First Site Of Metastasis Research Articles

Localization of the Sentinel Lymph Node in Melanoma Without Blue Dye.

The purpose of this study was to assess regional recurrence rates of patients who underwent sentinel lymph node biopsy (SLNB) using radiocolloid guidance alone. Isosulfan blue dye is commonly used along with Tc99-labeled radiocolloid localization in SLNB for melanoma. Blue dye has, however, been associated with allergic reactions, long-term staining of skin, and increased cost. We hypothesized that the rate of regional recurrence when SLNB is performed with radiocolloid alone would be comparable to established reports using both radiocolloid and blue dye. A prospectively collected database was retrospectively queried for patients who underwent SLNB for melanoma during the years 2005 through 2008. Data collected included patient demographics, primary lesion characteristics, operative details, and recurrence. The primary outcome was the rate of recurrence within the biopsied basin after negative SLNB's performed without isosulfan blue dye. In 215 patients, 279 nodal basins were identified. All patients underwent successful radiocolloid localization, and positive sentinel nodes were found in 40 patients (18.6%). Six of 175 patients with a negative SLNB developed a regional node recurrence as the first site of metastasis (3.4%). Among all 215 patients, 44 experienced recurrence of any kind (20.5%). Higher mitotic rate and Breslow depth were significantly associated with likelihood of recurrence. Success rates, node positivity rates, and rates of regional recurrence after SLNB for melanoma using radiocolloid alone are acceptable and similar to those of prior reports using blue dye plus radiocolloid.

Estrogen Receptor Status Predicts Late-Onset Skeletal Recurrence in Breast Cancer Patients.

Estrogen receptor-positive (ER+) breast cancer (BCa) often recurs after long latency, and is known to favor bone as a metastatic site. We hypothesized that skeletal recurrence of ER+ BCa follows a different chronological pattern from that of nonskeletal recurrence.We retrospectively evaluated 434 matched pairs of ER+ and ER− female patients who underwent surgery for clinically localized BCa between 2005 and 2009. Patient age, tumor size, lymph node involvement, and adjuvant treatment biases were adjusted by the propensity score method. We conducted competing risk analysis to determine the prognostic significance of ER expression status on the risk of overall recurrence and late recurrence (after 3 years). We also compared chronological patterns of ER+ and ER− tumor recurrence, stratified by the first metastatic site (skeletal vs nonskeletal).After 3 postoperative years, ER+ tumor had a significantly higher risk of overall distant recurrence than ER− tumor (P = 0.02). When further stratified by first site of metastasis, only late skeletal recurrence was significantly associated with ER status (P = 0.029). In multivariate analysis, ER and lymph node involvement status were significant prognostic factors for late skeletal recurrence, with adjusted hazard ratios of 5.2 (95% CI = 1.2–22.4, P = 0.025) and 5.2 (1.7–16.3, P = 0.005), respectively. For nonskeletal distant recurrence, tumor size (>2 cm) was the only significant risk factor with adjusted hazard ratio of 2.8 (1.4–5.7, P = 0.005). Annual hazard of skeletal recurrence events of ER+ tumors continued to exist up to 10 years, while annual hazard of nonskeletal recurrences decreased after peaking at 5 years. ER− tumor recurrences exhibited similar annual hazard patterns across skeletal and nonskeletal sites.ER expression and lymph node involvement status were strong predictors of BCa late-onset (>3 years) recurrences, especially in skeletal sites. Therefore, skeletal system surveillance is mandatory for long-term follow-up of this subpopulation.

Multidetector computed tomography features of pancreatic metastases from leiomyosarcoma: Experience at a tertiary cancer center.

