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Sample records for advanced breast tumors

  1. A Case of Locally Advanced Breast Cancer Complicated by Pulmonary Tumor Thrombotic Microangiopathy

    PubMed Central

    Kim, Hak Jin; Kwak, Mi Hyang; Kong, Sun-Young; Seong, Moon-Woo; Kang, Han-Sung; Lee, Keun Seok

    2012-01-01

    Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare, malignancy-related complication that causes marked pulmonary hypertension, right heart failure, and death. We report on a patient with locally advanced breast cancer whose course was complicated by fatal PTTM based on clinical and laboratory findings. PMID:23341791

  2. Reproducibility of Digital PCR Assays for Circulating Tumor DNA Analysis in Advanced Breast Cancer

    PubMed Central

    Hrebien, Sarah; O’Leary, Ben; Beaney, Matthew; Schiavon, Gaia; Fribbens, Charlotte; Bhambra, Amarjit; Johnson, Richard; Turner, Nicholas

    2016-01-01

    Circulating tumor DNA (ctDNA) analysis has the potential to allow non-invasive analysis of tumor mutations in advanced cancer. In this study we assessed the reproducibility of digital PCR (dPCR) assays of circulating tumor DNA in a cohort of patients with advanced breast cancer and assessed delayed plasma processing using cell free DNA preservative tubes. We recruited a cohort of 96 paired samples from 71 women with advanced breast cancer who had paired blood samples processed either immediately or delayed in preservative tubes with processing 48–72 hours after collection. Plasma DNA was analysed with multiplex digital PCR (mdPCR) assays for hotspot mutations in PIK3CA, ESR1 and ERBB2, and for AKT1 E17K. There was 94.8% (91/96) agreement in mutation calling between immediate and delayed processed tubes, kappa 0.88 95% CI 0.77–0.98). Discordance in mutation calling resulted from low allele frequency and likely stochastic effects. In concordant samples there was high correlation in mutant copies per ml plasma (r2 = 0.98; p<0.0001). There was elevation of total cell free plasma DNA concentrations in 10.3% of delayed processed tubes, although overall quantification of total cell free plasma DNA had similar prognostic effects in immediate (HR 3.6) and delayed (HR 3.0) tubes. There was moderate agreement in changes in allele fraction between sequential samples in quantitative mutation tracking (r = 0.84, p = 0.0002). Delayed processing of samples using preservative tubes allows for centralized ctDNA digital PCR mutation screening in advanced breast cancer. The potential of preservative tubes in quantitative mutation tracking requires further research. PMID:27760227

  3. Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

    PubMed Central

    Carrara, Guilherme Freire Angotti; Scapulatempo-Neto, Cristovam; Abrahão-Machado, Lucas Faria; Brentani, Maria Mitzi; Nunes, João Soares; Folgueira, Maria Aparecida Azevedo Koike; da Costa Vieira, René Aloisio

    2017-01-01

    OBJECTIVE: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01). CONCLUSIONS: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors. PMID:28355358

  4. Recent advances in microvascular autologous breast reconstruction after ablative tumor surgery

    PubMed Central

    Pollhammer, Michael S; Duscher, Dominik; Schmidt, Manfred; Huemer, Georg M

    2016-01-01

    Breast cancer is a ubiquitous disease and one of the leading causes of death in women in western societies. With overall increasing survival rates, the number of patients who need post-mastectomy reconstruction is on the rise. Especially since its psychological benefits have been broadly recognized, breast reconstruction has become a key component of breast cancer treatment. Evolving from the early beginnings of breast reconstruction with synthetic implants in the 1960s, microsurgical tissue transfer is on the way to become the gold standard for post oncology restoration of the breast. Particularly since the advent of perforator based free flap surgery, free tissue transfer has become as safe option for breast reconstruction with low morbidity. The lower abdominal skin and subcutaneous fat tissue typically offer enough volume to create an aesthetically satisfying breast mound. Nowadays, the most commonly used flap from this donor site is the deep inferior epigastric artery perforator flap. If the lower abdomen is not available as a donor site, the gluteal area and thigh provide a number of flaps suitable for breast reconstruction. If the required breast volume is small, and there is enough tissue available on the upper medial thigh, then a transverse upper gracilis flap may be a practicable method to reconstruct the breast. In case of a higher amount of required volume, a gluteal artery perforator flap is the best choice. However, what is crucial in addition to selecting the best flap option for the individual patient is the timing of the operation. In patients with confirmed post-mastectomy radiation therapy, it is advisable to perform microvascular breast reconstruction only in a delayed fashion. PMID:26862495

  5. Diagnosis of breast tumors after breast reduction.

    PubMed

    Beer, G M; Kompatscher, P; Hergan, K

    1996-01-01

    We conducted a retrospective study to evaluate the diagnosability of breast tumors after breast reductions as this is a frequent surgical procedure. The data should shed light on the hypothesis that routine screening methods concerning the diagnosis of breast tumors prove more difficult after breast operations. All women who had undergone breast reduction at our department between January 1989 and December 1994 were examined. During this period we counted 166 patients; the majority of them (n = 144) had undergone a bilateral breast reduction and the rest of them (n = 22) a unilateral breast reduction for various reasons. After the operation, all patients were checked in standardized intervals. Those who developed any kind of breast mass (n = 6) were recorded and examined by ultrasound and mammography, and occasionally by an additional fine-needle biopsy. In case any doubt about the dignity had remained, an excisional biopsy was carried out. In none of our patients was it possible to get a precise diagnosis of an ill-defined mass with ultrasound. With mammography, some of the existing masses, which were really scars, mimicked different kinds of tumors, and once a carcinoma was initially interpreted as scar tissue with oil cysts. The diagnosis of breast masses after breast reductions with routinely used screening methods has proved to be more difficult as breast reductions lead to architectural alterations of the remaining breast parenchyma. Such alterations can and should be documented shortly after the operation so that later occurring tumors are distinguished more easily. Therefore, a basic mammography 3 months after each breast reduction has to be claimed in order to facilitate further breast tumor diagnosis.

  6. Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers.

    PubMed

    Armstrong, Andrew J; Marengo, Matthew S; Oltean, Sebastian; Kemeny, Gabor; Bitting, Rhonda L; Turnbull, James D; Herold, Christina I; Marcom, Paul K; George, Daniel J; Garcia-Blanco, Mariano A

    2011-08-01

    During cancer progression, malignant cells undergo epithelial-mesenchymal transitions (EMT) and mesenchymal-epithelial transitions (MET) as part of a broad invasion and metastasis program. We previously observed MET events among lung metastases in a preclinical model of prostate adenocarcinoma that suggested a relationship between epithelial plasticity and metastatic spread. We thus sought to translate these findings into clinical evidence by examining the existence of EMT in circulating tumor cells (CTC) from patients with progressive metastatic solid tumors, with a focus on men with castration-resistant prostate cancer (CRPC) and women with metastatic breast cancer. We showed that the majority (> 80%) of these CTCs in patients with metastatic CRPC coexpress epithelial proteins such as epithelial cell adhesion molecule (EpCAM), cytokeratins (CK), and E-cadherin, with mesenchymal proteins including vimentin, N-cadherin and O-cadherin, and the stem cell marker CD133. Equally, we found that more than 75% of CTCs from women with metastatic breast cancer coexpress CK, vimentin, and N-cadherin. The existence and high frequency of these CTCs coexpressing epithelial, mesenchymal, and stem cell markers in patients with progressive metastases has important implications for the application and interpretation of approved methods to detect CTCs.

  7. Phyllodes tumor of the breast

    PubMed Central

    Herazo, Fernando; Gil, Monica; Echeverri, Carolina; Ángel, Gonzalo; Borrero, Mauricio; Madrid, Jorge; Jaramillo, Ricardo

    2015-01-01

    Introduction: Breast Phyllodes tumors are rare breast tumors present in less than 1% of new cases of breast cancer, usually occurring among middle-aged women (40-50 yrs). Objective: This study shows diagnostic experience, surgical management and follows up of patients with this disease during a period of ten years in a oncology referral center. Methods: Retrospectively, breast cancer registries at the institution were reviewed, identifying 77 patients with Phyllodes tumors between 2002 and 2012, who had been operated on at the Instituto de Cancerología - Clínica Las Américas, in Medellín (Colombia). Clinical and histopathological data belonging to these cases was captured and analyzed and descriptive statistics were used. Results: The follow up median was 22.5 months (IQR: 10.5-60.0), average age was 47.2 yrs (SD: 12.4), mean tumor size was 3.6 cm (SD: 4.6), 88.3% of the patients (68 cases) presented negative margins and none of them received adjuvant chemotherapy. Of the patients with Phyllodes tumors; 33.8% had benign, 31.2% had borderline and 35.0% had malignant tumor. Disease-free survival was 85.8% and overall survival was 94.5%. Discussion: Reported data in this article is in accordance with what has been reported in worldwide literature. In our cohort even the high mean size of the tumors, the risk of local relapse and metastatic disease is low than previously reported in literature. Trials with longer follow up and molecular trials in Phyllodes tumors are necessary to understand the behavior of these tumors in Hispanics population. PMID:26600624

  8. Talazoparib and HSP90 Inhibitor AT13387 in Treating Patients With Metastatic Advanced Solid Tumor or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple Negative Breast Cancer

    ClinicalTrials.gov

    2016-07-22

    Adult Solid Neoplasm; Estrogen Receptor Negative; Fallopian Tube Serous Neoplasm; HER2/Neu Negative; Ovarian Serous Adenocarcinoma; Ovarian Serous Tumor; Primary Peritoneal Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma

  9. Identification of Substances for Ubiquitin-Dependent Proteolysis During Breast Tumor Progression

    DTIC Science & Technology

    2008-10-01

    changes in ubiquitylation activity accompany the progression of breast tumors to more advanced disease . These activities likely drive breast tumor...We have found that key changes in ubiquitylation activity occur as breast tumors progress to advanced disease . The substrates of this activity...spread applications for the study of PTMs in human diseases . 3 Introduction Post-translational modifications (PTMs) are essential for the

  10. Targeted NGS, array-CGH, and patient-derived tumor xenografts for precision medicine in advanced breast cancer: a single-center prospective study

    PubMed Central

    Gonçalves, Anthony; Bertucci, François; Guille, Arnaud; Garnier, Severine; Adelaide, José; Carbuccia, Nadine; Cabaud, Oliver; Finetti, Pascal; Brunelle, Serge; Piana, Gilles; Tomassin-Piana, Jeanne; Paciencia, Maria; Lambaudie, Eric; Popovici, Cornel; Sabatier, Renaud; Tarpin, Carole; Provansal, Magali; Extra, Jean-Marc; Eisinger, François; Sobol, Hagay; Viens, Patrice; Lopez, Marc; Ginestier, Christophe; Charafe-Jauffret, Emmanuelle; Chaffanet, Max; Birnbaum, Daniel

    2016-01-01

    Background Routine feasibility and clinical impact of genomics-based tumor profiling in advanced breast cancer (aBC) remains to be determined. We conducted a pilot study to evaluate whether precision medicine could be prospectively implemented for aBC patients in a single center and to examine whether patient-derived tumor xenografts (PDX) could be obtained in this population. Results Thirty-four aBC patients were included. Actionable targets were found in 28 patients (82%). A targeted therapy could be proposed to 22 patients (64%), either through a clinical trial (n=15) and/or using already registered drugs (n=21). Ten patients (29%) eventually received targeted treatment, 2 of them deriving clinical benefit. Of 22 patients subjected to mouse implantation, 10 had successful xenografting (45%), mostly in triple-negative aBC. Methods aBC patients accessible to tumor biopsy were prospectively enrolled at the Institut Paoli-Calmettes in the BC-BIO study (ClinicalTrials.gov, NCT01521676). Genomic profiling was established by whole-genome array comparative genomic hybridization (aCGH) and targeted next-generation sequencing (NGS) of 365 candidate cancer genes. For a subset of patients, a sample of fresh tumor was orthotopically implanted in humanized cleared fat pads of NSG mice for establishing PDX. Conclusions Precision medicine can be implemented in a single center in the context of clinical practice and may allow genomic-driven treatment in approximately 30% of aBC patients. PDX may be obtained in a significant fraction of cases. PMID:27765906

  11. Minimal residual disease and circulating tumor cells in breast cancer

    PubMed Central

    2011-01-01

    Tumor cell dissemination in bone marrow or other organs is thought to represent an important step in the metastatic process. The detection of bone marrow disseminated tumor cells is associated with worse outcome in early breast cancer. Moreover, the detection of peripheral blood circulating tumor cells is an adverse prognostic factor in metastatic breast cancer, and emerging data suggest that this is also true for early disease. Beyond enumeration, the characterization of these cells has the potential to improve risk assessment, treatment selection and monitoring, and the development of novel therapeutic agents, and to advance our understanding of the biology of metastasis. PMID:22078011

  12. Minimal residual disease and circulating tumor cells in breast cancer.

    PubMed

    Ignatiadis, Michail; Reinholz, Monica

    2011-10-25

    Tumor cell dissemination in bone marrow or other organs is thought to represent an important step in the metastatic process. The detection of bone marrow disseminated tumor cells is associated with worse outcome in early breast cancer. Moreover, the detection of peripheral blood circulating tumor cells is an adverse prognostic factor in metastatic breast cancer, and emerging data suggest that this is also true for early disease. Beyond enumeration, the characterization of these cells has the potential to improve risk assessment, treatment selection and monitoring, and the development of novel therapeutic agents, and to advance our understanding of the biology of metastasis.

  13. [Therapeutic advances in breast cancer].

    PubMed

    Pestalozzi, B C

    2006-04-01

    The treatment of breast cancer has made significant improvements during the past ten years. For early breast cancer with a clinically negative axilla sentinel node biopsy has become the preferred approach. For endocrine therapy of postmenopausal patients the selective aromatase inhibitors have become standard in metastatic as well as in early breast cancer. Trastuzumab (Herceptin) plays an important role in the treatment of HER2-positive breast cancer in the metastatic and since 2005 also in the adjuvant setting. When chemotherapy is used to treat metastatic breast cancer drug combinations are superior to monotherapy only in terms of response rates. By contrast, in the adjuvant setting combination drug therapy is the standard. New methods of tissue analysis including expression patterns of mRNA and proteins are promising research strategies to further advance the field.

  14. New targeted therapies for breast cancer: A focus on tumor microenvironmental signals and chemoresistant breast cancers.

    PubMed

    Nwabo Kamdje, Armel Hervé; Seke Etet, Paul Faustin; Vecchio, Lorella; Tagne, Richard Simo; Amvene, Jeremie Mbo; Muller, Jean-Marc; Krampera, Mauro; Lukong, Kiven Erique

    2014-12-16

    Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy, including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemoresistance and serious adverse effects. Advances in our understanding of changes affecting the interactome in advanced and chemoresistant breast tumors have provided novel therapeutic targets, including, cyclin dependent kinases, mammalian target of rapamycin, Notch, Wnt and Shh. Inhibitors of these molecules recently entered clinical trials in mono- and combination therapy in metastatic and chemo-resistant breast cancers. Anticancer epigenetic drugs, mainly histone deacetylase inhibitors and DNA methyltransferase inhibitors, also entered clinical trials. Because of the complexity and heterogeneity of breast cancer, the future in therapy lies in the application of individualized tailored regimens. Emerging therapeutic targets and the implications for personalized-based therapy development in breast cancer are herein discussed.

  15. New targeted therapies for breast cancer: A focus on tumor microenvironmental signals and chemoresistant breast cancers

    PubMed Central

    Kamdje, Armel Hervé Nwabo; Etet, Paul Faustin Seke; Vecchio, Lorella; Tagne, Richard Simo; Amvene, Jeremie Mbo; Muller, Jean-Marc; Krampera, Mauro; Lukong, Kiven Erique

    2014-01-01

    Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy, including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemoresistance and serious adverse effects. Advances in our understanding of changes affecting the interactome in advanced and chemoresistant breast tumors have provided novel therapeutic targets, including, cyclin dependent kinases, mammalian target of rapamycin, Notch, Wnt and Shh. Inhibitors of these molecules recently entered clinical trials in mono- and combination therapy in metastatic and chemo-resistant breast cancers. Anticancer epigenetic drugs, mainly histone deacetylase inhibitors and DNA methyltransferase inhibitors, also entered clinical trials. Because of the complexity and heterogeneity of breast cancer, the future in therapy lies in the application of individualized tailored regimens. Emerging therapeutic targets and the implications for personalized-based therapy development in breast cancer are herein discussed. PMID:25516852

  16. Macroscopic Stiffness of Breast Tumors Predicts Metastasis

    PubMed Central

    Fenner, Joseph; Stacer, Amanda C.; Winterroth, Frank; Johnson, Timothy D.; Luker, Kathryn E.; Luker, Gary D.

    2014-01-01

    Mechanical properties of tumors differ substantially from normal cells and tissues. Changes in stiffness or elasticity regulate pro-metastatic behaviors of cancer cells, but effects have been documented predominantly in isolated cells or in vitro cell culture systems. To directly link relative stiffness of tumors to cancer progression, we combined a mouse model of metastatic breast cancer with ex vivo measurements of bulk moduli of freshly excised, intact tumors. We found a high, inverse correlation between bulk modulus of resected tumors and subsequent local recurrence and metastasis. More compliant tumors were associated with more frequent, larger local recurrences and more extensive metastases than mice with relatively stiff tumors. We found that collagen content of resected tumors correlated with bulk modulus values. These data establish that relative differences in tumor stiffness correspond with tumor progression and metastasis, supporting further testing and development of tumor compliance as a prognostic biomarker in breast cancer. PMID:24981707

  17. Augmented reality for breast tumors visualization.

    PubMed

    Ghaderi, Mohammad Ali; Heydarzadeh, Mehrdad; Nourani, Mehrdad; Gupta, Gopal; Tamil, Lakshman

    2016-08-01

    3D visualization of breast tumors are shown to be effective by previous studies. In this paper, we introduce a new augmented reality application that can help doctors and surgeons to have a more accurate visualization of breast tumors; this system uses a marker-based image-processing technique to render a 3D model of the tumors on the body. The model can be created using a combination of breast 3D mammography by experts. We have tested the system using an Android smartphone and a head-mounted device. This proof of concept can be useful for oncologists to have a more effective screening, and surgeons to plan the surgery.

  18. Advances in molecular imaging for breast cancer detection and characterization

    PubMed Central

    2012-01-01

    Advances in our ability to assay molecular processes, including gene expression, protein expression, and molecular and cellular biochemistry, have fueled advances in our understanding of breast cancer biology and have led to the identification of new treatments for patients with breast cancer. The ability to measure biologic processes without perturbing them in vivo allows the opportunity to better characterize tumor biology and to assess how biologic and cytotoxic therapies alter critical pathways of tumor response and resistance. By accurately characterizing tumor properties and biologic processes, molecular imaging plays an increasing role in breast cancer science, clinical care in diagnosis and staging, assessment of therapeutic targets, and evaluation of responses to therapies. This review describes the current role and potential of molecular imaging modalities for detection and characterization of breast cancer and focuses primarily on radionuclide-based methods. PMID:22423895

  19. Photonic Breast Tomography and Tumor Aggressiveness Assessment

    DTIC Science & Technology

    2008-07-01

    component involved application and further refinement of optical tomographic imaging using independent component analysis ( OPTICA ) for locating and cross...section imaging of a tumor in a model cancerous breast assembled using ex vivo breast tissue specimens. The OPTICA approach was able to detect...infrared imaging, optical tomography using independent component analysis ( OPTICA ), training, molecular imaging, cancer biology 16. SECURITY

  20. Freehand 3D ultrasound breast tumor segmentation

    NASA Astrophysics Data System (ADS)

    Liu, Qi; Ge, Yinan; Ou, Yue; Cao, Biao

    2007-12-01

    It is very important for physicians to accurately determine breast tumor location, size and shape in ultrasound image. The precision of breast tumor volume quantification relies on the accurate segmentation of the images. Given the known location and orientation of the ultrasound probe, We propose using freehand three dimensional (3D) ultrasound to acquire original images of the breast tumor and the surrounding tissues in real-time, after preprocessing with anisotropic diffusion filtering, the segmentation operation is performed slice by slice based on the level set method in the image stack. For the segmentation on each slice, the user can adjust the parameters to fit the requirement in the specified image in order to get the satisfied result. By the quantification procedure, the user can know the tumor size varying in different images in the stack. Surface rendering and interpolation are used to reconstruct the 3D breast tumor image. And the breast volume is constructed by the segmented contours in the stack of images. After the segmentation, the volume of the breast tumor in the 3D image data can be obtained.

  1. A Giant Phyllodes Tumor of the Breast

    PubMed Central

    Schillebeeckx, Charlotte; Verbeeck, Guy; Daenen, Geert; Servaes, Dirk; Bronckaers, Marc

    2016-01-01

    Phyllodes tumors of the breast are rare, accounting for less than 1% of the breast tumors. They are mostly seen in women between 45 and 49 years old. These are fast growing tumors with a large spectrum of behavior (from benign to metastatic) and can resemble fibroadenomas. Correct diagnosis mostly through core needle biopsy is important to decide whether a surgical excision has to be done. Here we report a case of a 57-year-old woman with a fast growing, ulcerated tumor in the left breast. Core needle biopsy suggested a malignant phyllodes tumor with heterologous liposarcomatous differentiation. Treatment with total mastectomy and adjuvant radiotherapy followed. Primary treatment is always surgery, whether radiotherapy or chemotherapy has to follow remains uncertain. There is a high-recurrence rate, especially when the surgical margins are narrow. PMID:27746880

  2. SU2C Phase Ib Study of Paclitaxel and MK-2206 in Advanced Solid Tumors and Metastatic Breast Cancer

    PubMed Central

    Gonzalez-Angulo, Ana M.; Krop, Ian; Akcakanat, Argun; Chen, Huiqin; Liu, Shuying; Li, Yisheng; Culotta, Kirk S.; Tarco, Emily; Piha-Paul, Sarina; Moulder-Thompson, Stacy; Velez-Bravo, Vivianne; Sahin, Aysegul A.; Doyle, Laurence A.; Do, Kim-Anh; Winer, Eric P.; Mills, Gordon B.; Kurzrock, Razelle

    2015-01-01

    Background: There is preclinical synergism between taxanes and MK-2206. We aim to determine the maximum tolerated dose, safety, and activity of combining MK-2206 and paclitaxel in metastatic cancer. Methods: Patients received weekly doses of paclitaxel at 80mg/m2 on day 1, followed by MK-2206 orally on day 2 escalated at 90mg, 135mg, and 200mg. Treatment continued until progression, excessive toxicity, or patient request. Blood and tissue were collected for pharmacokinetic and pharmacodynamics markers. A cycle consisted of three weeks of therapy. Dose-limiting toxicity (DLT) was defined as unacceptable toxicity during the first cycle. All statistical tests were two-sided. Results: Twenty-two patients were treated, nine in dose escalation and 13 in dose expansion. Median age was 55 years. Median number of cycles was four. Dose escalation was completed with no DLT. CTCAE Grade 3 or higher adverse events were fatigue (n = 2), rash (n = 2), hyperglycemia (n = 1), and neutropenia (n = 7). Four patients in the expansion phase required MK-2206 dose reduction. Phase II recommended dose was established as paclitaxel 80mg/m2 weekly on day 1, and MK-2206 135mg weekly on day 2. Paclitaxel systemic exposure was similar in the presence or absence of MK-2206. Plasma MK-2206 concentrations were similar to data from previous phase I monotherapy. There was a statistically significant decrease in expression of pAKT S473 (P = .01) and pAKT T308 (P = .002) after therapy. PI3K/AKT/mTOR downregulation in tumor tissues and circulating markers did not correlate with tumor response or clinical benefit. There were five objective responses, and nine patients had stable disease. Conclusion: MK-2206 was well tolerated with paclitaxel. Preliminary antitumor activity was documented. PMID:25688104

  3. Genomic landscapes of breast fibroepithelial tumors.

    PubMed

    Tan, Jing; Ong, Choon Kiat; Lim, Weng Khong; Ng, Cedric Chuan Young; Thike, Aye Aye; Ng, Ley Moy; Rajasegaran, Vikneswari; Myint, Swe Swe; Nagarajan, Sanjanaa; Thangaraju, Saranya; Dey, Sucharita; Nasir, Nur Diyana Md; Wijaya, Giovani Claresta; Lim, Jing Quan; Huang, Dachuan; Li, Zhimei; Wong, Bernice Huimin; Chan, Jason Yong Sheng; McPherson, John R; Cutcutache, Ioana; Poore, Gregory; Tay, Su Ting; Tan, Wai Jin; Putti, Thomas Choudary; Ahmad, Buhari Shaik; Iau, Philip; Chan, Ching Wan; Tang, Anthony P H; Yong, Wei Sean; Madhukumar, Preetha; Ho, Gay Hui; Tan, Veronique Kiak Mien; Wong, Chow Yin; Hartman, Mikael; Ong, Kong Wee; Tan, Benita K T; Rozen, Steven G; Tan, Patrick; Tan, Puay Hoon; Teh, Bin Tean

    2015-11-01

    Breast fibroepithelial tumors comprise a heterogeneous spectrum of pathological entities, from benign fibroadenomas to malignant phyllodes tumors. Although MED12 mutations have been frequently found in fibroadenomas and phyllodes tumors, the landscapes of genetic alterations across the fibroepithelial tumor spectrum remain unclear. Here, by performing exome sequencing of 22 phyllodes tumors followed by targeted sequencing of 100 breast fibroepithelial tumors, we observed three distinct somatic mutation patterns. First, we frequently observed MED12 and RARA mutations in both fibroadenomas and phyllodes tumors, emphasizing the importance of these mutations in fibroepithelial tumorigenesis. Second, phyllodes tumors exhibited mutations in FLNA, SETD2 and KMT2D, suggesting a role in driving phyllodes tumor development. Third, borderline and malignant phyllodes tumors harbored additional mutations in cancer-associated genes. RARA mutations exhibited clustering in the portion of the gene encoding the ligand-binding domain, functionally suppressed RARA-mediated transcriptional activation and enhanced RARA interactions with transcriptional co-repressors. This study provides insights into the molecular pathogenesis of breast fibroepithelial tumors, with potential clinical implications.

  4. Racial variation in breast tumor promoter methylation in the Carolina Breast Cancer Study

    PubMed Central

    Conway, Kathleen; Edmiston, Sharon N.; Tse, Chiu-Kit; Bryant, Christopher; Kuan, Pei Fen; Hair, Brionna Y.; Parrish, Eloise A.; May, Ryan; Swift-Scanlan, Theresa

    2015-01-01

    Background African American (AA) women are diagnosed with more advanced breast cancers and have worse survival than white women, but a comprehensive understanding of the basis for this disparity remains unclear. Analysis of DNA methylation, an epigenetic mechanism that can regulate gene expression, could help to explain racial differences in breast tumor clinical biology and outcomes. Methods DNA methylation was evaluated at 1287 CpGs in the promoters of cancer-related genes in 517 breast tumors of AA (n=216) or non-AA (n=301) cases in the Carolina Breast Cancer Study. Results Multivariable linear regression analysis of all tumors, controlling for age, menopausal status, stage, intrinsic subtype, and multiple comparisons (FDR), identified 7 CpG probes that showed significant (adjusted p<0.05) differential methylation between AAs and non-AAs. Stratified analyses detected an additional 4 CpG probes differing by race within hormone receptor-negative (HR−) tumors. Genes differentially methylated by race included DSC2, KCNK4, GSTM1, AXL, DNAJC15, HBII-52, TUSC3 and TES; the methylation state of several of these genes may be associated with worse survival in AAs. TCGA breast tumor data confirmed the differential methylation by race and negative correlations with expression for most of these genes. Several loci also showed racial differences in methylation in peripheral blood leukocytes (PBLs) from CBCS cases, indicating that these variations were not necessarily tumor-specific. Conclusions Racial differences in the methylation of cancer-related genes are detectable in both tumors and PBLs from breast cancer cases. Impact Epigenetic variation could contribute to differences in breast tumor development and outcomes between AAs and non-AAs. PMID:25809865

  5. Myosin 1e promotes breast cancer malignancy by enhancing tumor cell proliferation and stimulating tumor cell de-differentiation

    PubMed Central

    Ouderkirk-Pecone, Jessica L.; Goreczny, Gregory J.; Chase, Sharon E.; Tatum, Arthur H.; Turner, Christopher E.; Krendel, Mira

    2016-01-01

    Despite advancing therapies, thousands of women die every year of breast cancer. Myosins, actin-dependent molecular motors, are likely to contribute to tumor formation and metastasis via their effects on cell adhesion and migration and may provide promising new targets for cancer therapies. Using the MMTV-PyMT murine model of breast cancer, we identified Myosin 1e (MYO1E) as a novel tumor promoter. Tumor latency in mice lacking MYO1E was significantly increased, and tumors formed in the absence of MYO1E displayed unusual papillary morphology, with well-differentiated layers of epithelial cells covering fibrovascular cores, rather than solid sheets of tumor cells typically observed in this cancer model. These tumors were reminiscent of papillary breast cancer in humans that is typically non-invasive and often cured by tumor excision. MYO1E-null tumors exhibited decreased expression of the markers of cell proliferation, which was recapitulated in primary tumor cells derived from MYO1E-null mice. In agreement with our findings, meta-analysis of patient survival data indicated that MYO1E expression level was associated with reduced recurrence-free survival in basal-like breast cancer. Overall, our data suggests that MYO1E contributes to breast tumor malignancy and regulates the differentiation and proliferation state of breast tumor cells. PMID:27329840

  6. Phyllodes Tumor in a Lactating Breast

    PubMed Central

    Murthy, Sudha S.; Raju, K. V. V. N.; Nair, Haripreetha G.

    2016-01-01

    Phyllodes tumor is attributed to a small fraction of primary tumors of the breast. Such tumors occur rarely in pregnancy and lactation. We report a case of a 25-year-old lactating mother presenting with a lump in the left breast. Core needle biopsy was opined as phyllodes tumor with lactational changes, and subsequent wide local excision confirmed the diagnosis of benign phyllodes tumor with lactational changes. The characteristic gross and microscopic findings of a well-circumscribed lesion with leaf-like fibroepithelial growth pattern and typical nonuniform or diffuse stromal proliferation with periductal accentuation even in the absence of mitotic figures can help clinch the diagnosis. Benign phyllodes is known for its recurrence and requires wide excision and close follow-up. It is vital to identify these lesions even on limited biopsies as therapeutic options differ. This case is presented for its rarity and the diagnostic challenge it poses in limited biopsy. PMID:27081326

  7. Circulating Tumor Cells in Breast Cancer Patients: An Evolving Role in Patient Prognosis and Disease Progression

    PubMed Central

    Graves, Holly; Czerniecki, Brian J.

    2011-01-01

    In this paper, we examine the role of circulating tumor cells (CTCs) in breast cancer. CTCs are tumor cells present in the peripheral blood. They are found in many different carcinomas but are not present in patients with benign disease. Recent advances in theories regarding metastasis support the role of early release of tumor cells in the neoplastic process. Furthermore, it has been found that phenotypic variation exists between the primary tumor and CTCs. Of particular interest is the incongruency found between primary tumor and CTC HER2 status in both metastatic and early breast cancer. Overall, CTCs have been shown to be a poor prognostic marker in metastatic breast cancer. CTCs in early breast cancer are not as well studied, however, several studies suggest that the presence of CTCs in early breast cancer may also suggest a poorer prognosis. Studies are currently underway looking at the use of CTC level monitoring in order to guide changes in therapy. PMID:21253472

  8. Comprehensive molecular portraits of human breast tumors

    PubMed Central

    2012-01-01

    Summary We analyzed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, mRNA arrays, microRNA sequencing and reverse phase protein arrays. Our ability to integrate information across platforms provided key insights into previously-defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at > 10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the Luminal A subtype. We identified two novel protein expression-defined subgroups, possibly contributed by stromal/microenvironmental elements, and integrated analyses identified specific signaling pathways dominant in each molecular subtype including a HER2/p-HER2/HER1/p-HER1 signature within the HER2-Enriched expression subtype. Comparison of Basal-like breast tumors with high-grade Serous Ovarian tumors showed many molecular commonalities, suggesting a related etiology and similar therapeutic opportunities. The biologic finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biologic subtypes of breast cancer. PMID:23000897

  9. Unusual Benign Tumors of the Breast

    PubMed Central

    Adrada, Beatriz E; Krishnamurthy, Savitri; Carkaci, Selin; Posleman-Monetto, Flavia E; Ewere, Adesuwa; Whitman, Gary J

    2015-01-01

    The purpose of this article is to describe the imaging characteristics of a variety of benign breast tumors that may be encountered in daily practice, in order to formulate an appropriate differential diagnosis and to establish concordance between the imaging and the pathologic findings, and to assist the clinician with appropriate management. PMID:26085959

  10. Aminoglutethimide in advanced breast cancer.

    PubMed

    Ceci, G; Passalacqua, R; Bisagni, G; Bella, M; Cocconi, G

    1985-10-31

    From July 1980 to June 1983, 61 postmenopausal women with progressive metastatic breast cancer were treated with aminoglutethimide, 250 mg 4 times daily, plus cortisone acetate, 25 mg twice daily. Of 51 evaluable patients, an objective remission was observed in 22 (43%) (partial remission in 19, complete in 3), stable disease in 14 (27%), and progressive disease in 15 (30%). The median duration of response was 60 weeks (range 12+; 94+). The response rate was higher when the dominant disease site was soft tissue (50%) or bone (56%) rather than viscera (29%). Side effects were common but usually slight and transient. Somnolence (69%), dizziness (41%), nausea (35%) and skin rash (27%) were the most frequent. Serum levels of gamma-GT, alkaline phosphatase and total cholesterol rose during aminoglutethimide treatment, whereas levels of uric acid and indirect bilirubin decreased. Aminoglutethimide plus cortisone acetate appears to be an active and relatively safe treatment in advanced breast cancer and may be recommended as second-line endocrine treatment.

  11. Characterizing tumor changes during neoadjuvant treatment of locally advanced breast cancer patients (LABC) using dynamic-enhanced magnetic resonance imaging (DE-MRI)

    NASA Astrophysics Data System (ADS)

    Craciunescu, Oana I.; Jones, Ellen L.; Blackwell, Kimberly L.; Wong, Terence Z.; Rosen, Eric L.; Vujaskovic, Zeljko; MacFall, James R.; Liotcheva, Vlayka; Lora-Michiels, Michael; Prosnitz, Leonard R.; Samulski, Thaddeus V.; Dewhirst, Mark W.

    2005-04-01

    At Duke University Medical Center, selective LABC patients were treated on a protocol using neoadjuvant Myocet/Paclitaxel (ChT) and HT. With the purpose of generating perfusion/permeability parametric maps and to use gadolinium (Gd) enhancement curves to score and predict response to neoadjuvant treatment, a study was designed to acquire 3 sets of DE-MRI images along the 4 cycles of combined ChT and HT. A T1-weighted three-dimensional fast gradient echo technique was used over 30 minutes following bolus injection of Gd-based contrast agent. Perfusion/permeability maps were generated by fitting the signal intensity to a double exponential curve that generates washin (WiP) and washout (WoP), parameters that are associated with the tumors vascularity/permeability and cellularity. Based on the values of the WiP, the tumors were divided in lowWI (WiP < 100), mediumWI (100 200). During the HT treatments temperatures in the breast were measured invasively via a catheter inserted under CT guidance. Although minimum sampled temperatures give a crude indication of the temperature distribution, several thermal dose metrics were calculated for each of the HT fractions (e.g. T90, T50, T10). As expected, tumors that were more vascularized (i.e. higher WiP) heated less than tumors with low WiP, a degree on average. The adjuvant treatment also changed the shape and inhomogeneity of the perfusion/permeability maps, with dramatic changes after the first fraction in responders. The correlation between the thermal metrics and pathological response will be discussed, as well as possible correlation with other tumor physiology parameters. In conclusion, the Gd-enhancement analysis of DE-MRI images is able to generate information related to the tumor vascularity, permeability and cellularity that can correlate with the tumor's response to the neoadjuvant treatment in general, and to HT in particular. Work supported by a grant from the NCI CA42745.

  12. Phase Ib, Dose Escalation Study of Oral LDE225 in Combination With BKM120 in Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2016-02-18

    Dose Escalation; Safety; Preliminary Efficacy; Advanced Solid Tumors; Metastatic Breast Cancer; Advanced Pancreatic Adenocarcinoma; Metastatic Colorectal Cancer; Recurrent Glioblastoma Multiforme; Gastric Cancer; Gastroesophageal Junction Cancer; Triple Negative Metastatic Breast Cancer; Hormone Receptor Positive (ER+/PR+, and Her2-) Metastatic Breast Cancer

  13. [Advances in Research on miR-21 and Breast Cancer].

    PubMed

    Zhang, He; Zhang, Yulong; Zou, Linglin

    2015-06-01

    Breast cancer is a malignant tumor from normal breast epithelial. In recent years, many literature reports sought to determine the expression of predicted target genes of microRNA and their potential function, pathways and networks, which are involved in the tumorigenesis, metastasis and prognosis of breast cancer. The miR-21 has recently been found to be highly expressed in solid tumors than normal tissue, and it has exposed some layers of gene expression regulation that becomes a hot topic of breast cancer. This paper briefly reviews advances in research on miR-21 in breast cancer.

  14. Genetic and phenotypic diversity in breast tumor metastases

    PubMed Central

    Almendro, Vanessa; Kim, Hee Jung; Cheng, Yu-Kang; Gönen, Mithat; Itzkovitz, Shalev; Argani, Pedram; van Oudenaarden, Alexander; Sukumar, Saraswati; Michor, Franziska; Polyak, Kornelia

    2014-01-01

    Metastatic disease is the main cause of cancer-related mortality due to almost universal therapeutic resistance. Despite its high clinical relevance our knowledge of how cancer cell populations change during metastatic progression is limited. Here we investigated intratumor genetic and phenotypic heterogeneity during metastatic progression of breast cancer. We analyzed cellular genotypes and phenotypes at the single cell level by performing immuno-FISH in intact tissue sections of distant metastatic tumors from rapid autopsy cases and from primary tumors and matched lymph node metastases collected prior to systemic therapy. We calculated Shannon index of intratumor diversity in all cancer cells and within phneotypically distinct cell populations. We found that the extent of intratumor genetic diversity was similar regardless of the chromosomal region analyzed, implying that it may reflect an inherent property of the tumors. We observed that genetic diversity was highest in distant metastases and was generally concordant across lesions within the same patient, whereas treatment-naïve primary tumors and matched lymph node metastases were frequently genetically more divergent. In contrast, cellular phenotypes were more discordant between distant metastases than primary tumors and matched lymph node metastases. Diversity for 8q24 was consistently higher in HER2+ tumors compared to other subtypes and in metastases of triple negative tumors relative to primary sites. We conclude that our integrative method that couples ecologic models with experimental data in human tissue samples, could be used for the improved prognostication of cancer patients and for the design of more effective therapies for progressive disease. Major findings By defining quantitative measures of intratumor cellular genetic and phenotypic heterogeneity in primary and metastatic breast tumors and by assessing tumor topology, we determined that distant metastatic tumors are the most diverse, which

  15. Male Malignant Phyllodes Breast Tumor After Prophylactic Breast Radiotherapy and Bicalutamide Treatment: A Case Report.

    PubMed

    Karihtala, Peeter; Rissanen, Tarja; Tuominen, Hannu

    2016-07-01

    Phyllodes tumor in male breast is an exceptionally rare neoplasm with only few published case reports. Herein, we present a case of malignant phyllodes tumor in male breast nine years after prophylactic breast 10 Gy radiotherapy and after nine year bicalutamide treatment. The imaging findings of the tumor and pathological correlation are also presented.

  16. Circulating tumor cells in breast cancer

    PubMed Central

    Pukazhendhi, Geetha; Glück, Stefan

    2014-01-01

    Circulating tumor cell (CTC) measurement in peripheral blood of patients with breast cancer offers prognostic information. In this review, we will try to identify evidence that could be used for prognosis, predictive power to draw this tool to clinical utility. We reviewed 81 manuscripts, and categorized those in discovery datasets, prognostic factors in metastatic breast cancer, identification of clinical utility in early breast cancer and in novel approaches. With each patient responding differently to chemotherapy, more efficient markers would improve clinical outcome. Current CTC diagnostic techniques use epithelial markers predominantly; however, the most appropriate method is the measurement of circulating DNA. It has been hypothesized that micrometastasis occurs early in the development of tumors. That implies the presence of CTCs in nonmetastatic setting. The origin of stimulus for malignant transformation is yet unknown. The role of microenvironment as a stimulus is also being investigated. It has been shown that CTCs vary in numbers with chemotherapy. The markers, which are followed-up in the primary tumors, are also being studied on the CTCs. There is discordance of the human epidermal growth factor receptor-2 status between the primary tumor and CTCs. This review summarizes our current knowledge about the CTCs. With genetic profiling and molecular characterization of CTCs, it is possible to overcome the diagnostic difficulties. Evidence for clinical utility of CTC as prognostic and predictive marker is increasing. Appropriate patient stratification according to CTC determination among other tests, would make personalized cancer therapy more feasible. PMID:25191136

  17. MMP13 is potentially a new tumor marker for breast cancer diagnosis.

    PubMed

    Chang, Hui-Jen; Yang, Ming-Je; Yang, Yu-Hsiang; Hou, Ming-Feng; Hsueh, Er-Jung; Lin, Shiu-Ru

    2009-11-01

    Within the past decade, the incidence of breast cancer in Taiwan has been rising year after year. Breast cancer is the first most prevalent cancer and the fourth leading cause of cancer-related deaths among women in Taiwan. The early stage of breast cancer not only have a wider range of therapeutic options, but also obtain a higher success rate of therapy than those with advanced breast cancer. A test for tumor markers is the most convenient method to screen for breast cancer. However, the tumor markers currently available for breast cancer detection include carcinoembryonic antigen (CEA), carbohydrate antigen 15.3 (CA15.3), and carbohydrate antigen 27.29 (CA27.29) exhibited certain limitations. Poor sensitivity and specificity greatly limits the diagnostic accuracy of these markers. This study aims to identify potential tumor markers for breast cancer. At first, we analyzed genes expression in infiltrating lobular carcinoma, metaplastic carcinoma, and infiltrating ductal carcinoma of paired specimens (tumor and normal tissue) from breast cancer patients using microarray technology. We selected 371 overexpressed genes in all of the three cell type. In advanced breast cancer tissue, we detected four genes MMP13, CAMP, COL10A1 and FLJ25416 from 25 overexpressed genes which encoded secretion protein more specifically for breast cancer than other genes. After validation with 15 pairs of breast cancer tissue and paired to normal adjacent tissues by membrane array and quantitative RT-PCR, we found MMP13 was 100% overexpressed and confirmed to be a secreted protein by Western blot analysis of the cell culture medium. The expression level of MMP13 was also measured by immunohistochemical staining. We suggest that MMP13 is a highly overexpressed secretion protein in breast cancer tissue. It has potential to be a new tumor marker for breast cancer diagnosis.

  18. Transcatheter Arterial Embolization for Controlling Severe Bleeding From Recurrent Locally-Advanced Breast Cancer

    PubMed Central

    Aksoy, Şefika; Akçe, Bülent; Kılıçkesmez, Özgür; Gürsü, Rıza Umar; Çakır, Mehmet Semih; Nazlı, Mehmet Ali; Aren, Acar

    2016-01-01

    One of the rare but most challenging issues in the management of the locally-advanced breast cancer (LABC) is life-threatening bleeding from the fungating and/or ulcerating focus (foci) of these tumors. Breast surgeons may need the assistance of interventional radiologists to solve this urgent condition if surgery cannot provide sufficient benefit. Herein, we report a case of recurrent locally-advanced breast cancer that presented with sudden severe bleeding, which was stopped by an interventional radiologist via transcatheter arterial embolization (TAE). In addition, we evaluate the role of interventional radiology in patients with breast cancer who present with bleeding from the breast by reviewing the relevant literature.

  19. A Rare Breast Tumor: Dermatofibrosarcoma Protuberans

    PubMed Central

    Özcan, Tevhide Bilgen; Hacıhasanoğlu, Ezgi; Nazlı, Mehmet Ali; Aksoy, Şefika; Leblebici, Cem; Talu, Canan Kelten

    2016-01-01

    Dermatofibrosarcoma protuberans is a slow-growing, local aggressive fibrous tumor of the subcutaneous tissue, frequently seen in the proximal extremities and the trunk. Its occurrence in the breast is very rare. Herein, we present a female who presented with a breast mass, and aim to discuss pathological features and differential diagnosis of dermatofibrosarcoma protuberans. A 44-year-old female presented to our clinic with a mass on her breast. Physical examination revealed a 8×5.5 cm mass with multilobular nodules on the skin in the lower inner quadrant of her right breast. Her mammography revealed a hyperdense, 7.5×6.5 cm, well-demarcated, lobulated mass in the right breast, which caused nodules on the lower para-areolar portion of the breast skin. There was no axillary lymphadenopathy on both clinical and radiologic examinations. A core needle biopsy had been performed prior to her referral to our center, which revealed a ‘spindle cell lesion’. The patient underwent simple mastectomy. On macroscopic examination; the skin over the lesion appeared ulcerated, and there was a well-defined solid mass, which was pale white-tan on the cut surface. Microscopic examination revealed monotonous spindle cell proliferation arranged in storiform pattern within the collagenous stroma with irregular extensions into deep adipose tissue. There were no necrosis or nuclear pleomorphism. The mitotic rate was 2–3/10 HPF. Immunohistochemically tumor cells showed diffuse CD34 positivity, and S100, EMA and SMA negativity. Based on histopathological and immunohistochemical findings, the lesion was diagnosed as dermatofibrosarcoma protuberans. Local recurrence is expected in 20–50% of these cases. Its treatment requires complete surgical excision with wide margins. Distant metastases, although rare, have been reported.

  20. Decitabine in Treating Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2013-02-06

    Male Breast Cancer; Recurrent Bladder Cancer; Recurrent Breast Cancer; Recurrent Melanoma; Stage III Melanoma; Stage IV Bladder Cancer; Stage IV Breast Cancer; Stage IV Melanoma; Unspecified Adult Solid Tumor, Protocol Specific

  1. Collision tumor with inflammatory breast carcinoma and malignant phyllodes tumor: a case report and literature review.

    PubMed

    Shin, Young Duck; Lee, Seul Kee; Kim, Kyu Sun; Park, Mi Ja; Kim, Joo Heon; Yim, Hyun Sun; Choi, Young Jin

    2014-01-08

    There have been some reports of coincidental presentation of breast carcinoma and phyllodes tumor in the same breast. Most of the cases were carcinoma that arose from a phyllodes tumor with a histologically identified transitional area, and they behaved less aggressively than the usually encountered carcinoma. Collision tumors are rare clinical entities in which two histologically distinct tumor types show involvement at the same site. The occurrence of these tumors in the breast is extremely rare. Here, we report a case of 45-year-old woman who had both invasive ductal carcinoma as the finding of inflammatory carcinoma and a malignant phyllodes tumor in the same breast. There was no evidence of a transitional area between the phyllodes tumor and the invasive ductal carcinoma. To our knowledge, this is the first report of a collision tumor of inflammatory breast carcinoma coincident with a malignant phyllodes tumor in same breast.

  2. Malignant phyllodes tumor of the breast: a case study.

    PubMed

    Keim-Malpass, Jessica; Mills, Anne M; Showalter, Shayna L

    2014-10-01

    Malignant phyllodes tumors of the breast are rare, fast-growing tumors that can be difficult to diagnose. A case study is featured about a young adult patient who lacked insurance and received a delayed diagnosis of malignant phyllodes tumor of the breast. This article includes pertinent clinical and age-specific considerations for comprehensive management.

  3. [Papillary tumors of the breast].

    PubMed

    Hungermann, D; Decker, T; Bürger, H; Kersting, C; Böcker, W

    2006-09-01

    The term papilloma applies to benign proliferative epithelial breast lesions with a papillary architecture. The papillae in such lesions contain an arborizing fibrovascular core, glandular surface epithelium and a basal myoepithelial layer. A basement membrane encloses these structures. Papilloma may occur at any site in the ductal lobular system and according to its localization is subdivided into two types: solitary (central) papilloma which are located in the major nipple/subareolar ducts or large segmental ducts and multiple (peripheral) papillomas in cystically dilated terminal ductal lobular units (TDLU). Stromal changes, epithelial metaplasia and/or proliferations and neoplasia may alter the prototypical architecture. In a significant number of papillomas atypia can be identified which have to be classified as atypical proliferates of the ductal type. These lesions must be distinguished from the papillary type of ductal carcinoma in situ. Some 17% of all papilloma are associated with (synchronous) intraductal or invasive carcinoma, but these also act as an indicator for subsequent (metachronous) carcinoma. As a consequence, in minimally invasive biopsy papilloma has to be classified as B3 and usually has to be followed by surgical excision.

