the literature, as well as controversial in practice especially with well appearing children with the potential for a swift precarious demise. Further studies and meta-analyses to uncover the proper triggers for LA are warranted. Disclosures: No relevant conflicts of interest to declare.

e18007 Background: Imatinib mesylate is first-line therapy for chronic myeloid leukemia (CML) since its introduction in May, 2001. Once deadly, CML is now a chronic disorder due to this medication.We sought to analyze the impact on survival in our patient population at Beaumont Health System, a tertiary care facility, versus all hospitals in the United States. Methods: Patients with CML were identified and categorized as pre- or post-2001 when first seen. Analysis of survival in intervals of 12 months in the two groups was done with the Elekta’s National Oncology Data Alliance Database (NODA): 1990-2000 and 2001-2010. Overall 5-year survival results are reported. Results: Analysis of survival was performed on pre- and post-2001 populations in Beaumont patients versus their national counterparts. In the pre-2001 population, 580 patients nationwide and 34 patients from Beaumont were analyzed for a total of 614 patients. In the post-2001 population 1,602 patients nationwide and 122 patients from the Beaumont were analyzed for a total of 1,724 patients. The pre-2001 group nationally showed a survival probability of 28% ± 1.8%, patients in the Beaumont group showed a survival probability of 26% ± 8%. Patients in the post-2001 nationwide group showed a survival probability of 56% ±1.4%, the Beaumont group showed a survival probability of 48% ±5.0%. Both groups showed a significant survival advantage after 2001 in the era of imatinib as first-line therapy for CML. Patients in the national analysis showed a survival advantage of 28% and patients in the Beaumont analysis showed a survival advantage of 22%. Conclusions: This analysis provides evidence for a survival advantage in the post-2001 era of imatinib mesylate therapy a first-line therapy for CML on both a national and our institution level. Differences in numbers of patients analyzed, drug availability, and implementation of molecular monitoring could account for variability of the results. This data supports the revolutionary nature of this medication in the treatment of CML in the United States since 2001.

1541 Background: Worldwide ethnic variations in the distribution of BRCA1 and BRCA2 mutations of breast cancer patients have been recently recognized. This has led to investigations of the epidemiology, genetics and clinical characteristics of BRCA positive individuals within specific populations. This study aims to describe the findings of BRCA genetic testing in a cohort of Arab American women. Methods: A total of 73 women of Arab ancestry were evaluated in the Beaumont Cancer Genetics Program from Jan 2008 to Jan 2013. Criteria for genetic testing included a personal or family history suggestive of Hereditary Breast and Ovarian Cancer Syndrome (HBOC). Patients underwent comprehensive genetic counseling, followed by full sequence analysis for germline mutations in BRCA1 and BRCA2. Results: 63 women of Arab ancestry underwent genetic testing for BRCA1 and BRCA2. 13 (21%) patients were found to be mutation carriers, of whom 10 (16%) of the 63 had deleterious mutations (7 in BRCA2, and 3 in BRCA1), and 3 (5%) had variants of undetermined significance (VUS) in BRCA2. Of the 10 patients with deleterious mutations, 4 (40%) unrelated individuals had the same mutation, 5804del4, in exon 11 of BRCA2. The remaining patients had deleterious mutations in exon 2, exon 20, and exon 13 of BRCA2; one patient had a BRCA1 and BRCA2 mutation (exon 18). 7 of 10 patients with deleterious mutations had a cancer diagnosis, of which 5 had breast cancer, 1 had ovarian cancer, 1 had pancreatic cancer, and 3 were unaffected. Conclusions: This study demonstrates that BRCA mutations (predominantly in BRCA2) were seen in a significant proportion of Arab American women undergoing genetic testing for HBOC. A mutation in BRCA2, 5804del4, was seen in nearly half (4/10) of the carriers of deleterious mutations. This mutation, in exon 11, has not previously been associated with Arab ethnicity and may represent a founder mutation. Knowledge of the genetic spectrum, frequency, and clinical characteristics of BRCA mutation carriers will lead to greater understanding of hereditary cancer in Arab American women.