To describe the multidetector computed tomography features of pancreatic metastasis from leiomyosarcoma (LMS). Between January 1995 and December 2012, 13 consecutive patients (11 women, 2 men; mean age of 57 years; range, 38-78 years) with pancreatic metastases from LMS were included in our study. Imaging features including location, number, largest dimension, tumor attenuation and enhancement characteristics, presence of necrosis, pancreatic ductal dilatation, common bile duct (CBD) dilatation, presence of pancreatitis, and atrophy were documented. The most common site of origin of the pancreatic metastases from LMS was uterus (38.5%), followed by retroperitoneum (30.8%) and extremity (23.1%). None of the patients in our study had pancreas as the first site of metastasis. All patients developed pancreatic metastases at a median interval of 24 mo. Pancreatic metastases from LMS were solitary in 8/13 patients and multiple in 5/13 patients, had no predilection for any part of the pancreas, were hypovascular on arterial phase in 10/13 patients and associated with pancreatic duct dilatation in 3/13 patients. None had CBD dilatation. None of the pancreatic metastases in LMS cohort caused pancreatitis, and atrophy. Median duration of follow-up was 19 mo for LMS cohort during which two patients underwent resection of metastasis (median survival 45 mo) while the remaining underwent systemic therapy (median survival 13 mo). Pancreatic metastases from LMS are often solitary and hypovascular masses and less commonly associated with pancreatic ductal dilatation, CBD dilatation, pancreatitis or pancreatic atrophy. Surgical resection of solitary LMS pancreatic metastasis can be considered due to the long survival of these patients.

Super natural killer cells that target metastases in the tumor draining lymph nodes

Tumor draining lymph nodes are the first site of metastasis in most types of cancer. The extent of metastasis in the lymph nodes is often used in staging cancer progression. We previously showed that nanoscale TRAIL liposomes conjugated to human natural killer cells enhance their endogenous therapeutic potential in killing cancer cells cultured in engineered lymph node microenvironments. In this work, it is shown that liposomes decorated with apoptosis-inducing ligand TRAIL and an antibody against a mouse natural killer cell marker are carried to the tumor draining inguinal lymph nodes and prevent the lymphatic spread of a subcutaneous tumor in mice. It is shown that targeting natural killer cells with TRAIL liposomes enhances their retention time within the tumor draining lymph nodes to induce apoptosis in cancer cells. It is concluded that this approach can be used to kill cancer cells within the tumor draining lymph nodes to prevent the lymphatic spread of cancer.

Disease-Free Survival (Dfs) in the Lapatinib Alone Arm and Expanded Results of the Phase III Altto Trial (Big 2-06; Ncctg (Alliance) N063D) in the Adjuvant Treatment of Her2-Positive Early Breast Cancer (Ebc)

ABSTRACT Aim: The Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) Trial is a randomised phase III adjuvant breast cancer trial comparing 3 oral lapatinib (L)-containing regimens with trastuzumab (T), each given for 1 year. DFS results of L + T and T—> L compared to T, presented at ASCO 2014, showed a non-significant DFS benefit. Results of L vs T and key secondary analyses are presented for the first time. Methods: 8381 patients (pts) were randomised to receive either T (N = 2097), L (N = 2100), T —> L (N = 2091), or L + T (N = 2093) from 2007-2011. Primary comparison of L vs T evaluated non-inferiority at a margin of 1.11 and the futility boundary for this arm was crossed resulting in premature arm closure (Aug 2011). Pts in the L arm who were free of disease recurrence at that time were offered T as adjuvant treatment. Key secondary analyses including DFS by hormone receptor status and CNS endpoints are now presented. Results: In 4197 pts and at a median follow-up of 4.5 years, 366 (17%) DFS events in the L and 301 (14%) DFS events in the T arms were observed. 1090 (52%) pts in the L arm received at least one T dose. In post-hoc analysis, there was evidence that these pts benefitted from receiving T [hazard ratio (HR) = 0.67; 95% CI 0.49-0.91 from a time-dependent Cox model of DFS]. The non-inferiority HR was 1.34 (95% CI 1.15-1.56) in the ITT population; 1.45 for hormone receptor negative, 1.23 for hormone receptor positive. CNS as first site of metastases occurred in 2% of cases in all arms. AEs of any grade were more common with L than T: diarrhoea (64% vs 20%), rash or erythema (54% vs 20%) and hepatobiliary (25% vs 16%). Any cardiac events were infrequent in both arms, but more common in T compared to L (4.5% vs 1.9%; p Conclusions: Overall, L added to T did not statistically improve DFS. L did not appear to decrease the rate of CNS as first site of metastases. T confers a better outcome compared to L in pts with HER2-positive EBC and remains the standard of care. There is evidence of T benefit even when initiated later in the course of follow-up. Disclosure: E. De Azambuja: Disclosed an advisory role with GSK; honoraria from Roche; research funding from GSK; and travel grants from GSK/Roche; G. Viale: disclosed an advisory role with Roche and Dako; and honoraria from GSK, Roche, and Dako; R. Crescenzo: disclosed compensated employment with GlaxoSmithKline; and stock ownership with Glaxo SmithKline; K. Pritchard: disclosed an advisory role with Roche; honoraria from Roche; research funding from Roche; and expert testimony on behalf of Roche; C. Jackisch: disclosed honoraria from Roche and GSK; F. Boyle: disclosed honoraria from GlaxoSmithKline; and research funding from GlaxoSmithKline; R.D. Gelber: disclosed research funding from GSK and Roche; M. Piccart: disclosed consultancy with PharmaMar; honoraria from Amgen, Astellas, AstraZeneca, Bayer, Eli Lilly, Invivis, MSD, Novartis, Pfizer, Roche-Genentech, Sanofi Aventis, Symphogen, Synthon, and Verastem; research grants from most companies. All other authors have declared no conflicts of interest.