  4. Characterization of Gene Expression in Human Breast Tumor Endothelium

    DTIC Science & Technology

    2008-05-01

    to UV-induced apoptosis in primary culture of canine mammary gland tumors (7), and SFRP2 decreased apoptosis in cardiomyocytes exposed to hypoxia(8...microdissection (LCM) of vascular cells from frozen human breast tumors and normal breast tissue for genomic analysis. We found SFRP2 to have 6 fold increased...vascular cells from frozen human breast tumors , where the RNA was of high quality and sufficient for genomic analysis(6). We found 55 genes with > 4

  5. The perivascular niche regulates breast tumor dormancy

    PubMed Central

    Peinado, Héctor; Mori, Hidetoshi; Matei, Irina R.; Evason, Kimberley J.; Brazier, Hélène; Almeida, Dena; Koller, Antonius; Hajjar, Katherine A.; Stainier, Didier Y.R.; Chen, Emily I.; Lyden, David

    2013-01-01

    In a significant fraction of breast cancer patients, distant metastases emerge after years or even decades of latency. How disseminated tumor cells (DTCs) are kept dormant, and what ‘wakes them up’, are fundamental problems in tumor biology. To address these questions, we utilized metastasis assays in mice to show that dormant DTCs reside upon microvasculature of lung, bone marrow and brain. We then engineered organotypic microvascular niches to determine whether endothelial cells directly influence breast cancer cell (BCC) growth. These models demonstrated that endothelial-derived thrombospondin-1 induces sustained BCC quiescence. This suppressive cue was lost in sprouting neovasculature; time-lapse analysis showed that sprouting vessels not only permit, but accelerate BCC outgrowth. We confirmed this surprising result in dormancy models and in zebrafish, and identified active TGF-β1 and periostin as tumor-promoting, endothelial tip cell-derived factors. Our work reveals that stable microvasculature constitutes a ‘dormant niche,’ whereas sprouting neovasculature sparks micrometastatic outgrowth. PMID:23728425

  6. Clinical trials update: Medical management of advanced breast cancer.

    PubMed

    Major, Maureen A

    2003-12-01

    Selection of treatment for metastatic breast cancer depends on several factors: the status of estrogen receptors or progesterone receptors on breast cancer cells and the expression levels of human epidermal growth factor receptor-2. The presence of estrogen or progesterone receptors typically indicates slower-growing tumors that may be amenable to hormonal manipulation, which provides significant disease control while offering a better toxicity profile than conventional chemotherapy. The understanding of hormonal therapies in patients with postmenopausal metastatic breast cancer has advanced greatly in the past several decades. Aromatase inhibitors, although used initially as second-line therapy, recently have proved to be as effective as tamoxifen, if not superior to it, as first-line therapy for metastatic breast cancer. New data also suggest that letrozole provides significantly better objective responses than anastrozole as second-line therapy. Exemestane, a steroidal aromatase inhibitor, is an effective third-line therapy. Fulvestrant, an estrogen receptor antagonist with no known agonist effect, provides a new option for hormonal therapy. For patients with metastatic breast cancer and overexpression of human epidermal growth factor receptor-2 on tumor cells, the monoclonal antibody trastuzumab is the preferred option, either in combination with paclitaxel as first-line treatment, or as a single agent for second-line therapy. By extending the sequence of hormonal therapy, disease progression and the need for chemotherapy may be significantly delayed, potentially extending patient survival rates and improving quality of life.

  7. Palbociclib for Advanced Breast Cancer

    Cancer.gov

    An interim analysis of the PALOMA3 trial shows that women with hormone receptor-positive metastatic breast cancer who received palbociclib plus fulvestrant had longer progression-free survival rates than women who received a placebo plus fulvestrant.

  8. Photonic Breast Tomography and Tumor Aggressiveness Assessment

    DTIC Science & Technology

    2012-07-01

    approaches for detection of breast tumors in early stages of growth when those are more amenable to treatment; and (b) training of CCNY researchers at...classification method of Multiple Signal Classification ( MUSIC ). It provided the locations of small absorptive and scattering targets within a turbid...targets, the locations are determined using the MUSIC pseudo spectrum [11]     2 22 ( ) ( ) j T s p s p s p j s pP g g v g    X X X X

  9. Macrophage Polarization: Anti-cancer Strategies to Target Tumor-associated Macrophage in Breast Cancer.

    PubMed

    Tariq, Muhammad; Zhang, Jieqiong; Liang, Guikai; Ding, Ling; He, Qiaojun; Yang, Bo

    2017-01-20

    Tumor-associated macrophages (TAMs) are the most abundant inflammatory cells and orchestrate different stages of breast cancer development. TAMs participate in the tumor angiogenesis, matrix remodeling, invasion, immunosuppression, metastasis, and chemoresistance in breast cancer. Several clinical studies indicate the association between the high influx of TAMs in tumor with poor prognosis in hepatocellular, ovarian, cervical, and breast cancer. Previously developed hypotheses have proposed that TAMs participate in antitumor responses of the body, while recently many clinical and experimental studies have revealed that TAMs in tumor microenvironment predominantly resemble with M2-like polarized macrophages and produce a high amount of anti-inflammatory factors which are directly responsible for the development of tumor. Various studies have shown that TAMs in tumor either enhance or antagonize the anti-tumor efficacy of cytotoxic agents, antibodies-targeting cancer cells, and therapeutic agents depending on the nature of treatment. Thereby, multiple roles of TAMs suggests that it is very important to develop novel therapeutic strategies to target TAMs in breast tumor. In this review, we have discussed the functional role of TAMs in breast cancer and summarized available recent advances potential therapeutic strategies that effectively target to TAMs cells. This article is protected by copyright. All rights reserved.

  10. Adenoid cystic carcinoma of breast: Recent advances

    PubMed Central

    Miyai, Kosuke; Schwartz, Mary R; Divatia, Mukul K; Anton, Rose C; Park, Yong Wook; Ayala, Alberto G; Ro, Jae Y

    2014-01-01

    Adenoid cystic carcinoma (ACC) of the breast is a rare special subtype of breast cancer characterized by the presence of a dual cell population of luminal and basaloid cells arranged in specific growth patterns. Most breast cancers with triple-negative, basal-like breast features (i.e., tumors that are devoid of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, and express basal cell markers) are generally high-grade tumors with an aggressive clinical course. Conversely, while ACCs also display a triple-negative, basal-like phenotype, they are usually low-grade and exhibit an indolent clinical behavior. Many discoveries regarding the molecular and genetic features of the ACC, including a specific chromosomal translocation t(6;9) that results in a MYB-NFIB fusion gene, have been made in recent years. This comprehensive review provides our experience with the ACC of the breast, as well as an overview of clinical, histopathological, and molecular genetic features. PMID:25516849

  11. Pharmacokinetically Guided Everolimus in Patients With Breast Cancer, Pancreatic Neuroendocrine Tumors, or Kidney Cancer

    ClinicalTrials.gov

    2016-12-09

    Estrogen Receptor-positive Breast Cancer; Gastrinoma; Glucagonoma; HER2-negative Breast Cancer; Insulinoma; Mucositis; Oral Complications; Pancreatic Polypeptide Tumor; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Recurrent Islet Cell Carcinoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Renal Cell Cancer

  12. Imaging Tumor Hypoxia to Advance Radiation Oncology

    PubMed Central

    Lee, Chen-Ting; Boss, Mary-Keara

    2014-01-01

    Abstract Significance: Most solid tumors contain regions of low oxygenation or hypoxia. Tumor hypoxia has been associated with a poor clinical outcome and plays a critical role in tumor radioresistance. Recent Advances: Two main types of hypoxia exist in the tumor microenvironment: chronic and cycling hypoxia. Chronic hypoxia results from the limited diffusion distance of oxygen, and cycling hypoxia primarily results from the variation in microvessel red blood cell flux and temporary disturbances in perfusion. Chronic hypoxia may cause either tumor progression or regressive effects depending on the tumor model. However, there is a general trend toward the development of a more aggressive phenotype after cycling hypoxia. With advanced hypoxia imaging techniques, spatiotemporal characteristics of tumor hypoxia and the changes to the tumor microenvironment can be analyzed. Critical Issues: In this review, we focus on the biological and clinical consequences of chronic and cycling hypoxia on radiation treatment. We also discuss the advanced non-invasive imaging techniques that have been developed to detect and monitor tumor hypoxia in preclinical and clinical studies. Future Directions: A better understanding of the mechanisms of tumor hypoxia with non-invasive imaging will provide a basis for improved radiation therapeutic practices. Antioxid. Redox Signal. 21, 313–337. PMID:24329000

  13. Desmoid tumor following abdominally-based free flap breast reconstruction

    PubMed Central

    Oh, Christine; Hammoudeh, Ziyad S.

    2017-01-01

    Desmoid tumors are fibroblastic connective tissue tumors that most commonly develop within the anterior abdominal wall. The etiology of desmoid tumors has not been well defined; however, hereditary, hormonal, traumatic, and surgery-related causes have been implicated. Desmoid tumors are believed to arise from musculoaponeurotic structures. Development in the breast is very rare. Several reports of desmoid tumors arising in the vicinity of the fibrous capsule of a breast implant have been described, but to date, the authors are not aware of any published cases following autologous breast reconstruction. This report describes a desmoid tumor developing after a muscle-sparing free transverse rectus abdominis musculocutaneous (TRAM) flap for breast reconstruction and subsequent surgical management. PMID:28210557

  14. Development of a New Subclavian Arterial Infusion Chemotherapy Method for Locally or Recurrent Advanced Breast Cancer Using an Implanted Catheter-Port System After Redistribution of Arterial Tumor Supply

    SciTech Connect

    Takizawa, Kenji Shimamoto, Hiroshi Ogawa, Yukihisa Yoshimatsu, Misako Yagihashi, Kunihiro Nakajima, Yasuo; Kitanosono, Takashi

    2009-09-15

    Locally or recurrent advanced breast cancers can receive arterial blood supply from various arteries, such as the internal thoracic artery (ITA), the lateral thoracic artery, and the other small arterial branches originating from the subclavian artery. Failure to catheterize and subsequent formation of collateral arterial blood supply from various arteries are some of the reasons why the response to conventional selective transarterial infusion chemotherapy is limited and variable. To overcome this problem, we developed a new subclavian arterial infusion chemotherapy method using an implanted catheter-port system after redistribution of arterial tumor blood supply by embolizing the ITA. We named this technique ('redistributed subclavian arterial infusion chemotherapy' (RESAIC)). Using RESAIC, patients can be treated on an outpatient basis for extended periods of time. Eleven patients underwent RESAIC, and the complete remission and partial response rate in 10 evaluable patients was 90%: complete remission [CR] n = 4, partial remission n = 4, stable disease n = 1, and not evaluable n = 1. Three of four patients with CR had no distant metastasis, and modified radical mastectomy was performed 1 month after conclusion of RESAIC. The resected specimens showed no residual cancer cells, and pathologically confirmed complete remission was diagnosed in each of these cases. Although temporary grade-3 myelosuppression was seen in three patients who were previously treated by systemic chemotherapy, there was no other drug-induced toxicity or procedure-related complications. RESAIC produced a better response and showed no major complications compared with other studies despite the advanced stage of the cancers.

  15. Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications

    PubMed Central

    Kimbung, Siker; Kovács, Anikó; Danielsson, Anna; Bendahl, Pär-Ola; Lövgren, Kristina; Stolt, Marianne Frostvik; Tobin, Nicholas P.; Lindström, Linda; Bergh, Jonas; Einbeigi, Zakaria; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

    2015-01-01

    The relevance of the intrinsic subtypes for clinical management of metastatic breast cancer is not comprehensively established. We aimed to evaluate the prevalence and prognostic significance of drifts in tumor molecular subtypes during breast cancer progression. A well-annotated cohort of 304 women with advanced breast cancer was studied. Tissue microarrays of primary tumors and synchronous lymph node metastases were constructed. Conventional biomarkers were centrally assessed and molecular subtypes were assigned following the 2013 St Gallen guidelines. Fine-needle aspirates of asynchronous metastases were transcriptionally profiled and subtyped using PAM50. Discordant expression of individual biomarkers and molecular subtypes was observed during tumor progression. Primary luminal-like tumors were relatively unstable, frequently adopting a more aggressive subtype in the metastases. Notably, loss of ER expression and a luminal to non-luminal subtype conversion was associated with an inferior post-recurrence survival. In addition, ER and molecular subtype assessed at all tumor progression stages were independent prognostic factors for post-recurrence breast cancer mortality in multivariable analyses. Our results demonstrate that drifts in tumor molecular subtypes may occur during tumor progression, conferring adverse consequences on outcome following breast cancer relapse. PMID:26375671

  16. Breast cancer. Part 3: advanced cancer and psychological implications.

    PubMed

    Harmer, Victoria

    This is the last article in this 3-part series on breast cancer. The previous two articles have outlined the principles behind breast awareness and breast health, detailing common benign breast diseases, types of breast cancer and staging, and treatment for breast cancer, including surgery, chemotherapy, radiotherapy and endocrine treatment. The series concludes by giving information on advanced disease, including when a patient presents late with a fungating breast lesion, or if the disease has metastasized from the breast to other organs. Lymphoedema is also described and discussed, and the latter half of this article discusses psychological implications of breast cancer, from diagnosis through the individual treatments.

  17. Analysis of circulating tumor cells in patients with triple negative breast cancer during preoperative chemotherapy.

    PubMed

    Lavrov, A V; Zubtsova, Zh I; Zubtsov, D A; Frolova, M A; Ignatova, E O; Skrypnikova, M A; Malysheva, E V; Legchenko, E V; Petrovskii, A V; Utyashev, I A; Tyulyandin, S A; Gol'dshtein, D V

    2014-05-01

    The presence of circulating tumor cells in the blood of patients with triple negative breast cancer (early and locally advanced cancer) before and after preoperative chemotherapy was assessed using expression markers. Before therapy, circulating tumor cells were detected in 5 of 13 (38%) patients with early cancer and in 7 of 17 (41.2%) patients with locally advanced cancer. After therapy, the circulating immune cells were detected in one patient with locally advanced cancer, who had no circulating cells before therapy. The tumor was resistant to chemotherapy and the disease progressed. The detected circulating tumor cells were HER-2-positive, while the primary tumor was HER-2-negative. It was concluded that the circulating immune cells can be a potential marker of the efficiency of therapy and predictors of the disease course, while their phenotype can differ from the phenotype of the primary tumor.

  18. Clinical and cytopathological aspects in phyllodes tumors of the breast.

    PubMed

    Pătraşcu, Anca; Popescu, Carmen Florina; Pleşea, I E; Bădulescu, Adriana; Tănase, Florentina; Mateescu, Garofiţa

    2009-01-01

    The frequency of mesenchymal breast tumors is very low, being represented mostly by tumors with biphasic proliferation (phyllodes tumors) and less by other types of non-epithelial tumors. From clinical point of view, phyllodes tumors (PT) can mimic a breast carcinoma. Therefore, the preoperative diagnosis by cytological examination on material obtained by fine needle aspiration (FNA) is very important for adequate treatment of these tumors. In current study, we assessed clinical aspects of 79 phyllodes tumors regarding patient's age and localization of the tumors. In 17 out of 79 cases, it has been performed FNA within the tumors with further cytological examination on the smears obtained. The median age of the patients was 46.07-year-old, being progressively higher with grade of the tumors with significant values between benign and borderline tumors (p=0.04954) and between benign and malignant ones (p=0.02890). The distinguish on the smears of stromal fragments and naked stromal nuclei with variable grade of atypia regarding the tumoral type, in detriment of epithelial elements have been conclusive for fibroepithelial lesion as cytopathological diagnosis. The preoperative differentiation between a breast phyllodes tumor and a breast carcinoma is extremely important for avoiding of a useless radical surgery for the patient. If the fine needle aspiration was correctly performed, the accuracy of the cytodiagnosis has been 82% in current study.

  19. Maximizing Immune Response to Carbohydrate Antigens on Breast Tumors

    DTIC Science & Technology

    2003-08-01

    antigens expressed on breast tumors. Towards this end we are developing peptide mimotopes of tumor associated carbohydrate antigens as they are T cell...dependent antigens. In our progress to date we have shown the 1) immunization with peptide mimotope activates a specific cellular response to a model murine...tumor cell line; 2) vaccination of mice with peptide eradicates established tumor; 3) Immunization with DNA format of the peptide suppresses tumor

  20. Preliminary Evaluation of Preoperative Chemohormonotherapy-Induced Reduction of the Functional Infrared Imaging Score in Patients with Locally Advanced Breast Cancer

    DTIC Science & Technology

    2001-10-25

    ADVANCED BREAST CANCER John R. Keyserlingk1, Mariam Yassa1 Paul Ahlgren1 and Normand Belliveau1 Ville Marie Oncology Center; St. Mary’s Hospital...Montreal, Canada Abstract: 20 successive patients who received preoperative chemohormonotherapy (PCT) for locally advanced breast cancer underwent high...INTRODUCTION Approximately 10% of our current breast cancer patients present with sufficient tumor load to be classified as having locally advanced breast

  1. Computational Model for Tumor Oxygenation Applied to Clinical Data on Breast Tumor Hemoglobin Concentrations Suggests Vascular Dilatation and Compression

    PubMed Central

    Welter, Michael; Fredrich, Thierry; Rinneberg, Herbert; Rieger, Heiko

    2016-01-01

    below normal are less likely to respond to chemotherapy. Such behavior was recently reported for neo-adjuvant chemotherapy of locally advanced breast tumors. PMID:27547939

  2. Entinostat, Nivolumab, and Ipilimumab in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Locally Advanced or Metastatic HER2-Negative Breast Cancer

    ClinicalTrials.gov

    2017-03-10

    Breast Adenocarcinoma; HER2/Neu Negative; Invasive Breast Carcinoma; Metastatic Malignant Solid Neoplasm; Recurrent Breast Carcinoma; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Unresectable Solid Neoplasm

  3. Body Mass Index is Associated with Gene Methylation in Estrogen Receptor-Positive Breast Tumors

    PubMed Central

    Hair, Brionna Y.; Troester, Melissa A.; Edmiston, Sharon N.; Parrish, Eloise A.; Robinson, Whitney R.; Wu, Michael C.; Olshan, Andrew F.; Swift-Scanlan, Theresa; Conway, Kathleen

    2015-01-01

    Background Although obesity is associated with breast cancer incidence and prognosis, the underlying mechanisms are poorly understood. Identification of obesity-associated epigenetic changes in breast tissue may advance mechanistic understanding of breast cancer initiation and progression. The goal of this study, therefore, was to investigate associations between obesity and gene methylation in breast tumors. Methods Using the Illumina GoldenGate Cancer I Panel, we estimated the association between body mass index (BMI) and gene methylation in 345 breast tumor samples from Phase I of the Carolina Breast Cancer Study, a population based case-control study. Multivariable linear regression was used to identify sites that were differentially methylated by BMI. Stratification by tumor estrogen receptor status was also conducted. Results In the majority of the 935 probes analyzed (87%), the average beta value increased with obesity (BMI ≥ 30). Obesity was significantly associated with differential methylation (false discovery rate q-value < 0.05) in just 2 gene loci in breast tumor tissue overall and in 21 loci among estrogen receptor (ER)-positive tumors. Obesity was associated with methylation of genes that function in immune response, cell growth, and DNA repair. Conclusions Obesity is associated with altered methylation overall, and with hypermethylation among ER-positive tumors in particular, suggesting that obesity may influence the methylation of genes with known relevance to cancer. Some of these differences in methylation by obese status may influences levels of gene expression within breast cells. Impact If our results are validated, obesity-associated methylation sites could serve as targets for prevention and treatment research. PMID:25583948

  4. Huge malignant phyllodes breast tumor: a real entity in a new era of early breast cancer.

    PubMed

    Testori, Alberto; Meroni, Stefano; Errico, Valentina; Travaglini, Roberto; Voulaz, Emanuele; Alloisio, Marco

    2015-02-27

    Phyllodes tumor is an extremely rare tumor of the breast. It occurs in females in the third and fourth decades. The difficulty in distinguishing between phyllodes tumors and benign fibroadenoma may lead to misdiagnosis. Lymph node involvement is rarely described in phyllodes tumors; for this reason, sentinel node biopsy may be warranted. We present a case of a 33-year-old woman affected by huge tumor of the right breast with ulceration in the skin with a rapid tumor growth and with omolateral axillary metastasis.

  5. Current Issues and Clinical Evidence in Tumor-Infiltrating Lymphocytes in Breast Cancer

    PubMed Central

    Ahn, Sung Gwe; Jeong, Joon; Hong, SoonWon; Jung, Woo Hee

    2015-01-01

    With the advance in personalized therapeutic strategies in patients with breast cancer, there is an increasing need for biomarker-guided therapy. Although the immunogenicity of breast cancer has not been strongly considered in research or practice, tumor-infiltrating lymphocytes (TILs) are emerging as biomarkers mediating tumor response to treatments. Earlier studies have provided evidence that the level of TILs has prognostic value and the potential for predictive value, particularly in triple-negative and human epidermal growth factor receptor 2–positive breast cancer. Moreover, the level of TILs has been associated with treatment outcome in patients undergoing neoadjuvant chemotherapy. To date, no standardized methodology for measuring TILs has been established. In this article, we review current issues and clinical evidence for the use of TILs in breast cancer. PMID:26278518

  6. Extremely rare borderline phyllodes tumor in the male breast: a case report.

    PubMed

    Kim, Jung Gyu; Kim, Shin Young; Jung, Hae Yoen; Lee, Deuk Young; Lee, Jong Eun

    2015-01-01

    Phyllodes tumor of the male breast is an extremely rare disease, and far fewer cases of borderline phyllodes tumors than benign or malignant tumors in the male breast have been reported. We report a case of borderline phyllodes tumor in the male breast with imaging findings of the tumor and pathologic correlation.

  7. Tumor Tension Induces Persistent Inflammation and Promotes Breast Cancer Aggression

    DTIC Science & Technology

    2015-10-01

    Award Number: W81XWH-14-1-0056 TITLE: Tumor Tension Induces Persistent Inflammation and Promotes Breast Cancer Aggression PRINCIPAL INVESTIGATOR...Breast Cancer Aggression 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Ori Maller and Valerie M. Weaver email...ECM stiffening cooperate with inflammatory signaling to facilitate immune evasion and promote breast cancer aggression . In this progress report, I

  8. A Case of a Giant Borderline Phyllodes Tumor Early in Pregnancy Treated with Mastectomy and Immediate Breast Reconstruction.

    PubMed

    Gentile, Lori F; Gaillard, William Foster; Wallace, Jodi-Ann; Spiguel, Lisa R P; Alizadeh, Layla; Lentz, Ashley; Shaw, Christiana

    2016-11-01

    Breast tumors in pregnancy are often times diagnosed at advanced stages secondary to difficulty distinguishing between pathologic from normal physiologic changes. Often benign, phyllodes tumors are rare fibroepithelial stromal tumors of the breast, most commonly diagnosed in the 4th and 5th decades of life. However, these tumors may be characterized by malignancy with metastases in 10% of cases. In this paper, we report a novel case of a young woman presenting at 8 weeks gestation with a large borderline phyllodes tumor. An exceedingly rare condition, with only nine previously reported cases, phyllodes tumors in pregnancy frequently display more aggressive characteristics with larger median tumor size, more malignant potential, and more rapid growth rate. Here, we describe our experience safely and effectively treating this rare condition in a young gravid women with mastectomy and immediate breast reconstruction in the second trimester.

  9. Bilateral desmoid tumor of the breast: case seriesand literature review

    PubMed Central

    Wongmaneerung, Phanchaporn; Somwangprasert, Areewan; Watcharachan, Kirati; Ditsatham, Chagkrit

    2016-01-01

    Background Desmoid tumor of the breast is very rare and locally aggressive but has no distant metastasis. Bilateral lesions are extremely rare, found in only 4% of patients. Two cases of bilateral desmoid tumor of the breast are reported. The clinical presentation, diagnosis, imaging, treatment, and follow-up outcomes of recurrence as well as a brief literature review are provided. Case reports Case 1 is a 31-year-old woman who presented with nipple retraction. An ultrasound revealed BIRAD V in both breasts. She underwent a bilateral excisional biopsy under ultrasound mark with the pathology result of extra-abdominal desmoid tumor in both breasts. The patient had a bilateral mastectomy with silicone implantation due to the involved margins by excision. She remained tumor free after 7-year follow-up. Case 2 is a 28-year-old woman who presented with a lump on her right breast that she had discovered ~2 months earlier. An ultrasound showed a spiculated mass in the right breast and some circumscribed hypoechoic masses in both breasts. A bilateral breast excision was done. The pathology result was an extra-abdominal desmoid tumor. She had recurrence on both sides and underwent a mastectomy and silicone implantation. The tumor has not recurred after 1-year follow-up. Conclusion Imaging cannot distinguish between benign breast lesions and malignancy. Pathology results are helpful in making a definitive diagnosis. Given that the desmoid tumor is locally aggressive, a local excision with clear margins is recommended. Chemotherapy and hormonal treatment are controversial. PMID:27578999

  10. Recurrent angio-fibroma of breast masquerading as phyllodes tumor.

    PubMed

    Chaurasia, Jai K; Alam, Feroz; Shadan, Mariam; Naim, Mohammed

    2015-01-01

    A young Indian female presented with a recurring tumor in the right breast masquerading as phyllodes tumor. Patient had history of five times excision and recurrences of the tumor, diagnosed as fibrous phyllodes of the breast. Presently, a well-circumscribed tumor of about 10 cm size, comprising of benign fibrous-angiomatous tissue with evidence of foci of pyogenic vasculitis was observed. Immuno-histochemical markers for the myo-epithelial and epithelial elements excluded the possibility of fibrous phyllodes, inflammatory myofibroblastic tumor, desmoid fibromatosis, and metaplastic carcinoma. The present findings were diagnostic of an inflammatory angio-fibroma of the right breast, not reported in the earlier literature. The observations indicated that the female breast may be susceptible to spontaneous productive and common-antibiotic-resistant focal septic vascular inflammation giving rise to angio-fibromatous proliferation producing a well-defined tumor mass in the breast, distinguishable from the other breast lesions by the connective tissue stains and immuno-histochemical markers.

  11. Giant cell tumor of soft tissue arising in breast.

    PubMed

    May, Steve A; Deavers, Michael T; Resetkova, Erika; Johnson, Deborah; Albarracin, Constance T

    2007-10-01

    Primary giant cell tumor of soft tissue (GCT-ST) arising in breast is exceedingly rare. We report a case of a 60-year-old woman with a primary breast giant cell tumor that appeared histologically identical to giant cell tumor of bone and had a clinically malignant course. The patient presented with a cystic mass of the breast, suspected on imaging to be an organizing hematoma, possibly related to previous injury. Histopathological evaluation revealed a neoplasm composed of mononuclear cells admixed with osteoclast-like giant cells resembling giant cell tumor of bone. Immunohistochemical staining was positive for CD68, smooth muscle actin, and vimentin, but was negative for a panel of epithelial and additional muscle markers. These features were most consistent with GCT-ST, an uncommon neoplasm of low malignant potential. Despite aggressive surgical treatment achieving clear surgical margins, the patient expired with pulmonary metastases within a year of her initial presentation. This case demonstrates the difficulty of predicting clinical behavior of GCT-ST of breast on the basis of histological features and depth of tumor alone. To our knowledge, this is the first case report of a GCT-ST arising in the breast associated with a fatal outcome. The distinction of this entity from other more common primary breast tumors with giant cell morphology is also emphasized.

  12. Phyllodes tumors of the breast: diagnosis, treatment and prognostic factors related to recurrence

    PubMed Central

    Zhou, Zhi-Rui; Wang, Chen-Chen; Yang, Zhao-Zhi

    2016-01-01

    Phyllodes tumors of the breast are rare tumor types that consist of 0.3–1.0% in all breast tumors. The naming and classification of breast phyllodes tumor have been debated for years. Based on the classification criteria modified by WHO in 2003, this review mainly introduced the clinicopathologic characteristics, pre-operational diagnosis and the treatment of breast phyllodes tumors, and also summarized the prognostic factors related to tumor recurrence. PMID:28066617

  13. Male Breast Cancer

    MedlinePlus

    ... hasn't spread beyond your breast tissue. Radiation therapy Radiation therapy uses high-energy beams to kill ... option for men with advanced breast cancer. Hormone therapy Most men with male breast cancer have tumors ...

  14. Detection of cellular senescence within human invasive breast carcinomas distinguishes different breast tumor subtypes

    PubMed Central

    Cotarelo, Cristina L.; Schad, Arno; Kirkpatrick, Charles James; Sleeman, Jonathan P.; Springer, Erik; Schmidt, Marcus; Thaler, Sonja

    2016-01-01

    Oncogene-induced senescence is thought to act as a barrier to tumorigenesis by arresting cells at risk of malignant transformation. Nevertheless, numerous findings suggest that senescent cells may conversely promote tumor progression through the development of the senescence-associated secretome they produce. It is likely that the composition and the physiological consequences mediated by the senescence secretome are dependent on the oncogenes that trigger the senescence program. Breast cancer represents a heterogenous disease that can be divided into breast cancer subtypes due to different subsets of genetic and epigenetic abnormalities. As tumor initiation and progression of these breast cancer subtypes is triggered by diverse oncogenic stimuli, differences in the senescence secretomes within breast tumors might be responsible for tumor initiation, progression, metastasis and therapeutic response. Many studies have addressed the role of senescence as a barrier to tumor progression using murine xenograft models. However, few investigations have been performed to elucidate the degree to which senescent tumor cells are present within untreated human tumors, and if present, whether these senescent tumor cells may play a role in disease progression. In the present study we analysed the appearance of senescent cells within invasive breast cancers. Detection of cellular senescence by the use of SAβ-galactosidase (SAβ-gal) staining within invasive breast carcinoms from 129 untreated patients revealed differences in the amount of SAβ-gal+ tumor cells between breast cancer subtypes. The highest percentages of SAβ-gal+ tumor cells were found in HER2-positive and luminal A breast carcinomas whereas triple negative tumors showed either little or no positivity. PMID:27713152

  15. Cancer-associated adipocytes promotes breast tumor radioresistance

    SciTech Connect

    Bochet, Ludivine; Meulle, Aline; Imbert, Sandrine; Salles, Bernard; Valet, Philippe; Muller, Catherine

    2011-07-22

    Highlights: {yields} Tumor-surrounding adipocytes contribute to breast cancer progression. {yields} Breast tumor cells previously co-cultivated with mature adipocytes exhibit radioresistance. {yields} Increased in Chk1 phosphorylation is observed in irradiated co-cultivated tumor cells. {yields} IL-6 is over-expressed in tumor cells co-cultivated with adipocytes. {yields} IL-6 exposure confers increased Chk1 phosphorylation and radioresistance in tumor cells. -- Abstract: Mature adipocytes are excellent candidates to influence tumor behavior through heterotypic signaling processes since these cells produce hormones, growth factors, cytokines and other molecules, a heterogeneous group of molecules named adipokines. Using a 2D coculture system, we demonstrate that breast tumor cells previously co-cultivated with mature adipocytes exhibit radioresistance and an earlier and higher increase in the effector kinase Chk1, a phenotype that was associated with decreased cell death as compared to tumor cells grown alone. Interestingly, the adipocytes-induced tumor changes taking place during the coculture time preceding the exposure to IR were sufficient to confer the radioresistant effect. Notorious among the changes brought by adipocytes was the significant increase of IL-6 expression in tumor cells, whose activity may well account for the observed tumor cell protection from IR toxicity. Indeed, our data confirmed the protective role of this cytokine as tumor cells incubated after irradiation with recombinant IL-6 exhibit an increased in Chk1 phosphorylation and a radioresistant phenotype, thus far recapitulating the effects observed in the presence of adipocytes. Our current study sheds light on a new role of tumor-surrounding adipocytes in fostering a radioresistant phenotype in breast tumors, a finding that might have important clinical implications in obese patients that frequently exhibit aggressive diseases.

  16. ADAM12 produced by tumor cells rather than stromal cells accelerates breast tumor progression.

    PubMed

    Fröhlich, Camilla; Nehammer, Camilla; Albrechtsen, Reidar; Kronqvist, Pauliina; Kveiborg, Marie; Sehara-Fujisawa, Atsuko; Mercurio, Arthur M; Wewer, Ulla M

    2011-11-01

    Expression of ADAM12 is low in most normal tissues but is markedly increased in numerous human cancers, including breast carcinomas. We have previously shown that overexpression of ADAM12 accelerates tumor progression in a mouse model of breast cancer (PyMT). In this study, we found that ADAM12 deficiency reduces breast tumor progression in the PyMT model. However, the catalytic activity of ADAM12 seems to be dispensable for its tumor-promoting effect. Interestingly, we show that ADAM12 endogenously expressed in tumor-associated stroma in the PyMT model does not influence tumor progression, but that ADAM12 expression by tumor cells is necessary for tumor progression in these mice. This finding is consistent with our observation that in human breast carcinoma, ADAM12 is almost exclusively located in tumor cells and, only rarely, seen in the tumor-associated stroma. We hypothesized, however, that the tumor-associated stroma may stimulate ADAM12 expression in tumor cells, on the basis of the fact that TGF-β1 stimulates ADAM12 expression and is a well-known growth factor released from tumor-associated stroma. TGF-β1 stimulation of ADAM12-negative Lewis lung tumor cells induced ADAM12 synthesis, and growth of these cells in vivo induced more than 200-fold increase in ADAM12 expression. Our observation that ADAM12 expression is significantly higher in the terminal duct lobular units (TDLU) adjacent to human breast carcinoma compared with TDLUs found in normal breast tissue supports our hypothesis that tumor-associated stroma triggers ADAM12 expression.

  17. Sex steroids in human brain tumors and breast cancer.

    PubMed

    von Schoultz, E; Bixo, M; Bäckström, T; Silfvenius, H; Wilking, N; Henriksson, R

    1990-02-15

    The concentrations of three sex steroids, estradiol, progesterone and testosterone, were analyzed by radioimmunoassay after celite chromatography in brain tumor and breast cancer tissues. The concentrations in malignant gliomas and breast cancers showed interindividual variations, especially evident with regard to estradiol. High estradiol concentrations were recorded in two patients with malignant astrocytoma. The concentrations of 1.00 pg/mg and 3.32 pg/mg were 10 to 30 times as high as in normal female brain. In five of ten astrocytomas the estradiol concentration was higher than the lowest breast cancer value. The distribution of progesterone seemed more even, and the level was significantly lower in brain tumors and breast cancers as compared with female brain, perhaps indicating an increased metabolism. Testosterone levels were somewhat higher in brain tumors, as compared with breast cancers, but not different from values in brain tissue. There were no significant age or sex correlation or differences in the concentrations of steroids in the brain tumors. The results suggest that manipulation of sex steroid metabolism in malignant brain tumors can be of beneficial therapeutic value as has been shown for breast cancer and prostatic carcinoma.

  18. Systemic Therapies for Advanced Pancreatic Neuroendocrine Tumors

    PubMed Central

    Raj, Nitya; Reidy-Lagunes, Diane

    2016-01-01

    SYNOPSIS Pancreatic neuroendocrine tumors are a rare tumor type, and comprise 1-2% of all pancreatic neoplasms. When nonfunctional (i.e. nonhormone secreting), these tumors generally cause few symptoms and often go unnoticed for several years; for this reason, they are rarely localized at presentation, and are typically diagnosed in the presence of metastatic disease, most commonly to the liver. Although pancreatic neuroendocrine tumors can be less aggressive than other tumor types, the management poses a significant challenge because of the heterogeneous clinical presentations and varying degrees of aggressiveness. The therapy of pancreatic neuroendocrine tumors includes a multimodality approach and can often include surgery, liver-directed therapies (i.e. embolization), as well as targeted and cytotoxic systemic treatments. A variety of systemic therapies have been developed for the management of pancreatic neuroendocrine tumors. These therapies include somatostatin analogs (octreotide or lanreotide), a select group of cytotoxic chemotherapy agents (alkylating, fluorouracil and platinum drugs), as well as targeted or biologic agents (everolimus and sunitinib). This chapter will review the available systemic therapy options for advanced pancreatic neuroendocrine tumors. PMID:26614372

  19. Distinct tumor protein p53 mutants in breast cancer subgroups.

    PubMed

    Dumay, Anne; Feugeas, Jean-Paul; Wittmer, Evelyne; Lehmann-Che, Jacqueline; Bertheau, Philippe; Espié, Marc; Plassa, Louis-François; Cottu, Paul; Marty, Michel; André, Fabrice; Sotiriou, Christos; Pusztai, Lajos; de Thé, Hugues

    2013-03-01

    Tumor protein p53 (TP53) is mutated in approximately 30% of breast cancers, but this frequency fluctuates widely between subclasses. We investigated the p53 mutation status in 572 breast tumors, classified into luminal, basal and molecular apocrine subgroups. As expected, the lowest mutation frequency was observed in luminal (26%), and the highest in basal (88%) tumors. Luminal tumors showed significantly higher frequency of substitutions (82 vs. 65%), notably A/T to G/C transitions (31 vs. 15%), whereas molecular apocrine and basal tumors presented much higher frequencies of complex mutations (deletions/insertions) (36 and 33%, respectively, vs. 18%). Accordingly, missense mutations were significantly more frequent in luminal tumors (75 vs. 54%), whereas basal tumors displayed significantly increased rates of TP53 truncations (43 vs. 25%), resulting in loss of function and/or expression. Interestingly, as basal tumors, molecular apocrine tumors presented with a high rate of complex mutations, but paradoxically, these were not associated with increased frequency of p53 truncation. As in luminal tumors, this could reflect a selective pressure for p53 gain of function, possibly through P63/P73 inactivation. Collectively, these observations point not only to different mechanisms of TP53 alterations, but also to different functional consequences in the different breast cancer subtypes.

  20. Molecular Markers for Breast Cancer: Prediction on Tumor Behavior

    PubMed Central

    Banin Hirata, Bruna Karina; Oda, Julie Massayo Maeda; Losi Guembarovski, Roberta; Ariza, Carolina Batista; de Oliveira, Carlos Eduardo Coral; Watanabe, Maria Angelica Ehara

    2014-01-01

    Breast cancer is one of the most common cancers with greater than 1,300,000 cases and 450,000 deaths each year worldwide. The development of breast cancer involves a progression through intermediate stages until the invasive carcinoma and finally into metastatic disease. Given the variability in clinical progression, the identification of markers that could predict the tumor behavior is particularly important in breast cancer. The determination of tumor markers is a useful tool for clinical management in cancer patients, assisting in diagnostic, staging, evaluation of therapeutic response, detection of recurrence and metastasis, and development of new treatment modalities. In this context, this review aims to discuss the main tumor markers in breast carcinogenesis. The most well-established breast molecular markers with prognostic and/or therapeutic value like hormone receptors, HER-2 oncogene, Ki-67, and p53 proteins, and the genes for hereditary breast cancer will be presented. Furthermore, this review shows the new molecular targets in breast cancer: CXCR4, caveolin, miRNA, and FOXP3, as promising candidates for future development of effective and targeted therapies, also with lower toxicity. PMID:24591761

  1. Curcumin reverses breast tumor exosomes mediated immune suppression of NK cell tumor cytotoxicity

    PubMed Central

    Zhang, Huang-Ge; Kim, Helen; Liu, Cunren; Yu, Shaohua; Wang, Jianhua; Grizzle, William E.; Kimberly, Robert P.; Barnes, Stephen

    2007-01-01

    An important characteristic of tumors is that they at some point in their development overcome the surveillance of the immune system. Tumors secrete exosomes, multivesicular bodies containing a distinct set of proteins that can fuse with cells of the circulating immune system. Purified exosomes from TS/A breast cancer cells, but not non-exosomal fractions, inhibit (at concentrations of nanograms per ml protein) IL-2-induced natural killer (NK) cell cytotoxicity. The dietary polyphenol, curcumin (diferuloylmethane), partially reverses tumor exosome-mediated inhibition of natural killer cell activation, which is mediated through the impairment of the ubiquitin-proteasome system. Exposure of mouse breast tumor cells to curcumin causes a dose-dependent increase in ubiquitinated exosomal proteins compared to those in untreated TS/A breast tumor cells. Furthermore, exosomes isolated from tumor cells pretreated with curcumin have a much attenuated inhibition of IL-2 stimulated NK cell activation. Jak3-mediated activation of Stat5 is required for tumor cytotoxicity of IL-2 stimulated NK cells. TS/A tumor exosomes strongly inhibit activation of Stat5, whereas the tumor exosomes isolated from curcumin-pretreated tumor cells have a lowered potency for inhibition of IL-2 stimulated NK cell cytotoxicity. These data suggest that partial reversal of tumor exosome-mediated inhibition of NK cell tumor cytotoxicity may account for the anti-cancer properties curcumin. PMID:17555831

  2. Rare Malignant Tumors of the Breast

    PubMed Central

    Miller, Trevor; Albarracin, Constance; Carkaci, Selin; Whitman, Gary J; Adrada, Beatriz E

    2015-01-01

    While the more common forms of breast cancer are well understood and recognized, there are many important rare malignancies that are less appreciated. Many of these cancers have imaging findings that, when understood, help to formulate a more educated differential diagnosis. In this article, the clinical features, imaging, and pathologic findings of rare breast malignancies will be discussed. PMID:26664775

  3. Rare Malignant Tumors of the Breast.

    PubMed

    Miller, Trevor; Albarracin, Constance; Carkaci, Selin; Whitman, Gary J; Adrada, Beatriz E

    2015-01-01

    While the more common forms of breast cancer are well understood and recognized, there are many important rare malignancies that are less appreciated. Many of these cancers have imaging findings that, when understood, help to formulate a more educated differential diagnosis. In this article, the clinical features, imaging, and pathologic findings of rare breast malignancies will be discussed.

  4. Relationship between tumor biomarkers and efficacy in TH3RESA, a phase III study of trastuzumab emtansine (T-DM1) vs. treatment of physician's choice in previously treated HER2-positive advanced breast cancer.

    PubMed

    Kim, Sung-Bae; Wildiers, Hans; Krop, Ian E; Smitt, Melanie; Yu, Ron; Lysbet de Haas, Sanne; Gonzalez-Martin, Antonio

    2016-11-15

    In the phase III TH3RESA study (NCT01419197), 602 patients with HER2-positive advanced breast cancer who received prior taxane therapy and ≥2 HER2-directed regimens, including trastuzumab and lapatinib (advanced setting), were randomized to trastuzumab emtansine (T-DM1) or treatment of physician's choice (TPC). A statistically significant progression-free survival (PFS) benefit favoring T-DM1 was demonstrated. Here, we examine the relationship between HER2-related biomarkers and PFS in an exploratory analysis. Biomarkers assessed included HER2 (n = 505) and HER3 (n = 505) mRNA expression, PIK3CA mutation status (n = 410) and PTEN protein expression (n = 358). For biomarkers with continuous data (HER2, HER3, PTEN), subgroups were defined using median values (>median and ≤median). For all biomarker subgroups, median PFS was longer with T-DM1 vs. TPC. The PFS benefit favoring T-DM1 vs. TPC was numerically greater in the HER2 mRNA >median subgroup (7.2 vs. 3.4 months; unstratified hazard ratio [HR], 0.40; 95% CI, 0.28-0.59; p < 0.0001) vs. ≤median subgroup (5.5 vs. 3.9 months; HR, 0.68; 95% CI, 0.49-0.92; p = 0.0131). The PFS benefit with T-DM1 was similar among HER3, PIK3CA and PTEN subgroups. Consistent with other reports, benefit was seen with T-DM1 regardless of PIK3CA mutation status. In a multivariate analysis including an interaction term (treatment group by log2-transformed HER2 mRNA), patients with higher HER2 mRNA levels benefited more from receiving T-DM1 (HR, 0.84; 95% CI, 0.75-0.94; interaction p value = 0.0027). In summary, T-DM1 prolonged median PFS in all biomarker subgroups analyzed, including activating PIK3CA mutations, with numerically greater benefit in patients with tumors expressing HER2 mRNA >median vs. ≤median.

  5. Selective Mastectomy in the Management of Locally Advanced Breast Cancer

    SciTech Connect

    Ahern, Verity . E-mail: verity.ahern@swahs.healthnsw.gov.au; Boyages, John; Gebski, Val M. Stat; Moon, Dominic; Wilcken, Nicholas

    2007-07-15

    Purpose: To evaluate local control for patients with locally advanced noninflammatory breast cancer (LABC) managed by selective mastectomy. Methods and Materials: Between 1979 and 1996, 176 patients with LABC were prospectively managed by chemotherapy (CT)-irradiation (RT)-CT without routine mastectomy. All surviving patients were followed for a minimum of 5 years. Results: A total of 132 patients (75%) had a T4 tumor and 22 (12.5%) supraclavicular nodal disease. The clinical complete response rate was 91% (160/176), which included 13 patients who underwent mastectomy and 2 an iridium wire implant. The first site of failure was local for 43 patients (breast {+-} axilla for 38); 27 of these patients underwent salvage mastectomy and 11 did not for an overall mastectomy rate of 23% (40/176). If all 176 patients had undergone routine mastectomy (136 extra mastectomies), 11 additional patients may have avoided an unsalvageable first local relapse. The others would have either have not had a local relapse or would have suffered local relapse after distant disease. No tumor or treatment related factor was found to predict local disease at death. Median disease-free and overall survival for all patients was 26 and 52 months, respectively. Conclusions: Selective mastectomy in LABC may not jeopardize local control or survival.

  6. One - Carbon Metabolism and Methylation in Breast Tumors

    DTIC Science & Technology

    2006-06-01

    2) Extract DNA from tumor tissue and treat it with sodium metabisulphate to modify all unmethylated cytosines. Use modified DNA to determine the...important one-carbon nutrient that works intricately with folic acid. A B6 deficiency results in a decreased enzyme activity of serine hydroxymethyl ...cases ( N = 105) were women older than 39 years of age that presented with a suspicious breast mass that was later confirmed as breast cancer

  7. Role of Fetuin-A in Breast Tumor Cell Growth

    DTIC Science & Technology

    2009-03-01

    Growth PRINCIPAL INVESTIGATOR: Josiah Ochieng, Ph.D. CONTRACTING ORGANIZATION: Meharry Medical College Nashville, TN 37208...COVERED (From - To) 4. TITLE AND SUBTITLE Role of fetuin-A in Breast Tumor Cell Growth 5a. CONTRACT NUMBER W81XWH-07-1-0254 5b. GRANT NUMBER...hypothesis of this grant is that fetuin-A is a major serum derived growth factor for breast carcinoma cells and creates a favorable environment for the

  8. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models

    PubMed Central

    Liu, Huiping; Patel, Manishkumar R.; Prescher, Jennifer A.; Patsialou, Antonia; Qian, Dalong; Lin, Jiahui; Wen, Susanna; Chang, Ya-Fang; Bachmann, Michael H.; Shimono, Yohei; Dalerba, Piero; Adorno, Maddalena; Lobo, Neethan; Bueno, Janet; Dirbas, Frederick M.; Goswami, Sumanta; Somlo, George; Condeelis, John; Contag, Christopher H.; Gambhir, Sanjiv Sam; Clarke, Michael F.

    2010-01-01

    To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled with optical reporter fusion genes. These models recapitulate human cancer features not captured with previous models, including spontaneous metastasis in particular, and provide a useful platform for studies of breast tumor initiation and progression. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. These advances in BCSC imaging revealed that CD44+ cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy. PMID:20921380

  9. Advances in Cancer Immunotherapy in Solid Tumors

    PubMed Central

    Menon, Smitha; Shin, Sarah; Dy, Grace

    2016-01-01

    Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses. Drugs which block the immune regulatory checkpoints namely the PD-1/PDL1 and CTLA 4 pathway have shown tremendous promise in a wide spectrum of solid and hematological malignancies, significantly improving overall survival in newly diagnosed and heavily pretreated patients alike. Hence there is renewed enthusiasm in the field of immune oncology with current research focused on augmenting responses to checkpoint inhibitors by combination therapy as well as studies looking at other immune modulators and adoptive T cell therapy. In this article, we highlight the key clinical advances and concepts in immunotherapy with particular emphasis on checkpoint inhibition as well as the future direction in this field. PMID:27886124

  10. Noninvasive Characterization of Locally Advanced Breast Cancer Using Textural Analysis of Quantitative Ultrasound Parametric Images

    PubMed Central

    Tadayyon, Hadi; Sadeghi-Naini, Ali; Czarnota, Gregory J.