Abstract 4319 Background: CBs are highly variable at diagnosis and during the course of IT in AML patients. Assessing response to IT carries a huge implication on the prognosis of individual patient with AML. Our study investigates whether late clearance of CBs during IT using standard cytarabine + anthracycline regimen is associated with refractory phenotype. Methods: We retrospectively reviewed the chart of 83 AML patients (43 males, 40 females, mean age 61.7) who received standard cytarabine and anthracycline regimen during induction between January, 2000-January, 2011 at William Beaumont Health System. Data collected include complete blood count with blast count during course of induction, and bone marrow response. AML is considered refractory if morphological evaluation, flow cytometry or cytogenetic study was positive in the first bone marrow post induction. Response to IT was assessed according to Cancer and Leukemia Group B (CALGB) criteria as complete remission versus residual leukemia or treatment failure (failing to achieve complete remission). Results: We noted that 57 of 83 patients (68.7%) showed CBs at the time of diagnosis. During the IT, CBs clearance occurred within 7 days (early clearance) in 38 of these 57 patients. The remaining 19 patients had CBs persistent more than 7 days (delayed clearance). The frequency of bone marrow residual disease at count recovery post IT was significant higher in patients with late clearance and those with early clearance (84% vs 42%, p=0.0015). Further analysis of data showed the frequency of bone marrow residual disease was not significantly different between patients with no CBs at the diagnosis and those with early clearance of CBs (38% vs 42%, p=0.8). Conclusion: Adult AML patients with persistent CBs >7 days during IT with standard induction cytarabine and anthracycline regimen are more likely to have induction failure. CBs clearance can be used as an early assessment of response to the IT. Disclosures: No relevant conflicts of interest to declare.

628 Background: Varied clinico-pathological response to monoclonal antibodies like T has been reported either due to presence of antibodies, rapid clearance or low density of target receptor/antigens. This demands need for an assay to monitor serum T therapeutic levels to ensure appropriate dosage. Enzyme-linked immunosorbent assay (ELISA) is still the most widely used technique to detect T level in human serum which is expensive and time consuming. For the first time, we established a platform to detect T level by using a small (

e14608 Background: Beyond curative surgery, the optimal treatment for early stage pancreatic cancer is still a matter of debate. We conducted a comparative survival analysis between patients with resectable pancreatic cancer who received adjuvant treatment with either gemcitabine or 5-fluorouracil based chemotherapy and chemoradiation regimens. Methods: The Surveillance, Epidemiology and End Results (SEER)-Medicare database was used to identify patients with pancreatic cancer diagnosed from 1998 to 2005 who received curative surgery and adjuvant chemotherapy with either 5-fluorouracil or gemcitabine. These groups were subdivided by treatment with radiotherapy. Patients were followed until death, study endpoint or a maximum of five years after diagnosis. Results: 359 patients received 5-fluorouracil and 346 received gemcitabine. Compared to chemoradiation with 5-fluorouracil, outcomes for patients who received chemoradiation with gemcitabine did not differ. Patients who received gemcitabine without radiation had increased hazards (hazard ratio (HR) = 1.50 for high grade tumors (HGT), HR = 1.32 for low grade tumors (LGT)). However, outcomes of patients who received 5-fluorouracil without radiation varied with tumor grade. In LGT, patients had better outcomes with 5-fluorouracil when compared with chemoradiation with 5-fluorouracil (HR = 0.43). In HGT, the opposite was true (HR 2.10). Conclusions: Patients with low grade resectable pancreatic cancer may have better outcomes with 5-fluorouracil based chemotherapy without radiation when compared to 5-fluorouracil with radiation.