SAPHO Syndrome in a Patient with Breast Cancer Mimicking Bone Metastasis: A Case Report

Bone is the most common site to which breast cancer metastasizes (1). Bone represents the first site of metastasis for 26~50% of patients with metastatic breast cancer (2, 3). If hot uptake in a patient with breast cancer is noted on the bone scintigraphy, the possibility of bone metastasis should be considered. However, because metastatic arthritis rarely occurs and the costosternoclavicular region is not common site for metastasis, other possibility should be considered such as SAPHO syndrome; it is an acronym of syndrome of synovitis, acne, pustulosis, hyperostosis, and osteitis (4) and its diagnosis can be made on the base of the solely musculoskeletal system without even skin lesions. And the costosternoclavicular region is known to be typical site of it (4). So, if the sclerotic and hyperostotic bone change of costosternoclavicular region was incidentally found in early breast cancer patient, try to include the SAPHO syndrome as a possible differential diagnosis. Here, we present a patient with right breast cancer and incidentally found sclerotic and hyperostotic bony lesion of her left costosternoclavicular region, which was confirmed as chronic active inflammation without causative organism. INTRODUCTION

Analysis of Differential miRNA Expression in Primary Tumor and Stroma of Colorectal Cancer Patients

Microarray technology was used to profile miRNA expression in primary tumor and stromal tissue from paraffin embedded material of 51 patients with colorectal cancer. 26 miRNAs resulted differentially expressed with at least 2-fold change in tumor tissue with respect to stroma (16 more expressed in the tumor and 10 more expressed in the stroma). 10/26 were confirmed as differentially expressed at qRTPCR: miR-200c-3p, miR-141-3p, miR-200b-3p, miR-200a-3p, miR-1246, miR-92a-3p, miR-194-5p, miR-192-5p, miR-3651-5p, and miR-574-3p. No significant association was found between miRNA expressions and stage at diagnosis, site of primary tumor, first site of metastasis, progression-free, or overall survival.

Outcome of metastatic breast cancer in selected women with or without deleterious BRCA mutations

The aim of this study was to compare the time-to progression and overall survival (OS) in patients with metastatic breast cancer (MBC) with and without deleterious BRCA1/2 mutations. 195 women with MBC who were referred for BRCA genetic testing between 1997 and 2011 were included in the study. Logistic regression models and Cox proportional hazards models were fit to determine the associations between clinical variables and outcomes. Of 195 women with MBC, 21 % (n = 41) were positive for BRCA1/2 mutations. The number of metastatic sites at the time of metastatic disease was not different between BRCA1 versus BRCA2 carriers versus non-carriers (P = 0.77). The site of first metastasis was visceral-only in 70 % of BRCA1 carriers compared to 9 % in BRCA2 carriers and 37 % in non-carriers (P = 0.001). Median follow-up was 2.8 years. BRCA non-carriers and BRCA2 carriers had a longer time-to progression and OS compared to BRCA1 carriers (median time-to progression = 1.3 vs. 0.9 vs. 0.7 years; P = 0.31, and median OS = 4.88 vs. 4.94 vs. 1.34 years; P = 0.0065). In a multivariate model, no association was identified between BRCA positivity and time-to-event outcomes (P > 0.28). In addition, patients with triple-negative MBC carried a poorer prognosis irrespective of their BRCA status (P = 0.058 and P = 0.15 for the interaction term of BRCA status and triple-negative for time-to progression and OS, respectively). Our data indicate that BRCA1 carriers diagnosed with MBC have worse outcomes compared to BRCA2 carriers and non-carriers. However, the differences in outcome did not reach statistical significance likely due to small sample sizes.