    2014-01-01

    PURPOSE: The identification of tumor pathologic characteristics is an important part of breast cancer diagnosis, prognosis, and treatment planning but currently requires biopsy as its standard. Here, we investigated a noninvasive quantitative ultrasound method for the characterization of breast tumors in terms of their histologic grade, which can be used with clinical diagnostic ultrasound data. METHODS: Tumors of 57 locally advanced breast cancer patients were analyzed as part of this study. Seven quantitative ultrasound parameters were determined from each tumor region from the radiofrequency data, including mid-band fit, spectral slope, 0-MHz intercept, scatterer spacing, attenuation coefficient estimate, average scatterer diameter, and average acoustic concentration. Parametric maps were generated corresponding to the region of interest, from which four textural features, including contrast, energy, homogeneity, and correlation, were determined as further tumor characterization parameters. Data were examined on the basis of tumor subtypes based on histologic grade (grade I versus grade II to III). RESULTS: Linear discriminant analysis of the means of the parametric maps resulted in classification accuracy of 79%. On the other hand, the linear combination of the texture features of the parametric maps resulted in classification accuracy of 82%. Finally, when both the means and textures of the parametric maps were combined, the best classification accuracy was obtained (86%). CONCLUSIONS: Textural characteristics of quantitative ultrasound spectral parametric maps provided discriminant information about different types of breast tumors. The use of texture features significantly improved the results of ultrasonic tumor characterization compared to conventional mean values. Thus, this study suggests that texture-based quantitative ultrasound analysis of in vivo breast tumors can provide complementary diagnostic information about tumor histologic characteristics

  11. Optical assessment of tumor resection margins in the breast

    PubMed Central

    Brown, J. Quincy; Bydlon, Torre M.; Richards, Lisa M.; Yu, Bing; Kennedy, Stephanie A.; Geradts, Joseph; Wilke, Lee G.; Junker, Marlee; Gallagher, Jennifer; Barry, William; Ramanujam, Nimmi

    2011-01-01

    Breast conserving surgery, in which the breast tumor and surrounding normal tissue are removed, is the primary mode of treatment for invasive and in situ carcinomas of the breast, conditions that affect nearly 200,000 women annually. Of these nearly 200,000 patients who undergo this surgical procedure, between 20–70% of them may undergo additional surgeries to remove tumor that was left behind in the first surgery, due to the lack of intra-operative tools which can detect whether the boundaries of the excised specimens are free from residual cancer. Optical techniques have many attractive attributes which may make them useful tools for intra-operative assessment of breast tumor resection margins. In this manuscript, we discuss clinical design criteria for intra-operative breast tumor margin assessment, and review optical techniques appied to this problem. In addition, we report on the development and clinical testing of quantitative diffuse reflectance imaging (Q-DRI) as a potential solution to this clinical need. Q-DRI is a spectral imaging tool which has been applied to 56 resection margins in 48 patients at Duke University Medical Center. Clear sources of contrast between cancerous and cancer-free resection margins were identified with the device, and resulted in an overall accuracy of 75% in detecting positive margins. PMID:21544237

  12. Triple negative tumors accumulate significantly less methylglyoxal specific adducts than other human breast cancer subtypes.

    PubMed

    Chiavarina, Barbara; Nokin, Marie-Julie; Durieux, Florence; Bianchi, Elettra; Turtoi, Andrei; Peulen, Olivier; Peixoto, Paul; Irigaray, Philippe; Uchida, Koji; Belpomme, Dominique; Delvenne, Philippe; Castronovo, Vincent; Bellahcène, Akeila

    2014-07-30

    Metabolic syndrome and type 2 diabetes are associated with increased risk of breast cancer development and progression. Methylglyoxal (MG), a glycolysis by-product, is generated through a non-enzymatic reaction from triose-phosphate intermediates. This dicarbonyl compound is highly reactive and contributes to the accumulation of advanced glycation end products. In this study, we analyzed the accumulation of Arg-pyrimidine, a MG-arginine adduct, in human breast adenocarcinoma and we observed a consistent increase of Arg-pyrimidine in cancer cells when compared with the non-tumoral counterpart. Further immunohistochemical comparative analysis of breast cancer subtypes revealed that triple negative lesions exhibited low accumulation of Arg-pyrimidine compared with other subtypes. Interestingly, the activity of glyoxalase 1 (Glo-1), an enzyme that detoxifies MG, was significantly higher in triple negative than in other subtype lesions, suggesting that these aggressive tumors are able to develop an efficient response against dicarbonyl stress. Using breast cancer cell lines, we substantiated these clinical observations by showing that, in contrast to triple positive, triple negative cells induced Glo-1 expression and activity in response to MG treatment. This is the first report that Arg-pyrimidine adduct accumulation is a consistent event in human breast cancer with a differential detection between triple negative and other breast cancer subtypes.

  13. Intrinsic breast tumor subtypes, race, and long-term survival in the Carolina Breast Cancer Study

    PubMed Central

    O’Brien, Katie M.; Cole, Stephen R.; Tse, Chiu-Kit; Perou, Charles M.; Carey, Lisa A.; Foulkes, William D.; Dressler, Lynn G.; Geradts, Joseph; Millikan, Robert C.

    2010-01-01

    Purpose Previous research identified differences in breast cancer-specific mortality across four "intrinsic" tumor subtypes: luminal A, luminal B, basal-like, and human epidermal growth factor receptor 2 positive/estrogen receptor negative (HER2+/ER−). Experimental Design We used immunohistochemical markers to subtype 1149 invasive breast cancer patients (518 African American, 631 white) in the Carolina Breast Cancer Study, a population-based study of women diagnosed with breast cancer. Vital status was determined through 2006 using the National Death Index, with median follow-up of 9 years. Results Cancer subtypes luminal A, luminal B, basal-like and HER2+/ER- were distributed as 64%, 11%, 11% and 5% for whites, and 48%, 8%, 22% and 7% for African Americans, respectively. Breast cancer mortality was higher for patients with HER2+/ER- and basal-like breast cancer compared to luminal A and B. African Americans had higher breast-cancer specific mortality than whites, but the effect of race was statistically significant only among women with luminal A breast cancer. However, when compared to the luminal A subtype within racial categories, mortality for patients with basal-like breast cancer was higher among whites (HR=2.0, 95% CI: 1.2, 3.4) than African Americans (HR=1.5, 95% CI: 1.0, 2.4), with the strongest effect seen in postmenopausal white women (HR=3.9, 95% CI: 1.5, 10.0). Conclusions Our results confirm the association of basal-like breast cancer with poor prognosis, and suggest that basal-like breast cancer is not an inherently more aggressive disease in African American women compared to whites. Additional analyses are needed in populations with known treatment profiles to understand the role of tumor subtypes and race in breast cancer mortality, and in particular our finding that among women with luminal A breast cancer, African Americans have higher mortality than whites. PMID:21169259

  14. Pembrolizumab Combined With Itacitinib (INCB039110) and/or Pembrolizumab Combined With INCB050465 in Advanced Solid Tumors

    ClinicalTrials.gov

    2017-02-02

    Advanced Solid Tumors; Endometrial Cancer; Melanoma; Microsatellite Unstable (MSI) Colorectal Cancer; MMR-deficient Tumors; Non-small Cell Lung Cancer; Renal Cell Carcinoma; Head and Neck Squamous Cell Carcinoma; Triple Negative Breast Cancer; Transitional Cell Carcinoma of the Genitourinary Tract; Pancreatic Ductal Adenocarcinoma; Small Cell Lung Cancer

  15. Tungsten targets the tumor microenvironment to enhance breast cancer metastasis.

    PubMed

    Bolt, Alicia M; Sabourin, Valérie; Molina, Manuel Flores; Police, Alice M; Negro Silva, Luis Fernando; Plourde, Dany; Lemaire, Maryse; Ursini-Siegel, Josie; Mann, Koren K

    2015-01-01

    The number of individuals exposed to high levels of tungsten is increasing, yet there is limited knowledge of the potential human health risks. Recently, a cohort of breast cancer patients was left with tungsten in their breasts following testing of a tungsten-based shield during intraoperative radiotherapy. While monitoring tungsten levels in the blood and urine of these patients, we utilized the 66Cl4 cell model, in vitro and in mice to study the effects of tungsten exposure on mammary tumor growth and metastasis. We still detect tungsten in the urine of patients' years after surgery (mean urinary tungsten concentration at least 20 months post-surgery = 1.76 ng/ml), even in those who have opted for mastectomy, indicating that tungsten does not remain in the breast. In addition, standard chelation therapy was ineffective at mobilizing tungsten. In the mouse model, tungsten slightly delayed primary tumor growth, but significantly enhanced lung metastasis. In vitro, tungsten did not enhance 66Cl4 proliferation or invasion, suggesting that tungsten was not directly acting on 66Cl4 primary tumor cells to enhance invasion. In contrast, tungsten changed the tumor microenvironment, enhancing parameters known to be important for cell invasion and metastasis including activated fibroblasts, matrix metalloproteinases, and myeloid-derived suppressor cells. We show, for the first time, that tungsten enhances metastasis in an animal model of breast cancer by targeting the microenvironment. Importantly, all these tumor microenvironmental changes are associated with a poor prognosis in humans.

  16. Unusual aggressive breast cancer: metastatic malignant phyllodes tumor.

    PubMed

    Singer, Adam; Tresley, Jonathan; Velazquez-Vega, Jose; Yepes, Monica

    2013-02-01

    For the year of 2012, it has been estimated that breast cancer will account for the greatest number of newly diagnosed cancers and the second highest proportion of cancer related deaths among women. Breast cancer, while often lumped together as one disease, represents a diverse group of malignancies with different imaging findings, histological appearances and behavior. While most invasive primary breast cancers are epithelial derived adenocarcinomas, rare neoplasms such as the phyllodes tumor may arise from mesenchymal tissue. Compared to the breast adenocarcinoma, the phyllodes tumor tends to affect a younger population, follows a different clinical course, is associated with different imaging and histological findings and is managed distinctively. There may be difficulty in differentiating the phyllodes tumor from a large fibroadenoma, but the mammographer plays a key role in reviewing the clinical and imaging data in order to arrive at the correct diagnosis. Early diagnosis with proper surgical management can often cure non-metastatic phyllodes tumors. However, in rare cases where metastasis occurs, prognosis tends to be poor. This report describes the presentation, imaging findings and management of a metastatic malignant phyllodes tumor.

  17. Noncontact diffuse correlation tomography of human breast tumor

    PubMed Central

    He, Lian; Lin, Yu; Huang, Chong; Irwin, Daniel; Szabunio, Margaret M.; Yu, Guoqiang

    2015-01-01

    Abstract. Our first step to adapt our recently developed noncontact diffuse correlation tomography (ncDCT) system for three-dimensional (3-D) imaging of blood flow distribution in human breast tumors is reported. A commercial 3-D camera was used to obtain breast surface geometry, which was then converted to a solid volume mesh. An ncDCT probe scanned over a region of interest on the mesh surface and the measured boundary data were combined with a finite element framework for 3-D image reconstruction of blood flow distribution. This technique was tested in computer simulations and in vivo human breasts with low-grade carcinoma. Results from computer simulations suggest that relatively high accuracy can be achieved when the entire tumor is within the sensitive region of diffuse light. Image reconstruction with a priori knowledge of the tumor volume and location can significantly improve the accuracy in recovery of tumor blood flow contrasts. In vivo imaging results from two breast carcinomas show higher average blood flow contrasts (5.9- and 10.9-fold) in the tumor regions compared to the surrounding tissues, which are comparable with previous findings using diffuse correlation spectroscopy. The ncDCT system has the potential to image blood flow distributions in soft and vulnerable tissues without distorting tissue hemodynamics. PMID:26259706

  18. Tungsten Targets the Tumor Microenvironment to Enhance Breast Cancer Metastasis

    PubMed Central

    Bolt, Alicia M.; Sabourin, Valérie; Molina, Manuel Flores; Police, Alice M.; Negro Silva, Luis Fernando; Plourde, Dany; Lemaire, Maryse; Ursini-Siegel, Josie; Mann, Koren K.

    2015-01-01

    The number of individuals exposed to high levels of tungsten is increasing, yet there is limited knowledge of the potential human health risks. Recently, a cohort of breast cancer patients was left with tungsten in their breasts following testing of a tungsten-based shield during intraoperative radiotherapy. While monitoring tungsten levels in the blood and urine of these patients, we utilized the 66Cl4 cell model, in vitro and in mice to study the effects of tungsten exposure on mammary tumor growth and metastasis. We still detect tungsten in the urine of patients’ years after surgery (mean urinary tungsten concentration at least 20 months post-surgery = 1.76 ng/ml), even in those who have opted for mastectomy, indicating that tungsten does not remain in the breast. In addition, standard chelation therapy was ineffective at mobilizing tungsten. In the mouse model, tungsten slightly delayed primary tumor growth, but significantly enhanced lung metastasis. In vitro, tungsten did not enhance 66Cl4 proliferation or invasion, suggesting that tungsten was not directly acting on 66Cl4 primary tumor cells to enhance invasion. In contrast, tungsten changed the tumor microenvironment, enhancing parameters known to be important for cell invasion and metastasis including activated fibroblasts, matrix metalloproteinases, and myeloid-derived suppressor cells. We show, for the first time, that tungsten enhances metastasis in an animal model of breast cancer by targeting the microenvironment. Importantly, all these tumor microenvironmental changes are associated with a poor prognosis in humans. PMID:25324207

  19. Isolation of circulating epithelial and tumor progenitor cells with an invasive phenotype from breast cancer patients

    PubMed Central

    Lu, Janice; Fan, Tina; Zhao, Qiang; Zeng, Wei; Zaslavsky, Eva; Chen, John J.; Frohman, Michael A.; Golightly, Marc G.; Madajewicz, Stefan; Chen, Wen-Tien

    2009-01-01

    Recent research advances show that tumor cell intravasation (entry into the circulation) and metastasis occur very early in breast cancer progression. Clinical studies also illustrate the potential importance of detection of circulating tumor cells (CTCs) in outcomes of patients with metastatic breast cancer. Whether these cells exhibit the invasiveness and express tumor stem or progenitor markers, hallmark of the metastatic phenotype, is less well characterized. To detect CTCs with the invasive phenotype and to explore their molecular features, we applied a functional cell separation method, called collagen adhesion matrix (CAM) assay, as enrichment and identification steps. The CAM-coated device successfully recovered tumor cells spiked in one mL of blood with a 54%±9% (n=18) recovery rate and 0.5-35% purity, and detected invasive tumor cells in 10/10 blood samples (100% yield) from patients with metastatic breast cancer with a range of 18 to 256 CTCs/mL and average of 126±25 (mean±SD) CTCs/mL. CTCs were detected in blood samples of 28/54 (52%) stage I-III breast cancer patients with a mean count of 61 CTCs/mL. Furthermore, the relative frequency of these cells correlated to the staging, lymph node-status and survival of patients with early stage breast cancer. CAM-captured cells were capable of propagation in culture. Gene expression and multiplex flow cytometric analyses on CAM-captured cells demonstrated the existence of distinct populations of CTCs including these of epithelial lineage and stem or progenitor cells. Thus, CAM-initiated CTC detection provides advantages for examining invasiveness and tumor progenitor phenotypes. PMID:19662651

  20. Plumbagin inhibits breast tumor bone metastasis and osteolysis by modulating the tumor-bone microenvironment.

    PubMed

    Li, Z; Xiao, J; Wu, X; Li, W; Yang, Z; Xie, J; Xu, L; Cai, X; Lin, Z; Guo, W; Luo, J; Liu, M

    2012-09-01

    Bone metastasis is a common and serious consequence of breast cancer. Bidirectional interaction between tumor cells and the bone marrow microenvironment drives a so-called 'vicious cycle' that promotes tumor cell malignancy and stimulates osteolysis. Targeting these interactions and pathways in the tumor-bone microenvironment has been an encouraging strategy for bone metastasis therapy. In the present study, we examined the effects of plumbagin on breast cancer bone metastasis. Our data indicated that plumbagin inhibited cancer cell migration and invasion, suppressed the expression of osteoclast-activating factors, altered the cancer cell induced RANKL/OPG ratio in osteoblasts, and blocked both cancer cell- and RANKL-stimulated osteoclastogenesis. In mouse model of bone metastasis, we further demonstrated that plumbagin significantly repressed breast cancer cell metastasis and osteolysis, inhibited cancer cell induced-osteoclastogenesis and the secretion of osteoclast-activating factors in vivo. At the molecular level, we found that plumbagin abrogated RANKL-induced NF-κB and MAPK pathways by blocking RANK association with TRAF6 in osteoclastogenesis, and by inhibiting the expression of osteoclast-activating factors through the suppression of NF-κB activity in breast cancer cells. Taken together, our data demonstrate that plumbagin inhibits breast tumor bone metastasis and osteolysis by modulating the tumor-bone microenvironment and that plumbagin may serve as a novel agent in the treatment of tumor bone metastasis.

  1. RACE-ASSOCIATED BIOLOGICAL DIFFERENCES AMONG LUMINAL A BREAST TUMORS

    PubMed Central

    D’Arcy, Monica; Fleming, Jodie; Robinson, Whitney R.; Kirk, Erin L.; Perou, Charles M.; Troester, Melissa A.

    2015-01-01

    Purpose African American (AA) women have higher breast-cancer specific mortality rates. A higher prevalence of the worse outcome Basal-like breast cancer subtype contributes to this, but AA women also have higher mortality even within the more favorable outcomes Luminal A breast cancers. These differences may reflect treatment or health care access issues, inherent biological differences, or both. Methods To identify potential biological differences by race among Luminal A breast cancers, gene expression data from 108 CAU and 57 AA breast tumors were analyzed. Race-associated genes were next evaluated for associations with survival. Finally, expression of race- and survival-associated genes was evaluated in normal tissue of AA and CAU women. Results Six genes (ACOX2, MUC1, CRYBB2, PSPH, SQLE, TYMS) were differentially expressed by race among Luminal A breast cancers and were associated with survival (HR < 0.8, HR > 1.25). For all six genes, tumors in AA had higher expression of poor prognosis genes (CRYBB2, PSPH, SQLE, TYMS) and lower expression of good prognosis genes (ACOX2, MUC1). A score based on all six genes predicted survival in a large independent dataset (HR = 1.9 top vs. bottom quartile, 95% CI: 1.4 – 2.5). For four genes, normal tissue of AA and CAU women showed similar expression (ACOX2, MUC1, SQLE, TYMS), however, the poor outcome associated genes CRYBB2 and PSPH were more highly expressed in AA vs. CAU women’s normal tissue. Conclusions This analysis identified gene expression differences that may contribute to mortality disparities and suggests that among Luminal A breast tumors there are biological differences between AA and CAU patients. Some of these differences (CRYBB2 and PSPH) may exist from the earliest stages of tumor development, or even precede malignancy. PMID:26109344

  2. Microwave detection of breast tumors: comparison of skin subtraction algorithms

    NASA Astrophysics Data System (ADS)

    Fear, Elise C.; Stuchly, Maria A.

    2000-07-01

    Early detection of breast cancer is an important part of effective treatment. Microwave detection of breast cancer is of interest due to the contrast in dielectric properties of normal and malignant breast tissues. We are investigating a confocal microwave imaging system that adapts ideas from ground penetrating radar to breast cancer detection. In the proposed system, the patient lies prone with the breast extending through a hole in the examining table and encircled by an array of antennas. The breast is illuminated sequentially by each antenna with an ultrawideband signal, and the returns are recorded at the same antenna. Because the antennas are offset from the breast, the dominant component of the recorded returns is the reflection from the thin layer of breast skin. Two methods of reducing this reflection are compared, namely approximation of the signal with two time shifted, scaled and summed returns from a cylinder of skin, and subtraction of the mean of the set of aligned returns. Both approaches provide effective decrease of the skin signal, allowing for tumor detection.

  3. Palbociclib and Letrozole in Advanced Breast Cancer.

    PubMed

    Finn, Richard S; Martin, Miguel; Rugo, Hope S; Jones, Stephen; Im, Seock-Ah; Gelmon, Karen; Harbeck, Nadia; Lipatov, Oleg N; Walshe, Janice M; Moulder, Stacy; Gauthier, Eric; Lu, Dongrui R; Randolph, Sophia; Diéras, Véronique; Slamon, Dennis J

    2016-11-17

    Background A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than with letrozole alone in the initial treatment of postmenopausal women with estrogen-receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We performed a phase 3 study that was designed to confirm and expand the efficacy and safety data for palbociclib plus letrozole for this indication. Methods In this double-blind study, we randomly assigned, in a 2:1 ratio, 666 postmenopausal women with ER-positive, HER2-negative breast cancer, who had not had prior treatment for advanced disease, to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was progression-free survival, as assessed by the investigators; secondary end points were overall survival, objective response, clinical benefit response, patient-reported outcomes, pharmacokinetic effects, and safety. Results The median progression-free survival was 24.8 months (95% confidence interval [CI], 22.1 to not estimable) in the palbociclib-letrozole group, as compared with 14.5 months (95% CI, 12.9 to 17.1) in the placebo-letrozole group (hazard ratio for disease progression or death, 0.58; 95% CI, 0.46 to 0.72; P<0.001). The most common grade 3 or 4 adverse events were neutropenia (occurring in 66.4% of the patients in the palbociclib-letrozole group vs. 1.4% in the placebo-letrozole group), leukopenia (24.8% vs. 0%), anemia (5.4% vs. 1.8%), and fatigue (1.8% vs. 0.5%). Febrile neutropenia was reported in 1.8% of patients in the palbociclib-letrozole group and in none of the patients in the placebo-letrozole group. Permanent discontinuation of any study treatment as a result of adverse events occurred in 43 patients (9.7%) in the palbociclib-letrozole group and in 13 patients (5.9%) in the placebo-letrozole group. Conclusions Among patients with previously untreated ER-positive, HER2-negative advanced breast cancer, palbociclib

  4. Breast tumor angiogenesis analysis using 3D power Doppler ultrasound

    NASA Astrophysics Data System (ADS)

    Chang, Ruey-Feng; Huang, Sheng-Fang; Lee, Yu-Hau; Chen, Dar-Ren; Moon, Woo Kyung

    2006-03-01

    Angiogenesis is the process that correlates to tumor growth, invasion, and metastasis. Breast cancer angiogenesis has been the most extensively studied and now serves as a paradigm for understanding the biology of angiogenesis and its effects on tumor outcome and patient prognosis. Most studies on characterization of angiogenesis focus on pixel/voxel counts more than morphological analysis. Nevertheless, in cancer, the blood flow is greatly affected by the morphological changes, such as the number of vessels, branching pattern, length, and diameter. This paper presents a computer-aided diagnostic (CAD) system that can quantify vascular morphology using 3-D power Doppler ultrasound (US) on breast tumors. We propose a scheme to extract the morphological information from angiography and to relate them to tumor diagnosis outcome. At first, a 3-D thinning algorithm helps narrow down the vessels into their skeletons. The measurements of vascular morphology significantly rely on the traversing of the vascular trees produced from skeletons. Our study of 3-D assessment of vascular morphological features regards vessel count, length, bifurcation, and diameter of vessels. Investigations into 221 solid breast tumors including 110 benign and 111 malignant cases, the p values using the Student's t-test for all features are less than 0.05 indicating that the proposed features are deemed statistically significant. Our scheme focuses on the vascular architecture without involving the technique of tumor segmentation. The results show that the proposed method is feasible, and have a good agreement with the diagnosis of the pathologists.

  5. Recent advances in the medical treatment of breast cancer.

    PubMed

    Vorobiof, Daniel A

    2016-01-01

    Over the past few decades, the systemic therapy of breast cancer (early and advanced) has changed considerably. For the past 40-50 years, and since the discovery and further therapeutic use of tamoxifen, a selective estrogen receptor modulator, breast cancer treatment has become the model for the development and success of tailored medical treatment. Much still needs to be done in improving outcomes for all patients with breast cancer, and especially for those who have advanced breast cancer, a challenging area for medical oncologists. Ongoing international clinical trials are currently evaluating new therapeutic approaches and identifying specific biological subsets that could determine a patient's ability to respond to particular chemotherapeutic drugs.

  6. Blood vessel endothelium-directed tumor cell streaming in breast tumors requires the HGF/C-Met signaling pathway.

    PubMed

    Leung, E; Xue, A; Wang, Y; Rougerie, P; Sharma, V P; Eddy, R; Cox, D; Condeelis, J

    2016-11-28

    During metastasis to distant sites, tumor cells migrate to blood vessels. In vivo, breast tumor cells utilize a specialized mode of migration known as streaming, where a linear assembly of tumor cells migrate directionally towards blood vessels on fibronectin-collagen I-containing extracellular matrix (ECM) fibers in response to chemotactic signals. We have successfully reconstructed tumor cell streaming in vitro by co-plating tumors cells, macrophages and endothelial cells on 2.5 μm thick ECM-coated micro-patterned substrates. We found that tumor cells and macrophages, when plated together on the micro-patterned substrates, do not demonstrate sustained directional migration in only one direction (sustained directionality) but show random bi-directional walking. Sustained directionality of tumor cells as seen in vivo was established in vitro when beads coated with human umbilical vein endothelial cells were placed at one end of the micro-patterned 'ECM fibers' within the assay. We demonstrated that these endothelial cells supply the hepatocyte growth factor (HGF) required for the chemotactic gradient responsible for sustained directionality. Using this in vitro reconstituted streaming system, we found that directional streaming is dependent on, and most effectively blocked, by inhibiting the HGF/C-Met signaling pathway between endothelial cells and tumor cells. Key observations made with the in vitro reconstituted system implicating C-Met signaling were confirmed in vivo in mammary tumors using the in vivo invasion assay and intravital multiphoton imaging of tumor cell streaming. These results establish HGF/C-Met as a central organizing signal in blood vessel-directed tumor cell migration in vivo and highlight a promising role for C-Met inhibitors in blocking tumor cell streaming and metastasis in vivo, and for use in human trials.Oncogene advance online publication, 28 November 2016; doi:10.1038/onc.2016.421.

  7. Percutaneous image-guided ablation of breast tumors: an overview.

    PubMed

    Sag, Alan A; Maybody, Majid; Comstock, Christopher; Solomon, Stephen B

    2014-06-01

    Percutaneous non-surgical image-guided ablation is emerging as an adjunct or alternative to surgery in the management of benign and malignant breast tumors. This review covers the current state of the literature regarding percutaneous image-guided ablation modalities, clinical factors regarding patient selection, and future directions for research.

  8. High Residual Tumor Rate for Early Breast Cancer Patients Receiving Vacuum-assisted Breast Biopsy

    PubMed Central

    He, Xiao-Fang; Ye, Feng; Wen, Jia-Huai; Li, Shuai-Jie; Huang, Xiao-Jia; Xiao, Xiang-Sheng; Xie, Xiao-Ming

    2017-01-01

    Purpose: The objective of study is aiming to investigate the residual tumor rate after Vacuum-assisted Breast Biopsy (VABB) for early breast cancer excision and the efficacy of mammogram and ultrasound in detecting residual tumor. Methods: Patients who underwent VABB and were confirmed with breast cancer in Sun Yat-sen University Cancer Center from 2010 to 2015 were reviewed retrospectively. The residual tumor rate determined by histological examination was calculated, and then was compared with the results estimated by mammogram and ultrasound which were performed post VABB but before subsequent surgery. Univariate and multivariate analysis (logistic regression) were carried out to identify the independent risk factors associated with residual tumor. Results: In total, 126 eligible patients with early breast cancer were recruited for this study, of whom 79 (62.7%) had residual tumor and 47 (37.3 %) underwent complete excision. The residual tumor rates for lesions < 10mm, lesions 10 to 20 mm and lesions >20mm in size were 55.0%, 68.9% and 53.1%, respectively. The complete excision rates estimated by mammogram and ultrasound were 76.5% and 73.9%, with a negative predictive value of only 46.2% and 50.6%, respectively. In the multivariate logistic regression analysis, no specific factors were found associated with risk of residual tumor (all P > 0.05). Conclusions: There was a high residual tumor rate after VABB in early breast cancer. Both mammogram and ultrasound could not effectively detect the residual tumor after VABB. PMID:28261351

  9. Expression Quantitative Trait loci (QTL) in tumor adjacent normal breast tissue and breast tumor tissue.

    PubMed

    Quiroz-Zárate, Alejandro; Harshfield, Benjamin J; Hu, Rong; Knoblauch, Nick; Beck, Andrew H; Hankinson, Susan E; Carey, Vincent; Tamimi, Rulla M; Hunter, David J; Quackenbush, John; Hazra, Aditi

    2017-01-01

    We investigate 71 single nucleotide polymorphisms (SNPs) identified in meta-analytic studies of genome-wide association studies (GWAS) of breast cancer, the majority of which are located in intergenic or intronic regions. To explore regulatory impacts of these variants we conducted expression quantitative loci (eQTL) analyses on tissue samples from 376 invasive postmenopausal breast cancer cases in the Nurses' Health Study (NHS) diagnosed from 1990-2004. Expression analysis was conducted on all formalin-fixed paraffin-embedded (FFPE) tissue samples (and on 264 adjacent normal samples) using the Affymetrix Human Transcriptome Array. Significance and ranking of associations between tumor receptor status and expression variation was preserved between NHS FFPE and TCGA fresh-frozen sample sets (Spearman r = 0.85, p<10^-10 for 17 of the 21 Oncotype DX recurrence signature genes). At an FDR threshold of 10%, we identified 27 trans-eQTLs associated with expression variation in 217 distinct genes. SNP-gene associations can be explored using an open-source interactive browser distributed in a Bioconductor package. Using a new a procedure for testing hypotheses relating SNP content to expression patterns in gene sets, defined as molecular function pathways, we find that loci on 6q14 and 6q25 affect various gene sets and molecular pathways (FDR < 10%). Although the ultimate biological interpretation of the GWAS-identified variants remains to be uncovered, this study validates the utility of expression analysis of this FFPE expression set for more detailed integrative analyses.

  10. Expression Quantitative Trait loci (QTL) in tumor adjacent normal breast tissue and breast tumor tissue

    PubMed Central

    Quiroz-Zárate, Alejandro; Harshfield, Benjamin J.; Hu, Rong; Knoblauch, Nick; Beck, Andrew H.; Hankinson, Susan E.; Carey, Vincent; Tamimi, Rulla M.; Hunter, David J.; Quackenbush, John; Hazra, Aditi

    2017-01-01

    We investigate 71 single nucleotide polymorphisms (SNPs) identified in meta-analytic studies of genome-wide association studies (GWAS) of breast cancer, the majority of which are located in intergenic or intronic regions. To explore regulatory impacts of these variants we conducted expression quantitative loci (eQTL) analyses on tissue samples from 376 invasive postmenopausal breast cancer cases in the Nurses’ Health Study (NHS) diagnosed from 1990–2004. Expression analysis was conducted on all formalin-fixed paraffin-embedded (FFPE) tissue samples (and on 264 adjacent normal samples) using the Affymetrix Human Transcriptome Array. Significance and ranking of associations between tumor receptor status and expression variation was preserved between NHS FFPE and TCGA fresh-frozen sample sets (Spearman r = 0.85, p<10^-10 for 17 of the 21 Oncotype DX recurrence signature genes). At an FDR threshold of 10%, we identified 27 trans-eQTLs associated with expression variation in 217 distinct genes. SNP-gene associations can be explored using an open-source interactive browser distributed in a Bioconductor package. Using a new a procedure for testing hypotheses relating SNP content to expression patterns in gene sets, defined as molecular function pathways, we find that loci on 6q14 and 6q25 affect various gene sets and molecular pathways (FDR < 10%). Although the ultimate biological interpretation of the GWAS-identified variants remains to be uncovered, this study validates the utility of expression analysis of this FFPE expression set for more detailed integrative analyses. PMID:28152060

  11. Towards intraoperative assessment of tumor margins in breast surgery using optical coherence elastography (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Kennedy, Brendan F.; Wijesinghe, Philip; Allen, Wes M.; Chin, Lixin; Latham, Bruce; Saunders, Christobel M.; Sampson, David D.

    2016-03-01

    Surgical excision of tumor is a critical factor in the management of breast cancer. The most common surgical procedure is breast-conserving surgery. The surgeon's goal is to remove the tumor and a rim of healthy tissue surrounding the tumor: the surgical margin. A major issue in breast-conserving surgery is the absence of a reliable tool to guide the surgeon in intraoperatively assessing the margin. A number of techniques have been proposed; however, the re-excision rate remains high and has been reported to be in the range 30-60%. New tools are needed to address this issue. Optical coherence elastography (OCE) shows promise as a tool for intraoperative tumor margin assessment in breast-conserving surgery. Further advances towards clinical translation are limited by long scan times and small fields of view. In particular, scanning over sufficient areas to assess the entire margin in an intraoperative timeframe has not been shown to be feasible. Here, we present a protocol allowing ~75% of the surgical margins to be assessed within 30 minutes. To achieve this, we have incorporated a 65 mm-diameter (internal), wide-aperture annular piezoelectric transducer, allowing the entire surface of the excised tumor mass to be automatically imaged in an OCT mosaic comprised of 10 × 10 mm tiles. As OCT is effective in identifying adipose tissue, our protocol uses the wide-field OCT to selectively guide subsequent local OCE scanning to regions of solid tissue which often present low contrast in OCT images. We present promising examples from freshly excised human breast tissue.

  12. Characterization of spontaneous breast tumor in tree shrews (Tupaia belangeri chinenesis).

    PubMed

    Xia, Hou-Jun; Wang, Chun-Yan; Zhang, Hai-Lin; He, Bao-Li; Jiao, Jian-Lin; Chen, Ce-Shi

    2012-02-01

    Breast cancer is a common malignant tumor. It is essential to develop suitable animal models for discovering novel preventive and therapeutic approaches. Tree shrews (Tupaia belangeri chinensis) have a closer evolutionary relationship with humans than do rodents, which have been widely used in laboratory research. Spontaneous breast tumors were identified in tree shrews in 1960s; however, no detailed studies about tree shrew breast tumors have been conducted to date. Here, we characterized a spontaneous breast tumor from tree shrews by Haematoxylin Eosin (H&E) staining. This tumor was identified as a papillary tumor. Immunohistochemical staining (IHC) for progesterone receptor (PR), Ki-67 and cleaved caspase-3 showed that tumor cells were positive for PR, highly proliferative, and less apoptotic compared to normal breast epithelial cells. Thus, the spontaneous tumor of tree shrew is very close to human papillary tumors in terms of morphology and pathology and we concluded that tree shrew may be a suitable animal model for breast cancer research.

  13. Recurrent and pathological gene fusions in breast cancer: current advances in genomic discovery and clinical implications.

    PubMed

    Veeraraghavan, Jamunarani; Ma, Jiacheng; Hu, Yiheng; Wang, Xiao-Song

    2016-07-01

    Gene fusions have long been considered principally as the oncogenic events of hematologic malignancies, but have recently gained wide attention in solid tumors due to several milestone discoveries and the advancement of deep sequencing technologies. With the progress in deep sequencing studies of breast cancer transcriptomes and genomes, the discovery of recurrent and pathological gene fusions in breast cancer is on the focus. Recently, driven by new deep sequencing studies, several recurrent or pathological gene fusions have been identified in breast cancer, including ESR1-CCDC170, SEC16A-NOTCH1, SEC22B-NOTCH2, and ESR1-YAP1 etc. More important, most of these gene fusions are preferentially identified in the more aggressive breast cancers, such as luminal B, basal-like, or endocrine-resistant breast cancer, suggesting recurrent gene fusions as additional key driver events in these tumors other than the known drivers such as the estrogen receptor. In this paper, we have comprehensively summarized the newly identified recurrent or pathological gene fusion events in breast cancer, reviewed the contributions of new genomic and deep sequencing technologies to new fusion discovery and the integrative bioinformatics tools to analyze these data, highlighted the biological relevance and clinical implications of these fusion discoveries, and discussed future directions of gene fusion research in breast cancer.

  14. Breast Field Cancerization: Isolation and Comparison of Telomerase-Expressing Cells in Tumor and Tumor Adjacent, Histologically Normal Breast Tissue

    PubMed Central

    Trujillo, Kristina A.; Hines, William C.; Vargas, Keith M.; Jones, Anna C.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K.

    2011-01-01

    Telomerase stabilizes chromosomes by maintaining telomere length, immortalizes mammalian cells, and is expressed in more than 90% of human tumors. However, the expression of human telomerase reverse transcriptase (hTERT) is not restricted to tumor cells. We have previously shown that a subpopulation of human mammary epithelial cells (HMEC) in tumor-adjacent, histologically normal (TAHN) breast tissues expresses hTERT mRNA at levels comparable with levels in breast tumors. In the current study, we first validated a reporter for measuring levels of hTERT promoter activity in early-passage HMECs and then used this reporter to compare hTERT promoter activity in HMECs derived from tumor and paired TAHN tissues 1, 3, and 5 cm from the tumor (TAHN-1, TAHN-3, and TAHN-5, respectively). Cell sorting, quantitative real-time PCR, and microarray analyses showed that the 10% of HMECs with the highest hTERT promoter activity in both tumor and TAHN-1 tissues contain more than 95% of hTERT mRNA and overexpress many genes involved in cell cycle and mitosis. The percentage of HMECs within this subpopulation showing high hTERT promoter activity was significantly reduced or absent in TAHN-3 and TAHN-5 tissues. We conclude that the field of normal tissue proximal to the breast tumors contains a population of HMECs similar in hTERT expression levels and in gene expression to the HMECs within the tumor mass and that this population is significantly reduced in tissues more distal to the tumor. PMID:21775421

  15. [Considerations in rational use of tumor markers in breast carcinoma].

    PubMed

    Crombach, G

    1998-04-22

    The objective of this review is to determine clinical practical guidelines for the use of serum tumor markers in the care of breast cancer patients outside of clinical trials. Mucin antigens (CA 15-3, MCA, CA 549) and CEA are established markers in breast cancer. Owing to their low sensitivity, none of these markers can be recommended for screening, diagnosis or staging. During follow-up, increasing marker levels may indicate recurrence 3-6 months earlier than clinical and radiological examinations in about 40-50% of patients. However, the clinical benefit of this lead-time is not established. Tumor markers are able to monitor response to treatment in 70-80% of patients with metastatic breast cancer. However, paradoxical changes of the markers especially in the beginning of treatment, the insufficient concordance with tumor activity in 20-30% of the women, and the lack of curative therapy regimens limit the prospective clinical use of the markers in the individual patient. Therefore, marker changes require confirmation by radiological methods in most cases. The present data are insufficient to recommend routine use of tumor markers alone for monitoring breast cancer patients after primary treatment or during palliative therapy. However, in the absence of readily measurable disease (e. g. bone metastases) continuously increasing marker levels may be used to indicate treatment failure. If high-dose chemotherapy in metastatic breast cancer renders to be effective, the clinical impact of tumor markers will increase considerably. Until that time, the analytical performance and the sensitivity of the established marker assays should be improved, and the clinical role of newer marker tests (TPS, CA 27.29) should be evaluated.

  16. Mesenchymal tumors and tumor-like lesions of the breast: a contemporary approach review.

    PubMed

    Stolnicu, Simona; Moldovan, Cosmin; Podoleanu, Cristian; Georgescu, Rares

    2015-01-01

    The classification of the breast tumors has been revised and recently published in 2012 in the WHO blue book. Contrary to the epithelial tumors in the breast, mesenchymal tumors are rare and the classification for benign and malignant tumors is based on the same criteria in both categories, since no other specific diagnostic criteria, which would have an impact on prognosis, exist to date. The present review deals with minor changes mirroring the recent developments in the benign mesenchymal tumors (new additions are nodular fasciitis and atypical vascular lesions, while the haemangiopericytoma is removed) focusing especially on criteria to diagnose sarcomas, which represent a wide spectrum including very difficult lesions. The majority of sarcomas of the breast arise as a component of a malignant phyllodes tumor, while the pure forms are very rare. When a pure primary sarcoma of the breast is diagnosed, pathologists are encouraged to categorize the lesion according to the type of differentiation and to provide to the clinicians all the important prognostic parameters for the best treatment choice.

  17. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium

    PubMed Central

    Broeks, Annegien; Schmidt, Marjanka K.; Sherman, Mark E.; Couch, Fergus J.; Hopper, John L.; Dite, Gillian S.; Apicella, Carmel; Smith, Letitia D.; Hammet, Fleur; Southey, Melissa C.; Van ’t Veer, Laura J.; de Groot, Renate; Smit, Vincent T.H.B.M.; Fasching, Peter A.; Beckmann, Matthias W.; Jud, Sebastian; Ekici, Arif B.; Hartmann, Arndt; Hein, Alexander; Schulz-Wendtland, Ruediger; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sinn, Hans-Peter; Sohn, Christof; Tchatchou, Sandrine; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Ørsted, David D.; Kaur-Knudsen, Diljit; Milne, Roger L.; Pérez, Jose I. Arias; Zamora, Pilar; Rodríguez, Primitiva Menéndez; Benítez, Javier; Brauch, Hiltrud; Justenhoven, Christina; Ko, Yon-Dschun; Hamann, Ute; Fischer, Hans-Peter; Brüning, Thomas; Pesch, Beate; Chang-Claude, Jenny; Wang-Gohrke, Shan; Bremer, Michael; Karstens, Johann H.; Hillemanns, Peter; Dörk, Thilo; Nevanlinna, Heli A.; Heikkinen, Tuomas; Heikkilä, Päivi; Blomqvist, Carl; Aittomäki, Kristiina; Aaltonen, Kirsimari; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana M.; Kataja, Vesa; Auvinen, Päivi; Eskelinen, Matti; Soini, Ylermi; Chenevix-Trench, Georgia; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Holland, Helene; Lambrechts, Diether; Claes, Bart; Vandorpe, Thijs; Neven, Patrick; Wildiers, Hans; Flesch-Janys, Dieter; Hein, Rebecca; Löning, Thomas; Kosel, Matthew; Fredericksen, Zachary S.; Wang, Xianshu; Giles, Graham G.; Baglietto, Laura; Severi, Gianluca; McLean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Le Marchand, Loic; Kolonel, Laurence N.; Grenaker Alnæs, Grethe; Kristensen, Vessela; Børresen-Dale, Anne-Lise; Hunter, David J.; Hankinson, Susan E.; Andrulis, Irene L.; Marie Mulligan, Anna; O'Malley, Frances P.; Devilee, Peter; Huijts, Petra E.A.; Tollenaar, Rob A.E.M.; Van Asperen, Christi J.; Seynaeve, Caroline S.; Chanock, Stephen J.; Lissowska, Jolanta; Brinton, Louise; Peplonska, Beata; Figueroa, Jonine; Yang, Xiaohong R.; Hooning, Maartje J.; Hollestelle, Antoinette; Oldenburg, Rogier A.; Jager, Agnes; Kriege, Mieke; Ozturk, Bahar; van Leenders, Geert J.L.H.; Hall, Per; Czene, Kamila; Humphreys, Keith; Liu, Jianjun; Cox, Angela; Connley, Daniel; Cramp, Helen E.; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W.R.; Dunning, Alison M.; Easton, Douglas F.; Humphreys, Manjeet K.; Caldas, Carlos; Blows, Fiona; Driver, Kristy; Provenzano, Elena; Lubinski, Jan; Jakubowska, Anna; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Gorski, Bohdan; Gronwald, Jacek; Brennan, Paul; Sangrajrang, Suleeporn; Gaborieau, Valerie; Shen, Chen-Yang; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Hou, Ming-Feng; Huang, Chiun-Sheng; Anton-Culver, Hoda; Ziogas, Argyrios; Pharoah, Paul D.P.; Garcia-Closas, Montserrat

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER+ than ER− tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 × 10−18), rs3803662 (16q12) (P = 3.7 × 10−5), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 × 10−6 and P = 4.1 × 10−4, respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P ≤ 0.016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment. PMID:21596841

  18. CDDO-Me Redirects Activation of Breast Tumor Associated Macrophages

    PubMed Central

    Ball, Michael S.; Shipman, Emilie P.; Kim, Hyunjung; Liby, Karen T.; Pioli, Patricia A.

    2016-01-01

    Tumor-associated macrophages can account for up to 50% of the tumor mass in breast cancer patients and high TAM density is associated with poor clinical prognosis. Because TAMs enhance tumor growth, development, and metastatic potential, redirection of TAM activation may have significant therapeutic benefit. Our studies in primary human macrophages and murine breast TAMs suggest that the synthetic oleanane triterpenoid CDDO-methyl ester (CDDO-Me) reprograms the activation profile of TAMs from tumor-promoting to tumor-inhibiting. We show that CDDO-Me treatment inhibits expression of IL-10 and VEGF in stimulated human M2 macrophages and TAMs but increases expression of TNF-α and IL-6. Surface expression of CD206 and CD163, which are characteristic of M2 activation, is significantly attenuated by CDDO-Me. In contrast, CDDO-Me up-regulates surface expression of HLA-DR and CD80, which are markers of M1 activation, and importantly potentiates macrophage activation of autologous T cells but inhibits endothelial cell vascularization. These results show for the first time that CDDO-Me redirects activation of M2 macrophages and TAMs from immune-suppressive to immune-stimulatory, and implicate a role for CDDO-Me as an immunotherapeutic in the treatment of breast and potentially other types of cancer. PMID:26918785

  19. Serum tumor markers in patients with breast cancer.

    PubMed

    Lumachi, Franco; Basso, Stefano M M

    2004-10-01

    Several serum tumor markers have been investigated in patients with breast cancer for assessing outcome, predicting recurrence and monitoring the therapeutic response. There is a general consensus concerning their limited application in diagnosing malignancy; however, serum tumor markers can be considered for the early detection of recurrence. The most effective markers for this indication are cancer antigens (CA)15-3 and 27.29, and c-erbB-2, although their efficacy in establishing disease progression has not been determined to date. In terms of evaluating prognosis and predicting response to therapy, only the expression of c-erbB-2 has clinical evidence. To conclude, at present, no serum tumor marker is cost effective, and none can be used with confidence in the decision making regarding breast cancer patients.

  20. Metabolomic profiling of breast tumors using ductal fluid

    PubMed Central

    Do Canto, Luisa Matos; Marian, Catalin; Varghese, Rency S.; Ahn, Jaeil; Da Cunha, Patricia A.; Willey, Shawna; Sidawy, Mary; Rone, Janice D.; Cheema, Amrita K.; Luta, George; Nezami ranjbar, Mohammad R.; Ressom, Habtom W.; Haddad, Bassem R.

    2016-01-01

    Identification of new biomarkers for breast cancer remains critical in order to enhance early detection of the disease and improve its prognosis. Towards this end, we performed an untargeted metabolomic analysis of breast ductal fluid using an ultra-performance liquid chromatography coupled with a quadrupole time-of-light (UPLC-QTOF) mass spectrometer. We investigated the metabolomic profiles of breast tumors using ductal fluid samples collected by ductal lavage (DL). We studied fluid from both the affected breasts and the unaffected contralateral breasts (as controls) from 43 women with confirmed unilateral breast cancer. Using this approach, we identified 1560 ions in the positive mode and 538 ions in the negative mode after preprocessing of the UPLC-QTOF data. Paired t-tests applied on these data matrices identified 209 ions (positive and negative modes combined) with significant change in intensity level between affected and unaffected control breasts (adjusted P-values <0.05). Among these, 83 ions (39.7%) showed a fold change (FC) >1.2 and 66 ions (31.6%) were identified with putative compound names. The metabolites that we identified included endogenous metabolites such as amino acid derivatives (N-Acetyl-DL-tryptophan) or products of lipid metabolism such as N-linoleoyl taurine, trans-2-dodecenoylcarnitine, lysophosphatidylcholine LysoPC(18:2(9Z,12Z)), glycerophospholipids PG(18:0/0:0), and phosphatidylserine PS(20:4(5Z,8Z,11Z,14Z). Generalized LASSO regression further selected 21 metabolites when race, menopausal status, smoking, grade and TNM stage were adjusted for. A predictive conditional logistic regression model, using the LASSO selected 21 ions, provided diagnostic accuracy with the area under the curve of 0.956 (sensitivity/specificity of 0.907/0.884). This is the first study that shows the feasibility of conducting a comprehensive metabolomic profiling of breast tumors using breast ductal fluid to detect changes in the cellular microenvironment of

  1. Alternative therapies for metastatic breast cancer: multimodal approach targeting tumor cell heterogeneity

    PubMed Central

    Sambi, Manpreet; Haq, Sabah; Samuel, Vanessa; Qorri, Bessi; Haxho, Fiona; Hill, Kelli; Harless, William; Szewczuk, Myron R

    2017-01-01

    One of the primary challenges in developing effective therapies for malignant tumors is the specific targeting of a heterogeneous cancer cell population within the tumor. The cancerous tumor is made up of a variety of distinct cells with specialized receptors and proteins that could potentially be viable targets for drugs. In addition, the diverse signals from the local microenvironment may also contribute to the induction of tumor growth and metastasis. Collectively, these factors must be strategically studied and targeted in order to develop an effective treatment protocol. Targeted multimodal approaches need to be strategically studied in order to develop a treatment protocol that is successful in controlling tumor growth and preventing metastatic burden. Breast cancer, in particular, presents a unique problem because of the variety of subtypes of cancer that can arise and the multiple drug targets that could be exploited. For example, the tumor stage and subtypes often dictate the appropriate treatment regimen. Alternate multimodal therapies should consider the importance of time-dependent drug administration, as well as targeting the local and systemic tumor environment. Many reviews and papers have briefly touched on the clinical implications of this cellular heterogeneity; however, there has been very little discussion on the development of study models that reflect this diversity and on multimodal therapies that could target these subpopulations. Here, we summarize the current understanding of the origins of intratumoral heterogeneity in breast cancer subtypes, and its implications for tumor progression, metastatic potential, and treatment regimens. We also discuss the advantages and disadvantages of utilizing specific breast cancer models for research, including in vitro monolayer systems and three-dimensional mammospheres, as well as in vivo murine models that may have the capacity to encompass this heterogeneity. Lastly, we summarize some of the current

  2. Infrared microspectroscopic imaging of benign breast tumor tissue sections

    NASA Astrophysics Data System (ADS)

    Fabian, H.; Lasch, P.; Boese, M.; Haensch, W.