Abstract 3148 Background: VTEs are common complications in association with IT which may cause additional morbidity and mortality in AML patients. However, treating patients with AML is challenging because of the cytopenias due to chemotherapy and the high risk for bleeding during IT. This study investigates frequency, risk factors, and safety of using anticoagulation (AC) therapy for VTEs during IT. Method: We retrospectively reviewed the charts of AML patients who received IT between January, 2000-January, 2011 at William Beaumont Health Systems. Exclusion criteria included a documented personal history of inherited thrombophilia. Data retrieved included the following: patient characteristics, leukemia subtype, cytogenetic risk, location of the VTEs, FLT3 mutations, IT regimen used (cytarabine and anthracycline regimens or hypomethylating agents), AC therapy, bleeding complications, mortality related to AC therapy. All patients who received AC were initially treated with regular intravenous unfractionated heparin or subcutaneous low molecular weight heparin. Patients were subsequently started on oral warfarin during the first 10 days of the initial treatment with a targeted INR of 2.0–3.0. Results: We found 48 of 363 (13.2%) AML patients developed VTEs during IT. Of those patients, 56.3 % were female. The VTEs occurred most frequently in upper extremities (58%) and were catheter-related. Other locations for VTEs included lower extremities (21%), pulmonary embolism (15%), and mesenteric or portal veins (6%). We note that 41 patients (87%) received AC therapy. Of these, three patients (7.3%) had bleeding complications and no AC therapy-related deaths were observed. When the three cytogenetic risk groups were compared, there was no difference in the incidence of VTEs (good vs intermediate vs poor). Patients with FLT 3 mutations, however, had a significant higher incidence of VTEs when compared to patients without FLT3 mutations (55.3% vs 12% p Conclusions: We found that 13% of AML patients developed VTEs during IT, most commonly in upper extremities and were catheter-related. The risk for VTEs was markedly increased in patients with FLT3 mutations. Furthermore, using a cytarabine + anthracycline regimens carried a higher risk for VTEs when compared to regimens using a hypomethylating agents. Finally, using AC therapy during IT is relatively safe and is associated with low risk of bleeding complications. Disclosures: No relevant conflicts of interest to declare.

Abstract 2087 Background: During IT, AML patients may develop PI due to infection, leukostasis, pneumonitis, drug reaction or even acute respiratory distress syndrome. The risk association and the clinical outcome of such PI are poorly characterized in the literature. This study investigates the frequency, radiologic patterns, and outcome of PI during the IT of AML patients. Methods: We retrospectively reviewed 363 cases of AML patients who received IT either cytarabine and anthracycline regimens, or hypomethylating agents between January, 2000-January, 2011 at William Beaumont Health System. Of 363 patients, 120 developed PI during IT, those patients were divided into 2 groups based on distribution of the infiltrate presenting whether localized or diffuse infiltrate. Distribution of the infiltrate was evaluated by dividing the thorax vertically in the midline, then horizontally by two lines originating above and below the hilus resulting in six areas. Localized infiltrate was defined as involvement of 1–3 areas, and diffuse infiltrate was defined as >3 areas were involved. Detected by either Bronchioalveolar lavage culture or sputum culture revealing a pathogen other than coagulase-negative staphylococci or corynebacteria was considered as pathogenic microorganisms. Treatment end points were defined as resolve or persistence of the infiltrate or death. Data on pts characteristics, leukemia subtype, cytogenetic risk, microorganism type, white blood cell count (WBC) at diagnosis, neutrophils count at the time of the infiltrate reported, response to antibiotic and/or antifungal therapy, using respiratory support, mortality rate, were retrieved from the records. Results: Our study involved 120 patients. Of these, 33% developed PI during their IT. This population was 53.3 % female, median age 66 years (range 23–93). We noted that 63 patients (52.5%) had localized infiltrate and 57 patients (47.5%) had diffuse infiltrate. Of the 120 patients, 46 (39.3%) had pathogenic microorganisms. These microorganisms were found to be 50% gram positive, 32% gram negative, 10.8% fungal, and 4.3% anaerobic. All 120 patients received two broad-spectrum antibiotics and/or an antifungal. Of the total number of patients, 58 (48.7%) required intubation and ventilatory support. The repeat computed tomography at the end of the hospital stay (after the treatment) showed resolution of the infiltrate in 67 patients (55.8%). During our study, 46 patients died from PI (38.3 %). Further analysis of the data showed patients with localized PI (when compared to patients with diffuse infiltrate) were more likely to have positive pathogenic microorganisms (68.3% vs 8.8%, p Patients with diffuse infiltrate (when compared to patients with localized infiltrate) were more like to require intubation (78.9% vs 21%, p 100 Bil/L) at diagnosis (54.4% vs 0%, p Conclusions: During IT about one third of the AML patients developed PI. The radiological patterns of PI showed specific etiological and prognostic associations, may guide the clinical decision making processes. Diffuse PI is an unfavorable characteristic with overall dismal outcome. Disclosures: No relevant conflicts of interest to declare.