B-Flow Twinkling Sign in Preoperative Evaluation of Cervical Lymph Nodes in Patients with Papillary Thyroid Carcinoma

Papillary thyroid cancer (PTC) is the most common histologic type of differentiated thyroid cancer. The first site of metastasis is the cervical lymph nodes (LNs). The ultrasonography (US) is the best diagnostic method for the detection of cervical metastatic LNs. We use a new technique, B-flow imaging (BFI), recently used for evaluation of thyroid nodules, to estimate the presence of BFI twinkling signs (BFI-TS), within metastatic LNs in patients with PTC. Two hundred and fifty-two patients with known PTC were examined for preoperative evaluation with conventional US and BFI. Only 83 with at least one metastatic LN were included. All patients included underwent surgery; the final diagnosis was based on the results of histology. The following LN characteristics were evaluated: shape, abnormal echogenicity, absent hilum, calcifications, cystic appearance, peripheral vascularization, and BFI-TS. A total of 604 LNs were analyzed. Of these, 298 were metastatic, according to histopathology. The BFI-TS showed high values of specificity (99.7%) and sensitivity (80.9%). The combination of each conventional US sign with the BF-TS increases the specificity. Our findings suggest that BFI can be helpful in the selection of suspicious neck LNs that should be examined at cytologic examination for accurate preoperative staging and individual therapy selection.

Incidence and Patterns of Distant Metastases for Patients With Early-Stage Breast Cancer After Breast Conservation Treatment

BackgroundBreast conservation treatment (BCT), consisting of breast conservation surgery followed by definitive radiation therapy (RT), has been shown to be effective for early-stage breast cancer. Patterns of metastatic failure by specific anatomic site are not well described in the literature. MethodsA total of 1754 patients with stage I or II invasive carcinoma of the breast treated with BCT between 1977 and 2003 were identified. Patients were scored based on first site of metastasis: bone, brain, lung, liver, or other. Non–breast cancer deaths, contralateral breast cancer, and second malignancies were treated as competing risks events. Cumulative incidence functions for each competing event were calculated using competing risk methodology. Univariate analysis was performed to determine the hazard ratio (HR) associated with patient and tumor characteristics. ResultsThe most common event was non–breast cancer death (16.5% at 15 years; 95% confidence interval [CI], 13.9%-19.4%). The most common exclusive first site of metastasis was bone (5.9% at 15 years). The 4 most common anatomic sites of distant metastases as the first exclusive event were bone (41.1%), lung (22.4%), liver (7.3%), and brain (7.3%). ConclusionThe present study has demonstrated the site-specific risks of metastases. These data support current clinical practice of screening for site-specific metastatic disease after BCT based on concerning patient-specific signs or symptoms.

Incidence and Predictive Factors for Pulmonary Metastases After Curative Resection of Colon Cancer