    2003-12-01

    We have applied infrared microspectroscopic imaging for the examination of benign breast tumor tissue sections. The IR spectra of the sections were obtained by classical point microscopy with a movable stage and via a microscope equipped with a focal plane array detector. The infrared microscopic data were analysed using functional group mapping techniques and cluster analysis. The output values of the two procedures were reassembled into infrared images of the tissues, and were compared with standard staining images of the corresponding tissue region. The comparative examination of identical tissue sections by the two IR approaches enabled us to assess potential problems associated with tissue microheterogeneity. It was found that in case of fibroadenoma, a benign lesion located in breast ducts, point microscopy with a spot size of ˜30 μm is a useful practical approach which minimizes the possibility of 'contamination' of the spectra because of spectral averaging of all tissue components present in the corresponding microareas. A comparison of the spectra of the benign breast tumor with those of a malignant ductal carcinoma in situ revealed that IR microspectroscopy has the potential to differentiate between these two breast tumor types.

  3. WDR26 in Advanced Breast Cancer: A Novel Regulator of the P13K/AKT Pathway

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0539 TITLE: WDR26 in Advanced Breast Cancer : A Novel Regulator of the P13K/AKT Pathway PRINCIPAL INVESTIGATOR...5a. CONTRACT NUMBER WDR26 in Advanced Breast Cancer : A Novel Regulator of the P13K/AKT Pathway 5b. GRANT NUMBER W81XWH-14-1-0539 5c. PROGRAM...SUPPLEMENTARY NOTES 14. ABSTRACT The PI3K/AKT pathway is one of the most deregulated pathways in breast cancers (>70%), and a major contributor to tumor

  4. Infrared Spectra of Human Breast Tumor Tissue and Experimental Animal Tumors

    NASA Astrophysics Data System (ADS)

    Tolstorozhev, G. B.; Belkov, M. V.; Skornyakov, I. V.; Pekhnyo, V. I.; Kozachkova, A. N.; Tsarik, H. V.; Kutsenko, I. P.; Sharykina, N. I.; Butra, V. A.

    2015-01-01

    We have used Fourier transform IR spectroscopy methods to conduct comparative studies of human breast tumors and sarcoma 180 tumor grafted into mice. The IR spectral parameters used to identify tumor tissue in mice with the sarcoma 180 strain proved to be identical to the parameters for human breast tissue in cancer. In the presence of a malignant tumor in humans, the most intense C=O vibrational bands in the protein molecules are observed in the interval 1710-1680 cm-1. For a benign tumor, in the IR spectra of breast tissue the intense bands are located in the interval 1670-1650 cm-1. We spectroscopically monitored the diagnosis and the chemotherapy process using the model of sarcoma 180 in mice. As the therapeutic drugs, we used synthesized coordination compounds based on palladium complexes with diphosphonic acid derivatives. We demonstrate the promising potential of palladium complexes with zoledronic acid as an effective cytostatic. In therapy using a palladium complex with zoledronic acid, the effect of tumor growth inhibition is accompanied by a change in its spectral characteristics. The parameters of the IR spectra for tumor tissue after treatment are close to those of the IR spectra for healthy tissue.

  5. Breast Tumor Ablation by Selective Autophagic Degradation of Postmitotic Midbodies

    DTIC Science & Technology

    2014-08-01

    ADDRESS. 1. REPORT DATE 1 Aug 2014 2. REPORT TYPE Fnal 3. DATES COVERED 1 May 2012 - 30 Apr 2014 4. TITLE AND SUBTITLE Breast Tumor Ablation by...Cycle. 11, 7-8, 2012 . 4. 83. Chen C-T, Hehnly H, Doxsey S, Orchestrating vesicle transport, ESCRTs and kinase surveillance during abscission. Nature...Reviews Molecular Cell Biology, 13:483-8, 2012 . 5. Chen C-T, Kuo T-C, Doxsey S. A new potential breast therapeutic strategy: targeting post-mitotic

  6. Combination Therapy Shows Promise for Treating Advanced Breast Cancer

    Cancer.gov

    Adding the drug everolimus (Afinitor®) to exemestane helped postmenopausal women whose advanced breast cancer had stopped responding to hormonal therapy live about 4 months longer without the disease progressing than women who received exemestane alone.

  7. Advancing Breast Cancer Survivorship among African American Women

    PubMed Central

    Coughlin, Steven S.; Yoo, Wonsuk; Whitehead, Mary S.; Smith, Selina A.

    2015-01-01

    Purpose Advances have occurred in breast cancer survivorship but, for many African American women, challenges and gaps in relevant information remain. Methods This article identifies opportunities to address disparities in breast cancer survival and quality of life, and thereby to increase breast cancer survivorship among African American women. Results For breast cancer survivors, common side effects, lasting for long periods after cancer treatment, include fatigue, loss of strength, difficulty sleeping, and sexual dysfunction. For addressing physical and mental health concerns, a variety of interventions have been evaluated, including exercise and weight training, dietary interventions, yoga and mindfulness-based stress reduction, and support groups or group therapy. Obesity has been associated with breast cancer recurrence and poorer survival. Relative to white survivors, African American breast cancer survivors are more likely to be obese and less likely to engage in physical activity, although exercise improves overall quality of life and cancer-related fatigue. Considerable information exists about the effectiveness of such interventions for alleviating distress and improving quality of life among breast cancer survivors, but few studies have focused specifically on African American women with a breast cancer diagnosis. Studies have identified a number of personal factors that are associated with resilience, increased quality of life, and positive adaptation to a breast cancer diagnosis. Conclusions There is a need for a better understanding of breast cancer survivorship among African American women. Additional evaluations of interventions for improving the quality of life and survival of African American breast cancer survivors are desirable. PMID:26303657

  8. Phyllodes Tumor of the Breast: Analysis of 48 Patients

    PubMed Central

    Kılıç, Murat Özgür; Terzioğlu, Serdar Gökay; Bozkurt, Betül; Dağlar, Gül

    2016-01-01

    Objective Phyllodes tumor (PT) is a rare biphasic breast neoplasm that accounts for less than 1% of all breast tumors. The aim of this study was to evaluate the clinicopathologic features, diagnostic difficulties, and therapeutic outcomes of patients with PT. Materials and Methods A total of 48 female patients who underwent surgery for PT were included in the study. Patient characteristics, clinicopathologic features of tumors, diagnostic findings, surgical outcomes, adjuvant therapies, and follow-up findings were retrospectively evaluated. Results The mean age of patients was 35 years. Painless breast mass was the most common (85.4%) presenting symptom. Total excision with at least 1 cm macroscopic clear margins was the most frequently performed (87.5%) surgery. Most patients (n=34, 70.8%) had benign PT; however, borderline and malignant tumors were found in 9 (18.8%) and 5 (10.4%) patients, respectively. During the mean follow-up period of approximately 30 months, local and distant recurrence was detected in three (6.3%) patients and one (2.1%) patient, respectively. Patients with malignant PT had larger tumors than those with benign and borderline PTs (p=0.010). No significant difference in other clinical, diagnostic, and pathologic characteristics was found between the groups. Conclusion PT can be easily confused with other breast masses such as fibroadenoma due to the non-specific clinical and radiologic findings. Surgical excision with at least 1 cm clear margins is of great importance to reduce the risk of local recurrence. However, recurrence can develop even after appropriate surgery, thus patients should be closely followed up after surgery. PMID:28331755

  9. Veliparib, Oxaliplatin, and Capecitabine in Treating Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2014-04-01

    Adenocarcinoma of the Pancreas; Adenocarcinoma of the Stomach; BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Ovarian Mucinous Cystadenocarcinoma; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gastric Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  10. [Pulmonary Metastasis from a Phyllodes Tumor of the Breast Developing Sixteen Years after Initial Surgery].

    PubMed

    Chang, Sung-Soo; Nakano, Takayuki; Okamoto, Taku; Takabatake, Daisuke

    2015-11-01

    We report a case of solitary pulmonary metastasis from a phyllodes tumor of the breast appearing 16 years after initial surgery. The patient was a 56-year-old woman who had undergone surgical extirpation of a left breast tumor diagnosed as phyllodes tumor (borderline malignancy) in 1998, and a right breast tumor diagnosed as fibromatosis in 2000. Sixteen years after the initial operation, she consulted our hospital because of a chest X-ray abnormality detected at a screening examination. Chest computed tomography revealed a well defined nodular shadow in the left upper lobe of the lung. Surgery was done since primary lung cancer was suspected. However, pathological diagnosis was a pulmonary metastasis from the phyllodes tumor of the left breast. Right breast tumor was also diagnosed as a metastasis from the left breast tumor by histopathological re-evaluation.

  11. Accuracy of lesion boundary tracking in navigated breast tumor excision

    NASA Astrophysics Data System (ADS)

    Heffernan, Emily; Ungi, Tamas; Vaughan, Thomas; Pezeshki, Padina; Lasso, Andras; Gauvin, Gabrielle; Rudan, John; Engel, C. Jay; Morin, Evelyn; Fichtinger, Gabor

    2016-03-01

    PURPOSE: An electromagnetic navigation system for tumor excision in breast conserving surgery has recently been developed. Preoperatively, a hooked needle is positioned in the tumor and the tumor boundaries are defined in the needle coordinate system. The needle is tracked electromagnetically throughout the procedure to localize the tumor. However, the needle may move and the tissue may deform, leading to errors in maintaining a correct excision boundary. It is imperative to quantify these errors so the surgeon can choose an appropriate resection margin. METHODS: A commercial breast biopsy phantom with several inclusions was used. Location and shape of a lesion before and after mechanical deformation were determined using 3D ultrasound volumes. Tumor location and shape were estimated from initial contours and tracking data. The difference in estimated and actual location and shape of the lesion after deformation was quantified using the Hausdorff distance. Data collection and analysis were done using our 3D Slicer software application and PLUS toolkit. RESULTS: The deformation of the breast resulted in 3.72 mm (STD 0.67 mm) average boundary displacement for an isoelastic lesion and 3.88 mm (STD 0.43 mm) for a hyperelastic lesion. The difference between the actual and estimated tracked tumor boundary was 0.88 mm (STD 0.20 mm) for the isoelastic and 1.78 mm (STD 0.18 mm) for the hyperelastic lesion. CONCLUSION: The average lesion boundary tracking error was below 2mm, which is clinically acceptable. We suspect that stiffness of the phantom tissue affected the error measurements. Results will be validated in patient studies.

  12. Nonsurgical ablation of breast cancer: future options for small breast tumors.

    PubMed

    Sabel, Michael S

    2014-07-01

    The surgical management of breast cancer has evolved significantly, facilitated by advancements in technology and imaging and improvements in adjuvant therapy. The changes in surgical management have been characterized by equal or improved outcomes with significantly less morbidity. The next step in this evolution is the minimally invasive or noninvasive ablation of breast cancers as an alternative to lumpectomy. In this article, the various modalities for nonsurgical breast cancer ablation and the clinical experience are reviewed, and some of the next steps necessary for their clinical implementation are outlined.

  13. PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target

    PubMed Central

    Li, Jiarong; Karaplis, Andrew C.; Huang, Dao C.; Siegel, Peter M.; Camirand, Anne; Yang, Xian Fang; Muller, William J.; Kremer, Richard

    2011-01-01

    Parathyroid hormone–related protein (PTHrP) is a secreted factor expressed in almost all normal fetal and adult tissues. It is involved in a wide range of developmental and physiological processes, including serum calcium regulation. PTHrP is also associated with the progression of skeletal metastases, and its dysregulated expression in advanced cancers causes malignancy-associated hypercalcemia. Although PTHrP is frequently expressed by breast tumors and other solid cancers, its effects on tumor progression are unclear. Here, we demonstrate in mice pleiotropic involvement of PTHrP in key steps of breast cancer — it influences the initiation and progression of primary tumors and metastases. Pthrp ablation in the mammary epithelium of the PyMT-MMTV breast cancer mouse model caused a delay in primary tumor initiation, inhibited tumor progression, and reduced metastasis to distal sites. Mechanistically, it reduced expression of molecular markers of cell proliferation (Ki67) and angiogenesis (factor VIII), antiapoptotic factor Bcl-2, cell-cycle progression regulator cyclin D1, and survival factor AKT1. PTHrP also influenced expression of the adhesion factor CXCR4, and coexpression of PTHrP and CXCR4 was crucial for metastatic spread. Importantly, PTHrP-specific neutralizing antibodies slowed the progression and metastasis of human breast cancer xenografts. Our data identify what we believe to be new functions for PTHrP in several key steps of breast cancer and suggest that PTHrP may constitute a novel target for therapeutic intervention. PMID:22056386

  14. MTUS1 tumor suppressor and its miRNA regulators in fibroadenoma and breast cancer.

    PubMed

    Kara, Murat; Kaplan, Mehmet; Bozgeyik, Ibrahim; Ozcan, Onder; Celik, Ozgur Ilhan; Bozgeyik, Esra; Yumrutas, Onder

    2016-08-10

    Breast cancer is major public health problem predominantly effects female population. Current therapeutic approaches to deal with breast cancer are still lack of effectiveness. Thus, identifying/developing novel strategies to fight against breast cancer is very important. The frequent deletions at 8p21.3-22 chromosomal location nearby D8S254 marker enabled the discovery of a novel tumor suppressor gene, MTUS1. Subsequently, MTUS1 was demonstrated to be less expressed in a variety cancer types including breast cancer. Also, it is obvious that gene expression is widely regulated by miRNAs. Here, we aimed to report differential expression of MTUS1 and its regulatory miRNAs in breast cancer and fibroadenoma tissues. Dynamic analysis of MTUS1 expression levels and its miRNAs regulators were attained by Fluidigm 96×96 Dynamic Array Expression chips and reactions were performed in Fluidigm BioMark™ HD System qPCR. Consequently, MTUS1 mRNA levels were significantly diminished in breast cancer tissues and elevated in fibroadenoma tissues. Also, among MTUS1 targeting miRNAs, miR-183-5p was identified to be overexpressed in breast cancer and down-regulated in fibroadenoma tissues. Also, expression levels of MTUS1 and miR-183-5p were well correlated with clinical parameters. In particular, MTUS1 expression was found to be diminished and miR-183-5p expression was elevated with the advancing stage. In conclusion, as a potential therapeutic target, miR-183-5p can be a chief regulator of MTUS1 and MTUS1-miR-183-5p axis may have significant influence in the pathology of breast cancer.

  15. Innate immune recognition of breast tumor cells mediates CCL22 secretion favoring Treg recruitment within tumor environment

    PubMed Central

    Ménétrier-Caux, Christine; Faget, Julien; Biota, Cathy; Gobert, Michael; Blay, Jean-Yves; Caux, Christophe

    2012-01-01

    Regulatory T cells (Treg) have been reported of poor prognosis for overall survival in primary breast tumors (BT). As CCL22 plays a major role in Treg recruitment within primary BT we deciphered the mechanisms involved in the CCL22 production by breast epithelial tumor cells and propose herein the major role of their innate immune recognition in this production. PMID:22934274

  16. Innate immune recognition of breast tumor cells mediates CCL22 secretion favoring Treg recruitment within tumor environment.

    PubMed

    Ménétrier-Caux, Christine; Faget, Julien; Biota, Cathy; Gobert, Michael; Blay, Jean-Yves; Caux, Christophe

    2012-08-01

    Regulatory T cells (Treg) have been reported of poor prognosis for overall survival in primary breast tumors (BT). As CCL22 plays a major role in Treg recruitment within primary BT we deciphered the mechanisms involved in the CCL22 production by breast epithelial tumor cells and propose herein the major role of their innate immune recognition in this production.

  17. Periareolar incision for the management of benign breast tumors.

    PubMed

    Kong, Xiangnan; Chen, Xi; Jiang, Liyu; Ma, Tingting; Han, Baosan; Yang, Qifeng

    2016-11-01

    Benign breast tumors (BBTs) are common in women. The traditional surgical resection method for the various types of BBT leaves obvious scars and affects the appearance of the breast. The present study introduces the experience of a single institution in the treatment of BBT by periareolar incision. The clinical data of 153 patients (182 breasts) with BBT who had undergone a resection via a periareolar incision between January 2010 and December 2012 in Qilu Hospital, Shandong University (Jinan, Shandong, China), was retrospectively analyzed. All incisions were primary healing. Of the 153 patients, 1 (0.7%) developed a hematoma and 2 (1.3%) developed slight nipple ischemia. No infections or other complications were observed. During 1 month to 3 years of follow-up, the cosmetic effects were assessed. Periareolar incision is not only suitable for all types of breast surgery for benign tumor resection, but also has the advantage of a hidden incision, a small scar, no ischemic necrosis of the nipple areola, high patient satisfaction and good post-operative cosmetic effect. The technique is therefore a good surgical incision choice that is worthy of note.

  18. Periareolar incision for the management of benign breast tumors

    PubMed Central

    Kong, Xiangnan; Chen, Xi; Jiang, Liyu; Ma, Tingting; Han, Baosan; Yang, Qifeng

    2016-01-01

    Benign breast tumors (BBTs) are common in women. The traditional surgical resection method for the various types of BBT leaves obvious scars and affects the appearance of the breast. The present study introduces the experience of a single institution in the treatment of BBT by periareolar incision. The clinical data of 153 patients (182 breasts) with BBT who had undergone a resection via a periareolar incision between January 2010 and December 2012 in Qilu Hospital, Shandong University (Jinan, Shandong, China), was retrospectively analyzed. All incisions were primary healing. Of the 153 patients, 1 (0.7%) developed a hematoma and 2 (1.3%) developed slight nipple ischemia. No infections or other complications were observed. During 1 month to 3 years of follow-up, the cosmetic effects were assessed. Periareolar incision is not only suitable for all types of breast surgery for benign tumor resection, but also has the advantage of a hidden incision, a small scar, no ischemic necrosis of the nipple areola, high patient satisfaction and good post-operative cosmetic effect. The technique is therefore a good surgical incision choice that is worthy of note. PMID:27899991

  19. Comprehensive Quantitative Analysis of Ovarian and Breast Cancer Tumor Peptidomes

    SciTech Connect

    Xu, Zhe; Wu, Chaochao; Xie, Fang; Slysz, Gordon W.; Tolic, Nikola; Monroe, Matthew E.; Petyuk, Vladislav A.; Payne, Samuel H.; Fujimoto, Grant M.; Moore, Ronald J.; Fillmore, Thomas L.; Schepmoes, Athena A.; Levine, Douglas; Townsend, Reid; Davies, Sherri; Li, Shunqiang; Ellis, Matthew; Boja, Emily; Rivers, Robert; Rodriguez, Henry; Rodland, Karin D.; Liu, Tao; Smith, Richard D.

    2015-01-02

    Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective and robust analytical platform for comprehensive analyses of tissue peptidomes, which is suitable for high throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Moreover, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. Peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.

  20. Malignant phyllodes tumor of the breast: treatment and prognosis.

    PubMed

    Mituś, Jerzy; Reinfuss, Marian; Mituś, Jerzy W; Jakubowicz, Jerzy; Blecharz, Pawel; Wysocki, Wojciech M; Skotnicki, Piotr

    2014-01-01

    Surgery remains the mainstay of the treatment in patients with malignant phyllodes tumor of the breast (MPTB); however, the extent of surgery (breast conserving surgery [BCS] versus mastectomy) and the role of adjuvant radiotherapy have been controversial. We report a single institution's experience with MPTB. We discuss controversial therapeutic aspects of this rare tumor. Seventy patients with MPTB treated primarily with surgery were evaluated. The mean age was 50 years (21-76), and the mean size of the tumor was 6 cm. Thirty-four (48.6%) patients were treated with total mastectomy, and 36 (51.4%) were treated with BCS (lumpectomy or wide local excision). Microscopic surgical margins were free of tumor in all cases. In 64 (91.4%) patients, margins were ≥1 cm. Remaining 6 (8.6%) patients treated with BCS margins were <1 cm and subsequently radiotherapy was performed. Among 70 patients, 58 (82.9%) had no evidence of disease (NED) after 5 years. The extent of surgery was not significantly related to the 5-year NED survival rates (82.4% in patients who underwent mastectomy and 83.3% in patients who underwent BCS only or BCS with adjuvant irradiation). The 5-year NED survival rates in BCS (tumor-free margin ≥1 cm) and BCS with irradiation (tumor-free margin <1 cm) groups were identical (83.3%). Our data support the potential use of BCS in patients with MPTB. Mastectomy is indicated only if tumor-free margins cannot be obtained by BCS. Adjuvant radiotherapy may be considered if tumor-free margins are <1 cm.

  1. Harmonic Motion Microwave Doppler Imaging method for breast tumor detection.

    PubMed

    Top, Can Barıs; Tafreshi, Azadeh Kamali; Gençer, Nevzat G

    2014-01-01

    Harmonic Motion Microwave Doppler Imaging (HMMDI) method is recently proposed as a non-invasive hybrid breast imaging technique for tumor detection. The acquired data depend on acoustic, elastic and electromagnetic properties of the tissue. The potential of the method is analyzed with simulation studies and phantom experiments. In this paper, the results of these studies are summarized. It is shown that HMMDI method has a potential to detect malignancies inside fibro-glandular tissue.

  2. A bioimage informatics based reconstruction of breast tumor microvasculature with computational blood flow predictions.

    PubMed

    Stamatelos, Spyros K; Kim, Eugene; Pathak, Arvind P; Popel, Aleksander S

    2014-01-01

    Induction of tumor angiogenesis is among the hallmarks of cancer and a driver of metastatic cascade initiation. Recent advances in high-resolution imaging enable highly detailed three-dimensional geometrical representation of the whole-tumor microvascular architecture. This enormous increase in complexity of image-based data necessitates the application of informatics methods for the analysis, mining and reconstruction of these spatial graph data structures. We present a novel methodology that combines ex-vivo high-resolution micro-computed tomography imaging data with a bioimage informatics algorithm to track and reconstruct the whole-tumor vasculature of a human breast cancer model. The reconstructed tumor vascular network is used as an input of a computational model that estimates blood flow in each segment of the tumor microvascular network. This formulation involves a well-established biophysical model and an optimization algorithm that ensures mass balance and detailed monitoring of all the vessels that feed and drain blood from the tumor microvascular network. Perfusion maps for the whole-tumor microvascular network are computed. Morphological and hemodynamic indices from different regions are compared to infer their role in overall tumor perfusion.

  3. Photonic Breast Tomography and Tumor Aggressiveness Assessment

    DTIC Science & Technology

    2013-09-01

    Magnetic Resonance Spectroscopic Imaging Optical Techniques for Actuation, Sensing , and Imaging of Biological Systems Multi-functional tumor...Time Reversal Optical Tomography Non-negative Matrix Factorization- based Optical Tomography Optical Tomography based on Principal Component...of the two targets 3.9. Estimated size and absorption coefficient of the targets 4.1. Positions and optical strengths retrieved using ICA, PCA and

  4. Surgical adjuvant treatment of locally advanced breast cancer.

    PubMed Central

    Townsend, C M; Abston, S; Fish, J C

    1985-01-01

    The reported incidence of local recurrence after mastectomy for locally advanced breast cancer (TNM Stage III and IV) is between 30% and 50%. The purpose of this study was to evaluate the effect of radiation therapy (XRT) followed by total mastectomy on the incidence of local recurrence in patients with locally advanced breast cancer. Fifty-three patients who presented with locally advanced breast cancer, without distant metastases, were treated with XRT (4500-5000 R) to the breast, chest wall, and regional lymph nodes. Five weeks after completion of XRT, total mastectomy was performed. There were no operative deaths. The complications that occurred in 22 patients after surgery were flap necrosis, wound infection, and seroma. Patients have been followed from 3 to 134 months. Twenty-five patients are alive (3-134 months), 12 free of disease; 28 patients have died with distant metastases (6-67 months). Isolated local recurrence occurred in only two patients. Four patients had local and distant recurrence (total local recurrence is 6/53). The remaining patients all developed distant metastases. We have devised a treatment strategy which significantly decreases the incidence of local recurrence in patients with locally advanced breast cancer. However, the rapid appearance of distant metastases emphasizes the need for systemically active therapy in patients with locally advanced breast cancer. PMID:3994434

  5. Targeted delivery of albumin bound paclitaxel in the treatment of advanced breast cancer.

    PubMed

    Di Costanzo, Francesco; Gasperoni, Silvia; Rotella, Virginia; Di Costanzo, Federica

    2009-02-18

    Taxanes are chemotherapeutic agents with a large spectrum of antitumor activity when used as monotherapy or in combination regimens. Paclitaxel and docetaxel have poor solubility and require a complex solvent system for their commercial formulation, Cremophor EL(R) (CrEL) and Tween 80(R) respectively. Both these biological surfactants have recently been implicated as contributing not only to the hypersensitivity reactions, but also to the degree of peripheral neurotoxicity and myelosuppression, and may antagonize the cytotoxicity. Nab-paclitaxel, or nanoparticle albumin-bound paclitaxel (ABI-007; Abraxane(R)), is a novel formulation of paclitaxel that does not employ the CrEL solvent system. Nab-paclitaxel demonstrates greater efficacy and a favorable safety profile compared with standard paclitaxel in patients with advanced disease (breast cancer, non-small cell lung cancer, melanoma, ovarian cancer). Clinical studies in breast cancer have shown that nab-paclitaxel is significantly more effective than standard paclitaxel in terms of overall objective response rate (ORR) and time to progression. Nab-paclitaxel in combination with gemcitabine, capecitabine or bevacizumab has been shown to be very active in patients with advanced breast cancer. An economic analysis showed that nab-paclitaxel would be an economically reasonable alternative to docetaxel or standard paclitaxel in metastatic breast cancer. Favorable tumor ORR and manageable toxicities have been reported for nab-paclitaxel as monotherapy or in combination treatment in advanced breast cancer.

  6. Angiogenic Signaling in Living Breast Tumor Models

    DTIC Science & Technology

    2009-06-01

    Renal Physiol. 288:F1084–F1089. 12. Sipos, A., I. Toma, J. Kang, L. Rosivall, and J. Peti - Peterdi . 2007. Advances in renal (patho)physiology using...multiphoton microscopy. Kidney Int. 72:1188–1191. 13. Rosivall, L., S. Mirzahosseini, I. Toma, A. Sipos, and J. Peti - Peterdi . 2006. Fluid flow in the

  7. Adipose progenitor cells increase fibronectin matrix strain and unfolding in breast tumors

    NASA Astrophysics Data System (ADS)

    Chandler, E. M.; Saunders, M. P.; Yoon, C. J.; Gourdon, D.; Fischbach, C.

    2011-02-01

    Increased stiffness represents a hallmark of breast cancer that has been attributed to the altered physicochemical properties of the extracellular matrix (ECM). However, the role of fibronectin (Fn) in modulating the composition and mechanical properties of the tumor-associated ECM remains unclear. We have utilized a combination of biochemical and physical science tools to evaluate whether paracrine signaling between breast cancer cells and adipose progenitor cells regulates Fn matrix assembly and stiffness enhancement in the tumor stroma. In particular, we utilized fluorescence resonance energy transfer imaging to map the molecular conformation and stiffness of Fn that has been assembled by 3T3-L1 preadipocytes in response to conditioned media from MDA-MB231 breast cancer cells. Our results reveal that soluble factors secreted by tumor cells promote Fn expression, unfolding, and stiffening by adipose progenitor cells and that transforming growth factor-β serves as a soluble cue underlying these changes. In vivo experiments using orthotopic co-transplantation of primary human adipose-derived stem cells and MDA-MB231 into SCID mice support the pathological relevance of our results. Insights gained by these studies advance our understanding of the role of Fn in mammary tumorigenesis and may ultimately lead to improved anti-cancer therapies.

  8. Optical imaging of breast tumors and of gastrointestinal cancer by laser-induced fluorescence.

    PubMed

    Ebert, Bernd; Grosenick, Dirk

    2013-01-01

    Optical imaging offers a high potential for noninvasive detection of cancer in humans. Recent advances in instrumentation for diffuse optical imaging have led to new capabilities for the detection of cancer in highly scattering tissue such as the female breast. We review recent developments in the detection of breast cancer in humans by fluorescent contrast agents. So far, the unspecific contrast agents indocyanine green (ICG) and omocyanine have been applied, whereas molecular probes for direct targeted imaging of this disease are still in preclinical research. We discuss recent improvements in the differentiation of malignant and benign lesions with ICG based on its enhanced extravasation in breast cancer. Whereas fluorescence imaging in thick tissue layers is hampered by strong light scattering, tissue surfaces can be investigated with high spatial resolution. As an example for superficial tumors, lesions of the gastrointestinal tract (GI) are discussed. In these investigations, protoporphyrin IX is used as a tumor-specific (due to its strong enhancement in tumor cells) target for spectroscopic identification and imaging. We present a time-gated method for fluorescence imaging and spectroscopy with strong suppression of tissue autofluorescence and show results on patients with Barrett's esophagus and with colitis ulcerosa.

  9. Desmoid Tumor of the Chest Wall Mimicking Recurrent Breast Cancer: Multimodality Imaging Findings

    PubMed Central

    Choi, Kyeong A; An, Yeong Yi

    2016-01-01

    Desmoid tumor of breast is a rare benign, locally aggressive tumor with a high recurrence rate. It has been associated with scar from previous breast surgery or trauma. Especially in breast cancer patients with previous operation history, it may simulate recurrent breast cancer clinically and radiologically. We presented multimodality imaging findings (ultrasound, computed tomography, magnetic resonance imaging and positron emission tomography/computed tomography) of chest wall desmoid tumor mimicking recurrent breast cancer in a 38-year-old patient with a history of left modified mastectomy. The desmoid tumor is a rare benign tumor that should be considered in the differential diagnosis of malignant local tumor recurrence after breast cancer operation. Biopsy was required for accurate diagnosis and wide local excision was its appropriate surgical management. PMID:27895871

  10. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma.

    PubMed

    Kang, Tae Wook; Rhim, Hyunchul

    2015-09-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC.

  11. Detection of Circulating Tumor Cells in Breast Cancer Patients Using Cytokeratin-19 Real-Time RT-PCR

    PubMed Central

    Park, Hyung Seok; Han, Hyun Ju; Lee, Soohyeon; Kim, Gun Min; Park, Seho; Choi, Yeon A; Lee, Jeong Dong; Kim, Gi Moon

    2017-01-01

    Purpose The roles of circulating tumor cells (CTCs) as predictive and prognostic factors, as well as key mediators in the metastatic cascade, have been investigated. This study aimed to validate a method to quantify CTCs in peripheral blood using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay for cytokeratin (CK)-19 and to evaluate the utility of this assay in detecting CTCs in breast cancer patients. Materials and Methods Real-time monitoring PCR of fluorescently labeled specific hybridization probes for CK-19 mRNA was established. Peripheral blood samples from 30 healthy donors, 69 patients with early breast cancer, 47 patients with locally advanced breast cancer, and 126 patients with metastatic breast cancer were prospectively obtained and analyzed for CTC detection. Results CK-19 mRNA was not detectable in healthy subjects using the real-time RT-PCR method. The detection rates of CK-19 mRNA in breast cancer patients were 47.8% for early breast cancer (33/69), 46.8% for locally advanced breast cancer (22/47), and 61.1% for metastatic breast cancer (77/129). The detection rate of CK-19-positive CTCs in metastatic disease was slightly higher than early or locally advanced breast cancer; however, the detection rate according to disease burden was not statistically different (p=0.097). The detection rate was higher in patients with pleural metastasis (p=0.045). CTC detection was associated with poor survival (p=0.014). Conclusion A highly specific and sensitive CK-19 mRNA-based method to detect CTCs in peripheral blood in breast cancer patients can be used in further prospective studies to evaluate the predictive and prognostic importance of CTCs. PMID:27873491

  12. Andrographolide inhibits osteopontin expression and breast tumor growth through down regulation of PI3 kinase/Akt signaling pathway.

    PubMed

    Kumar, S; Patil, H S; Sharma, P; Kumar, D; Dasari, S; Puranik, V G; Thulasiram, H V; Kundu, G C

    2012-09-01

    Breast cancer is one of the most common cancers among women in India and around the world. Despite recent advancement in the treatment of breast cancer, the results of chemotherapy to date remain unsatisfactory, prompting a need to identify natural agents that could target cancer efficiently with least side effects. Andrographolide (Andro) is one such molecule which has been shown to possess inhibitory effect on cancer cell growth. In this study, Andro, a natural diterpenoid lactone isolated from Andrographis paniculata has been shown to inhibit breast cancer cell proliferation, migration and arrest cell cycle at G2/M phase and induces apoptosis through caspase independent pathway. Our experimental evidences suggest that Andro attenuates endothelial cell motility and tumor-endothelial cell interaction. Moreover, Andro suppresses breast tumor growth in orthotopic NOD/SCID mice model. The anti-tumor activity of Andro in both in vitro and in vivo model was correlated with down regulation of PI3 kinase/Akt activation and inhibition of pro-angiogenic molecules such as OPN and VEGF expressions. Collectively, these results demonstrate that Andro may act as an effective anti-tumor and anti-angiogenic agent for the treatment of breast cancer.

  13. Recent advances in the medical treatment of breast cancer

    PubMed Central

    Vorobiof, Daniel A.

    2016-01-01

    Over the past few decades, the systemic therapy of breast cancer (early and advanced) has changed considerably. For the past 40–50 years, and since the discovery and further therapeutic use of tamoxifen, a selective estrogen receptor modulator, breast cancer treatment has become the model for the development and success of tailored medical treatment. Much still needs to be done in improving outcomes for all patients with breast cancer, and especially for those who have advanced breast cancer, a challenging area for medical oncologists. Ongoing international clinical trials are currently evaluating new therapeutic approaches and identifying specific biological subsets that could determine a patient’s ability to respond to particular chemotherapeutic drugs. PMID:27990275

  14. [Usefulness of reductive surgery for elderly advanced breast cancer with bone metastases - a case report].

    PubMed

    Sakurai, Kenichi; Fujisaki, Shigeru; Nagashima, Saki; Maeda, Tetsuyo; Tomita, Ryouichi; Suzuki, Shuhei; Hara, Yukiko; Hirano, Tomohiro; Enomoto, Katsuhisa; Amano, Sadao

    2014-11-01

    We report the case of an elderly, advanced breast cancer patient with multiple bone metastases. Breast reduction surgery was useful for this patient. The patient was an 81-year-old woman who had a breast lump. A core needle biopsy for breast cancer led to a diagnosis of invasive ductal carcinoma. The mucinous carcinoma was estrogen receptor (ER) nd progesterone receptor (PgR) positive and HER2/neu negative. Due to patient complications, it was not possible to treat with chemotherapy. The patient was administrated aromatase inhibitors (AI) and zoledronic acid hydrate. However, the AI treatment was not effective, and so she was administered toremifene. Toremifene treatment was effective for 6 months, after which she received fulvestrant. Fulvestrant treatment maintained stable disease (SD)for 14 months. After 14 months of fulvestrant treatment, serum concentrations of the tumor markers CA15-3, CEA, and BCA225 increased. We therefore decided to perform surgical breast reduction surgery. The pathological diagnosis from the surgically resected specimen was mucinous carcinoma, positive for ER and HER2, and negative for PgR. After surgery, serum concentrations of the tumor markers decreased. Following surgery, the patient was administrated lapatinib plus denosumab plus fulvestrant. The patient remains well, without bone metastases, 2 years and 6 months after surgery.

  15. The expression of succinate dehydrogenase in breast phyllodes tumor.

    PubMed

    Choi, Junjeong; Kim, Do Hee; Jung, WooHee; Koo, Ja Seung

    2014-10-01

    The purpose of this study is to investigate the expression of succinate dehydrogenase (SDH)A, SDHB, and HIF-1α in phyllodes tumors and the association with clinic-pathologic factors. Using tissue microarray (TMA) for 206 phyllodes tumor cases, we performed immunohistochemical stains for SDHA, SDHB, and HIF-1α and analyzed their expression in regard to clinicopathologic parameters of each case. The cases were comprised of 156 benign, 34 borderline, and 16 malignant phyllodes tumors. The expression of stromal SDHA and epithelial- and stromal- SDHB increased as the tumor progressed from benign to malignant (P⟨0.001). There were five stromal SDHA-negative cases and 31 stromal SDHB-negative cases. SDHB negativity was associated with a lower histologic grade (P=0.054) and lower stromal atypia (P=0.048). Univariate analysis revealed that a shorter disease free survival (DFS) was associated with stromal SDHB high-positivity (P=0.013) and a shorter overall survival (OS) was associated with high-positivity of stromal SDHA and SDHB (P⟨0.001 and P⟨0.001, respectively). The multivariate Cox analysis with the variables stromal cellularity, stromal atypia, stromal mitosis, stromal overgrowth, tumor margin, stromal SDHA expression, and stromal SDHB expression revealed that stromal overgrowth was associated with a shorter DFS (hazard ratio: 24.78, 95% CI: 3.126-196.5, P=0.002) and a shorter OS (hazard ratio: 176.7, 95% CI: 8.466-3691, P=0.001). In conclusion, Tumor grade is positively correlated with SDHA and SDHB expression in the tumor stroma in phyllodes tumors of the breast. This result may be attributed to the increased metabolic demand in high grade tumors.

  16. Retrospective Analysis of Locally Advanced Noninflammatory Breast Cancer From Chennai, South India, 1990-1999

    SciTech Connect

    Shanta, Viswanathan Swaminathan, Rajaraman; Rama, Ranganathan M.Sc.; Radhika, Ramachandran M.S.

    2008-01-01

    Purpose: This was a retrospective observational study to elicit the outcome of the therapeutic strategy of concurrent neoadjuvant chemoradiotherapy protocol for locally advanced breast cancer. Methods and Materials: A large series of 1,117 consecutive cases of locally advanced breast cancer treated at the Cancer Institute (WIA), in Chennai, South India, between 1990 and 1999 and followed through 2004 formed the basis for this study. Disease-free survival was the main outcome, and nodal and tumor downstaging were the intermediate outcome measures studied. Results: Primary tumor downstaging was observed in 45% and nodal downstaging in 57.5%. The disease-free survival rate of nodal downstaged patients at 5, 10, and 15 years was 75%, 65%, and 58%, respectively. The corresponding rates for pre- and postoperative node-negative patients were 70%, 60%, and 59%. The best survival was seen among those who were tumor and node negative postoperatively. Nodal downstaging halved the risk of disease recurrence and death compared with node positivity, irrespective of tumor sterility. Conclusions: A randomized trial using cyclophosphamide, methotrexate, and 5-fluorouracil vs. an anthracycline-based regimen in the setting of concurrent chemoradiotherapy appears indicated. Additional preoperative chemotherapy to maximize nodal and tumor downstaging should be investigated. A change in postoperative chemotherapy according to nodal status could also be explored.

  17. Gene expression profiles of circulating tumor cells versus primary tumors in metastatic breast cancer.

    PubMed

    Onstenk, Wendy; Sieuwerts, Anieta M; Weekhout, Marleen; Mostert, Bianca; Reijm, Esther A; van Deurzen, Carolien H M; Bolt-de Vries, Joan B; Peeters, Dieter J; Hamberg, Paul; Seynaeve, Caroline; Jager, Agnes; de Jongh, Felix E; Smid, Marcel; Dirix, Luc Y; Kehrer, Diederik F S; van Galen, Anne; Ramirez-Moreno, Raquel; Kraan, Jaco; Van, Mai; Gratama, Jan W; Martens, John W M; Foekens, John A; Sleijfer, Stefan

    2015-06-28

    Before using circulating tumor cells (CTCs) as liquid biopsy, insight into molecular discrepancies between CTCs and primary tumors is essential. We characterized CellSearch-enriched CTCs from 62 metastatic breast cancer (MBC) patients with ≥5 CTCs starting first-line systemic treatment. Expression levels of 35 tumor-associated, CTC-specific genes, including ESR1, coding for the estrogen receptor (ER), were measured by reverse transcription quantitative polymerase chain reaction and correlated to corresponding primary tumors. In 30 patients (48%), gene expression profiles of 35 genes were discrepant between CTCs and the primary tumor, but this had no prognostic consequences. In 15 patients (24%), the expression of ER was discrepant. Patients with ER-negative primary tumors and ER-positive CTCs had a longer median TTS compared to those with concordantly ER-negative CTCs (8.5 versus 2.1 months, P = 0.05). From seven patients, an axillary lymph node metastasis was available. In two patients, the CTC profiles better resembled the lymph node metastasis than the primary tumor. Our findings suggest that molecular discordances between CTCs and primary tumors frequently occur, but that this bears no prognostic consequences. Alterations in ER-status between primary tumors and CTCs might have prognostic implications.

  18. Advances in Optical Spectroscopy and Imaging of Breast Lesions

    SciTech Connect

    Demos, S; Vogel, A J; Gandjbakhche, A H

    2006-01-03

    A review is presented of recent advances in optical imaging and spectroscopy and the use of light for addressing breast cancer issues. Spectroscopic techniques offer the means to characterize tissue components and obtain functional information in real time. Three-dimensional optical imaging of the breast using various illumination and signal collection schemes in combination with image reconstruction algorithms may provide a new tool for cancer detection and monitoring of treatment.

  19. Radiation-Associated Breast Tumors Display a Distinct Gene Expression Profile

    SciTech Connect

    Broeks, Annegien; Braaf, Linde M.; Wessels, Lodewyk F.A.; Vijver, Marc van de; De Bruin, Marie L.; Stovall, Marilyn; Russell, Nicola S.; Leeuwen, Flora E. van; Van't Veer, Laura J.

    2010-02-01

    Purpose: Women who received irradiation for Hodgkin's lymphoma have a strong increased risk for developing breast cancer. Approximately 90% of the breast cancers in these patients can be attributed to their radiation treatment, rendering such series extremely useful to determine whether a common radiation-associated cause underlies the carcinogenic process. Methods and Materials: In this study we used gene expression profiling technology to assess gene expression changes in radiation-associated breast tumors compared with a set of control breast tumors of women unexposed to radiation, diagnosed at the same age. RNA was obtained from fresh frozen tissue samples from 22 patients who developed breast cancer after Hodgkin's lymphoma (BfHL) and from 20 control breast tumors. Results: Unsupervised hierarchical clustering of the profile data resulted in a clustering of the radiation-associated tumors separate from the control tumors (p < 0.001). Using a supervised class prediction tool, a nearest centroid classifier of 198 probes was identified. The BfHL tumors were often of the intrinsic basal breast tumor subtype, and they showed a chromosomal instability profile and a higher expression of the proliferation marker Ki-67. Conclusion: These results indicate that radiation-associated tumors are different from other breast tumors on the basis of their expression profile and that they are mainly of one specific cause that is characterized by high proliferation and a more aggressive tumor type.

  20. Breast tumor characterization using near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Kang, Kyung A.; Chance, Britton; Zhao, Shiyin; Srinivasan, Sudhakar; Patterson, E.; Troupin, R.

    1993-09-01

    NIR time resolved spectroscopy (TRS) is one of the most feasible methods which can be used for the characterization of biological systems, due to its non-invasive nature and safety features in measurement. Breast cancer is the leading cause of death in women ages 40 - 44 and accounts for 32% of all cancer diagnosis in women. The occurrence rate is as high as one out of nine women in the USA. Breast cancer is the most common form of cancer and the second leading cause of cancer death in North America. Therefore, it is natural for researchers in the field of NIR spectroscopy to have strong interest in optical properties of normal and abnormal breast tissue. One of the main interests of NIR spectroscopy in breast cancer is the localization of the tumor. Another important feature is to characterize an anomaly non- invasively since more than 75% of mammographical anomalies are found to be benign. This could reduce the anxiety that the patients would have, as well as lower the clinical expense for the biopsy and operation (approximately $4,000 per a case).

  1. Recent Advances in Microwave Imaging for Breast Cancer Detection

    PubMed Central

    Kwon, Sollip

    2016-01-01

    Breast cancer is a disease that occurs most often in female cancer patients. Early detection can significantly reduce the mortality rate. Microwave breast imaging, which is noninvasive and harmless to human, offers a promising alternative method to mammography. This paper presents a review of recent advances in microwave imaging for breast cancer detection. We conclude by introducing new research on a microwave imaging system with time-domain measurement that achieves short measurement time and low system cost. In the time-domain measurement system, scan time would take less than 1 sec, and it does not require very expensive equipment such as VNA. PMID:28096808

  2. Current Trends in the Management of Phyllodes Tumors of the Breast

    PubMed Central

    Adesoye, Taiwo; Neuman, Heather B; Wilke, Lee G; Schumacher, Jessica R; Steiman, Jennifer; Greenberg, Caprice C

    2016-01-01

    Introduction National Comprehensive Cancer Network (NCCN) guidelines recommend wide excision without axillary staging to treat phyllodes tumors of the breast. Without prospective trials to guide management, NCCN also recommends consideration of radiation therapy (XRT). We describe current patterns of care for the multidisciplinary management of phyllodes tumors. Methods Using Surveillance, Epidemiology and End Results Program (SEER) data, we identified women diagnosed with phyllodes tumors between 2000 and 2012 who underwent surgical therapy. Trends in breast conserving surgery (BCS), nodal sampling and XRT were assessed using the Cochrane-Armitage test. Multivariable logistic regression was used to identify factors associated with treatment. Results Of 1,238 patients, 56.9% underwent BCS and 23.6% underwent nodal sampling (10.5% after BCS vs 40.9% after mastectomy). After surgery, 15.4% received adjuvant XRT (BCS, 12.9% and mastectomy, 18.8%). XRT utilization increased significantly over the study period (BCS, p=<0.0001; mastectomy, p=0.0003) while nodal sampling did not change significantly. Women were more likely to receive mastectomy if they were older or had larger tumors. Nodal sampling was also associated with older age, larger tumor size and receipt of mastectomy. Receipt of XRT was associated with later year of diagnosis, larger tumors and nodal assessment. Conclusion Over time, an increasing number of women received XRT after surgical management of phyllodes tumor, and one in four women underwent nodal sampling. While some of this practice can be attributed to concern about more advanced disease in the absence of strong data, there may be an educational gap regarding current guidelines and appropriate management. PMID:27334214

  3. Recent advances in the development of breast cancer vaccines

    PubMed Central

    Milani, Andrea; Sangiolo, Dario; Aglietta, Massimo; Valabrega, Giorgio

    2014-01-01

    The manipulation of the immune system through the administration of a vaccine to direct an effective and long-lasting immune response against breast cancer (BC) cells is an attractive strategy. Vaccines would have several theoretical advantages over standard therapies, including low toxicities, high specificity, and long-lasting efficacy due to the establishment of immunological memory. However, BC vaccines have failed to demonstrate meaningful results in clinical trials so far. This reflects the intrinsic difficulty in breaking the complex immune-escaping mechanisms developed by cancer cells. New vaccines should be able to elicit complex immunologic response involving multiple immune effectors such as cytotoxic and antibody-secreting B cells, innate immunity effectors, and memory cells. Moreover, especially in patients with large tumor burdens and metastatic disease, combining vaccines with other strategies, such as systemic BC therapies, passive immunotherapy, or immunomodulatory agents, could increase the effectiveness of each approach. Here, we review recent advances in BC vaccines, focusing on suitable targets and innovative strategies. We report results of most recent trials investigating active immunotherapy in BC and provide possible future perspectives in this field of research. PMID:25339848

  4. Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy.