Abstract 3837 Introduction: Flow cytometry (FC) is more sensitive but more expensive than cytomorphology in detection central nervous system (CNS) involvement by hematological malignancy. Previous studies have shown that cerebral spinal fluid (CSF) pleocytosis is absent in about one third of patients with positive FC findings. FC is often performed to investigate CNS involvement on all CSF specimens regardless of cell counts or morphology, which may lead over utilization of FC. Here we investigate the diagnostic value of FC evaluation of CSF specimens with low white blood cell (WBC) count. Methods: After IRB approval, we retrospectively reviewed the FC results of CSF samples studied for CNS involvement by hematological malignancy between Jul 2000 and Jun 2010 at William Beaumont Hospital, MI. The FC results were correlated with CSF WBC count, cytomorphology, and documented leptomeningeal symptoms at the time of the sample obtained. Results: Of 421 cases included in this study, 73 were acute leukemia and 348 were lymphoma. The mean age was 59 (range from 9–90). 9.5% (40/421) of patients had leptomeningeal symptoms. 13.3% (56/421) had atypical CSF WBC cytomorphology. 11% (46/421) had positive FC. Patients with either atypical cytomorphology or leptomengeal symptoms were more likely have positive FC (p Conclusion: In this study, we found that FC is more sensitive and specific than leptomeningeal symptoms or cytomorphology in detection of CNS involvement by hematological malignancy in both acute leukemia and lymphoma. However, its sensitivity is dependent on numbers of cells potentially available for analysis. Flow cytometry may not be indicated when CSF WBC count is extremely low ( Disclosures: No relevant conflicts of interest to declare.

Introduction Cancer-associated retinopathy (CAR) syndrome is rare paraneoplastic visual syndrome, usually associated with small-cell lung carcinoma. We report, to our knowledge, the first case in the English-language literature of CAR syndrome occurring in a patient with non-Hodgkin lymphoma (NHL) treated with intravenous immunoglobulin (IVIG). Case Report A 62-year-old male was diagnosed with stage IV B-cell follicular NHL treated with 6 cycles of R-CHOP (rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone). Five weeks after the last cycle, he presented with progressive decrease of vision in both eyes, flickering lights, and night blindness. On examination, corrected visual acuity was 20/80 and 20/100 in the right and left eye, respectively, and color vision was diminished bilaterally. Fundus examination revealed pallor of the optic disks while visual field examination showed profound field constriction. A multifocal electroretinogram revealed dysfunction of both rods and cones characteristic of diffuse photoreceptor degeneration that is supporting the diagnosis of CAR syndrome. Magnetic resonance imaging of the head and orbits showed no signs of metastases or other abnormalities. Western blot analysis of the patient's serum showed a positive antibody reaction with 23-kD component coinciding with the molecular mass of human recoverin. The patient was started on oral prednisone 60 mg daily. Three weeks later he still complained of decreased vision in both eyes. IVIG (400 mg/kg/day) was given for 4 doses. Following the second dose, the patient showed signs of improvement. Four weeks after finishing the full treatment, visual acuity improved to 20/40 in both the right and left eye, with no relapse during the 8-month follow-up period. Discussion To our knowledge, there has been only 1 previous report (in the French-language literature) of CAR syndrome in lymphoma patients. Matus et al described 2 NHL patients with symptoms of CAR, which was confirmed by the presence of anti-recoverin antibodies. Both cases were treated by corticosteroids with only minimal response. Since CAR syndrome is a rare condition, no specific treatment has been shown to be effective. Treating the underlining malignancy has not been shown to result in better visual outcomes, and immunosuppression with oral or intravenous corticosteroid exhibits only a transient or undetectable response. Furthermore, plasmapheresis has not been effective. Conclusion CAR may occur in NHL. IVIG may be an effective option for treating these patients, especially if started early enough before permanent retinal damage occurs.

e11031 Background: Docetaxel, doxorubucin, and cyclophosphamide (TAC) given in combination has been shown to be an effective treatment for breast cancer. Elevation of alkaline phosphatase with the ...

e19579 Background: Central venous port (CVP) failure is a common problem in cancer patients (pts) during chemotherapy. Risk factors include increasing age, male gender, and hematogenous malignancy....