To assess the actuarial incidence of pulmonary metastases as the first site of metastasis after R0 resection of colon cancer and to clarify predictive factors for pulmonary metastases as the first site of metastasis. Data for 746 patients who underwent R0 resection for colon cancer from 2000 to 2006 were reviewed. The mean duration of follow-up was 56.9months. Pulmonary metastases developed in 35 patients. Mean duration from colon surgery to identification of pulmonary metastases was 20.0months. The overall occurrence rates of 5-year pulmonary metastasis according to Union for International Cancer Control (UICC) stage were 0.6% (stage I), 2.2% (stage II), 9.8% (stage III), and 24.6% (stage IV), respectively. Surgery for pulmonary metastases was performed first 18 patients (51.4%), and 16 (88.9%) of these 18 patients achieved R0 surgery. Multivariate analysis revealed that presence of regional lymph node involvement and preoperative serum carcinoembryonic antigen level (≥5ng/ml) were significant independent risk factors for pulmonary metastases. Five-year actuarial incidence of pulmonary metastases increased significantly with increased number of risk factors (0 factors, 2.2%; 1 factor, 6.6%; 2 factors, 18.4%). The present study clearly demonstrated predictive factors for pulmonary metastases after R0 resection of colon cancer. Actuarial incidence of pulmonary metastases was significantly related to the number of risk factors present. The data should facilitate the establishment of novel algorithms for predicting pulmonary metastases after resection of colon cancer, which may lead to the appropriate surveillance strategies after colon surgery.

Near‐Infrared Fluorescent Silica‐Coated Gold Nanoparticle Clusters for X‐Ray Computed Tomography/Optical Dual Modal Imaging of the Lymphatic System

Lymph nodes (LNs) are often removed to prevent the spread of cancer because they are frequently the first site of metastases. However, the enucleation of LNs requires difficult operative techniques and lymphedema can result as a complication. Although lymphedema can be cured by anastomosis of a lymph vessel (LV) to a vein, the operative procedure is extremely difficult because LNs and LVs are too small and indistinct to be identified. Therefore, visualization of LNs and LVs is important. The combination of X-ray computed tomography (CT) and fluorescence imaging, CT/fluorescence dual modal imaging, enables the visualization of LNs and LVs before and during surgery. To accomplish this, near-infrared fluorescent silica-coated gold nanoparticle clusters (Au@SiO₂) with a high X-ray absorption coefficient are synthesized. Both fluorescence imaging and CT show that the Au@SiO₂ nanoparticles gradually accumulate in LNs through LVs. CT determines the location and size of the LNs and LVs without dissection, and fluorescence imaging facilitates their identification. The Au@SiO₂ nanoparticles have neither hepatotoxicity nor nephrotoxicity. The results demonstrate that CT/fluorescence dual modal imaging using Au@SiO₂ nanoparticles provides anatomical information, including the location and size of LNs and LVs for determining a surgery plan, and provides intraoperative visualization of LNs and LVs to facilitate the operation.

1207P - Prognostic Factors in Development of Brain Metastasis in Stage III Non-Small Cell Lung Cancer Patients After Definitive Treatment

ABSTRACT Purpose To determine the incidence and prognostic factors of brain metastatsis in locally advanced non-small cell lung cancer (NSCLC) patients who were curatively treated. Materials and methods Curatively treated 136 patients with stage IIIA/ IIIB NSCLC between 1997-2011 were retrospectively reviewed. M/F: 112/24. Median age was 61 (36-82). Median Karnofsky Performance Scale was 80 (70-100). 61 patients (45%) were IIIA. Histology was adenocarcinoma in 27%, and squamous cell cancer in 54%. Seventy patients had concomitant or sequential chemoradiotherapy (CRT), 16% had radiotherapy (RT). All patients received platinum based chemotherapy. Median 60 Gy was administered with conformal RT. The ratio and time to brain metastasis were noted. Age, gender, stage, histology and surgery were examined as prognostic factors. Results Median follow-up was 13 months (range, 2-61 months). Two-year survival rate was 31%. One-year incidence of brain metastasis was 28.7%. In univariate analysis showed that patients younger than 60 years of age had more brain metastases than older patients (36% vs 15%, p = 0.01). Brain was more frequently the first site of metastases in younger patients than >60years (22% vs 9%, p > 0.05). Histology also significantly effected the development of brain metastasis (43.2% in adenocarcinoma, 16.4% in epidermoid carcinoma, p = 0.004). On multivariate analysis, only age was found to be significant prognostic factor (p = 0.01) Conclusion Age and histology significantly effects development of brain metastasis in locally advanced NSCLC. Younger age was the only significant variable for brain metastasis. Disclosure All authors have declared no conflicts of interest.