    PubMed

    Parissenti, Amadeo M; Guo, Baoqing; Pritzker, Laura B; Pritzker, Kenneth P H; Wang, Xiaohui; Zhu, Mu; Shepherd, Lois E; Trudeau, Maureen E

    2015-08-01

    In a prior substudy of the CAN-NCIC-MA.22 clinical trial (ClinicalTrials.gov identifier NCT00066443), we observed that neoadjuvant chemotherapy reduced tumor RNA integrity in breast cancer patients, a phenomenon we term "RNA disruption." The purpose of the current study was to assess in the full patient cohort the relationship between mid-treatment tumor RNA disruption and both pCR post-treatment and, subsequently, disease-free survival (DFS) up to 108 months post-treatment. To meet these objectives, we developed the RNA disruption assay (RDA) to quantify RNA disruption and stratify it into 3 response zones of clinical importance. Zone 1 is a level of RNA disruption inadequate for pathologic complete response (pCR); Zone 2 is an intermediate level, while Zone 3 has high RNA disruption. The same RNA disruption cut points developed for pCR response were then utilized for DFS. Tumor RDA identified >fourfold more chemotherapy non-responders than did clinical response by calipers. pCR responders were clustered in RDA Zone 3, irrespective of tumor subtype. DFS was about 2-fold greater for patients with tumors in Zone 3 compared to Zone 1 patients. Kaplan-Meier survival curves corroborated these findings that high tumor RNA disruption was associated with increased DFS. DFS values for patients in zone 3 that did not achieve a pCR were similar to that of pCR recipients across tumor subtypes, including patients with hormone receptor positive tumors that seldom achieve a pCR. RDA appears superior to pCR as a chemotherapy response biomarker, supporting the prospect of its use in response-guided chemotherapy.

  5. Molecular Detection of Peripheral Blood Breast Cancer mRNA Transcripts as a Surrogate Biomarker for Circulating Tumor Cells

    PubMed Central

    Lasa, Adriana; Garcia, Arnal; Alonso, Carmen; Millet, Pilar; Cornet, Mónica; Cajal, Teresa Ramón y; Baiget, Montserrat; Barnadas, Agusti

    2013-01-01

    Circulating tumor cells (CTCs) are becoming a scientifically recognized indicator of primary tumors and/or metastasis. These cells can now be accurately detected and characterized as the result of technological advances. We analyzed the presence of CTCs in the peripheral blood of patients with metastatic breast cancer by real-time reverse-transcription PCR (RT-qPCR) using a panel of selected genes. The analysis of a single marker, without an EpCAM based enrichment approach, allowed the positive identification of 35% of the metastatic breast cancer patients. The analysis of five genes (SCGB2, TFF1, TFF3, Muc1, KRT20) performed in all the samples increased the detection to 61%. We describe a sensitive, reproducible and easy to implement approach to characterize CTC in patients with metastasic breast cancer. PMID:24058517

  6. Imaging heterogeneous absorption distribution of advanced breast cancer by optical tomography

    PubMed Central

    Xu, Yan; Zhu, Quing

    2010-01-01

    Tumor vascular patterns of advanced breast cancers are complex and heterogeneous. Two typical light absorption patterns of periphery enhancement and posterior shadowing have been observed when imaging these advanced cancers using optical tomography guided by ultrasound. We perform a series simulation and phantom experiments to systemically evaluate the effects of target parameters, target locations, and target optical properties on imaging periphery enhancement absorption distribution using reflection geometry. Large tumors are modeled as concentric semiellipsoidal targets of different outer shell and inner core optical properties. We show that larger targets of more than 3 to 4 cm diameter with outer shell thicknesses less than 1 cm can be resolved at a depth less than 3 cm. A clinical example is given to show the complex vasculature distributions seen from an advanced cancer. PMID:21198181

  7. Significance of Micrometastases: Circulating Tumor Cells and Disseminated Tumor Cells in Early Breast Cancer

    PubMed Central

    Oakman, Catherine; Pestrin, Marta; Bessi, Silvia; Galardi, Francesca; Di Leo, Angelo

    2010-01-01

    Adjuvant systemic therapy targets minimal residual disease. Our current clinical approach in the adjuvant setting is to presume, rather than confirm, the presence of minimal residual disease. Based on assessment of the primary tumor, we estimate an individual’s recurrence risk. Subsequent treatment decisions are based on characteristics of the primary tumor, with the presumption of consistent biology and treatment sensitivity between micrometastases and the primary lesion. An alternative approach is to identify micrometastatic disease. Detection of disseminated tumor cells (DTC) in the bone marrow and circulating tumor cells (CTC) from peripheral blood collection may offer quantification and biocharacterization of residual disease. This paper will review the prognostic and predictive potential of micrometastatic disease in early breast cancer. PMID:24281114

  8. Role of tumor markers and circulating tumors cells in the management of breast cancer.

    PubMed

    Saad, Ayman; Abraham, Jame

    2008-06-01

    Along with various imaging modalities, serologic tumor markers such as CA 15-3 and CA 27.29 have been used for decades to monitor treatment response in patients with metastatic breast cancer (MBC). Despite the frequent use of these markers, they lack high sensitivity and specificity for breast cancer progression. The prognostic significance of these markers remains indeterminate because of the conflicting outcome of many clinical trials. The circulating tumor cell (CTC) test has recently been studied in clinical trials in patients with MBC. Some of the studies showed that high levels of CTCs are correlated with poor survival in MBC. An intergroup trial is underway to determine the implication of changing treatment based on the CTC level. This article will discuss the current data on these markers, with special emphasis on the CTC test. The potential clinical utility of these markers will also be discussed.

  9. Computer-Aided Assessment of Tumor Grade for Breast Cancer in Ultrasound Images

    PubMed Central

    2015-01-01

    This study involved developing a computer-aided diagnosis (CAD) system for discriminating the grades of breast cancer tumors in ultrasound (US) images. Histological tumor grades of breast cancer lesions are standard prognostic indicators. Tumor grade information enables physicians to determine appropriate treatments for their patients. US imaging is a noninvasive approach to breast cancer examination. In this study, 148 3-dimensional US images of malignant breast tumors were obtained. Textural, morphological, ellipsoid fitting, and posterior acoustic features were quantified to characterize the tumor masses. A support vector machine was developed to classify breast tumor grades as either low or high. The proposed CAD system achieved an accuracy of 85.14% (126/148), a sensitivity of 79.31% (23/29), a specificity of 86.55% (103/119), and an AZ of 0.7940. PMID:25810750

  10. Epidemiologic Investigation of a Cluster of Cystosarcoma Phyllodes Tumors of the Female Breast.

    DTIC Science & Technology

    1997-09-01

    AD GRANT NUMBER DAMD17-94-J-4423 TITLE: Epidemiologie Investigation of a Cluster of Cystosarcoma Phyllodes Tumors of the Female Breast PRINCIPAL...SUBTITLE Epidemiologie Investigation of a Cluster of Cystosarcoraa Phyllodes Tumors of the Female Breast 3. REPORT TYPE AND DATES COVERED fAnnual...fibroepithelial tumor composed of an epithelial and a cellular stromal component. A significant number of cases of cystosarcoma phyllodes tumors were

  11. Pleomorphic liposarcoma arising in a malignant phyllodes tumor of breast: A rare occurrence.

    PubMed

    Sancheti, Sankalp M; Sawaimoon, Satyakam K; Ahmed, Rosina

    2015-01-01

    Primary malignant phyllodes tumor of the breast accounts for 0.3-1% of all the tumors of breast and only a couple of cases of pleomorphic liposarcoma (PL) arising in a malignant phyllodes (MP) tumor have been reported. A thorough sampling is most essential in phyllodes tumor, not only to detect high grade component of the neoplasm but also to diagnose heterologous elements in the same lesion elsewhere, as it may affect the prognosis adversely and may have a greater metastatic potential.

  12. Terahertz Imaging of Three-Dimensional Dehydrated Breast Cancer Tumors

    NASA Astrophysics Data System (ADS)

    Bowman, Tyler; Wu, Yuhao; Gauch, John; Campbell, Lucas K.; El-Shenawee, Magda

    2017-03-01

    This work presents the application of terahertz imaging to three-dimensional formalin-fixed, paraffin-embedded human breast cancer tumors. The results demonstrate the capability of terahertz for in-depth scanning to produce cross section images without the need to slice the tumor. Samples of tumors excised from women diagnosed with infiltrating ductal carcinoma and lobular carcinoma are investigated using a pulsed terahertz time domain imaging system. A time of flight estimation is used to obtain vertical and horizontal cross section images of tumor tissues embedded in paraffin block. Strong agreement is shown comparing the terahertz images obtained by electronically scanning the tumor in-depth in comparison with histopathology images. The detection of cancer tissue inside the block is found to be accurate to depths over 1 mm. Image processing techniques are applied to provide improved contrast and automation of the obtained terahertz images. In particular, unsharp masking and edge detection methods are found to be most effective for three-dimensional block imaging.

  13. Sunitinib treatment enhances metastasis of innately drug resistant breast tumors

    PubMed Central

    Wragg, Joseph W; Heath, Victoria L; Bicknell, Roy

    2017-01-01

    Anti-angiogenic therapies have failed to confer survival benefits in patients with metastatic breast cancer (mBC). However, to date there has not been an inquiry into roles for acquired versus innate drug resistance in this setting. In this study, we report roles for these distinct phenotypes in determining therapeutic response in a murine model of mBC resistance to the anti-angiogenic tyrosine kinase inhibitor sunitinib. Using tumor measurement and vascular patterning approaches, we differentiated tumors displaying innate versus acquired resistance. Bioluminescent imaging of tumor metastases to the liver, lungs and spleen revealed that sunitinib administration enhances metastasis, but only in tumors displaying innate resistance to therapy. Transcriptomic analysis of tumors displaying acquired versus innate resistance allowed the identification of specific biomarkers, many of which have a role in angiogenesis. In particular, aquaporin-1 upregulation occurred in acquired resistance, mTOR in innate resistance, and pleiotrophin in both settings, suggesting their utility as candidate diagnostics to predict drug response or to design tactics to circumvent resistance. Our results unravel specific features of antiangiogenic resistance, with potential therapeutic implications. PMID:28011623

  14. Identification of Tumor Rejection Antigens for Breast Cancer Using a Mouse Tumor Rejection Model

    DTIC Science & Technology

    2009-05-01

    high throughput antigen discovery tools have been developed that have greatly helped the identification of immunogenic proteins in breast cancer...streptomycin and L-glutamine. T cell enrichment Tumor-infiltrating lymphocytes (TIL) were harvested by mincing the tu- mor and screening. The TIL were...kinase 1. Multiple proteins involved in the Rho/Rho-associated, coiled coil–containing protein kinase (Rock) signal transduction pathway were found to

  15. Needle-based polarization-sensitive OCT of breast tumor (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Villiger, Martin; Lorenser, Dirk; McLaughlin, Robert A.; Quirk, Bryden C.; Kirk, Rodney W.; Bouma, Brett E.; Sampson, David D.

    2016-03-01

    OCT imaging through miniature needle probes has extended the range of OCT and enabled structural imaging deep inside breast tissue, with the potential to assist in the intraoperative assessment of tumor margins. However, in many situations, scattering contrast alone is insufficient to clearly identify and delineate malignant areas. Here, we present a portable, depth-encoded polarization-sensitive OCT system, connected to a miniature needle probe. From the measured polarization states we constructed the tissue Mueller matrix at each sample location and improved the accuracy of the measured polarization states through incoherent averaging before retrieving the depth-resolved tissue birefringence. With the Mueller matrix at hand, additional polarization properties such as depolarization are readily available. We then imaged freshly excised breast tissue from a patient undergoing lumpectomy. The reconstructed local retardation highlighted regions of connective tissue, which exhibited birefringence due to the abundance of collagen fibers, and offered excellent contrast to areas of malignant tissue, which exhibited less birefringence due to their different tissue composition. Results were validated against co-located histology sections. The combination of needle-based imaging with the complementary contrast provided by polarization-sensitive analysis offers a powerful instrument for advanced tissue imaging and has potential to aid in the assessment of tumor margins during the resection of breast cancer.

  16. Evaluation of Neoadjuvant Chemotherapy Response with Dynamic Contrast Enhanced Breast Magnetic Resonance Imaging in Locally Advanced Invasive Breast Cancer

    PubMed Central

    Gezer, Naciye Sinem; Orbay, Özge; Balcı, Pınar; Durak, Merih Guray; Demirkan, Binnaz; Saydam, Serdar

    2014-01-01

    Objective The reliability of traditional methods such as physical examination, ultrasonography (US) and mammography is limited in determining the type of treatment response in patients with neoadjuvant chemotherapy (NAC) application for locally advanced breast cancer (LABC). Dynamic contrast-enhanced magnetic resonance imaging (MRI) is gaining popularity in the evaluation of NAC response. This study aimed to compare NAC response as determined by dynamic contrast-enhanced breast MRI in patients with LABC to histopathology that is the gold standard; and evaluate the compatibility of MRI, mammography and US with response types. Materials and Methods The US, mammography and MRI findings of 38 patients who received NAC with a diagnosis of locally advanced breast cancer and surgical treatment were retrospectively analyzed and compared to histopathology results. Type of response to treatment was determined according to the “Criteria in Solid Tumors Response Evolution 1.1” by mammography, US and MRI criteria. The relationship between response types as defined by all three imaging modalities and histopathology were evaluated, and the correlation of response type as detected by MRI and pathological response and histopathological type of breast cancer was further determined. For statistical analysis, the chi-square, paired t test, correlation and kappa tests were used. Results There is a statistical moderate positive correlation between response type according to pathology and MRI (kappa: 0.63). There was a weak correlation between response type according to mammography or US and according to pathology (kappa: 0.2). When the distribution of treatment response by MRI is stratified according to histopathological types, partial response was higher in all histopathological types similar to the type of pathologic response. When compared with pathology MRI detected treatment response accurately in 84.2% of the patients. Conclusion Dynamic contrast-enhanced breast MRI appears to

  17. AZU-1: A Candidate Breast Tumor Suppressor and Biomarker for Tumor Progression

    SciTech Connect

    Chen, Huei-Mei; Schmeichel, Karen L; Mian, I. Saira; Lelie`vre, Sophie; Petersen, Ole W; Bissell, Mina J

    2000-02-04

    To identify genes misregulated in the final stages of breast carcinogenesis, we performed differential display to compare the gene expression patterns of the human tumorigenic mammary epithelial cells, HMT-3522-T4-2, with those of their immediate premalignant progenitors, HMT-3522-S2. We identified a novel gene, called anti-zuai-1 (AZU-1), that was abundantly expressed in non- and premalignant cells and tissues but was appreciably reduced in breast tumor cell types and in primary tumors. The AZU-1 gene encodes an acidic 571-amino-acid protein containing at least two structurally distinct domains with potential protein-binding functions: an N-terminal serine and proline-rich domain with a predicted immunoglobulin-like fold and a C-terminal coiled-coil domain. In HMT-3522 cells, the bulk of AZU-1 protein resided in a detergent-extractable cytoplasmic pool and was present at much lower levels in tumorigenic T4-2 cells than in their nonmalignant counterparts. Reversion of the tumorigenic phenotype of T4-2 cells, by means described previously, was accompanied by the up-regulation of AZU-1. In addition, reexpression of AZU-1 in T4-2 cells, using viral vectors, was sufficient to reduce their malignant phenotype substantially, both in culture and in vivo. These results indicate that AZU-1 is a candidate breast tumor suppressor that may exert its effects by promoting correct tissue morphogenesis.

  18. Poorer breast cancer survival outcomes in males than females might be attributable to tumor subtype

    PubMed Central

    Zhu, Shan; Wu, Juan; Li, Xiang; Liu, Qian; Wei, Wen; Sun, Shengrong

    2016-01-01

    Background & Aims Substantial controversy exists regarding the differences in tumor subtypes between male breast cancer (MBC) and female breast cancer (FBC). This is the largest population-based study to compare MBC and FBC patients. Methods Using data obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2012, a retrospective, population-based cohort study was conducted to investigate tumor subtype-specific differences in various characteristics, overall survival (OS) and breast cancer-specific mortality (BCSM) between males and females. Results In all, 181,814 BC patients (1,516 male and 180,298 female) were eligible for this study. The male patients were more likely to be black, older, and have lower histological grades, more advanced stages, larger tumors, more lymph node and distant metastases and human epidermal growth factor receptor 2 (HER2)-negative tumors (each p<0.05). A matched analysis showed that the 2-year OS was 91.2% and 93.7% and that the BCSM was 2.2% and 2.5% for male and female patients, respectively. The univariate analysis showed that male triple-negative (TN), hormone receptor (HoR)-positive/HER2-positive and HoR-positive/HER2-negative patients had poorer OS (p <0.01). Meanwhile, the HoR-positive/HER2-positive and TN subtypes were associated with a higher BCSM in MBC patients (p<0.01). The multivariate analysis revealed that TN MBC patients had poorer OS and BCSM (p<0.05). Simultaneously, the results showed that male patients in the HoR-positive/HER2-negative subgroup were less likely to die of BC when adjusting for other factors (p<0.05). Conclusions The analysis of 2-year OS and BCSM among the BC subtypes showed clear differences between MBC and FBC patients with the TN subtype; these differences warrant further investigation PMID:27655704

  19. A combining method for tumors detection from near-infrared breast imaging.

    PubMed

    Wang, Zhicheng; Liu, Jian; Tian, Jinwen; Xie, Zeping

    2005-01-01

    This paper introduces the new qualitative and quantitative methods, which can diagnose breast tumors. Qualitative methods include blood vessel display inside and outside of pathological changes part of breast, display of equivalent pixel curves at the part of pathological changes and display of breast tumor image edge. Accordingly, three feature extraction operators are proposed, i.e. the combination operators of anisotropic gradient and smoothing operator, an improved Sobel operator and an edge sharpening operator. Furthermore, quantitative diagnose approaches are discussed based on blood and oxygen contents according to abundant clinical data and pathological mechanism of breast tumors. The results of clinic show that the methods of combining qualitative and quantitative diagnose are effective for breast tumor images, especially for early and potential breast cancer.

  20. Investigation of the Role of Breast Tumor Kinase (Brk) in ERK5 and p38-Mediated Breast Cancer Cell

    DTIC Science & Technology

    2007-10-01

    signaling between normal (gut and skin epithelial cells) and neoplastic (breast cancer ) contexts. Proto-oncogenic Brk may constrain the Akt signaling...Tumor Kinase (Brk) in ERK5 and p38-Mediated Breast Cancer Cell PRINCIPAL INVESTIGATOR: Kristopher Lofgren...Mediated 5a. CONTRACT NUMBER Breast Cancer Cell 5b. GRANT NUMBER W81XWH-06-1-0752 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Kristopher Lofgren

  1. Inorganic Nanovehicle Targets Tumor in an Orthotopic Breast Cancer Model

    NASA Astrophysics Data System (ADS)

    Choi, Goeun; Kwon, Oh-Joon; Oh, Yeonji; Yun, Chae-Ok; Choy, Jin-Ho

    2014-03-01

    The clinical efficacy of conventional chemotherapeutic agent, methotrexate (MTX), can be limited by its very short plasma half-life, the drug resistance, and the high dosage required for cancer cell suppression. In this study, a new drug delivery system is proposed to overcome such limitations. To realize such a system, MTX was intercalated into layered double hydroxides (LDHs), inorganic drug delivery vehicle, through a co-precipitation route to produce a MTX-LDH nanohybrid with an average particle size of approximately 130 nm. Biodistribution studies in mice bearing orthotopic human breast tumors revealed that the tumor-to-liver ratio of MTX in the MTX-LDH-treated-group was 6-fold higher than that of MTX-treated-one after drug treatment for 2 hr. Moreover, MTX-LDH exhibited superior targeting effect resulting in high antitumor efficacy inducing a 74.3% reduction in tumor volume compared to MTX alone, and as a consequence, significant survival benefits. Annexin-V and propidium iodine dual staining and TUNEL analysis showed that MTX-LDH induced a greater degree of apoptosis than free MTX. Taken together, our data demonstrate that a new MTX-LDH nanohybrid exhibits a superior efficacy profile and improved distribution compared to MTX alone and has the potential to enhance therapeutic efficacy via inhibition of tumor proliferation and induction of apoptosis.

  2. Can Breast Tumors Affect the Oxidative Status of the Surrounding Environment? A Comparative Analysis among Cancerous Breast, Mammary Adjacent Tissue, and Plasma

    PubMed Central

    Panis, C.; Victorino, V. J.; Herrera, A. C. S. A.; Cecchini, A. L.; Simão, A. N. C.; Tomita, L. Y.; Cecchini, R.

    2016-01-01

    In this paper, we investigated the oxidative profile of breast tumors in comparison with their normal adjacent breast tissue. Our study indicates that breast tumors present enhanced oxidative/nitrosative stress, with concomitant augmented antioxidant capacity when compared to the adjacent normal breast. These data indicate that breast cancers may be responsible for the induction of a prooxidant environment in the mammary gland, in association with enhanced TNF-α and nitric oxide. PMID:26697139

  3. Can Breast Tumors Affect the Oxidative Status of the Surrounding Environment? A Comparative Analysis among Cancerous Breast, Mammary Adjacent Tissue, and Plasma.

    PubMed

    Panis, C; Victorino, V J; Herrera, A C S A; Cecchini, A L; Simão, A N C; Tomita, L Y; Cecchini, R

    2015-01-01

    In this paper, we investigated the oxidative profile of breast tumors in comparison with their normal adjacent breast tissue. Our study indicates that breast tumors present enhanced oxidative/nitrosative stress, with concomitant augmented antioxidant capacity when compared to the adjacent normal breast. These data indicate that breast cancers may be responsible for the induction of a prooxidant environment in the mammary gland, in association with enhanced TNF-α and nitric oxide.

  4. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma

    PubMed Central

    Kang, Tae Wook; Rhim, Hyunchul

    2015-01-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

  5. Label-Free Raman Imaging to Monitor Breast Tumor Signatures.

    PubMed

    Manciu, Felicia S; Ciubuc, John D; Parra, Karla; Manciu, Marian; Bennet, Kevin E; Valenzuela, Paloma; Sundin, Emma M; Durrer, William G; Reza, Luis; Francia, Giulio

    2016-07-04

    Although not yet ready for clinical application, methods based on Raman spectroscopy have shown significant potential in identifying, characterizing, and discriminating between noncancerous and cancerous specimens. Real-time and accurate medical diagnosis achievable through this vibrational optical method largely benefits from improvements in current technological and software capabilities. Not only is the acquisition of spectral information now possible in milliseconds and analysis of hundreds of thousands of data points achieved in minutes, but Raman spectroscopy also allows simultaneous detection and monitoring of several biological components. Besides demonstrating a significant Raman signature distinction between nontumorigenic (MCF-10A) and tumorigenic (MCF-7) breast epithelial cells, our study demonstrates that Raman can be used as a label-free method to evaluate epidermal growth factor activity in tumor cells. Comparative Raman profiles and images of specimens in the presence or absence of epidermal growth factor show important differences in regions attributed to lipid, protein, and nucleic acid vibrations. The occurrence, which is dependent on the presence of epidermal growth factor, of new Raman features associated with the appearance of phosphothreonine and phosphoserine residues reflects a signal transduction from the membrane to the nucleus, with concomitant modification of DNA/RNA structural characteristics. Parallel Western blotting analysis reveals an epidermal growth factor induction of phosphorylated Akt protein, corroborating the Raman results. The analysis presented in this work is an important step toward Raman-based evaluation of biological activity of epidermal growth factor receptors on the surfaces of breast cancer cells. With the ultimate future goal of clinically implementing Raman-guided techniques for the diagnosis of breast tumors (e.g., with regard to specific receptor activity), the current results just lay the foundation for

  6. Role of chemotherapy in the management of advanced thymic tumors.

    PubMed

    Evans, Tracey L; Lynch, Thomas J

    2005-01-01

    Chemotherapy has an important role in the treatment of advanced thymic tumors. Early stage tumors are successfully treated with surgery. Locally advanced tumors (Masaoka stage III and IVA) are often treated with combined modality treatment including surgery, radiation, and chemotherapy. For patients with curable thymic tumors, the ability to attain a complete resection is a critical prognostic factor. Locally advanced tumors have a relatively high risk of recurrence and decreased rates of long-term survival. A multimodality approach including induction chemotherapy and postoperative radiation therapy can improve complete resection rates and long-term outcomes. Thymic tumors are chemoresponsive with optimal responses achieved with cisplatin-based combination chemotherapy. Chemotherapy with radiation can result in long-term progression-free survival for patients with locally advanced disease who remain inoperable following induction therapy. Patients with disseminated (stage IVB) thymic tumors can also have significant disease response and palliation of symptoms when treated with chemotherapy. Octreotide and corticosteroids also have shown efficacy. For best results, it is important that thoracic surgeons, radiation oncologists, and medical oncologists work together to obtain the best local control of tumor and optimal treatment of metastases.

  7. Cerebellar metastases of recurrent phyllodes tumor breast; a rare phenomenon reflecting the unpredictable outcome.

    PubMed

    Singh, Jyotsna; Majumdar, Kaushik; Gupta, Rahul; Batra, Vineeta Vijay

    2015-01-01

    Carcinomas of lung, breast, colon, kidney, and malignant melanomas are the most common malignancies that metastasize to the central nervous system (CNS). Phyllodes tumor is a rare fibroepithelial tumor of the breast, often having unpredictable recurrences, with increasing histological grade and distant metastasis. Malignant forms exist, which may develop distant metastases usually to the lung, pleura, bone, and liver. CNS metastasis of phyllodes tumor is rare and associated with a poor prognosis, with resistance to chemotherapy and radiation. We present a rare case of cerebellar metastasis in recurrent phyllodes tumor breast with subsequent rapid downhill course.

  8. Prevalence of Papillomaviruses, Polyomaviruses, and Herpesviruses in Triple-Negative and Inflammatory Breast Tumors from Algeria Compared with Other Types of Breast Cancer Tumors

    PubMed Central

    Corbex, Marilys; Bouzbid, Sabiha; Traverse-Glehen, Alexandra; Aouras, Hayette; McKay-Chopin, Sandrine; Carreira, Christine; Lankar, Abdelaziz; Tommasino, Massimo; Gheit, Tarik

    2014-01-01

    Background The possible role of viruses in breast cancer etiology remains an unresolved question. We hypothesized that if some viruses are involved, it may be in a subgroup of breast cancers only. Epidemiological arguments drove our interest in breast cancer subgroups that are more frequent in Africa, namely inflammatory breast cancer (IBC) and triple-negative breast cancer. We tested whether viral prevalence was significantly higher in these subgroups. Materials and Methods One hundred fifty-five paraffin-embedded malignant breast tumors were randomly selected at the pathology laboratory of the University Hospital of Annaba (Algeria) to include one third of IBC and two thirds of non-IBC. They were tested for the presence of DNA from 61 viral agents (46 human papillomaviruses, 10 polyomaviruses, and 5 herpesviruses) using type-specific multiplex genotyping assays, which combine multiplex PCR and bead-based Luminex technology. Results Viral DNA was found in 22 (17.9%) of 123 tumors. The most prevalent viruses were EBV1 and HPV16. IBC tumors carried significantly more viruses (any type) than non-IBC tumors (30% vs. 13%, p<0.04). Similarly, triple-negative tumors displayed higher virus-positivity than non-triple-negative tumors (44% vs. 14%, p<0.009). Conclusions Our results suggest an association between the presence of viral DNA and aggressive breast cancer phenotypes (IBC, triple-negative). While preliminary, they underline the importance of focusing on subgroups when studying viral etiology in breast cancer. Further studies on viruses in breast cancer should be conducted in much larger samples to confirm these initial findings. PMID:25478862

  9. Ipsilateral Breast Tumor Relapse: Local Recurrence Versus New Primary Tumor and the Effect of Whole-Breast Radiotherapy on the Rate of New Primaries

    SciTech Connect

    Gujral, Dorothy M.; Sumo, Georges; Owen, John R.; Ashton, Anita; Bliss, Judith M.; Haviland, Joanne; Yarnold, John R.

    2011-01-01

    Purpose: The justification for partial breast radiotherapy after breast conservation surgery assumes that ipsilateral breast tumor relapses (IBTR) outside the index quadrant are mostly new primary (NP) tumors that develop despite radiotherapy. We tested the hypothesis that whole-breast radiotherapy (WBRT) is ineffective in preventing NP by comparing development rates in irradiated and contralateral breasts after tumor excision and WBRT. Methods and Materials: We retrospectively reviewed 1,410 women with breast cancer who were entered into a prospective randomized trial of radiotherapy fractionation and monitored annually for ipsilateral breast tumor relapses (IBTR) and contralateral breast cancer (CLBC). Cases of IBTR were classified into local recurrence (LR) or NP tumors based on location and histology and were subdivided as definite or likely depending on clinical data. Rates of ipsilateral NP and CLBC were compared over a 15-year period of follow-up. Results: At a median follow-up of 10.1 years, there were 150 documented cases of IBTR: 118 (79%) cases were definite or likely LR; 27 (18%) cases were definite or likely NP; and 5 (3%) cases could not be classified. There were 71 cases of CLBC. The crude proportion of definite-plus-likely NP was 1.9% (27/1,410) patients compared with 5% (71/1,410) CLBC patients. Cumulative incidence rates at 5, 10, and 15 years were 0.8%, 2.0%, and 3.5%, respectively, for definite-plus-likely NP and 2.4%, 5.8%, and 7.9%, respectively for CLBC, suggesting a difference in the rates of NP and CLBC. Conclusions: This analysis suggests that WBRT reduces the rate of ipsilateral NP tumors. The late presentation of NP has implications for the reporting of trials that are testing partial breast radiotherapy.

  10. Cardiac Safety Study of Entinostat in Men and Women With Advanced Solid Tumors

    ClinicalTrials.gov

    2017-02-24

    Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Digestive System Neoplasms; Endocrine Gland Neoplasms; Carcinoma, Non-Small-Cell Lung; Lung Diseases; Breast Neoplasms; Breast Diseases; Renal Neoplasm; Solid Tumors

  11. Three-dimensional in vitro co-culture model of breast tumor using magnetic levitation.

    PubMed

    Jaganathan, Hamsa; Gage, Jacob; Leonard, Fransisca; Srinivasan, Srimeenakshi; Souza, Glauco R; Dave, Bhuvanesh; Godin, Biana

    2014-10-01

    In this study, we investigate a novel in vitro model to mimic heterogeneous breast tumors without the use of a scaffold while allowing for cell-cell and tumor-fibroblast interactions. Previous studies have shown that magnetic levitation system under conventional culturing conditions results in the formation of three-dimensional (3D) structures, closely resembling in vivo tissues (fat tissue, vasculature, etc.). Three-dimensional heterogeneous tumor models for breast cancer were designed to effectively model the influences of the tumor microenvironment on drug efficiency. Various breast cancer cells were co-cultured with fibroblasts and then magnetically levitated. Size and cell density of the resulting tumors were measured. The model was phenotypically compared to in vivo tumors and examined for the presence of ECM proteins. Lastly, the effects of tumor stroma in the 3D in vitro model on drug transport and efficiency were assessed. Our data suggest that the proposed 3D in vitro breast tumor is advantageous due to the ability to: (1) form large-sized (millimeter in diameter) breast tumor models within 24 h; (2) control tumor cell composition and density; (3) accurately mimic the in vivo tumor microenvironment; and (4) test drug efficiency in an in vitro model that is comparable to in vivo tumors.

  12. CBL enhances breast tumor formation by inhibiting tumor suppressive activity of TGF-β signaling.

    PubMed

    Kang, J M; Park, S; Kim, S J; Hong, H Y; Jeong, J; Kim, H-S; Kim, S-J

    2012-12-13

    Casitas B-lineage lymphoma (CBL) protein family functions as multifunctional adaptor proteins and E3 ubiquitin ligases that are implicated as regulators of signaling in various cell types. Recent discovery revealed mutations of proto-oncogenic CBL in the linker region and RING finger domain in human acute myeloid neoplasm, and these transforming mutations induced carcinogenesis. However, the adaptor function of CBL mediated signaling pathway during tumorigenesis has not been well characterized. Here, we show that CBL is highly expressed in breast cancer cells and significantly inhibits transforming growth factor-β (TGF-β) tumor suppressive activity. Knockdown of CBL expression resulted in the increased expression of TGF-β target genes, PAI-I and CDK inhibitors such as p15(INK4b) and p21(Cip1). Furthermore, we demonstrate that CBL is frequently overexpressed in human breast cancer tissues, and the loss of CBL decreases the tumorigenic activity of breast cancer cells in vivo. CBL directly binds to Smad3 through its proline-rich motif, thereby preventing Smad3 from interacting with Smad4 and blocking nuclear translocation of Smad3. CBL-b, one of CBL protein family, also interacted with Smad3 and knockdown of both CBL and CBL-b further enhanced TGF-β transcriptional activity. Our findings provide evidence for a previously undescribed mechanism by which oncogenic CBL can block TGF-β tumor suppressor activity.

  13. Effect of soy isoflavones on the growth of human breast tumors: findings from preclinical studies

    PubMed Central

    Kwon, Youngjoo

    2014-01-01

    Breast cancer is the most common cancer among women worldwide, and many women with breast cancer live more than 5 years after their diagnosis. Breast cancer patients and survivors have a greater interest in taking soy foods and isoflavone supplements. However, the effect of isoflavones on breast cancer remains controversial. Thus, it is critical to determine if and when isoflavones are beneficial or detrimental to breast cancer patients. According to the available preclinical data, high concentrations of isoflavones inhibit the proliferation of breast cancer cells, regardless of their estrogen receptor (ER) status. In comparison, genistein, a major isoflavone, has stimulated tumor growth at low concentrations and mitigated tamoxifen efficacy in ER-positive breast cancer. Studies have indicated that the relative levels of genistein and estrogen at the target site are important to determine the genistein effect on the ER-positive tumor growth. However, studies using ovariectomized mice and subcutaneous xenograft models might not truly reflect estrogen concentrations in human breast tumors. Moreover, it may be an oversimplification that isoflavones stimulate hormone-dependent tumor growth due to their potential estrogenic effect since studies also suggest nonestrogenic anticancer effects of isoflavones and ER-independent anticancer activity of tamoxifen. Therefore, the concentrations of isoflavones and estrogen in human breast tumors should be considered better in future preclinical studies and the parameters that can estimate those levels in breast tumors are required in human clinical/epidemiological investigation. In addition, it will be important to identify the molecular mechanisms that either inhibit or promote the growth of breast cancer cells by soy isoflavones, and use those molecules to evaluate the relevance of the preclinical findings to the human disease and to predict the health effects of isoflavones in human breast tumors. PMID:25493176

  14. [Malignant phyllode tumor of the breast with features of intraductal carcinoma].

    PubMed

    Alò, P L; Andreano, T; Monaco, S; Sebastiani, V; Eleuteri Serpieri, D; Di Tondo, U

    2001-04-01

    Malignant phyllode tumor is a rare biphasic breast tumor consisting of a malignant mesenchymal component and an epithelial component that is usually benign. We report an unusual case of a malignant phyllode tumor of the breast with neoplastic features of both the epithelial and stromal components. The patient was a 39-year-old woman with family history for breast carcinoma. Grossly, the excised tumor was a 9 x 7 x 5.5 cm gray lobulated mass with infiltrative margins and necrotic-hemorrhagic areas. Histologically the tumor consisted mainly of neoplastic mesenchyme with non invasive comedo, cribriform and micropapillary features of the ducts. Three months after the excision of the neoplastic mass, the patient developed an infiltrating ductal carcinoma of the opposite breast. Hereditary and bilateral tumors are commonly associated with germline mutations. Tissue from both neoplasms however did not express either BRCA1 or BRCA2 mutations.

  15. Gene expression in local stroma reflects breast tumor states and predicts patient outcome

    PubMed Central

    Bainer, Russell; Frankenberger, Casey; Rabe, Daniel; An, Gary; Gilad, Yoav; Rosner, Marsha Rich

    2016-01-01

    The surrounding microenvironment has been implicated in the progression of breast tumors to metastasis. However, the degree to which metastatic breast tumors locally reprogram stromal cells as they disrupt tissue boundaries is not well understood. We used species-specific RNA sequencing in a mouse xenograft model to determine how the metastasis suppressor RKIP influences transcription in a panel of paired tumor and stroma tissues. We find that gene expression in metastatic breast tumors is pervasively correlated with gene expression in local stroma of both mouse xenografts and human patients. Changes in stromal gene expression elicited by tumors better predicts subtype and patient survival than tumor gene expression, and genes with coordinated expression in both tissues predict metastasis-free survival. These observations support the use of stroma-based strategies for the diagnosis and prognosis of breast cancer. PMID:27982086

  16. Prognostic significance of tumor subtypes in male breast cancer: a population-based study.

    PubMed

    Leone, José Pablo; Leone, Julieta; Zwenger, Ariel Osvaldo; Iturbe, Julián; Vallejo, Carlos Teodoro; Leone, Bernardo Amadeo

    2015-08-01

    Substantial controversy exists about the prognostic role of tumor subtypes in male breast cancer (MaBC). The aim of this study was to analyze the characteristics of each tumor subtype in MaBC and its association with prognosis compared with other factors. We evaluated MaBC patients between 2010 and 2012 with known estrogen receptor, progesterone receptor [together hormone receptor (HR)] status, and human epidermal growth factor receptor 2 (HER2) status reported to the Surveillance, Epidemiology, and End Results program. Patients were classified as: HR-positive/HER2-negative, HR-positive/HER2-positive, HR-negative/HER2-positive, and triple-negative (TN). Univariate and multivariate analyses determined the effect of each variable on overall survival (OS). We included 960 patients. Patient distribution was 84.9 % HR-positive/HER2-negative, 11.6 % HR-positive/HER2-positive, 0.6 % HR-negative/HER2-positive, and 2.9 % TN. TN patients were younger, had higher grade, presented with more advanced stage, were more likely to have mastectomy, and to die of breast cancer (all P < 0.05). Univariate analysis showed that HER2 positivity was associated with shorter OS (hazard ratio 1.90, P = 0.031) and TN patients had worse prognosis (hazard ratio 5.10, P = 0.0004). In multivariate analysis, older patients (hazard ratio 3.10, P = 0.032), those with stage IV (hazard ratio 16.27, P < 0.001) and those with TN tumors (hazard ratio 4.61, P = 0.002) had significantly worse OS. We observed significant differences in patient characteristics according to tumor subtype. HER2-positive and TN represented a small proportion of cases. In addition to age and stage, tumor subtype has clear influence on OS in MaBC.

  17. Quantitative analysis of peri-tumor tissue elasticity based on shear-wave elastography for breast tumor classification.

    PubMed

    Xiao, Yang; Zeng, Jie; Qian, Ming; Zheng, Rongqin; Zheng, Hairong

    2013-01-01

    For shear-wave elastography (SWE) images, the most common site of tumor-associated stiffness is generally in the surrounding stroma rather than the tumor itself. The aim of this study is to assess the value of the peri-tumor tissue elasticity in the classification of breast tumors. SWE images of 106 breast tumors (65 benign, 41 malignant) were collected from 82 consecutive patients. By applying the image processing method, 5 elastographic features of the peri-tumor area (elasticity modulus mean, maximum, standard deviation, hardness degree and elasticity ratio) were computed to represent peri-tumor tissue elasticity. B-mode Breast Imaging Reporting and Data System (BI-RADS) were used for comparing the diagnostic performances between the grayscale US and color SWE images. Histopathologic results were used as the reference standard. The t-test, point biserial correlation coefficient and receiver operating characteristic (ROC) curve analysis were performed for statistical analysis. As a result, the Az values (area under ROC curve) were 0.92, 0.95, 0.94, 0.91, and 0.98 for the classifiers using the five elastographic features respectively, and 0.91 for BI-RADS assessment. The results showed that the peri-tumor tissue elasticity could provide valuable information for breast tumor classification.

  18. The Opportunity of Precision Medicine for Breast Cancer with Context-Sensitive Tumor Suppressor Maspin.

    PubMed

    Bernardo, Margarida M; Dzinic, Sijana H; Matta, Maria J; Dean, Ivory; Saker, Lina; Sheng, Shijie

    2017-03-06

    To improve the precision of molecular diagnosis and to develop and guide targeted therapies of breast cancer, it is essential to determine mechanisms that underlie the specific tumor phenotypes. To this end, the application of a snapshot of gene expression profile for breast cancer diagnosis and prognosis is fundamentally challenged since the tissue-based data are derived from heterogonous cell types and are not likely to reflect the dynamics of context-dependent tumor progression and drug sensitivity. The intricate network of epithelial differentiation program can be concertedly controlled by tumor suppressor maspin, a homologue of clade B serine protease inhibitors (serpin), through its multifaceted molecular interactions in multiple subcellular localizations. Unlike most other serpins that are expressed in multiple and cell types, maspin is epithelial specific and has distinct roles in luminal and myoepithelial cells. Endogenously expressed maspin has been found in the nucleus and cytoplasm, and detected on the surface of cell membrane. It is also secreted free and as an exosomal cargo protein. Research in the field has led to the identification of the maspin targets and maspin-associated molecules, as well as the structural determinants of its suppressive functions. The current review discusses the possibility for maspin to serve as a cell type-specific and context-sensitive marker to improve the precision of breast cancer diagnosis and prognosis. These advancements further suggest a new window of opportunity for designing novel maspin-based chemotherapeutic agents with improved anti-cancer potency. This article is protected by copyright. All rights reserved.

  19. Dynamic thermal modeling of the normal and tumorous breast under elastic deformation.

    PubMed

    Jiang, Li; Zhan, Wang; Loew, Murray H

    2008-01-01

    To quantify the complex relationships between (1) the temperature, and temperature differences, on the surface of the breast as recorded by infrared thermal imaging and (2) the underlying physiological and pathological factors, we have developed a dynamic finite element method for comprehensive modeling of both the thermal and elastic properties of normal and tumorous breast tissues. In the steady state, the gravity-induced deformation is found to cause markedly asymmetric surface temperatures even though all thermal-elastic properties are symmetrical. In the dynamic state, the time course of breast thermal imaging in cold-stress and thermal-recovery procedures is found to be useful in characterizing the origins of the thermal contrast on the breast surface. The tumor-induced thermal contrast has slower temporal behavior than the deformation-induced thermal contrast on the breast surface, which may lead to improvements in breast-tumor diagnosis.

  20. Advancement and prospects of tumor gene therapy.

    PubMed

    Zhang, Chao; Wang, Qing-Tao; Liu, He; Zhang, Zhen-Zhu; Huang, Wen-Lin

    2011-03-01

    Gene therapy is one of the most attractive fields in tumor therapy. In past decades, significant progress has been achieved. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. Several therapeutic strategies have evolved, including gene-based (tumor suppressor genes, suicide genes, antiangiogenic genes, cytokine and oxidative stress-based genes) and RNA-based (antisense oligonucleotides and RNA interference) approaches. In addition, immune response-based strategies (dendritic cell- and T cell-based therapy) are also under investigation in tumor gene therapy. This review highlights the progress and recent developments in gene delivery systems, therapeutic strategies, and possible clinical directions for gene therapy.

  1. miRNA expression profiling of formalin-fixed paraffin-embedded (FFPE) hereditary breast tumors

    PubMed Central

    Tanić, Miljana; Yanowski, Kira; Andrés, Eduardo; Gómez-López, Gonzalo; Socorro, María Rodríguez-Pinilla; Pisano, David G.; Martinez-Delgado, Beatriz; Benítez, Javier

    2014-01-01

    Hereditary breast cancer constitutes only 5–10% of all breast cancer cases and is characterized by strong family history of breast and/or other associated cancer types. Only ~ 25% of hereditary breast cancer cases carry a mutation in BRCA1 or BRCA2 gene, while mutations in other rare high and moderate-risk genes and common low penetrance variants may account for additional 20% of the cases. Thus the majority of cases are still unaccounted for and designated as BRCAX tumors. MicroRNAs are small non-coding RNAs that play important roles as regulators of gene expression and are deregulated in cancer. To characterize hereditary breast tumors based on their miRNA expression profiles we performed global microarray miRNA expression profiling on a retrospective cohort of 80 FFPE breast tissues, including 66 hereditary breast tumors (13 BRCA1, 10 BRCA2 and 43 BRCAX), 10 sporadic breast carcinomas and 4 normal breast tissues, using Exiqon miRCURY LNA™ microRNA Array v.11.0. Here we describe in detail the miRNA microarray expression data and tumor samples used for the study of BRCAX tumor heterogeneity (Tanic et al., 2013) and biomarkers associated with positive BRCA1/2 mutation status (Tanic et al., 2014). Additionally, we provide the R code for data preprocessing and quality control. PMID:26484152

  2. Didymin reverses phthalate ester-associated breast cancer aggravation in the breast cancer tumor microenvironment

    PubMed Central

    HSU, YA-LING; HSIEH, CHIA-JUNG; TSAI, EING-MEI; HUNG, JEN-YU; CHANG, WEI-AN; HOU, MING-FENG; KUO, PO-LIN

    2016-01-01

    The present study demonstrated two novel findings. To the best of our knowledge, it is the first study to demonstrate that regulated upon activation, normal T-cell expressed and secreted (RANTES), produced by breast tumor-associated monocyte-derived dendritic cells (TADCs) following breast cancer cell exposure to phthalate esters, may contribute to the progression of cancer via enhancement of cancer cell proliferation, migration and invasion. Furthermore, the present study revealed that didymin, a dietary flavonoid glycoside present in citrus fruits, was able to reverse phthalate ester-mediated breast cancer aggravation. MDA-MB-231 cells were treated with butyl benzyl phthalate (BBP), di-n-butyl phthalate (DBP) or di-2-ethylhexyl phthalate (DEHP). Subsequently, the conditioned medium (CM) was harvested and cultured with monocyte-derived dendritic cells (mdDCs). Cultures of MDA-MB-231 cells with the conditioned medium of BBP-, DBP- or DEHP-MDA-MB-231 tumor-associated mdDCs (BBP-, DBP- or DEHP-MDA-TADC-CM) demonstrated enhanced proliferation, migration and invasion. Exposure of the MDA-MB-231 cells to DBP induced the MDA-TADCs to produce the inflammatory cytokine RANTES, which subsequently induced MDA-MB-231 cell proliferation, migration and invasion. Depleting RANTES reversed the effects of DBP-MDA-TADC-mediated MDA-MB-231 cell proliferation, migration and invasion. In addition, didymin was observed to suppress phthalate-mediated breast cancer cell proliferation, migration and invasion. The present study suggested that didymin was capable of preventing phthalate ester-associated cancer aggravation. PMID:26893687

  3. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

    PubMed Central

    Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-01-01

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and PARP, which resulted from suppression of MCL-1 and BCL-2 expression in the cells. APA also inactivated the Akt/mTOR pathway in breast cancer cells. Thus, APA exerts a strong anti-tumor effect on breast cancer cells, most likely through induction of apoptosis. Our study is the first to identify this novel anti-tumor compound and provides a new strategy for isolation and separation of single compounds from herbs. PMID:26943775

  4. Breast Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Breast Cancer What is Breast Cancer? How Tumors Form The body is made up ... tumors form in the breast tissue. Who Gets Breast Cancer? Breast cancer is one of the most common ...

  5. Advances in Medical Management of Early Stage and Advanced Breast Cancer: 2015.

    PubMed

    Witherby, Sabrina; Rizack, Tina; Sakr, Bachir J; Legare, Robert D; Sikov, William M

    2016-01-01

    Standard management of early stage and advanced breast cancer has been improved over the past few years by knowledge gained about the biology of the disease, results from a number of eagerly anticipated clinical trials and the development of novel agents that offer our patients options for improved outcomes or reduced toxicity or both. This review highlights recent major developments affecting the systemic therapy of breast cancer, broken down by clinically relevant patient subgroups and disease stage, and briefly discusses some of the ongoing controversies in the treatment of breast cancer and promising therapies on the horizon.

  6. An approach to parameter estimation for breast tumor by finite element method

    NASA Astrophysics Data System (ADS)

    Xu, A.-qing; Yang, Hong-qin; Ye, Zhen; Su, Yi-ming; Xie, Shu-sen

    2009-02-01

    The temperature of human body on the surface of the skin depends on the metabolic activity, the blood flow, and the temperature of the surroundings. Any abnormality in the tissue, such as the presence of a tumor, alters the normal temperature on the skin surface due to increased metabolic activity of the tumor. Therefore, abnormal skin temperature profiles are an indication of diseases such as tumor or cancer. This study is to present an approach to detect the female breast tumor and its related parameter estimations by combination the finite element method with infrared thermography for the surface temperature profile. A 2D simplified breast embedded a tumor model based on the female breast anatomical structure and physiological characteristics was first established, and then finite element method was used to analyze the heat diffuse equation for the surface temperature profiles of the breast. The genetic optimization algorithm was used to estimate the tumor parameters such as depth, size and blood perfusion by minimizing a fitness function involving the temperature profiles simulated data by finite element method to the experimental data obtained by infrared thermography. This preliminary study shows it is possible to determine the depth and the heat generation rate of the breast tumor by using infrared thermography and the optimization analysis, which may play an important role in the female breast healthcare and diseases evaluation or early detection. In order to develop the proposed methodology to be used in clinical, more accurate anatomy 3D breast geometry should be considered in further investigations.