e12024 Background: The hereditary breast-ovarian cancer syndrome accounts for an estimated 10%-15% of breast cancer diagnosed in the United States each year. BRCA1 and 2 genes account for the majority of inherited breast and ovarian cancers. Identification of BRCA1 and 2 mutation carriers is an important focus in the prevention and early detection of breast and ovarian cancer. This study describes the clinical characteristics of patients with BRCA1 and BRCA2 mutation at a community-based hospital. Methods: A retrospective review was conducted of all women with BRCA1/2 mutation that were managed at the cancer genetics clinic at our institution from 2005-2008. Results: 145 patients were evaluated. 100 patients (69%) had a BRCA1, 45 (31%) had BRCA2. 84 patients had breast cancer. The majority of patients (90%) had a diagnosis of infiltrating ductal carcinoma, 7.1% had infiltrating lobular carcinoma. 63.6% had ductal carcinoma-in-situ and only 3% had lobular carcinoma in situ. 45.2% were ER positive, 30% were...

Background Taxotere, a semisynthetic compound structurally related to taxol, has a broad spectrum of activity in murine transplantable tumors; in the B16 melanoma model, it caused a total log cell kill 2.5 times greater than that caused by taxol at equitoxic doses. Purpose We conducted a phase I study of Taxotere (a) to determine its qualitative and quantitative toxic effects and a starting dose for phase II trials, (b) to investigate its clinical pharmacology, and (c) to document its antitumor activity. Methods Taxotere was given as a 1-hour infusion at a starting dose of 1 mg/m2 per day for 5 consecutive days. The 5-day course of therapy was repeated every 21 days. Thirty-nine cancer patients with advanced disease were entered in the study; at least three patients were entered at each dose level. Initial dose escalations were planned at 100% increments until biologic activity was observed; subsequent escalations were planned at 50% increments until grade 2 toxicity (the National Cancer Institute's Common Toxicity Criteria) occurred and then at 25% increments until the maximum tolerated dose was established. Results Thirty-nine patients were entered in the study. Successive dose levels used were 1, 4, 8, 16, 12, and 14 mg/m2 per day. The dose-limiting toxic effects were granulocytopenia and concurrent mucositis. Grade 4 granulocytopenia associated with grade 3 mucositis developed in six of 12 patients treated at a dose of 16 mg/m2 per day, two of 10 treated at 12 mg/m2 per day, and two of eight treated at 14 mg/m2 per day. Because these toxic effects occurred concurrently, all patients so affected developed neutropenic fevers and required hospitalization. Neither cardiac nor neurologic toxic effects were noted. Anti-tumor activity was observed in six patients with ovarian cancer and in one with breast carcinoma. Although pharmacokinetic parameters were consistent between day 1 and day 5 for individual patients, considerable variation existed among those treated at the same dose level. A relationship was observed between the area under the curve for plasma concentration of drug x time (AUC) on day 1 and the percentage decrease in absolute granulocyte counts. Conclusion Granulocytopenia associated with oral mucositis is the dose-limiting toxicity of this schedule. We recommended a starting dose of 14 mg/m2 per day for phase II studies of this 5-day schedule. Dose modifications on days 2-5 based on the day-1 AUC may allow individualized dosing.

The natural history and current management of carcinoma of the breast in men is reviewed. Articles published from 1942 to 1992 on the natural history, clinical manifestations, diagnosis, and treatment of carcinoma of the breast in men were identified using CANCERLINE and MEDLINE. Carcinoma of the breast affects approximately 1000 men per year in the United States; 300 men per year will die of metastatic disease. The mean age at diagnosis is 59 years. The causes of breast cancer in men are unknown. The most common clinical manifestation of breast cancer in men is a painless, firm subareolar mass or a mass in the upper outer quadrant of the breast. Diagnosis can be confirmed by fine-needle aspiration or surgical biopsy. Infiltrating ductal carcinoma is the predominant histologic type. Treatment is similar to that of women with breast cancer. Men with axillary nodal metastasis should receive adjuvant systemic combination chemotherapy or tamoxifen, or both, after primary surgical treatment. Because most men with carcinoma of the breast have estrogen- and progesterone-receptor-positive tumors, distant metastatic disease should be treated initially with hormonal therapies. The epidemiology, prognostic factors, survival by stage, pattern of metastasis, and response to treatment in men are similar to those in women with breast carcinoma. The data suggest, however, that breast cancers in men are more likely to respond to hormonal manipulation.