Prophylactic Cranial Irradiation for Patients With Limited-Stage Small-Cell Lung Cancer With Response to Chemoradiation

BackgroundPrevious clinical studies have generally reported that prophylactic cranial irradiation (PCI) was given to patients with a complete response (CR) to chemotherapy and chest radiotherapy in limited-stage small-cell lung cancer (SCLC). It is not clear if those with incomplete response (IR) would benefit from PCI. Patients and MethodsThe Saskatchewan experience from 1981 through 2007 was reviewed. Patients were treated with chest radiotherapy and chemotherapy with or without PCI (typical doses: 2500 cGy in 10 fractions over 2 weeks, 3000 cGy in 15 fractions over 3 weeks, or 3000 cGy in 10 fractions over 2 weeks). ResultsThere were 289 patients treated for curative intent, 177/289 (61.2%) of whom received PCI. For the whole group of 289 patients, PCI resulted in significant overall survival (OS) and cause-specific survival (CSS) benefit (P = .0011 and 0.0005, respectively). The time to symptoms of first recurrence at any site with or without PCI was significantly different: 16.9 vs. 13.2 months (P = .0006). PCI significantly delayed the time to symptoms of first recurrence in the brain: 20.7 vs. 10.6 months (P < .0001). The first site of metastasis was the brain for 12.5% and 45.5% patients with CR with and without PCI, respectively (P = .02) and in 6.1% and 27.6% of patients with IR with and without PCI, respectively (P = .05). For the 93 patients with IR, PCI did not confer OS or CSS benefit (P = .32 and 0.39, respectively). ConclusionsPatients with IR benefited from PCI, with a reduced rate of and a delayed time for the development of brain metastases, although without significant OS or CSS benefit. PCI could be considered for all patients with limited-stage SCLC responding to chemoradiation.

Systematic Review of CNS Metastasis in Patients with Breast Cancer (P07.113)

Objective: To review the existing literature on the issue of brain metastasis in relationship to the breast cancer and the factors are relevant to the higher incidence of brain metastasis and patients survival. Background Brain metastases are the most common intracranial tumors in adults, accounting for more than one-half of brain tumors. Breast cancer is the 2 nd most common cause of brain metastases. Progressive neurologic disability often results and the prognosis is generally poor. Design/Methods: We did a systematic research using the pubmed and Yale library search engine including all relevant articles in the past 20 years (refined MRI and modern treatment became available). A total of 38 papers fulfilled the above criteria and furnished the optimum information. Results: Many factors correlated with higher incidence of brain metastasis like younger age, ethnicity, and size of the primary tumor ( 2cm: 70-80%). Multiple brain lesions is common than solitary brain lesions. Incidence rate of BCBM increased from 15% to 80% over the span of 5 years. Brain was the first site of metastasis in 13%- 45% (mean 30%).The most common site of metastasis was cerebral grey and white matter and cerebellum. The most common symptoms were headache (15-58%), motor weakness (13-38%) and seizures (5-23%). Triple negative BC was associated with the worst prognosis while the HER2+/HR+, HER2+/HR-, HER2-/HR+ showed inconsistent results. Whole brain radiation therapy, neurosurgery, stereotactic radio surgery and medical therapy have a role in the management with promising role of chemotherapeutic agents in the recent literature. The median survival for patients with metastatic breast cancer is 18 to 24 months, although the range extends from only a few months to many years. Conclusions: Brain metastasis remains a major complication of breast cancer and indicates an unfavorable prognosis. Biomarkers play a key role in the treatment and survival outcome. Disclosure: Dr. Azadi has nothing to disclose. Dr. Mittal has nothing to disclose. Dr. Tavassoli has nothing to disclose. Dr. Jabbari has nothing to disclose.

Abstract 3290: A novel model of breast cancer metastasis: Killing two birds with one stone