  7. A Case of Large Phyllodes Tumor Causing “Rupture” of the Breast: A Unique Presentation

    PubMed Central

    Nabi, Junaid; Akhter, S. M. Quamrul; Authoy, Fatema N.

    2013-01-01

    Introduction. Phyllodes tumors are rare fibroepithelial tumors which constitute less than 1% of all known breast neoplasms. The importance of recognizing these tumors lies in the need to differentiate them from fibroadenomas and other benign breast lesions to avoid inappropriate surgical management. We report a case of large phyllodes tumor which caused rupture of the breast and presented as an external fungating breast mass, a presentation which is exceedingly rare. Case Presentation. A 32-year-old female presented with a 1-year history of a mass in her right breast and eruption of the mass through the skin for the last 3 months. On physical examination, an ulcerated, irregular, and nodular mass measuring 9 × 8 cms was found hanging in the lower and outer quadrant of the right breast. Ultrasonography revealed an exophytic mass with heterogeneous echotexture and vascularity. Under general anesthesia, the tumor was excised. The resected specimen was 9.5 × 8.5 × 4.5 cm in size and the tumor was not invasive to the surrounding tissues. Histological examination confirmed a benign case of Phyllodes tumor. Conclusion. Clinicians should be aware of the myriad ways in which Phyllodes can present. A rapidly growing breast mass in a female should raise strong suspicion for Phyllodes. It is necessary to differentiate it from fibroadenomas to avoid inappropriate surgical management which may lead to local recurrence. PMID:23762692

  8. Hormone Receptor and ERBB2 Status in Gene Expression Profiles of Human Breast Tumor Samples

    PubMed Central

    Dvorkin-Gheva, Anna; Hassell, John A.

    2011-01-01

    The occurrence of large publically available repositories of human breast tumor gene expression profiles provides an important resource to discover new breast cancer biomarkers and therapeutic targets. For example, knowledge of the expression of the estrogen and progesterone hormone receptors (ER and PR), and that of the ERBB2 in breast tumor samples enables choice of therapies for the breast cancer patients that express these proteins. Identifying new biomarkers and therapeutic agents affecting the activity of signaling pathways regulated by the hormone receptors or ERBB2 might be accelerated by knowledge of their expression levels in large gene expression profiling data sets. Unfortunately, the status of these receptors is not invariably reported in public databases of breast tumor gene expression profiles. Attempts have been made to employ a single probe set to identify ER, PR and ERBB2 status, but the specificity or sensitivity of their prediction is low. We enquired whether estimation of ER, PR and ERBB2 status of profiled tumor samples could be improved by using multiple probe sets representing these three genes and others with related expression. We used 8 independent datasets of human breast tumor samples to define gene expression signatures comprising 24, 51 and 14 genes predictive of ER, PR and ERBB2 status respectively. These signatures, as demonstrated by sensitivity and specificity measures, reliably identified hormone receptor and ERBB2 expression in breast tumors that had been previously determined using protein and DNA based assays. Our findings demonstrate that gene signatures can be identified which reliably predict the expression status of the estrogen and progesterone hormone receptors and that of ERBB2 in publically available gene expression profiles of breast tumor samples. Using these signatures to query transcript profiles of breast tumor specimens may enable discovery of new biomarkers and therapeutic targets for particular subtypes of

  9. Tumor markers in breast cancer- European Group on Tumor Markers recommendations.

    PubMed

    Molina, Rafael; Barak, Vivian; van Dalen, Arie; Duffy, Michael J; Einarsson, Roland; Gion, Massimo; Goike, Helenka; Lamerz, Rolf; Nap, Marius; Sölétormos, György; Stieber, Petra

    2005-01-01

    Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins (CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin (trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy.

  10. Tumor STAT1 transcription factor activity enhances breast tumor growth and immune suppression mediated by myeloid-derived suppressor cells.

    PubMed

    Hix, Laura M; Karavitis, John; Khan, Mohammad W; Shi, Yihui H; Khazaie, Khashayarsha; Zhang, Ming

    2013-04-26

    Previous studies had implicated the IFN-γ transcription factor signal transducer and activator of transcription 1 (STAT1) as a tumor suppressor. However, accumulating evidence has correlated increased STAT1 activation with increased tumor progression in multiple types of cancer, including breast cancer. Indeed, we present evidence that tumor up-regulation of STAT1 activity in human and mouse mammary tumors correlates with increasing disease progression to invasive carcinoma. A microarray analysis comparing low aggressive TM40D and highly aggressive TM40D-MB mouse mammary carcinoma cells revealed significantly higher STAT1 activity in the TM40D-MB cells. Ectopic overexpression of constitutively active STAT1 in TM40D cells promoted mobilization of myeloid-derived suppressor cells (MDSCs) and inhibition of antitumor T cells, resulting in aggressive tumor growth in tumor-transplanted, immunocompetent mice. Conversely, gene knockdown of STAT1 in the metastatic TM40D-MB cells reversed these events and attenuated tumor progression. Importantly, we demonstrate that in human breast cancer, the presence of tumor STAT1 activity and tumor-recruited CD33(+) myeloid cells correlates with increasing disease progression from ductal carcinoma in situ to invasive carcinoma. We conclude that STAT1 activity in breast cancer cells is responsible for shaping an immunosuppressive tumor microenvironment, and inhibiting STAT1 activity is a promising immune therapeutic approach.

  11. Multiplexed ion beam imaging of human breast tumors.

    PubMed

    Angelo, Michael; Bendall, Sean C; Finck, Rachel; Hale, Matthew B; Hitzman, Chuck; Borowsky, Alexander D; Levenson, Richard M; Lowe, John B; Liu, Scot D; Zhao, Shuchun; Natkunam, Yasodha; Nolan, Garry P

    2014-04-01

    Immunohistochemistry (IHC) is a tool for visualizing protein expression that is employed as part of the diagnostic workup for the majority of solid tissue malignancies. Existing IHC methods use antibodies tagged with fluorophores or enzyme reporters that generate colored pigments. Because these reporters exhibit spectral and spatial overlap when used simultaneously, multiplexed IHC is not routinely used in clinical settings. We have developed a method that uses secondary ion mass spectrometry to image antibodies tagged with isotopically pure elemental metal reporters. Multiplexed ion beam imaging (MIBI) is capable of analyzing up to 100 targets simultaneously over a five-log dynamic range. Here, we used MIBI to analyze formalin-fixed, paraffin-embedded human breast tumor tissue sections stained with ten labels simultaneously. The resulting data suggest that MIBI can provide new insights into disease pathogenesis that will be valuable for basic research, drug discovery and clinical diagnostics.

  12. Laser immunotherapy for treatment of patients with advanced breast cancer and melanoma

    NASA Astrophysics Data System (ADS)

    Li, Xiaosong; Hode, Tomas; Guerra, Maria C.; Ferrel, Gabriela L.; Nordquist, Robert E.; Chen, Wei R.

    2011-02-01

    Laser immunotherapy (LIT) was developed for the treatment of metastatic tumors. It combines local selective photothermal interaction and active immunological stimulation to induce a long-term, systemic anti-tumor immunity. During the past sixteen years, LIT has been advanced from bench-top to bedside, with promising outcomes. In our pre-clinical and preliminary clinical studies, LIT has demonstrated the capability in inducing immunological responses, which not only can eradicate the treated primary tumors, but also can eliminate untreated metastases at distant sites. Specifically, LIT has been used to treat advanced melanoma and breast cancer patients during the past five years. LIT was shown to be effective in controlling both primary tumors and distant metastases in late-stage patients, who have failed conventional therapies such as surgery, chemotherapy, radiation, and other more advanced approaches. The methodology and the development of LIT are presented in this paper. The patients' responses to LIT are also reported in this paper. The preliminary results obtained in these studies indicated that LIT could be an effective modality for the treatment of patients with late-stage, metastatic cancers, who are facing severely limited options.

  13. Breast tumor subgroups reveal diverse clinical prognostic power

    PubMed Central

    Liu, Zhaoqi; Zhang, Xiang-Sun; Zhang, Shihua

    2014-01-01

    Predicting the outcome of cancer therapies using molecular features and clinical observations is a key goal of cancer biology, which has been addressed comprehensively using whole patient datasets without considering the effect of tumor heterogeneity. We hypothesized that molecular features and clinical observations have different prognostic abilities for different cancer subtypes, and made a systematic study using both clinical observations and gene expression data. This analysis revealed that (1) gene expression profiles and clinical features show different prognostic power for the five breast cancer subtypes; (2) gene expression data of the normal-like subgroup contains more valuable prognostic information and survival associated contexts than the other subtypes, and the patient survival time of the normal-like subtype is more predictable based on the gene expression profiles; and (3) the prognostic power of many previously reported breast cancer gene signatures increased in the normal-like subtype and reduced in the other subtypes compared with that in the whole sample set. PMID:24499868

  14. Circulating tumor DNA and circulating tumor cells in metastatic triple negative breast cancer patients.

    PubMed

    Madic, Jordan; Kiialainen, Anna; Bidard, Francois-Clement; Birzele, Fabian; Ramey, Guillemette; Leroy, Quentin; Rio Frio, Thomas; Vaucher, Isabelle; Raynal, Virginie; Bernard, Virginie; Lermine, Alban; Clausen, Inga; Giroud, Nicolas; Schmucki, Roland; Milder, Maud; Horn, Carsten; Spleiss, Olivia; Lantz, Olivier; Stern, Marc-Henri; Pierga, Jean-Yves; Weisser, Martin; Lebofsky, Ronald

    2015-05-01

    Circulating tumor DNA (ctDNA) is a new circulating tumor biomarker which might be used as a prognostic biomarker in a way similar to circulating tumor cells (CTCs). Here, we used the high prevalence of TP53 mutations in triple negative breast cancer (TNBC) to compare ctDNA and CTC detection rates and prognostic value in metastatic TNBC patients. Forty patients were enrolled before starting a new line of treatment. TP53 mutations were characterized in archived tumor tissues and in plasma DNA using two next generation sequencing (NGS) platforms in parallel. Archived tumor tissue was sequenced successfully for 31/40 patients. TP53 mutations were found in 26/31 (84%) of tumor samples. The same mutation was detected in the matched plasma of 21/26 (81%) patients with an additional mutation found only in the plasma for one patient. Mutated allele fractions ranged from 2 to 70% (median 5%). The observed correlation between the two NGS approaches (R(2) = 0.903) suggested that ctDNA levels data were quantitative. Among the 27 patients with TP53 mutations, CTC count was ≥1 in 19 patients (70%) and ≥5 in 14 patients (52%). ctDNA levels had no prognostic impact on time to progression (TTP) or overall survival (OS), whereas CTC numbers were correlated with OS (p = 0.04) and marginally with TTP (p = 0.06). Performance status and elevated LDH also had significant prognostic impact. Here, absence of prognostic impact of baseline ctDNA level suggests that mechanisms of ctDNA release in metastatic TNBC may involve, beyond tumor burden, biological features that do not dramatically affect patient outcome.

  15. Isolation and molecular characterization of cancer stem cells in MMTV-Wnt-1 murine breast tumors.

    PubMed

    Cho, Robert W; Wang, Xinhao; Diehn, Maximilian; Shedden, Kerby; Chen, Grace Y; Sherlock, Gavin; Gurney, Austin; Lewicki, John; Clarke, Michael F

    2008-02-01

    In human breast cancers, a phenotypically distinct minority population of tumorigenic (TG) cancer cells (sometimes referred to as cancer stem cells) drives tumor growth when transplanted into immunodeficient mice. Our objective was to identify a mouse model of breast cancer stem cells that could have relevance to the study of human breast cancer. To do so, we used breast tumors of the mouse mammary tumor virus (MMTV)-Wnt-1 mice. MMTV-Wnt-1 breast tumors were harvested, dissociated into single-cell suspensions, and sorted by flow cytometry on Thy1, CD24, and CD45. Sorted cells were then injected into recipient background FVB/NJ female syngeneic mice. In six of seven tumors examined, Thy1+CD24+ cancer cells, which constituted approximately 1%-4% of tumor cells, were highly enriched for cells capable of regenerating new tumors compared with cells of the tumor that did not fit this profile ("not-Thy1+CD24+"). Resultant tumors had a phenotypic diversity similar to that of the original tumor and behaved in a similar manner when passaged. Microarray analysis comparing Thy1+CD24+ tumor cells to not-Thy1+CD24+ cells identified a list of differentially expressed genes. Orthologs of these differentially expressed genes predicted survival of human breast cancer patients from two different study groups. These studies suggest that there is a cancer stem cell compartment in the MMTV-Wnt-1 murine breast tumor and that there is a clinical utility of this model for the study of cancer stem cells.

  16. Relevance of circulating tumor cells, extracellular nucleic acids, and exosomes in breast cancer.

    PubMed

    Friel, Anne M; Corcoran, Claire; Crown, John; O'Driscoll, Lorraine

    2010-10-01

    Early detection of cancer is vital to improved overall survival rates. At present, evidence is accumulating for the clinical value of detecting occult tumor cells in peripheral blood, plasma, and serum specimens from cancer patients. Both molecular and cellular approaches, which differ in sensitivity and specificity, have been used for such means. Circulating tumor cells and extracellular nucleic acids have been detected within blood, plasma, and sera of cancer patients. As the presence of malignant tumors are clinically determined and/or confirmed upon biopsy procurement-which in itself may have detrimental effects in terms of stimulating cancer progression/metastases-minimally invasive methods would be highly advantageous to the diagnosis and prognosis of breast cancer and the subsequent tailoring of targeted treatments for individuals, if reliable panels of biomarkers suitable for such an approach exist. Herein, we review the current advances made in the detection of such circulating tumor cells and nucleic acids, with particular emphasis on extracellular nucleic acids, specifically extracellular mRNAs and discuss their clinical relevance.

  17. Even With Very Small Breast Tumors, Studies Find HER2 Status Matters | Division of Cancer Prevention

    Cancer.gov

    Two retrospective studies have found that women with HER2-positive breast tumors (that is, tumors that produce too much of the HER2 protein) that are 1 centimeter or smaller had a higher risk of their disease returning within 5 years than women with similarly small HER2-negative tumors. |

  18. MDA-7/IL-24 functions as a tumor suppressor gene in vivo in transgenic mouse models of breast cancer.

    PubMed

    Menezes, Mitchell E; Shen, Xue-Ning; Das, Swadesh K; Emdad, Luni; Guo, Chunqing; Yuan, Fang; Li, You-Jun; Archer, Michael C; Zacksenhaus, Eldad; Windle, Jolene J; Subler, Mark A; Ben-David, Yaacov; Sarkar, Devanand; Wang, Xiang-Yang; Fisher, Paul B

    2015-11-10

    Melanoma differentiation associated gene-7/Interleukin-24 (MDA-7/IL-24) is a novel member of the IL-10 gene family that selectively induces apoptosis and toxic autophagy in a broad spectrum of human cancers, including breast cancer, without harming normal cells or tissues. The ability to investigate the critical events underlying cancer initiation and progression, as well as the capacity to test the efficacy of novel therapeutics, has been significantly advanced by the development of genetically engineered mice (GEMs) that accurately recapitulate specific human cancers. We utilized three transgenic mouse models to better comprehend the in vivo role of MDA-7/IL-24 in breast cancer. Using the MMTV-PyMT spontaneous mammary tumor model, we confirmed that exogenously introducing MDA-7/IL-24 using a Cancer Terminator Virus caused a reduction in tumor burden and also produced an antitumor "bystander" effect. Next we performed xenograft studies in a newly created MMTV-MDA-7 transgenic model that over-expresses MDA-7/IL-24 in the mammary glands during pregnancy and lactation, and found that MDA-7/IL-24 overexpression delayed tumor growth following orthotopic injection of a murine PDX tumor cell line (mPDX) derived from a tumor formed in an MMTV-PyMT mouse. We also crossed the MMTV-MDA-7 line to MMTV-Erbb2 transgenic mice and found that MDA-7/IL-24 overexpression delayed the onset of mammary tumor development in this model of spontaneous mammary tumorigenesis as well. Finally, we assessed the role of MDA-7/IL-24 in immune regulation, which can potentially contribute to tumor suppression in vivo. Our findings provide further direct in vivo evidence for the role of MDA-7/IL-24 in tumor suppression in breast cancer in immune-competent transgenic mice.

  19. TU-EF-207-00: Advances in Breast Imaging

    SciTech Connect

    2015-06-15

    Breast imaging technology is advancing on several fronts. In digital mammography, the major technological trend has been on optimization of approaches for performing combined mammography and tomosynthesis using the same system. In parallel, photon-counting slot-scan mammography is now in clinical use and more efforts are directed towards further development of this approach for spectral imaging. Spectral imaging refers to simultaneous acquisition of two or more energy-windowed images. Depending on the detector and associated electronics, there are a number of ways this can be accomplished. Spectral mammography using photon-counting detectors can suppress electronic noise and importantly, it enables decomposition of the image into various material compositions of interest facilitating quantitative imaging. Spectral imaging can be particularly important in intravenously injected contrast mammography and eventually tomosynthesis. The various approaches and applications of spectral mammography are discussed. Digital breast tomosynthesis relies on the mechanical movement of the x-ray tube to acquire a number of projections in a predefined arc, typically from 9 to 25 projections over a scan angle of +/−7.5 to 25 degrees depending on the particular system. The mechanical x-ray tube motion requires relatively long acquisition time, typically between 3.7 to 25 seconds depending on the system. Moreover, mechanical scanning may have an effect on the spatial resolution due to internal x-ray filament or external mechanical vibrations. New x-ray source arrays have been developed and they are aimed at replacing the scanned x-ray tube for improved acquisition time and potentially for higher spatial resolution. The potential advantages and challenges of this approach are described. Combination of digital mammography and tomosynthesis in a single system places increased demands on certain functional aspects of the detector and overall performance, particularly in the tomosynthesis

  20. Boron neutron capture therapy applied to advanced breast cancers: Engineering simulation and feasibility study of the radiation treatment protocol

    NASA Astrophysics Data System (ADS)

    Sztejnberg Goncalves-Carralves, Manuel Leonardo

    This dissertation describes a novel Boron Neutron Capture Therapy (BNCT) application for the treatment of human epidermal growth factor receptor type 2 positive (HER2+) breast cancers. The original contribution of the dissertation is the development of the engineering simulation and the feasibility study of the radiation treatment protocol for this novel combination of BNCT and HER2+ breast cancer treatment. This new concept of BNCT, representing a radiation binary targeted treatment, consists of the combination of two approaches never used in a synergism before. This combination may offer realistic hope for relapsed and/or metastasized breast cancers. This treatment assumes that the boronated anti-HER2 monoclonal antibodies (MABs) are administrated to the patient and accumulate preferentially in the tumor. Then the tumor is destroyed when is exposed to neutron irradiation. Since the use of anti-HER2 MABs yields good and promising results, the proposed concept is expected to amplify the known effect and be considered as a possible additional treatment approach to the most severe breast cancers for patients with metastasized cancer for which the current protocol is not successful and for patients refusing to have the standard treatment protocol. This dissertation makes an original contribution with an integral numerical approach and proves feasible the combination of the aforementioned therapy and disease. With these goals, the dissertation describes the theoretical analysis of the proposed concept providing an integral engineering simulation study of the treatment protocol. An extensive analysis of the potential limitations, capabilities and optimization factors are well studied using simplified models, models based on real CT patients' images, cellular models, and Monte Carlo (MCNP5/X) transport codes. One of the outcomes of the integral dosimetry assessment originally developed for the proposed treatment of advanced breast cancers is the implementation of BNCT

  1. Relationship of Clinical and Pathologic Nodal Staging in Locally Advanced Breast Cancer: Current Controversies in Daily Practice?

    PubMed Central

    De Felice, Francesca; Musio, Daniela; Bulzonetti, Nadia; Raffetto, Nicola; Tombolini, Vincenzo

    2014-01-01

    Systemic neo-adjuvant therapy plays a primary role in the management of locally advanced breast cancer. Without having any negative effect in overall survival, induction chemotherapy potentially assures a surgery approach in unresectable disease or a conservative treatment in technically resectable disease and acts on a well-vascularized tumor bed, without the modifications induced by surgery. A specific issue has a central function in the neo-adjuvant setting: lymph nodes status. It still represents one of the strongest predictors of long-term prognosis in breast cancer. The discussion of regional radiation therapy should be a matter of debate, especially in a pathological complete response. Currently, the indication for radiotherapy is based on the clinical stage before the surgery, even for the irradiation of the loco-regional lymph nodes. Regardless of pathological down-staging, radiation therapy is accepted as standard adjuvant treatment in locally advanced breast cancer. PMID:25247013

  2. Stationary Digital Tomosynthesis System for Early Detection of Breast Tumors

    DTIC Science & Technology

    2012-05-01

    Breast cancer is the most common type of cancer occurring in women...Early detection is considered as the best hope for decreasing the mortality rate from breast cancer [1-4]. Digital breast tomosynthesis (DBT) has the...potential to improve the effectiveness of early breast cancer screening at a similar dose and comparable cost as the full-field digital

  3. Cell surface profiling with peptide libraries yields ligand arrays that classify breast tumor subtypes.

    PubMed

    Dane, Karen Y; Gottstein, Claudia; Daugherty, Patrick S

    2009-05-01

    Cancer heterogeneity renders risk stratification and therapy decisions challenging. Thus, genomic and proteomic methodologies have been used in an effort to identify biomarkers that can differentiate tumor subtypes to improve therapeutic outcome. Here, we report a generally applicable strategy to generate tumor type-specific peptide ligand arrays. Peptides that specifically recognize breast tumor-derived cell lines (MDA-MB-231, MCF-7, and T47-D) were identified using cell-displayed peptide libraries carrying an intrinsic fluorescent marker allowing for sorting and characterization with quantitative flow cytometry. Tumor cell specificity was achieved by depleting libraries of ligands binding to normal mammary epithelial cells (HMEC and MCF-10A). Although integrin binding RGD motifs were favored by some cell lines, screening with RGD competitors yielded several novel consensus motifs exhibiting improved tumor specificity. The resultant peptide array contained multiple consensus motifs exhibiting strong similarity to breast tumor-associated proteins. Profiling a panel of breast cancer cell lines with the peptide array revealed receptor expression patterns distinctive for luminal or basal tumor subtypes. In addition, peptide displaying bacteria and peptide functionalized microparticles enabled fluorescent labeling of tumor cells and frozen tumor tissue sections. Our results indicate that cell surface profiling using highly specific breast tumor cell binding ligands may provide an efficient route for tumor subtype classification, biomarker identification, and for the development of targeted diagnostics and therapeutics.

  4. Evaluation of Neoadjuvant Chemotherapy Response in Women with Locally Advanced Breast Cancer Using Ultrasound Elastography1

    PubMed Central

    Falou, Omar; Sadeghi-Naini, Ali; Prematilake, Sameera; Sofroni, Ervis; Papanicolau, Naum; Iradji, Sara; Jahedmotlagh, Zahra; Lemon-Wong, Sharon; Pignol, Jean-Philippe; Rakovitch, Eileen; Zubovits, Judit; Spayne, Jacqueline; Dent, Rebecca; Trudeau, Maureen; Boileau, Jean Francois; Wright, Frances C; Yaffe, Martin J; Czarnota, Gregory J

    2013-01-01

    PURPOSE: Ultrasound elastography is a new imaging technique that can be used to assess tissue stiffness. The aim of this study was to investigate the potential of ultrasound elastography for monitoring treatment response of locally advanced breast cancer patients undergoing neoadjuvant therapy. METHODS: Fifteen women receiving neoadjuvant chemotherapy had the affected breast scanned before, 1, 4, and 8 weeks following therapy initiation, and then before surgery. Changes in elastographic parameters related to tissue biomechanical properties were then determined and compared to clinical and pathologic tumor response after mastectomy. RESULTS: Patients who responded to therapy demonstrated a significant decrease (P < .05) in strain ratios and strain differences 4 weeks after treatment initiation compared to non-responding patients. Mean strain ratio and mean strain difference for responders was 81 ± 3% and 1 ± 17% for static regions of interest (ROIs) and 81 ± 3% and 6 ± 18% for dynamic ROIs, respectively. In contrast, these parameters were 102±2%, 110±17%, 101±4%, and 109±30% for non-responding patients, respectively. Strain ratio using static ROIs was found to be the best predictor of treatment response, with 100% sensitivity and 100% specificity obtained 4 weeks after starting treatment. CONCLUSIONS: These results suggest that ultrasound elastography can be potentially used as an early predictor of tumor therapy response in breast cancer patients. PMID:23418613

  5. Lapatinib in Combination With Radiation Diminishes Tumor Regrowth in HER2+ and Basal-Like/EGFR+ Breast Tumor Xenografts

    SciTech Connect

    Sambade, Maria J.; Kimple, Randall J.; Camp, J. Terese; Peters, Eldon; Livasy, Chad A.; Sartor, Carolyn I.; Shields, Janiel M.

    2010-06-01

    Purpose: To determine whether lapatinib, a dual epidermal growth factor receptor (EGFR)/HER2 kinase inhibitor, can radiosensitize EGFR+ or HER2+ breast cancer xenografts. Methods and Materials: Mice bearing xenografts of basal-like/EGFR+ SUM149 and HER2+ SUM225 breast cancer cells were treated with lapatinib and fractionated radiotherapy and tumor growth inhibition correlated with alterations in ERK1 and AKT activation by immunohistochemistry. Results: Basal-like/EGFR+ SUM149 breast cancer tumors were completely resistant to treatment with lapatinib alone but highly growth impaired with lapatinib plus radiotherapy, exhibiting an enhancement ratio average of 2.75 and a fractional tumor product ratio average of 2.20 during the study period. In contrast, HER2+ SUM225 breast cancer tumors were highly responsive to treatment with lapatinib alone and yielded a relatively lower enhancement ratio average of 1.25 during the study period with lapatinib plus radiotherapy. Durable tumor control in the HER2+ SUM225 model was more effective with the combination treatment than either lapatinib or radiotherapy alone. Immunohistochemical analyses demonstrated that radiosensitization by lapatinib correlated with ERK1/2 inhibition in the EGFR+ SUM149 model and with AKT inhibition in the HER2+ SUM225 model. Conclusion: Our data suggest that lapatinib combined with fractionated radiotherapy may be useful against EGFR+ and HER2+ breast cancers and that inhibition of downstream signaling to ERK1/2 and AKT correlates with sensitization in EGFR+ and HER2+ cells, respectively.

  6. Pattern of Ipsilateral Breast Tumor Recurrence After Breast-Conserving Therapy

    SciTech Connect

    Jobsen, Jan; Palen, Job van der; Riemersma, Sietske; Heijmans, Harald; Ong, Francisca; Struikmans, Henk

    2014-08-01

    Purpose: To analyze the incidence and prognostic factors of ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) in a large, population-based, single-center study with long-term follow-up. Methods and Materials: We analyzed 3595 cases in which BCT was performed in 3824 women with stage I or II breast cancer. The incidence of IBTR was analyzed over time and was based on IBTR as first event. Results: The 15-year local relapse-free survival was 90.9%. The hazard estimates for IBTR showed a time course with 2 peaks, the first at approximately 5 years and the second, twice as high, at 12 years. Stratifying subjects by age and margin status showed that, for women ≤40 years old with negative margins, adjuvant systemic therapy led to a 5-fold reduced risk of recurrence compared to none, and the presence of lymph vascular space invasion (LVSI) had a 3-fold increased risk compared to its absence. For women >40 years old, the presence of LVSI (hazard ratio [HR] 2.5) and the presence of lobular carcinoma in situ in the lumpectomy specimen (HR 2.3) were the only 2 risk factors. Conclusions: We demonstrated a pattern in risk of IBTR over time, with 2 peaks, first at approximately 5 years and a second, much higher peak at approximately 12 years, especially for women ≤40 years old. For women ≤40 years old with tumor-free resection margins, we noted that the absence of adjuvant systemic therapy and the presence of LVSI were independent prognostic factors of IBTR. For women >40 years old, the presence of LVSI and the presence of lobular carcinoma in situ were independent risk factors.

  7. Loss of the tumor suppressor spinophilin (PPP1R9B) increases the cancer stem cell population in breast tumors.

    PubMed

    Ferrer, I; Verdugo-Sivianes, E M; Castilla, M A; Melendez, R; Marin, J J; Muñoz-Galvan, S; Lopez-Guerra, J L; Vieites, B; Ortiz-Gordillo, M J; De León, J M; Praena-Fernandez, J M; Perez, M; Palacios, J; Carnero, A

    2016-05-01

    The spinophilin (Spn, PPP1R9B) gene is located at 17q21.33, a region frequently associated with microsatellite instability and loss of heterozygosity, especially in breast tumors. Spn is a regulatory subunit of phosphatase1a (PP1), which targets the catalytic subunit to distinct subcellular locations. Spn downregulation reduces PPP1CA activity against the retinoblastoma protein, pRb, thereby maintaining higher levels of phosphorylated pRb. This effect contributes to an increase in the tumorigenic properties of cells in certain contexts. Here, we explored the mechanism of how Spn downregulation contributes to the malignant phenotype and poor prognosis in breast tumors and found an increase in the stemness phenotype. Analysis of human breast tumors showed that Spn mRNA and protein are reduced or lost in 15% of carcinomas, correlating with a worse prognosis, a more aggressive tumor phenotype and triple-negative tumors, whereas luminal tumors showed high Spn levels. Downregulation of Spn by shRNA increased the stemness properties along with the expression of stem-related genes (Sox2, KLF4, Nanog and OCT4), whereas ectopic overexpression of Spn cDNA reduced these properties. Breast tumor stem cells appeared to have low levels of Spn mRNA, and Spn loss correlated with increased stem-like cell appearance in breast tumors as indicated by an increase in CD44+/CD24- cells. A reduction of the levels of PPP1CA mimicked the cancer stem-like cell phenotype of Spn downregulation, suggesting that the mechanism of Spn involves PP1a. These increased cancer stem cell-like properties with reduced Spn might account for the malignant phenotype observed in Spn-loss tumors and may contribute to a worse patient prognosis.

  8. Serotonin transporter antagonists target tumor-initiating cells in a transgenic mouse model of breast cancer

    PubMed Central

    Hallett, Robin M.; Girgis-Gabardo, Adele; Gwynne, William D.; Giacomelli, Andrew O.; Bisson, Jennifer N.P.; Jensen, Jeremy E.; Dvorkin-Gheva, Anna; Hassell, John A.

    2016-01-01

    Accumulating data suggests that the initiation and progression of human breast tumors is fueled by a rare subpopulation of tumor cells, termed breast tumor-initiating cells (BTIC), which resist radiotherapy and chemotherapy. Consequently, therapies that abrogate BTIC activity are needed to achieve durable cures for breast cancer patients. To identify such therapies we used a sensitive assay to complete a high-throughput screen of small molecules, including approved drugs, with BTIC-rich mouse mammary tumor cell populations. We found that inhibitors of the serotonin reuptake transporter (SERT) and serotonin receptors, which include approved drugs used to treat mood disorders, were potent inhibitors of mouse BTIC activity as determined by functional sphere-forming assays and the initiation of tumor formation by transplant of drug-exposed tumor cells into syngeneic mice. Moreover, sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI), synergized with docetaxel (Taxotere) to shrink mouse breast tumors in vivo. Hence drugs targeting the serotonergic system might be repurposed to treat breast cancer patients to afford more durable breast cancer remissions. PMID:27447971

  9. Anemia and jejunal intussusception: An unusual presentation for a metastatic phyllodes breast tumor

    PubMed Central

    Schechet, Sidney A.; Askenasy, Erik P.; Dhamne, Sagar; Scott, Bradford G.

    2011-01-01

    INTRODUCTION Phyllodes tumor of the breast is a rare cause of breast cancer, accounting for less than 0.5% of breast cancers. These tumors are classified as benign, borderline, or malignant, with malignant tumors compromising nearly 25% of cases. Metastases occur in 20% of malignant tumors, lungs, bones, liver and brain being the frequent sites of metastases. PRESENTATION OF CASE We present a case of a metastatic phyllodes tumor to the small bowel causing jejunal intussusception, symptomatic anemia, and small bowel obstruction. DISCUSSION Patients with phyllodes tumor of the breast can develop disease recurrence even years after initial treatment. Phyllodes tumor metastasizing to the small bowel is extremely rare, with only three known previously described case reports in the literature. CONCLUSION High risk patients, with a past medical history of phyllodes breast cancer, should be monitored closely. Even years after breast cancer treatment, these patients may present with gastrointestinal complaints such as obstruction or bleeding, and therefore metastatic disease to the small bowel should be considered on the differential with subsequent abdominal imaging obtained. PMID:22288047

  10. Single Unpurified Breast Tumor-Initiating Cells from Multiple Mouse Models Efficiently Elicit Tumors in Immune-Competent Hosts

    PubMed Central

    Kurpios, Natasza A.; Girgis-Gabardo, Adele; Hallett, Robin M.; Rogers, Stephen; Gludish, David W.; Kockeritz, Lisa; Woodgett, James; Cardiff, Robert; Hassell, John A.

    2013-01-01

    The tumor-initiating cell (TIC) frequency of bulk tumor cell populations is one of the criteria used to distinguish malignancies that follow the cancer stem cell model from those that do not. However, tumor-initiating cell frequencies may be influenced by experimental conditions and the extent to which tumors have progressed, parameters that are not always addressed in studies of these cells. We employed limiting dilution cell transplantation of minimally manipulated tumor cells from mammary tumors of several transgenic mouse models to determine their tumor-initiating cell frequency. We determined whether the tumors that formed following tumor cell transplantation phenocopied the primary tumors from which they were isolated and whether they could be serially transplanted. Finally we investigated whether propagating primary tumor cells in different tissue culture conditions affected their resident tumor-initiating cell frequency. We found that tumor-initiating cells comprised between 15% and 50% of the bulk tumor cell population in multiple independent mammary tumors from three different transgenic mouse models of breast cancer. Culture of primary mammary tumor cells in chemically-defined, serum-free medium as non-adherent tumorspheres preserved TIC frequency to levels similar to that of the primary tumors from which they were established. By contrast, propagating the primary tumor cells in serum-containing medium as adherent populations resulted in a several thousand-fold reduction in their tumor-initiating cell fraction. Our findings suggest that experimental conditions, including the sensitivity of the transplantation assay, can dramatically affect estimates of tumor initiating cell frequency. Moreover, conditional on cell culture conditions, the tumor-initiating cell fraction of bulk mouse mammary tumor cell preparations can either be maintained at high or low frequency in vitro thus permitting comparative studies of tumorigenic and non-tumorigenic cancer cells

  11. Inhibition of primary breast tumor growth and metastasis using a neuropilin-1 transmembrane domain interfering peptide

    PubMed Central

    Arpel, Alexia; Gamper, Coralie; Spenlé, Caroline; Fernandez, Aurore; Jacob, Laurent; Baumlin, Nadège; Laquerriere, Patrice; Orend, Gertraud; Crémel, Gérard; Bagnard, Dominique

    2016-01-01

    The transmembrane domains (TMD) in membrane receptors play a key role in cell signaling. As previously shown by us a peptide targeting the TMD of neuropilin-1 (MTP-NRP1), blocks cell proliferation, cell migration and angiogenesis in vitro, and decreases glioblastoma growth in vivo. We now explored the clinical potential of MTP-NRP1 on breast cancer models and demonstrate that MTP-NRP1 blocks proliferation of several breast cancer lines including the MDA-MB-231, a triple negative human breast cancer cell line. In models with long term in vivo administration of the peptide, MTP-NRP1 not only reduced tumor volume but also decreased number and size of breast cancer metastases. Strikingly, treating mice before tumors developed protected from metastasis establishment/formation. Overall, our results report that targeting the TMD of NRP1 in breast cancer is a potent new strategy to fight against breast cancer and related metastasis. PMID:27351129

  12. Advanced MR Imaging in Pediatric Brain Tumors, Clinical Applications.

    PubMed

    Lequin, Maarten; Hendrikse, Jeroen

    2017-02-01

    Advanced MR imaging techniques, such as spectroscopy, perfusion, diffusion, and functional imaging, have improved the diagnosis of brain tumors in children and also play an important role in defining surgical as well as therapeutic responses in these patients. In addition to the anatomic or structural information gained with conventional MR imaging sequences, advanced MR imaging techniques also provide physiologic information about tumor morphology, metabolism, and hemodynamics. This article reviews the physiology, techniques, and clinical applications of diffusion-weighted and diffusion tensor imaging, MR spectroscopy, perfusion MR imaging, susceptibility-weighted imaging, and functional MR imaging in the setting of neuro-oncology.

  13. An Open-Label Study of a Novel JAK-inhibitor, INCB047986, Given in Patients With Advanced Malignancies

    ClinicalTrials.gov

    2015-02-03

    Advanced Solid Tumors; Advanced Hodgkin's Lymphoma; Advanced Aggressive Non-Hodgkin's Lymphoma; Advanced Indolent Non-Hodgkin's Lymphoma; Advanced Pancreatic Adenocarcinoma; Advanced Triple-Negative Breast Cancer; Advanced Urothelial Carcinoma

  14. Locomotor proteins in tissues of primary tumors and metastases of ovarian and breast cancer

    NASA Astrophysics Data System (ADS)

    Kondakova, I. V.; Yunusova, N. V.; Spirina, L. V.; Shashova, E. E.; Kolegova, E. S.; Kolomiets, L. A.; Slonimskaya, E. M.; Villert, A. B.

    2016-08-01

    The paper discusses the capability for active movement in an extracellular matrix, wherein remodeling of the cytoskeleton by actin binding proteins plays a significant role in metastases formation. We studied the expression of actin binding proteins and β-catenin in tissues of primary tumors and metastases of ovarian and breast cancer. Contents of p45 Ser β-catenin and the actin severing protein gelsolin were decreased in metastases of ovarian cancer relative to primary tumors. The level of the cofilin, functionally similar to gelsolin, was significantly higher in metastases compared to primary ovarian and breast tumor tissue. In breast cancer, significant increase in the number of an actin monomer binder protein thymosin-β4 was observed in metastases as compared to primary tumors. The data obtained suggest the involvement of locomotor proteins in metastases formation in ovarian and breast cancer.

  15. Clinical Implementation of Novel Targeted Therapeutics in Advanced Breast Cancer.

    PubMed

    Chamberlin, Mary D; Bernhardt, Erica B; Miller, Todd W

    2016-11-01

    The majority of advanced breast cancers have genetic alterations that are potentially targetable with drugs. Through initiatives such as The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), data can be mined to provide context for next-generation sequencing (NGS) results in the landscape of advanced breast cancer. Therapies for targets other than estrogen receptor alpha (ER) and HER2, such as cyclin-dependent kinases CDK4 and CDK6, were recently approved based on efficacy in patient subpopulations, but no predictive biomarkers have been found, leaving clinicians to continue a trial-and-error approach with each patient. Next-generation sequencing identifies potentially actionable alterations in genes thought to be drivers in the cancerous process including phosphatidylinositol 3-kinase (PI3K), AKT, fibroblast growth factor receptors (FGFRs), and mutant HER2. Epigenetically directed and immunologic therapies have also shown promise for the treatment of breast cancer via histone deacetylases (HDAC) 1 and 3, programmed T cell death 1 (PD-1), and programmed T cell death ligand 1 (PD-L1). Identifying biomarkers to predict primary resistance in breast cancer will ultimately affect clinical decisions regarding adjuvant therapy in the first-line setting. However, the bulk of medical decision-making is currently made in the secondary resistance setting. Herein, we review the clinical potential of PI3K, AKT, FGFRs, mutant HER2, HDAC1/3, PD-1, and PD-L1 as therapeutic targets in breast cancer, focusing on the rationale for therapeutic development and the status of clinical testing. J. Cell. Biochem. 117: 2454-2463, 2016. © 2016 Wiley Periodicals, Inc.

  16. Prognostic Impact of Time to Ipsilateral Breast Tumor Recurrence after Breast Conserving Surgery

    PubMed Central

    Gosset, Marie; Hamy, Anne-Sophie; Mallon, Peter; Delomenie, Myriam; Mouttet, Delphine; Pierga, Jean-Yves; Lae, Marick; Fourquet, Alain; Rouzier, Roman; Reyal, Fabien; Feron, Jean-Guillaume

    2016-01-01

    Background The poor prognosis of patients who experience ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) is established. A short time between primary cancer and IBTR is a prognostic factor but no clinically relevant threshold was determined. Classification of IBTR may help tailor treatment strategies. Purpose We determined a specific time frame, which differentiates IBTR into early and late recurrence, and identified prognostic factors for patients with IBTR at time of the recurrence. Methods We analyzed 2209 patients with IBTR after BCS. We applied the optimal cut-points method for survival data to determine the cut-off times to IBTR. A subgroup analysis was performed by hormone receptor (HR) status. Survival analyses were performed using a Cox proportional hazard model to determine clinical features associated with distant-disease-free survival (DDFS) after IBTR. We therefor built decision trees. Results On the 828 metastatic events observed, the majority occurred within the first 3 months after IBTR: 157 in the HR positive group, 98 in the HR negative group. We found different prognostic times to IBTR: 49 months in the HR positive group, 33 in the HR negative group. After multivariate analysis, time to IBTR was the first discriminant prognostic factor in both groups (HR 0.65 CI95% [0.54–0.79] and 0.42 [0.30–0.57] respectively). The other following variables were significantly correlated with the DDFS: the initial number of positive lymph nodes for both groups, the initial tumor size and grade for HR positive tumors. Conclusion A short interval time to IBTR is the strongest factor of poor prognosis and reflects occult distant disease. It would appear that prognosis after IBTR depends more on clinical and histological parameters than on surgical treatment. A prospective trial in a low-risk group of patients to validate the safety of salvage BCS instead of mastectomy in IBTR is needed. PMID:27494111

  17. CD24 Is Not Required for Tumor Initiation and Growth in Murine Breast and Prostate Cancer Models.

    PubMed

    Cremers, Natascha; Neeb, Antje; Uhle, Tanja; Dimmler, Arno; Rothley, Melanie; Allgayer, Heike; Fodde, Riccardo; Sleeman, Jonathan Paul; Thiele, Wilko

    2016-01-01

    CD24 is a small, heavily glycosylated, GPI-linked membrane protein, whose expression has been associated with the tumorigenesis and progression of several types of cancer. Here, we studied the expression of CD24 in tumors of MMTV-PyMT, Apc1572/T+ and TRAMP genetic mouse models that spontaneously develop mammary or prostate carcinoma, respectively. We found that CD24 is expressed during tumor development in all three models. In MMTV-PyMT and Apc1572T/+ breast tumors, CD24 was strongly but heterogeneously expressed during early tumorigenesis, but decreased in more advanced stages, and accordingly was increased in poorly differentiated lesions compared with well differentiated lesions. In prostate tumors developing in TRAMP mice, CD24 expression was strong within hyperplastic lesions in comparison with non-hyperplastic regions, and heterogeneous CD24 expression was maintained in advanced prostate carcinomas. To investigate whether CD24 plays a functional role in tumorigenesis in these models, we crossed CD24 deficient mice with MMTV-PyMT, Apc1572T/+ and TRAMP mice, and assessed the influence of CD24 deficiency on tumor onset and tumor burden. We found that mice negative or positive for CD24 did not significantly differ in terms of tumor initiation and burden in the genetic tumor models tested, with the exception of Apc1572T/+ mice, in which lack of CD24 reduced the mammary tumor burden slightly but significantly. Together, our data suggest that while CD24 is distinctively expressed during the early development of murine mammary and prostate tumors, it is not essential for the formation of tumors developing in MMTV-PyMT, Apc1572T/+ and TRAMP mice.

  18. Homocysteine Is an Oncometabolite in Breast Cancer, Which Promotes Tumor Progression and Metastasis

    DTIC Science & Technology

    2014-09-01

    tissues and compare the expression levels in normal mouse mammary gland . For this, we used biological triplicates by preparing RNA from tumor tissues...homocysteine to be increased 4.5-fold in MMTV-HRAS mouse breast tumor tissues compared to age-matched wild type mouse mammary tissues. Similarly, the...levels of homocysteine went up 7.3-fold in MMTV-PyMT mouse breast cancer tissues 3 compared to age-matched wild type mouse mammary tissues

  19. Effects of radiation on tumor hemodynamics and NF-kappaB in breast tumors

    NASA Astrophysics Data System (ADS)

    Stantz, Keith M.; Cao, Ning; Liu, Bo; Cao, Minsong; Chin-Sinex, Helen; Mendonca, Marc; Li, Jian Jian

    2010-02-01

    Purpose: The purpose of this study is to monitor in vivo the IR dose dependent response of NF-κB and tumor hemodynamics as a function of time. Material and Methods: An MDA-231 breast cancer cell line was stably transfected with a firefly luciferase gene within the NF-kappaB promoter. Tumors on the right flank irradiated with a single fractionated dose of 5Gy or 10Gy. Over two weeks, photoacoustic spectroscopy (PCT-S), bioluminescence imaging (BLI), and dynamic contrast enhanced CT (DCE-CT) was used to monitor hemoglobin status, NF-kappaB expression, and physiology, respectively. Results: From the BLI, an increase in NF-kappaB expression was observed in both the right (irradiation) and left (nonirradiated) tumors, which peaked at 8-12 hours, returned to basal levels after 24 hours, and increased a second time from 3 to 7 days. This data identifies both a radiation-induced bystander effect and a bimodal longitudinal response associated with NF-κB-controlled luciferase promoter. The physiological results from DCE-CT measured an increase in perfusion (26%) two days after radiation and both a decrease in perfusion and an increase in fp by week 1 (10Gy cohort). PCT-S measured increased levels of oxygen saturation two days post IR, which did not change after 1 week. Initially, NF-κB would modify hemodynamics to increase oxygen delivery after IR insult. The secondary response appears to modulate tumor angiogenesis. Conclusions: A bimodal response to radiation was detected with NF-kappaB-controlled luciferase reporter with a concomitant hemodynamic response associated with tumor hypoxia. Experiments are being performed to increase statistics.

  20. Circulating tumor cells: advances in isolation and analysis, and challenges for clinical applications

    PubMed Central

    Harouaka, Ramdane; Kang, Zhigang; Zheng, Siyang; Cao, Liang

    2013-01-01

    Circulating tumor cells (CTCs) are rare cancer cells released from tumors into the bloodstream that are thought to have a key role in cancer metastasis. The presence of CTCs has been associated with worse prognosis in several major cancer types, including breast, prostate and colorectal cancer. There is considerable interest in CTC research and technologies for their potential use as cancer biomarkers that may enhance cancer diagnosis and prognosis, facilitate drug development, and improve the treatment of cancer patients. This review provides an update on recent progress in CTC isolation and molecular characterization technologies. Furthermore, the review covers significant advances and limitations in the clinical applications of CTC-based assays for cancer prognosis, response to anti-cancer therapies, and exploratory studies in biomarkers predictive of sensitivity and resistance to cancer therapies. PMID:24134902

  1. Three-Dimensional Breast Cancer Models Mimic Hallmarks of Size-Induced Tumor Progression.

    PubMed

    Singh, Manjulata; Mukundan, Shilpaa; Jaramillo, Maria; Oesterreich, Steffi; Sant, Shilpa

    2016-07-01

    Tumor size is strongly correlated with breast cancer metastasis and patient survival. Increased tumor size contributes to hypoxic and metabolic gradients in the solid tumor and to an aggressive tumor phenotype. Thus, it is important to develop three-dimensional (3D) breast tumor models that recapitulate size-induced microenvironmental changes and, consequently, natural tumor progression in real time without the use of artificial culture conditions or gene manipulations. Here, we developed size-controlled multicellular aggregates ("microtumors") of subtype-specific breast cancer cells by using non-adhesive polyethylene glycol dimethacrylate hydrogel microwells of defined sizes (150-600 μm). These 3D microtumor models faithfully represent size-induced microenvironmental changes, such as hypoxic gradients, cellular heterogeneity, and spatial distribution of necrotic/proliferating cells. These microtumors acquire hallmarks of tumor progression in the same cell lines within 6 days. Of note, large microtumors of hormone receptor-positive cells exhibited an aggressive phenotype characterized by collective cell migration and upregulation of mesenchymal markers at mRNA and protein level, which was not observed in small microtumors. Interestingly, triple-negative breast cancer (TNBC) cell lines did not show size-dependent upregulation of mesenchymal markers. In conclusion, size-controlled microtumor models successfully recapitulated clinically observed positive association between tumor size and aggressive phenotype in hormone receptor-positive breast cancer while maintaining clinically proven poor correlation of tumor size with aggressive phenotype in TNBC. Such clinically relevant 3D models generated under controlled experimental conditions can serve as precise preclinical models to study mechanisms involved in breast tumor progression as well as antitumor drug effects as a function of tumor progression. Cancer Res; 76(13); 3732-43. ©2016 AACR.