Abstract American women carry a lifetime risk of 1:8 of developing breast cancer, with metastatic disease remaining incurable. Between 70-80% of breast cancer patients diagnosed with metastases will exhibit lesions in their skeleton and in 25% of patients bone is the first site of metastasis. Breast cancer bone metastases are most frequently osteolytic. Thus, patients exhibiting bone lesions might suffer from nerve compression, bone fractures, hypercalcemia, pain, or paralysis. Existing treatment strategies for patients with bone metastases are palliative and designed to limit cancer-associated bone loss. It has been difficult to study breast cancer dissemination to bone due to lack of good animal models and little biopsy tissue availability. For human xenografts to establish bone lesions, human breast cancer cells are injected into the left ventricle of the heart, a procedure technically challenging and not 100% efficient. Resulting bone lesions are slow to develop and may be easy to miss on x-ray examination. Here, we show that a well-described parental MDA-MB-231 breast cancer cell line recapitulates progression of human disease when injected intravenously through the lateral tail vein into athymic nude mice. For reasons yet unclear, 30-50% of animals develop rapid and extremely lytic bone lesions in lumbar, sacral and caudal vertebrae and hind limbs. Similar to breast cancer patients, these animals exhibit pathologic fractures and paralysis, necessitating euthanasia within 4 weeks after cell inoculation. Interestingly, animals not affected by bone metastases go on to develop overt lung metastases within 10-12 weeks after cell inoculation. Bioluminescence imaging studies indicated presence of luciferase-tagged MDA-MB-231 cells in lungs of all mice at 2 and 24 hours post-cell inoculation. Within three weeks post-injection, large lesions were detected in the lumbar to caudal vertebrae regions and hind limbs of mice injected with luciferase-tagged (6/15 mice) or parental MDA-MB-231 cells (7/13 mice). Bone osteolysis was confirmed by x-ray, and paralysis occurred as early as 3 weeks after cell injection. Cytogenetic “finger printing” preformed by the institutional core facility confirmed that cell lines used exhibit properties of MDA-MB-231 cells consistent with ATCC profile. Furthermore, molecular comparison of these cell lines with MDA-MB-231 cells obtained from other sources, including ATCC, revealed no differences. Unexpectedly, when examined in an orthotopic breast cancer model, MDA-MB-231 cells used in these studies produced rapidly growing tumors that spontaneously metastasized to lymph nodes and lungs, while MDA-MB-231 cells purchased from ATCC were completely non-tumorigenic. Studies are underway to determine a molecular mechanism responsible for this aggressive metastatic phenotype. This model may serve as a valuable tool for screening new therapeutics aimed to stop growth of metastases at multiple sites. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3290. doi:1538-7445.AM2012-3290

Patterns of Metastasis and Survival in Breast Cancer Patients: A Preliminary Study in an iranian Population

Due to lack of sufficient data on characteristics of breast cancer patients and risk factors for developing metastasis in Iran this study was designed to understand clinical aspects impacting on survival. A cross-sectional study on breast cancer patients was conducted in an oncology clinic of the university hospital between 1995 and 2010. Data were retrieved from medical records and included age, menopausal status, tumor diameter, number of involved nodes, histopathological type, estrogen and progesterone receptor expression, c-erbB-2, primary and secondary metastasis sites, overall survival, disease free interval and type of chemotherapy protocol. The results were analyzed with SPSS 13 software.The mean age of the patients was 49.2 (27-89) years. The primary tumors were mainly ER positive (48%) and PR negative (49.3%). The status of lymph nodes dissected and examined in these patients was unknown in 19 patients (25.3%) while 18 patients (24%) had positive lymph nodes with no report on the number of involved nodes. All of the patients had received antracyclin based chemotherapy in an adjuvant or metastatic setting. Adjuvant hormonal therapy was administered to receptor positive patients. In average, overall survival after recurrence was 30 months (95%CI 24.605-35.325) for non-skeletal versus 42 months (95%CI 31.211-52.789) for skeletal metastasis (P= 0.002). The median survival was also greater for receptor positive patients; 39 months (95%CI 33.716-44.284) for PR+ versus 26 months (95%CI 19.210-32.790) for PR- (P=0.047) and 38 months (95%CI 32.908-43.092) for ER+ versus 27 months (95%CI 18.780-35.220) for ER- patients (P=0.016). No relation was found between site of first metastasis and hormone receptor, age, tumor diameter, DFI and menopausal status. Sites of metastasis were independent of age, size of the tumor, menopausal and hormone receptor status in this study. Overall survival provided significant relations with respect to receptor status and bone metastasis.