  2. Serpin E2 promotes breast cancer metastasis by remodeling the tumor matrix and polarizing tumor associated macrophages

    PubMed Central

    Smirnova, Tatiana; Bonapace, Laura; MacDonald, Gwen; Kondo, Shunya; Wyckoff, Jeffrey; Ebersbach, Hilmar; Fayard, Bérengère; Doelemeyer, Arno; Coissieux, Marie-May; Heideman, Marinus R.; Bentires-Alj, Mohamed; Hynes, Nancy E.

    2016-01-01

    The extracellular serine protease inhibitor serpinE2 is overexpressed in breast cancer and has been shown to foster metastatic spread. Here, we investigated the hypothesis that serpinE2 creates tumor-promoting conditions in the tumor microenvironment (TME) by affecting extracellular matrix remodeling. Using two different breast cancer models, we show that blocking serpinE2, either by knock-down (KD) in tumor cells or in response to a serpinE2 binding antibody, decreases metastatic dissemination from primary tumors to the lungs. We demonstrate that in response to serpinE2 KD or antibody treatment there are dramatic changes in the TME. Multiphoton intravital imaging revealed deposition of a dense extracellular collagen I matrix encapsulating serpinE2 KD or antibody-treated tumors. This is accompanied by a reduction in the population of tumor-promoting macrophages, as well as a decrease in chemokine ligand 2, which is known to affect macrophage abundance and polarization. In addition, TIMP-1 secretion is increased, which may directly inhibit matrix metalloproteases critical for collagen degradation in the tumor. In summary, our findings suggest that serpinE2 is required in the extracellular milieu of tumors where it acts in multiple ways to regulate tumor matrix deposition, thereby controlling tumor cell dissemination. PMID:27793045

  3. Performance analysis of a dedicated breast MR-HIFU system for tumor ablation in breast cancer patients

    NASA Astrophysics Data System (ADS)

    Deckers, R.; Merckel, L. G.; de Senneville, B. Denis; Schubert, G.; Köhler, M.; Knuttel, F. M.; Mali, W. P. Th M.; Moonen, C. T. W.; van den Bosch, M. A. A. J.; Bartels, L. W.

    2015-07-01

    MR-guided HIFU ablation is a promising technique for the non-invasive treatment of breast cancer. A phase I study was performed to assess the safety and treatment accuracy and precision of MR-HIFU ablation in breast cancer patients (n=10 ) using a newly developed MR-HIFU platform dedicated to applications in the breast. In this paper a technical analysis of the performance of the dedicated breast MR-HIFU system during breast tumors ablation is described. The main points of investigation were the spatial targeting accuracy and precision of the system and the performance of real-time respiration-corrected MR thermometry. The mean targeting accuracy was in the range of 2.4-2.6 mm, whereas the mean targeting precision was in the range of 1.5-1.8 mm. To correct for respiration-induced magnetic field fluctuations during MR temperature mapping a look-up-table (LUT)-based correction method was used. An optimized procedural sedation protocol in combination with the LUT-based correction method allowed for precise MR thermometry during the ablation procedure (temperature standard deviation <3 °C). No unwanted heating in the near field (i.e. skin) nor in the far field (pectoral muscle) was detected. The newly developed dedicated breast MR-HIFU system allows for safe, accurate and precise ablation of breast tumors.

  4. Quantitative ultrasound assessment of breast tumor response to chemotherapy using a multi-parameter approach

    PubMed Central

    Tadayyon, Hadi; Sannachi, Lakshmanan; Gangeh, Mehrdad; Sadeghi-Naini, Ali; Tran, William; Trudeau, Maureen E.; Pritchard, Kathleen; Ghandi, Sonal; Verma, Sunil; Czarnota, Gregory J.

    2016-01-01

    Purpose This study demonstrated the ability of quantitative ultrasound (QUS) parameters in providing an early prediction of tumor response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC). Methods Using a 6-MHz array transducer, ultrasound radiofrequency (RF) data were collected from 58 LABC patients prior to NAC treatment and at weeks 1, 4, and 8 of their treatment, and prior to surgery. QUS parameters including midband fit (MBF), spectral slope (SS), spectral intercept (SI), spacing among scatterers (SAS), attenuation coefficient estimate (ACE), average scatterer diameter (ASD), and average acoustic concentration (AAC) were determined from the tumor region of interest. Ultrasound data were compared with the ultimate clinical and pathological response of the patient's tumor to treatment and patient recurrence-free survival. Results Multi-parameter discriminant analysis using the κ-nearest-neighbor classifier demonstrated that the best response classification could be achieved using the combination of MBF, SS, and SAS, with an accuracy of 60 ± 10% at week 1, 77 ± 8% at week 4 and 75 ± 6% at week 8. Furthermore, when the QUS measurements at each time (week) were combined with pre-treatment (week 0) QUS values, the classification accuracies improved (70 ± 9% at week 1, 80 ± 5% at week 4, and 81 ± 6% at week 8). Finally, the multi-parameter QUS model demonstrated a significant difference in survival rates of responding and non-responding patients at weeks 1 and 4 (p=0.035, and 0.027, respectively). Conclusion This study demonstrated for the first time, using new parameters tested on relatively large patient cohort and leave-one-out classifier evaluation, that a hybrid QUS biomarker including MBF, SS, and SAS could, with relatively high sensitivity and specificity, detect the response of LABC tumors to NAC as early as after 4 weeks of therapy. The findings of this study also suggested that incorporating pre-treatment QUS

  5. Malignant phyllodes tumor of the breast with liposarcomatous differentiation and intraductal hyperplasia.

    PubMed

    Ayadi-Kaddour, Aïda; Zeddini, Abdelfatteh; Braham, Emna; Ismail, Olfa; Mlika, Mona; Guelmami, Karim; El Mezni, Faouzi

    2015-01-01

    Phyllodes tumor of the breast is a biphasic fibroepithelial neoplasm. 10 to 20% of phyllodes tumor show malignant transformation, often in the form of stroma, which usually shows fibrosarcomatous differentiation and rarely heterologous sarcomatous elements. Liposarcomatous differentiation is not common among phyllodes tumors. The correct diagnosis of heterologous liposarcomatous differentiation in a malignant PT requires identification of the biphasic component of the tumor. We reported a case of malignant phyllodes tumor which initially transformed into liposarcoma, in addition to a very rare intraductal hyperplasia and flat epithelial atypia. The patient was a 75-year-old woman, with a lump in the left breast without axillary lymphadenopathy. She also have a positive family history of breast carcinoma. She underwent surgery and still alive and disease free after one year.

  6. Pancreatic neuroendocrine tumors: clinical features, diagnosis and medical treatment: advances

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato; Jensen, Robert T.

    2013-01-01

    Pancreatic neuroendocrine tumors (pNETs) comprise with gastrointestinal carcinoids, the main groups of gastrointestinal neuroendocrine tumors (GI-NETs). Although these two groups of GI-NETs share many features including histological aspects; over-/ectopic expression of somatostatin receptors; the ability to ectopically secrete hormones/peptides/amines which can result in distinct functional syndromes; similar approaches used for tumor localization and some aspects of treatment, it is now generally agreed they should be considered separate. They differ in their pathogenesis, hormonal syndromes produced, many aspects of biological behavior and most important, in their response to certain anti-tumor treatment (chemotherapy, molecular targeted therapies). In this chapter the clinical features of the different types of pNETs will be considered as well as aspects of their diagnosis and medical treatment of the hormone-excess state. Emphasis will be on controversial areas or recent advances. The other aspects of the management of these tumors (surgery, treatment of advanced disease, tumor localization) are not dealt with here, because they are covered in other chapters in this volume. PMID:23582916

  7. Superior anti-tumor efficacy of diisopropylamine dichloroacetate compared with dichloroacetate in a subcutaneous transplantation breast tumor model

    PubMed Central

    Yan, Chen; Chen, Aiping; Meng, Gang; Wei, Jiwu; Yu, Decai; Ding, Yitao

    2016-01-01

    Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, has anti-tumor properties in various carcinoma models. Diisopropylamine dichloroacetate (DADA), an over-the-counter drug for chronic liver disease, is a derivative of DCA. To date, few studies have evaluated the anticancer potential of DADA in breast cancer. In this study, MDA-MB-231 cells, a breast adenocarcinoma cell line, were used in in vitro and in vivo experiments to evaluate the anti-tumor efficacy of DADA and DCA. The half maximal inhibitory concentration (IC50) of DADA (7.1 ± 1.1 mmol/L) against MDA-MB-231 cells was significantly lower than that of DCA (15.6 ± 2.0 mmol/L); 100 mg/kg (0.0004 mol/kg) DADA was better than 100 mg/kg (0.0008 mol/kg) DCA at suppressing the growth of subcutaneous transplantation breast tumor at the same dose after 24 days intervention. Histological examination showed that both DCA and DADA interventions led to necrosis, inflammation, and fibrosis of tumor tissue in a mouse subcutaneous transplantation breast tumor model. DADA treatment inhibited Ki67 expression in tumor tissue. In vitro experiments showed that DADA could inhibit lactic acid production and glucose uptake in MDA-MB-231 cells at 10 mmol/L and these effects were stronger than DCA. DADA administration also induced complete autophagy during early treatment stages and incomplete autophagy and cell death at later treatment stages. In conclusion, DADA showed better anti-tumor efficacy than DCA in a breast cancer model. PMID:27582548

  8. Coexistence of benign phyllodes tumor and invasive ductal carcinoma in distinct breasts: case report.

    PubMed

    Neto, Guerino Barbalaco; Rossetti, Claudia; Souza, Natalia A; LA Fonseca, Fernando; Azzalis, Ligia Ajaime; Junqueira, Virginia Berlanga Campos; Valenti, Vitor E; de Abreu, Luiz Carlos

    2012-04-25

    This report describes a rare case of coexistence of benign phyllodes tumor, which measured 9 cm in the right breast, and invasive ductal carcinoma of 6 cm in the left breast, synchronous and independent, in a 66-year-old patient. The patient underwent a bilateral mastectomy due to the size of both lesions. Such situations are rare and usually refer to the occurrence of ductal or lobular carcinoma in situ when associated with malignant phyllodes tumors, and more often in ipsilateral breast or intra-lesional.

  9. Coexistence of benign phyllodes tumor and invasive ductal carcinoma in distinct breasts: case report

    PubMed Central

    2012-01-01

    This report describes a rare case of coexistence of benign phyllodes tumor, which measured 9 cm in the right breast, and invasive ductal carcinoma of 6 cm in the left breast, synchronous and independent, in a 66-year-old patient. The patient underwent a bilateral mastectomy due to the size of both lesions. Such situations are rare and usually refer to the occurrence of ductal or lobular carcinoma in situ when associated with malignant phyllodes tumors, and more often in ipsilateral breast or intra-lesional. PMID:22534285

  10. Breast tumor detection using UWB circular-SAR tomographic microwave imaging.

    PubMed

    Oloumi, Daniel; Boulanger, Pierre; Kordzadeh, Atefeh; Rambabu, Karumudi

    2015-01-01

    This paper describes the possibility of detecting tumors in human breast using ultra-wideband (UWB) circular synthetic aperture radar (CSAR). CSAR is a subset of SAR which is a radar imaging technique using a circular data acquisition pattern. Tomographic image reconstruction is done using a time domain global back projection technique adapted to CSAR. Experiments are conducted on a breast phantoms made of pork fat emulating normal and cancerous conditions. Preliminary experimental results show that microwave imaging of a breast phantom using UWB-CSAR is a simple and low-cost method, efficiently capable of detecting the presence of tumors.

  11. New approach to breast tumor detection based on fluorescence x-ray analysis

    PubMed Central

    Hayashi, Yasuhiko; Okuyama, Fumio

    2010-01-01

    A new technical approach to breast-tumor detection is proposed. The technique is based on fluorescence x-ray analysis, and can identify a miniature malignant tumor within the breast. The primary beam intensity needed in fluorescence x-ray analysis is on a lower order of magnitude than that used in mammography. Thus, the newly-proposed technique would enable detection of a still tiny breast cancer while dramatically lowering the radiation dose. Field-emission x-ray sources might be a key for translating this concept into a medical technique. PMID:20930932

  12. Advances in the treatment of advanced oestrogen-receptor-positive breast cancer.

    PubMed

    Turner, Nicholas C; Neven, Patrick; Loibl, Sibylle; Andre, Fabrice

    2016-12-06

    Oestrogen-receptor-positive breast cancer is the most common subtype of breast cancer. Endocrine therapies that target the dependence of this subtype on the oestrogen receptor have substantial activity, yet the development of resistance to therapy is inevitable in advanced cancer. Major progress has been made in identifying the drivers of oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into major advances in the treatment of advanced breast cancer, with several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of mTOR and inhibitors of the cyclin-dependent kinases CDK4 and CDK6 substantially improve progression-free survival. A new wave of targeted therapies is being developed, including inhibitors of PI3K, AKT, and HER2, and a new generation of oestrogen-receptor degraders. Considerable challenges remain in patient selection, deciding on the most appropriate order in which to administer therapies, and establishing whether cross-resistance occurs between therapies.

  13. Impact of palbociclib combinations on treatment of advanced estrogen receptor-positive/human epidermal growth factor 2-negative breast cancer

    PubMed Central

    Boér, Katalin

    2016-01-01

    Breast cancer is a heterogeneous disease with multiple subgroups based on clinical and molecular characteristics. For the largest subgroup of breast cancers, hormone receptor-positive/human epidermal growth factor 2 (HER2)-negative tumors, hormone treatment is the mainstay of therapy and is likely to result in significant improvement in disease outcomes. However, some of these cancers demonstrate de novo or acquired resistance to endocrine therapy. Despite intensive research to develop new strategies to enhance the efficacy of currently available treatment options for hormone receptor-positive breast cancer, progress has been slow, and there were few advances for a period of 10 years. In 2012, a new molecularly targeted therapeutic strategy, inhibition of mammalian target of rapamycin with everolimus, was introduced into clinical practice. Everolimus, in combination with a steroidal aromatase inhibitor, exemestane, resulted in an increase in progression-free survival, but not overall survival in patients with estrogen receptor (ER)+ve advanced disease who had progressed on hormone therapy. In 2015, the first cyclin-dependent kinases 4/6 (CDK4/6) inhibitor, palbociclib, received accelerated US Food and Drug Administration approval for use in combination with letrozole for the treatment of postmenopausal ER+ve/HER2−ve advanced breast cancer as initial, endocrine-based therapy. The addition of palbociclib to endocrine therapy resulted in longer progression-free survival than letrozole alone. One year later, palbociclib received a new indication, use in combination with fulvestrant, in both premenopausal and postmenopausal females with advanced breast cancer of the same subtype with disease progression following endocrine therapy. Adding palbociclib to fulvestrant resulted in a significantly increased median progression-free survival compared to fulvestrant monotherapy. These new combination regimens of palbociclib with endocrine agents represent an important

  14. Use of radioimmunoguided surgery after induction chemotherapy in locally advanced breast cancer.

    PubMed

    Badellino, F; Bertoglio, S; Mariani, G; Meszaros, P; Canavese, G; Percivale, P

    1998-12-01

    Twenty-one patients with histologically proven locally advanced breast cancer (LABC) were treated with a combined modality approach based on primary chemotherapy and radical modified mastectomy followed by adjuvant chemotherapy. Surgery was performed by using radioimmunoguided surgery (RIGS) technique with the preoperative injection of Iodine-125 labeled monoclonal antibodies (MoAbs) B72.3 anti-TAG (11 patients, Group A) and FO23C5 anti-carcinoembryonic antigen (CEA; 10 patients, Group B). The role of RIGS was defined at surgery by using an intraoperative hand-held gamma-detecting probe (GDP) to locate the primary tumor, possible clinically occult multicentric foci and ipsilateral lymph node metastases. In Group A, RIGS correctly defined the primary tumor in seven out of 11 patients (63.3%) and was able to find multicentric tumors in two out of four patients (50%). Positive lymph nodes were identified by RIGS in three out of eight patients (37.5%). In Group B, patients RIGS correctly located the primary in 4/10 cases (40%); in two RIGS-positive cases, the tumor was clinically not evident after primary chemotherapy (yT0). RIGS correctly identified multicentric foci of tumor in one out of two cases (50%). Correct lymph nodal RIGS assessment was observed in three out of nine patients (33.3%). No RIGS false-positive findings occurred in the 21 patients included in the study. RIGS appears to be a reliable technique for the intraoperative diagnosis and staging of breast cancer with a potential role especially when conservative surgery is planned after primary chemotherapy in LABC.

  15. Tracking nonpalpable breast cancer for breast-conserving surgery with carbon nanoparticles: implication in tumor location and lymph node dissection.

    PubMed

    Jiang, Yanyan; Lin, Nan; Huang, Sheng; Lin, Chongping; Jin, Na; Zhang, Zaizhong; Ke, Jun; Yu, Yinghao; Zhu, Jianping; Wang, Yu

    2015-03-01

    To examine the feasibility of using carbon nanoparticles to track nonpalpable breast cancer for breast-conserving surgery. During breast-conserving surgery, it is often very challenging to determine the boundary of tumor and identify involved lymph nodes. Currently used methods are useful in identifying tumor location, but do not provide direct visual guidance for resection margin during surgery. The study was approved by the Institutional Review Board of the Fuzhou General Hospital (Fuzhou, China). The current retrospective analysis included 16 patients with nonpalpable breast cancer receiving breast-conserving surgery under the guidance of preoperative marking using a carbon nanoparticle, as well as 3 patients receiving carbon nanoparticle marking followed by neoadjuvant treatment and then breast-conserving surgery. The Tumor Node Metastasis stage in the 16 cases included: T1N0M0 in 7, T1N1M0 in 2, T2N0M0 in 4, and T2N1M0 in the remaining 3 cases. The nanoparticle was injected at 12 sites at 0.5 cm away from the apparent edge under colored ultrasonography along 6 tracks separated by 60 degrees (2 sites every track). Lymph node status was also examined. The resection edge was free from cancer cells in all 16 cases (and the 3 cases with neoadjuvant treatment). Cancer cells were identified in majority of stained lymph nodes, but not in any of the unstained lymph nodes. No recurrence or metastasis was noticed after the surgery (2 to 22-month follow-up; median: 6 months). Tracking nonpalpable breast cancer with carbon nanoparticle could guide breast-conserving surgery.

  16. Studies on breast tumor tissues with ATR-FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Yu, Ge; Xu, Jialin; Niu, Yun; Zhang, Cunzhou; Zhang, Chunping

    2005-01-01

    The original and deconvoluted spectra of Attenuated Total Reflection (ATR) FTIR have been determined for both benign and malignant tumor tissues samples and the spectral differences have been investigated between the two types of samples. In comparison with the benign samples, the characteristic changes of malignant ones mainly involve: The prominent bands 1652 and 1645cm-1 due to the proteins in the α-helical and the unordered-random-coils substructures become stronger compared to those in the β-sheet and the turns substructures, suggesting that the former type of proteins increase in content in contrast to the later. The phospodiester band 1083 cm-1 of the nucleic acids becomes strongest on cancer tissues spectra and its area ratio to the amide II band 1548cm-1 rises greatly, indicating that the DNA content rises remarkably. The collagen proteins reduce in content while phosphorylated ones rise, and some hydrogen bonding is nearly broken in amino acid residue C-O (H) groups. The glycogen content decreases, and the CH2 content is higher than CH3 one. These results suggest that ATR-FTIR spectroscopy has the potential to become a powerful tool for biochemical studies and in vivo diagnosis of human breast cancers.

  17. Fulvestrant, a selective estrogen receptor down-regulator, sensitizes estrogen receptor negative breast tumors to chemotherapy.

    PubMed

    Jiang, Donghai; Huang, Yuan; Han, Ning; Xu, Mingjie; Xu, Liang; Zhou, Lin; Wang, Shu; Fan, Weimin

    2014-05-01

    Drug resistance frequently results in poor prognosis and high 5-year recurrence rate in estrogen receptor-negative (ER-) breast cancer patients. Herein, we examined the reversal effects of fulvestrant on multidrug resistance (MDR) in ER- breast cancer cells. Co-administration of fulvestrant significantly sensitized ER- MDR tumors to paclitaxel both in vitro and in vivo. Further analyses indicated that fulvestrant did not affect P-gp expression, but could inhibit P-gp function and subsequently reverse P-gp mediated drug resistance in ER- breast cancer cells. These results showed that combination of fulvestrant and chemotherapeutic agents might provide an effective treatment for ER- MDR breast cancers.

  18. Primary radiation therapy for locally advanced breast cancer

    SciTech Connect

    Sheldon, T.; Hayes, D.F.; Cady, B.; Parker, L.; Osteen, R.; Silver, B.; Recht, A.; Come, S.; Henderson, I.C.; Harris, J.R.

    1987-09-15

    The optimal local-regional treatment for patients with Stage III breast cancer has not been determined. To evaluate the effectiveness of radiation therapy as local treatment for such patients, the results of 192 patients (five with bilateral disease) treated with radiation therapy without mastectomy between July 1, 1968 and December 31, 1981 were reviewed. Excisional biopsy (gross tumor removal) was performed in only 54 of the 197 breasts. Patients typically received 4500 to 5000 cGy in 5 weeks to the breast and draining lymph nodes; a local boost to areas of gross disease was delivered to 157 patients. Multi-agent chemotherapy was given to 53 patients. The median follow-up was 65 months. The actuarial probability of survival for the entire group was 41% at 5 years and 23% at 10 years. The probability of relapse-free survival (RFS) was 30% at 5 years and 19% at 10 years. The addition of multi-agent chemotherapy was associated with a significantly improved 5-year RFS (40% versus 26%, P = 0.02). The 5-year survival rate was 51% for patients who received adjuvant multi-agent chemotherapy and 38% for patients who did not (P = 0.16). The actuarial rate of local-regional tumor control (not censored for distant failure) for all patients was 73% at 5 years and 68% at ten years, and the crude incidence of local-regional control was 78%. Local-regional tumor control was principally influenced by radiation dose. Patients who received 6000 cGy or greater to the primary site had a better 5-year rate of control in the breast than did patients who received less than 6000 cGy (83% versus 70%, P = 0.06). Significant complications were seen in 15 patients (8%); these included moderate or severe arm edema in six patients and brachial plexopathy in four patients. Cosmetic results at last evaluation were excellent or good in 56% of evaluable patients, fair in 25%, and poor in 19%.

  19. Alpha2-Adrenergic Receptors and Breast Tumor Stroma: A Novel Pathway Driving Breast Cancer Growth and Metastasis

    DTIC Science & Technology

    2014-10-01

    transforming growth factor- beta (TGF-ß) were measured in tumor homogenates (14). DEX treatment did not alter tumor MMP-2, -3, and pro-MMP-9 (Fig. 4A-C) or...progression and should be further explored, especially in the context of evaluating the safety of ß- blockers in breast cancer patients...of bio-behavioural factors on tumour biology: pathways and mechanisms. Nat Rev Cancer 6: 240-8 3. Cole SW, Sood AK. 2012. Molecular pathways: beta

  20. Juvenile fibroadenoma and granular cell tumor of the breast in an adolescent.

    PubMed

    Marshall, Andre P; Spottswood, Stephanie E; Grau, Ana M; Jackson, Gretchen Purcell

    2012-10-01

    We describe a case of a 15-year-old girl who presented with 2 painful masses in her right breast. Ultrasound confirmed the presence of 2 lesions, both of which appeared noncharacteristic for fibroadenomas. Both lesions were surgically resected. One was found to be a fibroadenoma and the other a granular cell tumor, both benign upon further histologic evaluation. Breast masses are rare in the pediatric population. The finding of a concurrent fibroadenoma and granular cell tumor is unique and has not been previously reported. Granular cell tumors of the breast are relatively uncommon. Often, they are mistaken for a breast malignancy. The concerning clinical and radiographic findings in this patient warranted operative excision.

  1. Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant.

    PubMed

    van Roosmalen, Wies; Le Dévédec, Sylvia E; Golani, Ofra; Smid, Marcel; Pulyakhina, Irina; Timmermans, Annemieke M; Look, Maxime P; Zi, Di; Pont, Chantal; de Graauw, Marjo; Naffar-Abu-Amara, Suha; Kirsanova, Catherine; Rustici, Gabriella; Hoen, Peter A C 't; Martens, John W M; Foekens, John A; Geiger, Benjamin; van de Water, Bob

    2015-04-01

    Tumor cell migration is a key process for cancer cell dissemination and metastasis that is controlled by signal-mediated cytoskeletal and cell matrix adhesion remodeling. Using a phagokinetic track assay with migratory H1299 cells, we performed an siRNA screen of almost 1,500 genes encoding kinases/phosphatases and adhesome- and migration-related proteins to identify genes that affect tumor cell migration speed and persistence. Thirty candidate genes that altered cell migration were validated in live tumor cell migration assays. Eight were associated with metastasis-free survival in breast cancer patients, with integrin β3-binding protein (ITGB3BP), MAP3K8, NIMA-related kinase (NEK2), and SHC-transforming protein 1 (SHC1) being the most predictive. Examination of genes that modulate migration indicated that SRPK1, encoding the splicing factor kinase SRSF protein kinase 1, is relevant to breast cancer outcomes, as it was highly expressed in basal breast cancer. Furthermore, high SRPK1 expression correlated with poor breast cancer disease outcome and preferential metastasis to the lungs and brain. In 2 independent murine models of breast tumor metastasis, stable shRNA-based SRPK1 knockdown suppressed metastasis to distant organs, including lung, liver, and spleen, and inhibited focal adhesion reorganization. Our study provides comprehensive information on the molecular determinants of tumor cell migration and suggests that SRPK1 has potential as a drug target for limiting breast cancer metastasis.

  2. Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant

    PubMed Central

    van Roosmalen, Wies; Le Dévédec, Sylvia E.; Golani, Ofra; Smid, Marcel; Pulyakhina, Irina; Timmermans, Annemieke M.; Look, Maxime P.; Zi, Di; Pont, Chantal; de Graauw, Marjo; Naffar-Abu-Amara, Suha; Kirsanova, Catherine; Rustici, Gabriella; Hoen, Peter A.C. ‘t; Martens, John W.M.; Foekens, John A.; Geiger, Benjamin; van de Water, Bob

    2015-01-01

    Tumor cell migration is a key process for cancer cell dissemination and metastasis that is controlled by signal-mediated cytoskeletal and cell matrix adhesion remodeling. Using a phagokinetic track assay with migratory H1299 cells, we performed an siRNA screen of almost 1,500 genes encoding kinases/phosphatases and adhesome- and migration-related proteins to identify genes that affect tumor cell migration speed and persistence. Thirty candidate genes that altered cell migration were validated in live tumor cell migration assays. Eight were associated with metastasis-free survival in breast cancer patients, with integrin β3–binding protein (ITGB3BP), MAP3K8, NIMA-related kinase (NEK2), and SHC-transforming protein 1 (SHC1) being the most predictive. Examination of genes that modulate migration indicated that SRPK1, encoding the splicing factor kinase SRSF protein kinase 1, is relevant to breast cancer outcomes, as it was highly expressed in basal breast cancer. Furthermore, high SRPK1 expression correlated with poor breast cancer disease outcome and preferential metastasis to the lungs and brain. In 2 independent murine models of breast tumor metastasis, stable shRNA-based SRPK1 knockdown suppressed metastasis to distant organs, including lung, liver, and spleen, and inhibited focal adhesion reorganization. Our study provides comprehensive information on the molecular determinants of tumor cell migration and suggests that SRPK1 has potential as a drug target for limiting breast cancer metastasis. PMID:25774502

  3. HER2-Positive Circulating Tumor Cells in Breast Cancer

    PubMed Central

    Ignatiadis, Michail; Rothé, Françoise; Chaboteaux, Carole; Durbecq, Virginie; Rouas, Ghizlane; Criscitiello, Carmen; Metallo, Jessica; Kheddoumi, Naima; Singhal, Sandeep K.; Michiels, Stefan; Veys, Isabelle; Rossari, José; Larsimont, Denis; Carly, Birgit; Pestrin, Marta; Bessi, Silvia; Buxant, Frédéric; Liebens, Fabienne; Piccart, Martine; Sotiriou, Christos

    2011-01-01

    Purpose Circulating Tumor Cells (CTCs) detection and phenotyping are currently evaluated in Breast Cancer (BC). Tumor cell dissemination has been suggested to occur early in BC progression. To interrogate dissemination in BC, we studied CTCs and HER2 expression on CTCs across the spectrum of BC staging. Methods Spiking experiments with 6 BC cell lines were performed and blood samples from healthy women and women with BC were analyzed for HER2-positive CTCs using the CellSearch®. Results Based on BC cell lines experiments, HER2-positive CTCs were defined as CTCs with HER2 immunofluoresence intensity that was at least 2.5 times higher than the background. No HER2-positive CTC was detected in 42 women without BC (95% confidence interval (CI) 0–8.4%) whereas 4.1% (95%CI 1.4–11.4%) of 73 patients with ductal/lobular carcinoma in situ (DCIS/LCIS) had 1 HER2-positive CTC/22.5 mL, 7.9%, (95%CI 4.1–14.9%) of 101 women with non metastatic (M0) BC had ≥1 HER2-positive CTC/22.5 mL (median 1 cell, range 1–3 cells) and 35.9% (95%CI 22.7–51.9%) of 39 patients with metastatic BC had ≥1 HER2-positive CTC/7.5 mL (median 1.5 cells, range 1–42 cells). In CTC-positive women with DCIS/LCIS or M0 BC, HER2-positive CTCs were more commonly detected in HER2-positive (5 of 5 women) than HER2-negative BC (5 of 12 women) (p = 0.03). Conclusion HER2-positive CTCs were detected in DCIS/LCIS or M0 BC irrespective of the primary tumor HER2 status. Nevertheless, their presence was more common in women with HER2-positive disease. Monitoring of HER2 expression on CTCs might be useful in trials with anti-HER2 therapies. PMID:21264346

  4. Ultrasonic Nakagami imaging: a strategy to visualize the scatterer properties of benign and malignant breast tumors.

    PubMed

    Tsui, Po-Hsiang; Yeh, Chih-Kuang; Liao, Yin-Yin; Chang, Chien-Cheng; Kuo, Wen-Hung; Chang, King-Jen; Chen, Chiung-Nien

    2010-02-01

    Previous studies have demonstrated the usefulness of the Nakagami parameter in characterizing breast tumors by ultrasound. However, physicians or radiologists may need imaging tools in a clinical setting to visually identify the properties of breast tumors. This study proposed the ultrasonic Nakagami image to visualize the scatterer properties of breast tumors and then explored its clinical performance in classifying benign and malignant tumors. Raw data of ultrasonic backscattered signals were collected from 100 patients (50 benign and 50 malignant cases) using a commercial ultrasound scanner with a 7.5 MHz linear array transducer. The backscattered signals were used to form the B-scan and the Nakagami images of breast tumors. For each tumor, the average Nakagami parameter was calculated from the pixel values in the region-of-interest in the Nakagami image. The receiver operating characteristic (ROC) curve was used to evaluate the clinical performance of the Nakagami image. The results showed that the Nakagami image shadings in benign tumors were different from those in malignant cases. The average Nakagami parameters for benign and malignant tumors were 0.69 +/- 0.12 and 0.55 +/- 0.12, respectively. This means that the backscattered signals received from malignant tumors tend to be more pre-Rayleigh distributed than those from benign tumors, corresponding to a more complex scatterer arrangement or composition. The ROC analysis showed that the area under the ROC curve was 0.81 +/- 0.04 and the diagnostic accuracy was 82%, sensitivity was 92% and specificity was 72%. The results showed that the Nakagami image is useful to distinguishing between benign and malignant breast tumors.

  5. Effects of Herceptin on circulating tumor cells in HER2 positive early breast cancer.

    PubMed

    Zhang, J-L; Yao, Q; Chen Y Wang, J-H; Wang, H; Fan, Q; Ling, R; Yi, J; Wang, L

    2015-03-20

    The objective of this study was to determine the changes in peripheral blood circulating tumor cells in HER2-positive early breast cancer before and after Herceptin therapy, and to explore the effects of the HER2 gene and Herceptin on circulating tumor cells. CK19 mRNA expression in peripheral blood was evaluated by qRT-PCR as an index of circulating tumor cells in 15 cases of HER-2-positive breast cancer and 18 cases of HER2-negative breast cancer before, and after chemotherapy as well. Ten cases of HER2-positive breast cancer continued on Herceptin therapy for 3 months after chemotherapy, and their peripheral blood was again drawn and assayed for CK-19 mRNA expression. Preoperatively, all cases of HER2-positive cancer were positive for CK19 mRNA in peripheral blood, but 6 cases of HER2-negative breast cancer were positive (33.3%), where there was a substantial difference between the two groups. After 6 cycles of adjuvant chemotherapy, CK19 positive rates in cases of HER2-positive and -negative breast cancer reduced by 93.3 and 11.1%, respectively, with a significant difference still existing. After 3 months of Herceptin therapy, expression of CK19 mRNA declined considerably in 10 cases of HER2 positive breast cancer (113.66 ± 88.65 vs 63.35 ± 49.27, P = 0.025). HER-2 gene expression closely correlated with circulating tumor cells in peripheral blood of early breast cancer patients. Moreover, Herceptin, a monoclonal antibody for HER2, can reduce the number of circulating tumor cells, which can be an early predictive factor for Herceptin therapy effectiveness against breast cancer.

  6. Asymmetric Cancer Hallmarks in Breast Tumors on Different Sides of the Body

    PubMed Central

    Campoy, Emanuel M.; Laurito, Sergio R.; Branham, María T.; Urrutia, Guillermo; Mathison, Angela; Gago, Francisco; Orozco, Javier; Urrutia, Raul; Mayorga, Luis S.; Roqué, María

    2016-01-01

    During the last decades it has been established that breast cancer arises through the accumulation of genetic and epigenetic alterations in different cancer related genes. These alterations confer the tumor oncogenic abilities, which can be resumed as cancer hallmarks (CH). The purpose of this study was to establish the methylation profile of CpG sites located in cancer genes in breast tumors so as to infer their potential impact on 6 CH: i.e. sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, induction of angiogenesis, genome instability and invasion and metastasis. For 51 breast carcinomas, MS-MLPA derived-methylation profiles of 81 CpG sites were converted into 6 CH profiles. CH profiles distribution was tested by different statistical methods and correlated with clinical-pathological data. Unsupervised Hierarchical Cluster Analysis revealed that CH profiles segregate in two main groups (bootstrapping 90–100%), which correlate with breast laterality (p = 0.05). For validating these observations, gene expression data was obtained by RealTime-PCR in a different cohort of 25 tumors and converted into CH profiles. This analyses confirmed the same clustering and a tendency of association with breast laterality (p = 0.15). In silico analyses on gene expression data from TCGA Breast dataset from left and right breast tumors showed that they differed significantly when data was previously converted into CH profiles (p = 0.033). We show here for the first time, that breast carcinomas arising on different sides of the body present differential cancer traits inferred from methylation and expression profiles. Our results indicate that by converting methylation or expression profiles in terms of Cancer Hallmarks, it would allow to uncover veiled associations with clinical features. These results contribute with a new finding to the better understanding of breast tumor behavior, and can moreover serve as proof of principle for other

  7. Asymmetric Cancer Hallmarks in Breast Tumors on Different Sides of the Body.

    PubMed

    Campoy, Emanuel M; Laurito, Sergio R; Branham, María T; Urrutia, Guillermo; Mathison, Angela; Gago, Francisco; Orozco, Javier; Urrutia, Raul; Mayorga, Luis S; Roqué, María

    2016-01-01

    During the last decades it has been established that breast cancer arises through the accumulation of genetic and epigenetic alterations in different cancer related genes. These alterations confer the tumor oncogenic abilities, which can be resumed as cancer hallmarks (CH). The purpose of this study was to establish the methylation profile of CpG sites located in cancer genes in breast tumors so as to infer their potential impact on 6 CH: i.e. sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, induction of angiogenesis, genome instability and invasion and metastasis. For 51 breast carcinomas, MS-MLPA derived-methylation profiles of 81 CpG sites were converted into 6 CH profiles. CH profiles distribution was tested by different statistical methods and correlated with clinical-pathological data. Unsupervised Hierarchical Cluster Analysis revealed that CH profiles segregate in two main groups (bootstrapping 90-100%), which correlate with breast laterality (p = 0.05). For validating these observations, gene expression data was obtained by RealTime-PCR in a different cohort of 25 tumors and converted into CH profiles. This analyses confirmed the same clustering and a tendency of association with breast laterality (p = 0.15). In silico analyses on gene expression data from TCGA Breast dataset from left and right breast tumors showed that they differed significantly when data was previously converted into CH profiles (p = 0.033). We show here for the first time, that breast carcinomas arising on different sides of the body present differential cancer traits inferred from methylation and expression profiles. Our results indicate that by converting methylation or expression profiles in terms of Cancer Hallmarks, it would allow to uncover veiled associations with clinical features. These results contribute with a new finding to the better understanding of breast tumor behavior, and can moreover serve as proof of principle for other

  8. Ipsilateral breast tumor recurrence after breast conservation therapy: Outcomes of salvage mastectomy vs. salvage breast-conserving surgery and prognostic factors for salvage breast preservation

    SciTech Connect

    Alpert, Tracy E.; Kuerer, Henry M.; Arthur, Douglas W.; Lannin, Donald R.; Haffty, Bruce G. . E-mail: hafftybg@umdnj.edu

    2005-11-01

    Purpose: To compare outcomes of salvage mastectomy (SM) and salvage breast-conserving surgery (SBCS) and study the feasibility of SBCS. Methods and Materials: Of 2,038 patients treated with breast-conserving therapy at Yale-New Haven Hospital before 1999, 166 sustained an ipsilateral breast tumor recurrence (IBTR). Outcomes and prognostic factors of patients treated with SM or SBCS were compared. Patients were considered amenable to SBCS if the recurrence was localized on mammogram and physical examination, and had pathologic size <3 cm, confined to the biopsy site, without skin or lymphovascular invasion, and with {<=}3 positive nodes. Results: Of the 146 patients definitively managed at IBTR, surgery was SM (n = 116) or SBCS (n 30). The median length of follow-up after IBTR was 13.8 years. The SM and SBCS cohorts had no significant differences, except at IBTR the SM cohort had a greater tumor size (p = 0.049). Of the SM cohort, 65.5% were considered appropriate for SBCS, and a localized relapse was predicted by estrogen-receptor positive, diploid, and detection of recurrence by mammogram. Multicentric disease correlated with BRCA1/2 mutation, estrogen-receptor negative, lymph node positive at relapse, and detection of recurrence by physical examination. Survival after IBTR was 64.5% at 10 years, with no significant difference between SM (65.7%) and SBCS (58.0%). Only 2 patients in the SBCS cohort subsequently had a second IBTR, and were salvaged with mastectomy. Conclusions: While mastectomy is considered the standard surgical salvage of IBTR, SBCS is feasible and prognostic factors are related to favorable tumor biology and early detection. Patients with BRCA1/2 germline mutations may be less appropriate for SBCS, as multicentric disease was more prevalent. Patients who underwent SBCS had comparable outcomes as those who underwent SM, but remain at continued risk for IBTR. A prospective trial evaluating repeat lumpectomy and partial breast reirradiation is

  9. Tumor Twitter: Cellular Communication in the Breast Cancer Stem Cell Niche

    PubMed Central

    Brooks, Michael D.; Wicha, Max S.

    2015-01-01

    Summary Communication between the diverse assortment of cells that constitute the tumor microenvironment plays an important role in tumor development. Using a p53 null mouse model, Zhang and colleagues describe a novel feedback loop involving breast cancer stem cells and their progeny mediated by Wnt2, CXCL12, and IL6. PMID:25941337

  10. ErbB3 downregulation enhances luminal breast tumor response to antiestrogens

    PubMed Central

    Morrison, Meghan M.; Hutchinson, Katherine; Williams, Michelle M.; Stanford, Jamie C.; Balko, Justin M.; Young, Christian; Kuba, Maria G.; Sánchez, Violeta; Williams, Andrew J.; Hicks, Donna J.; Arteaga, Carlos L.; Prat, Aleix; Perou, Charles M.; Earp, H. Shelton; Massarweh, Suleiman; Cook, Rebecca S.

    2013-01-01

    Aberrant regulation of the erythroblastosis oncogene B (ErbB) family of receptor tyrosine kinases (RTKs) and their ligands is common in human cancers. ErbB3 is required in luminal mammary epithelial cells (MECs) for growth and survival. Since breast cancer phenotypes may reflect biological traits of the MECs from which they originate, we tested the hypothesis that ErbB3 drives luminal breast cancer growth. We found higher ERBB3 expression and more frequent ERBB3 gene copy gains in luminal A/B breast cancers compared with other breast cancer subtypes. In cell culture, ErbB3 increased growth of luminal breast cancer cells. Targeted depletion of ErbB3 with an anti-ErbB3 antibody decreased 3D colony growth, increased apoptosis, and decreased tumor growth in vivo. Treatment of clinical breast tumors with the antiendocrine drug fulvestrant resulted in increased ErbB3 expression and PI3K/mTOR signaling. Depletion of ErbB3 in fulvestrant-treated tumor cells reduced PI3K/mTOR signaling, thus decreasing tumor cell survival and tumor growth. Fulvestrant treatment increased phosphorylation of all ErbB family RTKs; however, phospho-RTK upregulation was not seen in tumors treated with both fulvestrant and anti-ErbB3. These data indicate that upregulation of ErbB3 in luminal breast cancer cells promotes growth, survival, and resistance to fulvestrant, thus suggesting ErbB3 as a target for breast cancer treatment. PMID:23999432

  11. Pancreatic neuroendocrine tumors: clinical features, diagnosis and medical treatment: advances.

    PubMed

    Ito, Tetsuhide; Igarashi, Hisato; Jensen, Robert T

    2012-12-01

    Pancreatic neuroendocrine tumors (pNETs) comprise with gastrointestinal carcinoids, the main groups of gastrointestinal neuroendocrine tumors (GI-NETs). Although these two groups of GI-NETs share many features including histological aspects; over-/ectopic expression of somatostatin receptors; the ability to ectopically secrete hormones/peptides/amines which can result in distinct functional syndromes; similar approaches used for tumor localization and some aspects of treatment, it is now generally agreed they should be considered separate. They differ in their pathogenesis, hormonal syndromes produced, many aspects of biological behaviour and most important, in their response to certain anti-tumour treatment (chemotherapy, molecular targeted therapies). In this chapter the clinical features of the different types of pNETs will be considered as well as aspects of their diagnosis and medical treatment of the hormone-excess state. Emphasis will be on controversial areas or recent advances. The other aspects of the management of these tumors (surgery, treatment of advanced disease, tumor localization) are not dealt with here, because they are covered in other chapters in this volume.

  12. Combining support vector machine with genetic algorithm to classify ultrasound breast tumor images.

    PubMed

    Wu, Wen-Jie; Lin, Shih-Wei; Moon, Woo Kyung

    2012-12-01

    To promote the classification accuracy and decrease the time of extracting features and finding (near) optimal classification model of an ultrasound breast tumor image computer-aided diagnosis system, we propose an approach which simultaneously combines feature selection and parameter setting in this study. In our approach ultrasound breast tumors were segmented automatically by a level set method. The auto-covariance texture features and morphologic features were first extracted following the use of a genetic algorithm to detect significant features and determine the near-optimal parameters for the support vector machine (SVM) to identify the tumor as benign or malignant. The proposed CAD system can differentiate benign from malignant breast tumors with high accuracy and short feature extraction time. According to the experimental results, the accuracy of the proposed CAD system for classifying breast tumors is 95.24% and the computing time of the proposed system for calculating features of all breast tumor images is only 8% of that of a system without feature selection. Furthermore, the time of finding (near) optimal classification model is significantly than that of grid search. It is therefore clinically useful in reducing the number of biopsies of benign lesions and offers a second reading to assist inexperienced physicians in avoiding misdiagnosis.

  13. A Case of Giant Borderline Phyllodes Tumor of the Breast Associated with Hypoglycemia.

    PubMed

    Saito, Yuki; Suzuki, Yasuhiro; Inomoto, Chie; Kumaki, Nobue; Yokoyama, Kozue; Ogiya, Rin; Oshitanai, Risa; Terao, Mayako; Tsuda, Banri; Morioka, Tooru; Niikura, Naoki; Okamura, Takuho; Masuda, Shinobu; Tokuda, Yutaka

    2016-09-20

    We report a patient with a giant phyllodes tumor of the right breast associated with a hypoglycemic attack. A 48-year-old woman experienced a loss of consciousness and was transferred via ambulance to our hospital emergency department. Upon arrival, her blood glucose level was 26 mg/dl, and a giant tumor (>20 cm in diameter) with skin ulceration was observed on the right breast. Core needle biopsy led to a histological diagnosis of a phyllodes tumor of the breast. Ultrasonography and computed tomography detected neither distant metastasis nor a pancreatic endocrine tumor. Her preoperative serum insulin-like growth factor (IGF)-II and insulin levels were 1,330 ng/ml (normal range, 519-1067 ng/ml) and <1.0 µU/ml, respectively. Following a simple mastectomy, the 24-h postoperative serum IGF-II and insulin levels were 496 ng/ml and 10.0 µU/ml, respectively. The IGF-II levels detected in the phyllodes tumor and normal breast tissue were 10,600 ng/Wg (wet weight in grams) and 855 ng/Wg. We conclude from these findings that the hypoglycemic attack was related to the elevated IGF-II level in the giant phyllodes tumor of the breast.

  14. Hypoxia-inducible factor 1α promotes primary tumor growth and tumor-initiating cell activity in breast cancer

    PubMed Central

    2012-01-01

    Introduction Overexpression of the oxygen-responsive transcription factor hypoxia-inducible factor 1α (HIF-1α) correlates with poor prognosis in breast cancer patients. The mouse mammary tumor virus polyoma virus middle T (MMTV-PyMT) mouse is a widely utilized preclinical mouse model that resembles human luminal breast cancer and is highly metastatic. Prior studies in which the PyMT model was used demonstrated that HIF-1α is essential to promoting carcinoma onset and lung metastasis, although no differences in primary tumor end point size were observed. Using a refined model system, we investigated whether HIF-1α is directly implicated in the regulation of tumor-initiating cells (TICs) in breast cancer. Methods Mammary tumor epithelial cells were created from MMTV-PyMT mice harboring conditional alleles of Hif1a, followed by transduction ex vivo with either adenovirus β-galactosidase or adenovirus Cre to generate wild-type (WT) and HIF-1α-null (KO) cells, respectively. The impact of HIF-1α deletion on tumor-initiating potential was investigated using tumorsphere assays, limiting dilution transplantation and gene expression analysis. Results Efficient deletion of HIF-1α reduced primary tumor growth and suppressed lung metastases, prolonging survival. Loss of HIF-1α led to reduced expression of markers of the basal lineage (K5/K14) in cells and tumors and of multiple genes involved in the epithelial-to-mesenchymal transition. HIF-1α also enhanced tumorsphere formation at normoxia and hypoxia. Decreased expression of several genes in the Notch pathway as well as Vegf and Prominin-1 (CD133)was observed in response to Hif1a deletion. Immunohistochemistry confirmed that CD133 expression was reduced in KO cells and in tumorspheres. Tumorsphere formation was enhanced in CD133hi versus CD133neg cells sorted from PyMT tumors. Limiting dilution transplantation of WT and KO tumor cells into immunocompetent recipients revealed > 30-fold enrichment of TICs in WT cells

  15. Mapping of a Breast Carcinoma Tumor Suppressor Gene to Chromosome 11p15.5.

    DTIC Science & Technology

    1996-07-01

    Noblett, B. D., Pedone, C. A. Chromosome llp 15 deletions in human malignant astrocytomas and primitive neuroectodermal tumors . Genomics 14: 799-801...AD GRANT NUMBER: DAMDI7-94-J-4175 TITLE: Mapping of a Breast Carcinoma Tumor Suppressor Gene to Chromosome 11p15.5 PRINCIPAL INVESTIGATOR: Tracy...SUBTITLE 5. FUNDING NUMBERS Mapping of a Breast Carcinoma Tumor Suppressor Gene to Chromosome 11p15.5 DAMD17-94-J-4175 6. AUTHOR(S) Tracy Moore, Ph.D. 7

  16. Chemokine axes in breast cancer: factors of the tumor microenvironment reshape the CCR7-driven metastatic spread of luminal-A breast tumors.