Time Course and Pattern of Metastasis of Cutaneous Melanoma Differ between Men and Women

BackgroundThis study identified sex differences in progression of cutaneous melanoma.Methodology/Principal FindingsOf 7,338 patients who were diagnosed as an invasive primary CM without clinically detectable metastases from 1976 to 2008 at the University of Tuebingen in Germany, 1,078 developed subsequent metastases during follow up. The metastatic pathways were defined in these patients and analyzed using the Kaplan-Meier method. Multivariate survival analysis was performed using Cox modeling. In 18.7% of men and 29.2% of women (P<0.001) the first metastasis following diagnosis of primary tumor was locoregional as satellite/in-transit metastasis. The majority of men (54.0%) and women (47.6%, P = 0.035) exhibited direct regional lymph node metastasis. Direct distant metastasis from the stage of the primary tumor was observed in 27.3% of men and 23.2% of women (P = 0.13). Site of first metastasis was the most important prognostic factor of survival after recurrence in multivariate analysis (HR:1.3; 95% CI: 1.0–1.6 for metastasis to the regional lymph nodes vs. satellite/in-transit recurrence, and HR:5.5; 95% CI: 4.2–7.1 for distant metastasis vs. satellite/in-transit recurrence, P<0.001). Median time to distant metastasis was 40.5 months (IQR, 58.75) in women and 33 months (IQR, 44.25) in men (P = 0.002). Five-year survival after distant recurrence probability was 5.2% (95% CI: 1.4–2.5) for men compared with 15.3% (95% CI: 11.1–19.5; P = 0.008) for women.Conclusions/SignificanceBoth, the pattern of metastatic spread with more locoregional metastasis in women, and the time course with retracted metastasis in women contributed to the more favorable outcome of women. Furthermore, the total rate of metastasis is increased in men. Interestingly, there is also a much more favorable long term survival of women after development of distant metastasis. It remains a matter of debate and of future research, whether hormonal or immunologic factors may be responsible for these sex differences.

Survival after brain metastases in Asian patients with HER2+ breast cancer.

543 Background: HER2+ breast cancer is associated with an increased risk of brain metastases (BM). In Asia there is variable utilization of anti-HER2 therapy including trastuzumab (T) and lapatinib (L). This study described anti-HER2 treatment patterns in Asia and evaluated survival after BM in relation to anti-HER2 therapy use. Methods: A retrospective cohort study of 311 Asian patients with HER2+ breast cancer diagnosed with BM between Jan 2006 and Dec 2008 across 14 medical centers in six countries was conducted. Demographics, tumor characteristics, treatment, and dates of all metastases were collected from medical records. Results: Median age was 50 years (range: 23-80). 43% were premenopausal and 43% hormone receptor positive. 76% had multiple brain lesions; 11% had both parenchymal and leptomeningeal involvement. Brain was the first site of metastases in 21%. Prior to BM, 60% (n=186) received anti-HER2 therapy, primarily T in the metastatic setting. These patients had a longer interval between breas...

Metastatic tumors to the jaw bones: Retrospective analysis from an Indian tertiary referral center

Being a tertiary referral center, we encounter the highest number of oral cancer patients in India, and there is direct involvement of the jaw bone in approximately 40% of these cases. There are no large case series from the Indian subcontinent on metastatic tumors to the jaw bones. With this retrospective analysis, we intend to estimate the incidence of this rare manifestation in the jaw bones in our patients and compare it with the available literature. All patients with biopsy proven metastatic disease involving jaw bones having complete clinical data were included. Nineteen out of 10,411 oral cancer patients who reported between the years 2000 and 2005 were included. Breast and thyroid malignancies (5/19 each) were commonest in the females to metastasize to the mandible, whereas in the males, there was no predominant site that resulted in jaw bone metastasis, although mandible was commonly affected. Neuroblastoma of adrenal gland metastasized to maxilla in the age group ranging from 4 months to 16 years. maxilla was the commonest jaw bone affected in this age group. in five cases, jaw bone was found to be the first site of metastasis. There is variation in the primary site that causes metastasis to the jaw bones depending on age, sex and geographic distribution. Jaw bone metastases are rare and can be the first site of metastasis. We get approximately four cases in a year with metastatic disease manifesting in the jaw bones. Metastasis to jaw bone is associated with poor prognosis.