    PubMed

    Weitzenfeld, Polina; Kossover, Olga; Körner, Cindy; Meshel, Tsipi; Wiemann, Stefan; Seliktar, Dror; Legler, Daniel F; Ben-Baruch, Adit

    2016-06-01

    Chemokine axes have been shown to mediate site-specific metastasis in breast cancer, but their relevance to different subtypes has been hardly addressed. Here, with the focus on the CCR7-CCL21 axis, patient datasets demonstrated that luminal-A tumors express relatively low CCR7 levels compared with more aggressive disease subtypes. Furthermore, lymph node metastasis was not associated with high CCR7 levels in luminal-A patients. The metastatic pattern of luminal-A breast tumors may be influenced by the way luminal-A tumor cells interpret signals provided by factors of the primary tumor microenvironment. Thus, CCR7-expressing human luminal-A cells were stimulated simultaneously by factors representing 3 tumor microenvironment arms typical of luminal-A tumors, hormonal, inflammatory, and growth stimulating: estrogen + TNF-α + epidermal growth factor. Such tumor microenvironment stimulation down-regulated the migration of CCR7-expressing tumor cells toward CCL21 and inhibited the formation of directional protrusions toward CCL21 in a novel 3-dimensional hydrogel system. CCL21-induced migration of CCR7-expressing tumor cells depended on PI3K and MAPK activation; however, when CCR7-expressing cancer cells were prestimulated by tumor microenvironment factors, CCL21 could not effectively activate these signaling pathways. In vivo, pre-exposure of the tumor cells to tumor microenvironment factors has put restraints on CCL21-mediated lymph node-homing cues and shifted the metastatic pattern of CCR7-expressing cells to the aggressive phenotype of dissemination to bones. Several of the aspects were also studied in the CXCR4-CXCL12 system, demonstrating similar patient and in vitro findings. Thus, we provide novel evidence to subtype-specific regulation of the CCR7-CCL21 axis, with more general implications to chemokine-dependent patterns of metastatic spread, revealing differential regulation in the luminal-A subtype.

  17. Using Computer-extracted Image Phenotypes from Tumors on Breast MRI to Predict Breast Cancer Pathologic Stage

    PubMed Central

    Burnside, Elizabeth S.; Drukker, Karen; Li, Hui; Bonaccio, Ermelinda; Zuley, Margarita; Ganott, Marie; Net, Jose M.; Sutton, Elizabeth; Brandt, Kathleen R.; Whitman, Gary; Conzen, Suzanne; Lan, Li; Ji, Yuan; Zhu, Yitan; Jaffe, Carl; Huang, Erich; Freymann, John; Kirby, Justin; Morris, Elizabeth; Giger, Maryellen

    2015-01-01

    Background To demonstrate that computer-extracted image phenotypes (CEIPs) of biopsy-proven breast cancer on MRI can accurately predict pathologic stage. Methods We used a dataset of de-identified breast MRIs organized by the National Cancer Institute in The Cancer Imaging Archive. We analyzed 91 biopsy-proven breast cancer cases with pathologic stage (stage I = 22; stage II = 58; stage III = 11) and surgically proven nodal status (negative nodes = 46, ≥ 1 positive node = 44, no nodes examined = 1). We characterized tumors by (a) radiologist measured size, and (b) CEIP. We built models combining two CEIPs to predict tumor pathologic stage and lymph node involvement, evaluated them in leave-one-out cross-validation with area under the ROC curve (AUC) as figure of merit. Results Tumor size was the most powerful predictor of pathologic stage but CEIPs capturing biologic behavior also emerged as predictive (e.g. stage I+II vs. III demonstrated AUC = 0.83). No size measure was successful in the prediction of positive lymph nodes but adding a CEIP describing tumor “homogeneity,” significantly improved this discrimination (AUC = 0.62, p=.003) over chance. Conclusions Our results indicate that MRI phenotypes show promise for predicting breast cancer pathologic stage and lymph node status. PMID:26619259

  18. Breast Adenomyoepithelioma: Ultrasonography, Elastography, Digital Mammography, Contrast-Enhanced Digital Mammography, and Pathology Findings of This Rare Type of Breast Tumor.

    PubMed

    Gkali, Christina An; Chalazonitis, Athanasios N; Feida, Eleni; Dimitrakakis, Constantine; Sotiropoulou, Maria

    2015-09-01

    Breast adenomyoepithelioma is considered as an uncommon breast tumor. It is evaluated as a variant of intraductal papilloma. The treatment of choice is local resection with free margins. It is the first case of breast adenomyoepithelioma reported with conventional ultrasonography, elastography (both free-hand and acoustic radiation force impulse imaging), digital mammography, contrast-enhanced digital mammography, and pathology findings. A 35-year-old white woman presented with a painless lump of the left breast. Treatment was local resection with free margins. There has been no recurrence for 6 months. Although breast adenomyoepithelioma is an uncommon breast tumor, its awareness is imperative because the differential diagnosis from other breast tumors is quite extensive.

  19. Tumor Specific Gene Expression and Tumor Specific Vector Replication for Systematic Chemotherapy Sensitization Treatment of Breast Cancer

    DTIC Science & Technology

    2003-07-01

    which were growing subcutaneously in severe combined immunodeficiency (SCID) mice, induced regression of these tumors. Such vectors may therefore be...positive breast cancer cells in severe combined immunodeficiency (SCID) mice. We also demonstrate that the vector that contains the tyrosinase N

  20. Blockade of PAR1 signaling with cell-penetrating pepducins inhibits Akt-survival pathways in breast cancer cells and suppresses tumor survival and metastasis

    PubMed Central

    Yang, Eric; Boire, Adrienne; Agarwal, Anika; Nguyen, Nga; O'Callaghan, Katie; Tu, Powen; Kuliopulos, Athan; Covic, Lidija

    2009-01-01

    Protease-activated receptor 1 (PAR1) is a G protein-coupled receptor that is not expressed in normal breast epithelia, but is up-regulated in invasive breast carcinomas. In the present study, we found that matrix metalloprotease-1 (MMP-1) robustly activates the PAR1-Akt survival pathway in breast carcinoma cells. This process is blocked by a cell-penetrating lipopeptide ‘pepducin’, P1pal-7, which is a potent inhibitor of cell viability in breast carcinoma cells expressing PAR1. Both a MMP-1 inhibitor and P1pal-7 significantly promote apoptosis in breast tumor xenografts and inhibit metastasis to the lungs by up to 88%. Dual therapy with P1pal-7 and taxotere inhibits the growth of MDA-MB-231 xenografts by 95%. Consistently, biochemical analysis of xenograft tumors treated with P1pal-7 or MMP-1 inhibitor demonstrated attenuated Akt activity. Ectopic expression of constitutively active Akt rescues breast cancer cells from the synergistic cytotoxicity of P1pal-7 and taxotere, suggesting that Akt is a critical component of PAR1-dependent cancer cell viability. Together, these findings indicate that blockade of MMP1-PAR1 signaling may provide a benefit beyond treatment with taxotere alone in advanced, metastatic breast cancer. PMID:19622769

  1. Phyllodes Tumor of the Breast With Malignant Melanoma Component: A Case Report.

    PubMed

    Vergine, Marco; Guy, Catherine; Taylor, Mark R

    2015-09-01

    Phyllodes tumors of the breast display a wide variation in histological appearance and are classified into benign, borderline, and malignant categories based on a combination of histological parameters. These tumors may include a malignant heterologous component that is believed to originate through a process of multidirectional differentiation from a cancer stem cell. In these cases, the tumor is classified as a malignant phyllodes tumor. Among the heterologous elements that have been described in malignant phyllodes tumors are rhabdomyosarcoma, chondrosarcoma, osteosarcoma, liposarcoma and angiosarcoma. We present the first case of a phyllodes tumor with a malignant melanoma component in the breast of a 71-year-old lady, discussing the clinical implications of this diagnosis.

  2. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study

    SciTech Connect

    Schaake-Koning, C.; van der Linden, E.H.; Hart, G.; Engelsman, E.

    1985-10-01

    Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together. LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results. In conclusion: adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer.

  3. p53 deficiency induces cancer stem cell pool expansion in a mouse model of triple-negative breast tumors.

    PubMed

    Chiche, A; Moumen, M; Romagnoli, M; Petit, V; Lasla, H; Jézéquel, P; de la Grange, P; Jonkers, J; Deugnier, M-A; Glukhova, M A; Faraldo, M M

    2016-10-24

    Triple-negative breast cancer is a heterogeneous disease characterized by the expression of basal cell markers, no estrogen or progesterone receptor expression and a lack of HER2 overexpression. Triple-negative tumors often display activated Wnt/β-catenin signaling and most have impaired p53 function. We studied the interplay between p53 loss and Wnt/β-catenin signaling in stem cell function and tumorigenesis, by deleting p53 from the mammary epithelium of K5ΔNβcat mice displaying a constitutive activation of Wnt/β-catenin signaling in basal cells. K5ΔNβcat transgenic mice present amplification of the basal stem cell pool and develop triple-negative mammary carcinomas. The loss of p53 in K5ΔNβcat mice led to an early expansion of mammary stem/progenitor cells and accelerated the formation of triple-negative tumors. In particular, p53-deficient tumors expressed high levels of integrins and extracellular matrix components and were enriched in cancer stem cells. They also overexpressed the tyrosine kinase receptor Met, a feature characteristic of human triple-negative breast tumors. The inhibition of Met kinase activity impaired tumorsphere formation, demonstrating the requirement of Met signaling for cancer stem cell growth in this model. Human basal-like breast cancers with predicted mutated p53 status had higher levels of MET expression than tumors with wild-type p53. These results connect p53 loss and β-catenin activation to stem cell regulation and tumorigenesis in triple-negative cancer and highlight the role of Met signaling in maintaining cancer stem cell properties, revealing new cues for targeted therapies.Oncogene advance online publication, 24 October 2016; doi:10.1038/onc.2016.396.

  4. The class I HDAC inhibitor Romidepsin targets inflammatory breast cancer tumor emboli and synergizes with paclitaxel to inhibit metastasis.

    PubMed

    Robertson, Fredika M; Chu, Khoi; Boley, Kimberly M; Ye, Zaiming; Liu, Hui; Wright, Moishia C; Moraes, Ricardo; Zhang, Xuejun; Green, Tessa L; Barsky, Sanford H; Heise, Carla; Cristofanilli, Massimo

    2013-01-01

    Inflammatory breast cancer (IBC) is the most metastatic variant of locally advanced breast cancer. IBC has distinctive characteristics including invasion of tumor emboli into the skin and rapid disease progression. Given our previous studies suggesting that HDAC inhibitors have promise in targeting IBC, the present study revealed that the class I HDAC inhibitor Romidepsin (FK-288, Istodax; Celgene Corporation, Summit, NJ) potently induced destruction of IBC tumor emboli and lymphatic vascular architecture. associated with inhibition of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1alpha, (HIF1alpha) proteins in the Mary-X pre-clinical model of IBC. Romidepsin treatment induced clinically relevant biomarkers in including induction of acetylated Histone 3 (Ac-H3) proteins, apoptosis, and increased p21WAF1/CIP1. Romidepsin, alone and synergistically when combined with Paclitaxel, effectively eliminated both primary tumors and metastatic lesions at multiple sites formed by the SUM149 IBC cell line. This is the first report of the ability of an HDAC inhibitor to eradicate IBC tumor emboli, to destroy the integrity of lymphatic vessel architecture and to target metastasis. Furthermore, Romidepsin, in combination with a taxane, warrants evaluation as a therapeutic strategy that may effectively target the skin involvement and rapid metastasis that are hallmarks of IBC.

  5. Assessing Vascular Oxygen Dynamics for Breast Tumor Prognosis: Comparison Between MR BOLD and Near Infrared Method

    DTIC Science & Technology

    2005-09-01

    channel NIR system against the fiber optic needle measurements . Aim 2: To compare and correlate the measurement results of the breast tumors under...Kodibagkar, Anca Constantinescu, Ralph Mason, “Tumor oxygen dynamics measured simultaneously by near-infrared spectroscopy and MR EPI imaging,” in...tumors measured by NIR spectroscopy and 19 F MRS of PFOB,” OSA Biomedical Topical Meetings, Technical Digest, SuH5, Miami Beach, FL, April 7-10, 2002

  6. Epidemiologic Investigation of a Cluster of Cystosarcoma Phyllode Tumors of the Female Breast

    DTIC Science & Technology

    1995-09-14

    ABSTRACT (Maximum 200 words) Cystosarcoma phyllodes is an uncommon breast neoplasm. It is a fibroepithelial tumor composed of an epithelial and a...cellular stromal component. A significant number of cases of cystosarcoma phyllodes tumors were diagnosed over the last several years at a single hospital...the number expected, with a total of 97 women diagnosed with new tumors since 1987. However, the incidence of cystosarcoma phyllodes does not appear

  7. Epidemiologic Investigation of a Cluster of Cystosarcoma Phyllodes Tumors of the Female Breast

    DTIC Science & Technology

    1998-09-01

    An epidemiologic investigation of a cluster of cases of phyllodes tumors of the female breast was undertaken. A total of 114 cases with biopsy...confirmation have been identified. Most were in northern New Jersey. The occurrence of multiple primary phyllodes tumors in a single patient was found to be...significantly more frequent than in prior series. Investigations concerning phyllodes tumor occurrence in neighboring counties did not reveal any

  8. Defining Tumor Cell and Immune Cell Behavior in Vivo during Pulmonary Metastasis of Breast Cancer

    DTIC Science & Technology

    2014-09-01

    outcome of which is still to be determined. 15. SUBJECT TERMS Lung Metastasis, Intravital Imaging , Tumor Immunology, Tumor Microparticles 16. SECURITY...metastatic fitness in the lung. 2) KEYWORDS: Metastasis, Intravital Imaging , Lung, Breast Cancer, 3) ACCOMPLISHMENTS: What were the major goals of the... intravital imaging of Lung Metastasis b) Characterization of Tumor Cell Behavior During Pulmonary Seeding via 2-photon microscopy c) Characterization of

  9. Automated detection of breast tumor in MRI and comparison of kinetic features for assessing tumor response to chemotherapy

    NASA Astrophysics Data System (ADS)

    Aghaei, Faranak; Tan, Maxine; Zheng, Bin

    2015-03-01

    Dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI) is used increasingly in diagnosis of breast cancer and assessment of treatment efficacy in current clinical practice. The purpose of this preliminary study is to develop and test a new quantitative kinetic image feature analysis method and biomarker to predict response of breast cancer patients to neoadjuvant chemotherapy using breast MR images acquired before the chemotherapy. For this purpose, we developed a computer-aided detection scheme to automatically segment breast areas and tumors depicting on the sequentially scanned breast MR images. From a contrast-enhancement map generated by subtraction of two image sets scanned pre- and post-injection of contrast agent, our scheme computed 38 morphological and kinetic image features from both tumor and background parenchymal regions. We applied a number of statistical data analysis methods to identify effective image features in predicting response of the patients to the chemotherapy. Based on the performance assessment of individual features and their correlations, we applied a fusion method to generate a final image biomarker. A breast MR image dataset involving 68 patients was used in this study. Among them, 25 had complete response and 43 had partially response to the chemotherapy based on the RECIST guideline. Using this image feature fusion based biomarker, the area under a receiver operating characteristic curve is AUC = 0.850±0.047. This study demonstrated that a biomarker developed from the fusion of kinetic image features computed from breast MR images acquired pre-chemotherapy has potentially higher discriminatory power in predicting response of the patients to the chemotherapy.

  10. Hypercholesterolemia induces angiogenesis and accelerates growth of breast tumors in vivo.

    PubMed

    Pelton, Kristine; Coticchia, Christine M; Curatolo, Adam S; Schaffner, Carl P; Zurakowski, David; Solomon, Keith R; Moses, Marsha A

    2014-07-01

    Obesity and metabolic syndrome are linked to an increased prevalence of breast cancer among postmenopausal women. A common feature of obesity, metabolic syndrome, and a Western diet rich in saturated fat is a high level of circulating cholesterol. Epidemiological reports investigating the relationship between high circulating cholesterol levels, cholesterol-lowering drugs, and breast cancer are conflicting. Here, we modeled this complex condition in a well-controlled, preclinical animal model using innovative isocaloric diets. Female severe combined immunodeficient mice were fed a low-fat/no-cholesterol diet and then randomized to four isocaloric diet groups: low-fat/no-cholesterol diet, with or without ezetimibe (cholesterol-lowering drug), and high-fat/high-cholesterol diet, with or without ezetimibe. Mice were implanted orthotopically with MDA-MB-231 cells. Breast tumors from animals fed the high-fat/high-cholesterol diet exhibited the fastest progression. Significant differences in serum cholesterol level between groups were achieved and maintained throughout the study; however, no differences were observed in intratumoral cholesterol levels. To determine the mechanism of cholesterol-induced tumor progression, we analyzed tumor proliferation, apoptosis, and angiogenesis and found a significantly greater percentage of proliferating cells from mice fed the high-fat/high-cholesterol diet. Tumors from hypercholesterolemic animals displayed significantly less apoptosis compared with the other groups. Tumors from high-fat/high-cholesterol mice had significantly higher microvessel density compared with tumors from the other groups. These results demonstrate that hypercholesterolemia induces angiogenesis and accelerates breast tumor growth in vivo.

  11. Rare case of breast tumor secondary to rectal adenocarcinoma.

    PubMed

    Sanchez, Lisette Delgado; Chelliah, Thandavababu; Meisher, Irina; Niranjan, Selvanayagam

    2008-10-01

    Primary breast cancer is the most common malignancy in women. Metastatic cancer to the breast is very rare. Colorectal cancers usually metastasize to the liver and the lung; other sites of metastasis from colon cancer are uncommon and are usually found in association with extensive liver and/or lung metastases. This is a report of a rare case of aggressive rectal cancer with metastasis to the breast without liver or lung metastases.

  12. Occult Primary Neuroendocrine Tumor Metastasis to the Breast Detected on Screening Mammogram

    PubMed Central

    Policeni, Fabiana; Pakalniskis, Brittany; Yang, Limin

    2016-01-01

    Metastatic tumors are rare in the breast. Well-differentiated neuroendocrine tumors (WDNETs) are slow-growing neoplasms that arise from neuroendocrine cells, particularly in the gastrointestinal tract and bronchial tree. Metastatic WDNET to the breast is a rare entity. We present a case report of ileal WDNET metastatic to the breast which was initially identified as a small mass in the patient's left breast on screening mammography. Targeted ultrasound identified a suspicious mass, and ultrasound-guided percutaneous core biopsy was performed. Pathology revealed metastatic WDNET. Breast magnetic resonance imaging (MRI) was then performed and demonstrated left axillary Level 2 lymphadenopathy, and liver lesions were suspicious for metastasis. The patient underwent abdominal computed tomography (CT) to evaluate for distant metastatic disease. A spiculated mass was found near the ileocecal valve, suggestive of primary ileal WDNET. In addition, CT identified multiple liver lesions, most compatible with metastasis. Indium 111 OctreoScan confirmed radiotracer uptake in the ileum consistent with primary neuroendocrine tumor. In this report, we review the imaging characteristics of metastatic WDNET to the breast by different imaging modalities including mammogram, ultrasound, and breast MRI. PMID:27761301

  13. Ultrashort Microwave-Pumped Real-Time Thermoacoustic Breast Tumor Imaging System.

    PubMed

    Ye, Fanghao; Ji, Zhong; Ding, Wenzheng; Lou, Cunguang; Yang, Sihua; Xing, Da

    2016-03-01

    We report the design of a real-time thermoacoustic (TA) scanner dedicated to imaging deep breast tumors and investigate its imaging performance. The TA imaging system is composed of an ultrashort microwave pulse generator and a ring transducer array with 384 elements. By vertically scanning the transducer array that encircles the breast phantom, we achieve real-time, 3D thermoacoustic imaging (TAI) with an imaging speed of 16.7 frames per second. The stability of the microwave energy and its distribution in the cling-skin acoustic coupling cup are measured. The results indicate that there is a nearly uniform electromagnetic field in each XY-imaging plane. Three plastic tubes filled with salt water are imaged dynamically to evaluate the real-time performance of our system, followed by 3D imaging of an excised breast tumor embedded in a breast phantom. Finally, to demonstrate the potential for clinical applications, the excised breast of a ewe embedded with an ex vivo human breast tumor is imaged clearly with a contrast of about 1:2.8. The high imaging speed, large field of view, and 3D imaging performance of our dedicated TAI system provide the potential for clinical routine breast screening.

  14. A Trial of PT2977 Tablets In Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2016-12-22

    Advanced Solid Tumors; Solid Tumor; Solid Carcinoma; Solid Tumor, Adult; ccRCC; RCC, Clear Cell Adenocarcinoma; RCC; Kidney Cancer; Clear Cell Renal Cell Carcinoma; Renal Cell Carcinoma, Metastatic; Renal Cell Carcinoma Recurrent; Renal Cell Carcinoma, Clear Cell Adenocarcinoma

  15. The joint contribution of tumor phenotype and education to breast cancer survival disparity between Hispanic and non-Hispanic white women.

    PubMed

    Boone, S D; Baumgartner, K B; Joste, N E; Pinkston, C M; Yang, D; Baumgartner, R N

    2014-03-01

    Some studies suggest that Hispanic women are more likely to have ER- and triple-negative (ER-/PR-/HER2-) tumors and subsequently poorer prognosis than non-Hispanic white (NHW) women. In addition, only a handful of studies have examined period-specific effects of tumor phenotype and ethnicity on breast cancer survival, leaving the time-varying effects of hormonal status and ethnicity on breast cancer survival poorly defined. This study describes short and long-term breast cancer survival by ethnicity at 0-5 years and 5+ years post-diagnosis using data from the New Mexico Health, Eating, Activity, and Lifestyle cohort of Hispanic and NHW women ages 29-88 years newly diagnosed with stages I-IIIA breast cancer. The survival rate for Hispanics at 0-5 years was 82.2 % versus 94.3 % for NHW. Hispanics were more likely to have larger tumors, more advanced stage, and ER- phenotypes compared to NHW women. There was a significantly higher risk of breast cancer mortality in Hispanics over 5 years of follow-up compared to NHW (HR = 2.78, 95 % CI 1.39-5.56), adjusting for age, tumor phenotype, stage, and tumor size. This ethnic difference in survival, however, was attenuated and no longer statistically significant when additional adjustment was made for education, although a >1.5-fold increase in mortality was observed. In contrast, there was no difference between ethnic groups for survival after 5 years (HR = 1.08, 95 % CI 0.36-3.24). Our results indicate that the difference in survival between Hispanic and NHW women with breast cancer occurs in the first few years following diagnosis and is jointly associated with tumor phenotype and socio-demographic factors related to education.

  16. Chemotherapy enhances tumor vascularization via Notch signaling-mediated formation of tumor-derived endothelium in breast cancer.

    PubMed

    Zhang, Peng; He, Dongxu; Chen, Zhen; Pan, Qiongxi; Du, Fangfang; Zang, Xian; Wang, Yan; Tang, Chunlei; Li, Hong; Lu, He; Yao, Xiaoqiang; Jin, Jian; Ma, Xin

    2016-10-15

    It is believed that tumor cells can give rise to endothelial cells and tumor endothelium has a neoplastic origin. Yet, the stimuli and underlying mechanism remain unclear. Here, we demonstrate that adriamycin or paclitaxel, first-line chemotherapy agent, induced breast cancer cells to generate morphological, phenotypical and functional features of endothelial cells in vitro. In xenografts models, challenges from adriamycin or paclitaxel induced cancer cells to generate the majority of microvessels. Importantly, in breast cancer specimens from patients with neoadjuvant anthracycline-based or taxane-based chemotherapy, tumor-derived endothelial microvessels, lined by EGFR-amplified or/and TP53(+)-CD31(+) endothelial cells, was significantly higher in patients with progressive or stable disease (PD/SD) than in those with a partial or complete response (PR/CR). Further, exposure to the Notch signaling inhibitor and gene silencing studies showed that Notch signaling inhibition or silencing Nothc4/Dll3 decreased endothelial markers and function of tumor-derived endothelial cells under chemotherapy treatment, which may be through VEGFR3. Thus, our findings demonstrate that chemotherapy induces functional tumor-derived endothelial microvessels by mediating Notch signaling and VEGF signaling, and may provide new targets for anti-angiogenesis therapy in breast cancer.

  17. Expected resolution and detectability of adenocarcinoma tumors within human breast in time-resolved images

    NASA Astrophysics Data System (ADS)

    Gandjbakhche, Amir H.; Nossal, Ralph J.; Dadmarz, Roya; Schwartzentruber, Douglas; Bonner, Robert F.

    1995-04-01

    The prospects for time-resolved optical mammography rests on the ability to detect adenocarcinoma within the breast with sufficient resolution and specificity to compete with X-ray mammography. We characterized the optical properties of an unusually large (6 cm diameter) fresh adenocarcinoma and normal breast tissue (determined by histology to be predominantly adipose tissue) obtained from a patient undergoing mastectomy. Large specimens (5 mm thick and 3 cm wide) allowed the determination of absorption and scattering coefficients and their spatial heterogeneity as probed with a 1 mm diameter laser beam at 633 nm and 800 nm utilizing total reflectance and transmittance measure with integrating spheres. The difference between scattering coefficients of the malignant tumor and those of normal (principally adipose) breast tissue at 633 nm was much greater than the heterogeneity within each sample. This scattering difference is the principal source of contrast, particularly in time-resolved images. However, the high scattering coefficient of normal breast tissue at 633 nm limits the practicality of time-resolved mammography of a human breast compressed to 5 cm. Although the scattering coefficient of the normal breast tissue decreases at 800 nm, the differences between the optical properties of normal and abnormal breast tissue also are reduced. We used these empirical results in theoretical expressions obtained from random walk theory to quantify the expected resolution, contrast, and the detected intensity of 3, 6, and 9 mm tumors within otherwise homogeneous human breasts as a function of the gating-time of time-resolved optical mammography.

  18. Claudin-2 promotes breast cancer liver metastasis by facilitating tumor cell interactions with hepatocytes.

    PubMed

    Tabariès, Sébastien; Dupuy, Fanny; Dong, Zhifeng; Monast, Anie; Annis, Matthew G; Spicer, Jonathan; Ferri, Lorenzo E; Omeroglu, Atilla; Basik, Mark; Amir, Eitan; Clemons, Mark; Siegel, Peter M

    2012-08-01

    We previously identified claudin-2 as a functional mediator of breast cancer liver metastasis. We now confirm that claudin-2 levels are elevated in liver metastases, but not in skin metastases, compared to levels in their matched primary tumors in patients with breast cancer. Moreover, claudin-2 is specifically expressed in liver-metastatic breast cancer cells compared to populations derived from bone or lung metastases. The increased liver tropism exhibited by claudin-2-expressing breast cancer cells requires claudin-2-mediated interactions between breast cancer cells and primary hepatocytes. Furthermore, the reduction of the claudin-2 expression level, either in cancer cells or in primary hepatocytes, diminishes these heterotypic cell-cell interactions. Finally, we demonstrate that the first claudin-2 extracellular loop is essential for mediating tumor cell-hepatocyte interactions and the ability of breast cancer cells to form liver metastases in vivo. Thus, during breast cancer liver metastasis, claudin-2 shifts from acting within tight-junctional complexes to functioning as an adhesion molecule between breast cancer cells and hepatocytes.

  19. The CD44+/CD24- phenotype is enriched in basal-like breast tumors

    PubMed Central

    Honeth, Gabriella; Bendahl, Pär-Ola; Ringnér, Markus; Saal, Lao H; Gruvberger-Saal, Sofia K; Lövgren, Kristina; Grabau, Dorthe; Fernö, Mårten; Borg, Åke; Hegardt, Cecilia

    2008-01-01

    Introduction Human breast tumors are heterogeneous and consist of phenotypically diverse cells. Breast cancer cells with a CD44+/CD24- phenotype have been suggested to have tumor-initiating properties with stem cell-like and invasive features, although it is unclear whether their presence within a tumor has clinical implications. There is also a large heterogeneity between tumors, illustrated by reproducible stratification into various subtypes based on gene expression profiles or histopathological features. We have explored the prevalence of cells with different CD44/CD24 phenotypes within breast cancer subtypes. Methods Double-staining immunohistochemistry was used to quantify CD44 and CD24 expression in 240 human breast tumors for which information on other tumor markers and clinical characteristics was available. Gene expression data were also accessible for a cohort of the material. Results A considerable heterogeneity in CD44 and CD24 expression was seen both between and within tumors. A complete lack of both proteins was evident in 35% of the tumors, while 13% contained cells of more than one of the CD44+/CD24-, CD44-/CD24+ and CD44+/CD24+ phenotypes. CD44+/CD24- cells were detected in 31% of the tumors, ranging in proportion from only a few to close to 100% of tumor cells. The CD44+/CD24- phenotype was most common in the basal-like subgroup – characterized as negative for the estrogen and progesterone receptors as well as for HER2, and as positive for cytokeratin 5/14 and/or epidermal growth factor receptor, and particularly common in BRCA1 hereditary tumors, of which 94% contained CD44+/CD24- cells. The CD44+/CD24- phenotype was surprisingly scarce in HER2+ tumors, which had a predominantly CD24+ status. A CD44+/CD24- gene expression signature was generated, which included CD44 and α6-integrin (CD49f) among the top-ranked overexpressed genes. Conclusion We demonstrate an association between basal-like and particularly BRCA1 hereditary breast cancer and

  20. Rottlerin exerts its anti-tumor activity through inhibition of Skp2 in breast cancer cells

    PubMed Central

    Hou, Yingying; Wang, Lixia; Ye, Xiantao; Zhao, Zhe; Zhou, Xiuxia; Li, Yali; Wang, Zhiwei

    2016-01-01

    Studies have investigated the tumor suppressive role of rottlerin in carcinogenesis. However, the molecular mechanisms of rottlerin-induced anti-tumor activity are largely unclear. Skp2 (S-phase kinase associated protein 2) has been validated to play an oncogenic role in a variety of human malignancies. Therefore, inactivation of Skp2 could be helpful for the treatment of human cancers. In the current study, we explore whether rottlerin could inhibit Skp2 expression, leading to inhibition of cell growth, migration and invasion in breast cancer cells. We found that rottlerin treatment inhibited cell growth, induced apoptosis and cell cycle arrest. We also revealed that rottlerin suppressed cell migration and invasion in breast cancer cells. Mechanically, we observed that rottlerin significantly down-regulated the expression of Skp2 in breast cancer cells. Importantly, overexpression of Skp2 abrogated rottlerin-mediated tumor suppressive activity, whereas down-regulation of Skp2 enhanced rottlerin-triggered anti-tumor function. Strikingly, we identified that rottlerin exhibited its anti-tumor potential partly through inactivation of Skp2 in breast cancer. Our findings indicate that rottlerin could be a potential safe agent for the treatment of breast cancer. PMID:27582552

  1. Unusual malignant tumors of the breast: MRI features and pathologic correlation.

    PubMed

    Linda, Anna; Zuiani, Chiara; Girometti, Rossano; Londero, Viviana; Machin, Piernicola; Brondani, Giovanni; Bazzocchi, Massimo

    2010-08-01

    Unusual malignant breast tumors are well-differentiated subtypes of invasive ductal carcinoma, including mucinous, tubular, medullary and papillary carcinomas, and account for about 10% of malignant breast tumors. They are increasingly being encountered during magnetic resonance imaging (MRI) examinations of the breast. Therefore, breast radiologists should be aware of their appearance on MRI. This review provides an overview of MRI characteristics of a range of unusual tumors (mucinous carcinoma, medullary carcinoma, tubular carcinoma, intraductal papillary carcinoma, intracystic papillary carcinoma and invasive papillary carcinoma), highlighting specific clues for diagnosis and correlating MRI and pathologic features. Many unusual breast tumors exhibit MRI features similar to those of benign or low suspicious lesions (oval shape, well-defined margins, high signal intensity on T2-weighted images, continuous increase kinetics, i.e. type I dynamic curve), leading to a possible misdiagnosis. Nevertheless, an understanding of pathologic features of these tumors, especially tissue content (mucinous, fibrous) and growth pattern, can help to define some specific clues for their diagnosis.

  2. Effect of Obesity and Chronic Inflammation on TRAIL-Based Immunotherapy for Advanced Breast Cancer

    DTIC Science & Technology

    2014-04-01

    Inflammation on TRAIL-Based Immunotherapy for Advanced Breast Cancer PRINCIPAL INVESTIGATOR: Thomas S. Griffith, Ph.D. CONTRACTING ORGANIZATION...CONTRACT NUMBER Immunotherapy for Advanced Breast Cancer 5b. GRANT NUMBER W81XWH-11-1-0271 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Thomas...increased risk of developing cancers , including breast cancer . The reasons for this are likely complex and multi- factorial, but a state of generalized

  3. Ranitidine modifies myeloid cell populations and inhibits breast tumor development and spread in mice

    PubMed Central

    Vila-Leahey, Ava; Oldford, Sharon A.; Marignani, Paola A.; Wang, Jun; Haidl, Ian D.; Marshall, Jean S.

    2016-01-01

    ABSTRACT Histamine receptor 2 (H2) antagonists are widely used clinically for the control of gastrointestinal symptoms, but also impact immune function. They have been reported to reduce tumor growth in established colon and lung cancer models. Histamine has also been reported to modify populations of myeloid-derived suppressor cells (MDSCs). We have examined the impact of the widely used H2 antagonist ranitidine, on both myeloid cell populations and tumor development and spread, in three distinct models of breast cancer that highlight different stages of cancer progression. Oral ranitidine treatment significantly decreased the monocytic MDSC population in the spleen and bone marrow both alone and in the context of an orthotopic breast tumor model. H2 antagonists ranitidine and famotidine, but not H1 or H4 antagonists, significantly inhibited lung metastasis in the 4T1 model. In the E0771 model, ranitidine decreased primary tumor growth while omeprazole treatment had no impact on tumor development. Gemcitabine treatment prevented the tumor growth inhibition associated with ranitidine treatment. In keeping with ranitidine-induced changes in myeloid cell populations in non-tumor-bearing mice, ranitidine also delayed the onset of spontaneous tumor development, and decreased the number of tumors that developed in LKB1−/−/NIC mice. These results indicate that ranitidine alters monocyte populations associated with MDSC activity, and subsequently impacts breast tumor development and outcome. Ranitidine has potential as an adjuvant therapy or preventative agent in breast cancer and provides a novel and safe approach to the long-term reduction of tumor-associated immune suppression. PMID:27622015

  4. Salinomycin efficiency assessment in non-tumor (HB4a) and tumor (MCF-7) human breast cells.

    PubMed

    Niwa, Andressa Megumi; D Epiro, Gláucia Fernanda Rocha; Marques, Lilian Areal; Semprebon, Simone Cristine; Sartori, Daniele; Ribeiro, Lúcia Regina; Mantovani, Mário Sérgio

    2016-06-01

    The search for anticancer drugs has led researchers to study salinomycin, an ionophore antibiotic that selectively destroys cancer stem cells. In this study, salinomycin was assessed in two human cell lines, a breast adenocarcinoma (MCF-7) and a non-tumor breast cell line (HB4a), to verify its selective action against tumor cells. Real-time assessment of cell proliferation showed that HB4a cells are more resistant to salinomycin than MCF-7 tumor cell line, and these data were confirmed in a cytotoxicity assay. The half maximal inhibitory concentration (IC50) values show the increased sensitivity of MCF-7 cells to salinomycin. In the comet assay, only MCF-7 cells showed the induction of DNA damage. Flow cytometric analysis showed that cell death by apoptosis/necrosis was only induced in the MCF-7 cells. The increased expression of GADD45A and CDKN1A genes was observed in all cell lines. Decreased expression of CCNA2 and CCNB1 genes occurred only in tumor cells, suggesting G2/M cell cycle arrest. Consequently, cell death was activated in tumor cells through strong inhibition of the antiapoptotic genes BCL-2, BCL-XL, and BIRC5 genes in MCF-7 cells. These data demonstrate the selectivity of salinomycin in killing human mammary tumor cells. The cell death observed only in MCF-7 tumor cells was confirmed by gene expression analysis, where there was downregulation of antiapoptotic genes. These data contribute to clarifying the mechanism of action of salinomycin as a promising antitumor drug and, for the first time, we observed the higher resistance of HB4a non-tumor breast cells to salinomycin.

  5. Use and duration of chemotherapy in patients with metastatic breast cancer according to tumor subtype and line of therapy.

    PubMed

    Seah, Davinia S E; Luis, Ines Vaz; Macrae, Erin; Sohl, Jessica; Litsas, Georgia; Winer, Eric P; Lin, Nancy U; Burstein, Harold J

    2014-01-01

    Benefits of chemotherapy vary in patients with metastatic breast cancer (MBC). This article describes the impact of tumor subtype and the line of therapy on the duration of chemotherapy. Clinicopathologic characteristics were extracted from the medical records of 199 consecutive patients with MBC at Dana-Farber Cancer Institute and analyzed according to subtype. Tumor subtypes were classified as hormone receptor (HR)-positive, triple-negative (TNBC), or HER2-amplified breast cancer. Duration of chemotherapy of each line was defined as the start of a chemotherapy regimen to the start of the next line of therapy as a result of progression or toxicity. There were 96, 44, and 59 patients with HR(+), TNBC, and HER2-amplified breast cancer, respectively. Median age at MBC diagnosis was 53 years. Median overall survivals were 32 and 54 months for HER2-amplified disease, 36 months for HR(+) breast cancer, and 17 months for TNBC (P<.0001). Patients with HER2-amplified disease received the most lines (median, 4; P=.032) and the longest duration of chemotherapy for every line. The median duration of chemotherapy in HER2-amplified patients remained at more than 4 months even out to sixth-line therapy. Patients with TNBC tended to receive the shortest duration of chemotherapy for every line of therapy. Tumor subtypes influence the number of lines, duration of chemotherapy, and survival. Among patients with HR(+) and HER2-amplified disease who undergo chemotherapy beyond the third line, substantial rates of prolonged therapies suggest clinical benefit. The role of advanced (greater than third) chemotherapy lines in improving survival of all patients with MBC warrants further study.

  6. Natural and adaptive IgM antibodies in the recognition of tumor-associated antigens of breast cancer (Review)

    PubMed Central

    DÍAZ-ZARAGOZA, MARIANA; HERNÁNDEZ-ÁVILA, RICARDO; VIEDMA-RODRÍGUEZ, RUBÍ; ARENAS-ARANDA, DIEGO; OSTOA-SALOMA, PEDRO

    2015-01-01

    For early detection of cancer, education and screening are important, but the most critical factor is the development of early diagnostic tools. Methods that recognize the warning signs of cancer and take prompt action lead to an early diagnosis; simple tests can identify individuals in a healthy population who have the disease but have not developed symptoms. Early detection of cancer is significant and is one of the most promising approaches by which to reduce the growing cancer burden and guide curative treatment. The early diagnosis of patients with breast cancer is challenging, since it is the most common cancer in women worldwide. Despite the advent of mammography in screening for breast cancer, low-resource, low-cost alternative tools must be implemented to complement mammography findings. IgM is part of the first line of defense of an organism and is responsible for recognizing and eliminating infectious particles and removing transformed cells. Most studies on breast cancer have focused on the development of IgG-like molecules as biomarkers or as a treatment for the advanced stages of cancer, but autoantibodies (IgM) and tumor-associated antigens (proteins or carbohydrates with aberrant structures) have not been examined as early diagnostic tools for breast cancer. The present review summarizes the function of natural and adaptive IgM in eliminating cancer cells in the early stages of pathology and their value as early diagnostic tools. IgM, as a component of the immune system, is being used to identify tumor-associated antigens and tumor-associated carbohydrate antigens. PMID:26133558

  7. Hypothesized role of pregnancy hormones on HER2+ breast tumor development.

    PubMed

    Cruz, Giovanna I; Martínez, María Elena; Natarajan, Loki; Wertheim, Betsy C; Gago-Dominguez, Manuela; Bondy, Melissa; Daneri-Navarro, Adrian; Meza-Montenegro, María Mercedes; Gutierrez-Millan, Luis Enrique; Brewster, Abenaa; Schedin, Pepper; Komenaka, Ian K; Castelao, J Esteban; Carracedo, Angel; Redondo, Carmen M; Thompson, Patricia A

    2013-01-01

    Breast cancer incidence rates have declined among older but not younger women; the latter are more likely to be diagnosed with breast cancers carrying a poor prognosis. Epidemiological evidence supports an increase in breast cancer incidence following pregnancy with risk elevated as much as 10 years post-partum. We investigated the association between years since last full-term pregnancy at the time of diagnosis (≤10 or >10 years) and breast tumor subtype in a case series of premenopausal Hispanic women (n = 627). Participants were recruited in the United States, Mexico, and Spain. Cases with known estrogen receptor (ER), progesterone receptor (PR), and HER2 status, with one or more full-term pregnancies ≥1 year prior to diagnosis were eligible for this analysis. Cases were classified into three tumor subtypes according to hormone receptor (HR+ = ER+ and/or PR+; HR- = ER- and PR-) expression and HER2 status: HR+/HER2-, HER2+ (regardless of HR), and triple negative breast cancer. Case-only odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for HER2+ tumors in reference to HR+/HER2- tumors. Participants were pooled in a mixed-effects logistic regression model with years since pregnancy as a fixed effect and study site as a random effect. When compared to HR+/HER2- cases, women with HER2+ tumors were more likely be diagnosed in the post-partum period of ≤10 years (OR = 1.68; 95 % CI, 1.12-2.52). The effect was present across all source populations and independent of the HR status of the HER2+ tumor. Adjusting for age at diagnosis (≤45 or >45 years) did not materially alter our results (OR = 1.78; 95 % CI, 1.08-2.93). These findings support the novel hypothesis that factors associated with the post-partum breast, possibly hormonal, are involved in the development of HER2+ tumors.

  8. STC1 expression is associated with tumor growth and metastasis in breast cancer.

    PubMed

    Chang, Andy C-M; Doherty, Judy; Huschtscha, Lily I; Redvers, Richard; Restall, Christina; Reddel, Roger R; Anderson, Robin L

    2015-01-01

    Stanniocalcin-1 (STC1) is a secreted glycoprotein implicated in several pathologies including retinal degeneration, cerebral ischemia, angiogenesis and inflammation. Aberrant STC1 expression has been reported in breast cancer but the significance of this is not clear. High levels of STC1 expression were found in the aggressive 4T1 murine mammary tumor cells and in the MDA-MB-231 human breast cancer line. To investigate its significance, stable clones with STC1 down-regulation using shRNA were generated in both tumor models. The consequences of STC1 down-regulation on cell proliferation, chemotactic invasion, tumor growth and metastasis were assessed. Down-regulation of STC1 in the 4T1 murine mammary tumor cells had a major impact on mammary tumor growth. This observation was replicated in a second tumor model with the MDA-MB-231 human breast cancer line, with a significant reduction in primary tumor formation and a major inhibition of metastasis as well. Interestingly, in both models, proliferation in vitro was not affected. Subsequent microarray gene expression profiling identified 30 genes to be significantly altered by STC1 down-regulation, the majority of which are associated with known hallmarks of carcinogenesis. Furthermore, bioinformatic analysis of breast cancer datasets revealed that high expression of STC1 is associated with poor survival. This is the first study to show definitively that STC1 plays an oncogenic role in breast cancer, and indicates that STC1 could be a potential therapeutic target for treatment of breast cancer patients.

  9. Neoadjuvant Chemotherapy Creates Surgery Opportunities For Inoperable Locally Advanced Breast Cancer

    PubMed Central

    Wang, Minghao; Hou, Lingmi; Chen, Maoshan; Zhou, Yan; Liang, Yueyang; Wang, Shushu; Jiang, Jun; Zhang, Yi

    2017-01-01

    Neoadjuvant chemotherapy (NAC), the systematic chemotherapy given to patients with locally advanced and inoperable breast caner, has been proven to be of great clinical values. Many scientific reports confirmed NAC could effectively eliminate sub-clinical disseminated lesions of tumor, and improve long-term and disease-free survival rate of patients with locally advanced breast cancer (LABC); however, up to now, LABC is still a serious clinical issue given improved screening and early diagnosis. This study, with main focus on inoperable LABC, investigated the values of NAC in converting inoperable LABC into operable status and assessed the prognosis. Sixty-one patients with inoperable LABC were initially treated with neoadjuvant chemotherapy; their local conditions were improved to operable status. Radical surgery was exerted on 49 patients. Original chemotherapy was performed after surgery, followed by local radiotherapy. And endocrine therapy was optional according to the hormone receptor status. The quality of life for most patients with skin diabrosis was obviously improved because their local conditions were under control. For all recruited cases, the survival duration and life quality were significantly improved in patients who finished both NAC and surgery compared to those who did not. Further more, this study demonstrates improved prognostic consequences. PMID:28327615

  10. Metastatic brain tumor

    MedlinePlus

    ... them create an advance directive and power of attorney for health care. Support Groups You can ease ... surgery Brain tumor - children Breast cancer Increased intracranial pressure Lung cancer - small cell Melanoma Renal cell carcinoma ...

  11. The ubiquitin E3 ligase ITCH enhances breast tumor progression by inhibiting the Hippo tumor suppressor pathway.

    PubMed

    Salah, Zaidoun; Itzhaki, Ella; Aqeilan, Rami I

    2014-11-15

    The Hippo kinase pathway is emerging as a conserved signaling pathway that is essential for organ growth and tumorigenesis. Recently, we reported that the ubiquitin E3 ligase ITCH negatively regulates LATS1, thereby increasing YAP activity, which leads to increased cell proliferation and decreased apoptosis. Here, we investigated the role of ITCH in breast tumorigenesis. In particular, we show that ITCH enhances epithelial-to-mesenchymal transition (EMT) through boosting YAP oncogenic function. By contrast, a point mutation in the catalytic domain or WW1 domain of ITCH abolished its EMT-mediated effects. Furthermore, while overexpression of ITCH expression in breast cells is associated with increased incidence of mammary tumor formation and progression, its knockdown inhibited breast cancer cell tumorigenicity and metastasis. Importantly, YAP knockdown was able to attenuate ITCH pro-tumorigenic functions. Lastly, we found that ITCH expression is significantly upregulated in invasive and metastatic breast cancer cases and is associated with worse survival. Together, our results reveal that ITCH pro-tumorigenic functions in breast cancer are mediated, at least in part, through inactivation of the Hippo tumor suppressor pathway.

  12. The ubiquitin E3 ligase ITCH enhances breast tumor progression by inhibiting the Hippo tumor suppressor pathway

    PubMed Central

    Salah, Zaidoun; Itzhaki, Ella; Aqeilan, Rami I

    2014-01-01

    The Hippo kinase pathway is emerging as a conserved signaling pathway that is essential for organ growth and tumorigenesis. Recently, we reported that the ubiquitin E3 ligase ITCH negatively regulates LATS1, thereby increasing YAP activity, which leads to increased cell proliferation and decreased apoptosis. Here, we investigated the role of ITCH in breast tumorigenesis. In particular, we show that ITCH enhances epithelial-to-mesenchymal transition (EMT) through boosting YAP oncogenic function. By contrast, a point mutation in the catalytic domain or WW1 domain of ITCH abolished its EMT-mediated effects. Furthermore, while overexpression of ITCH expression in breast cells is associated with increased incidence of mammary tumor formation and progression, its knockdown inhibited breast cancer cell tumorigenicity and metastasis. Importantly, YAP knockdown was able to attenuate ITCH pro-tumorigenic functions. Lastly, we found that ITCH expression is significantly upregulated in invasive and metastatic breast cancer cases and is associated with worse survival. Together, our results reveal that ITCH pro-tumorigenic functions in breast cancer are mediated, at least in part, through inactivation of the Hippo tumor suppressor pathway. PMID:25350971

  13. Targeting tumor vasculature through oncolytic virotherapy: recent advances.

    PubMed

    Toro Bejarano, Marcela; Merchan, Jaime R

    2015-01-01

    The oncolytic virotherapy field has made significant advances in the last decade, with a rapidly increasing number of early- and late-stage clinical trials, some of them showing safety and promising therapeutic efficacy. Targeting tumor vasculature by oncolytic viruses (OVs) is an attractive strategy that offers several advantages over nontargeted viruses, including improved tumor viral entry, direct antivascular effects, and enhanced antitumor efficacy. Current understanding of the biological mechanisms of tumor neovascularization, novel vascular targets, and mechanisms of resistance has allowed the development of oncolytic viral vectors designed to target tumor neovessels. While some OVs (such as vaccinia and vesicular stomatitis virus) can intrinsically target tumor vasculature and induce vascular disruption, the majority of reported vascular-targeted viruses are the result of genetic manipulation of their viral genomes. Such strategies include transcriptional or transductional endothelial targeting, "armed" viruses able to downregulate angiogenic factors, or to express antiangiogenic molecules. The above strategies have shown preclinical safety and improved antitumor efficacy, either alone, or in combination with standard or targeted agents. This review focuses on the recent efforts toward the development of vascular-targeted OVs for cancer treatment and provides a translational/clinical perspective into the future development of new generation biological agents for human cancers.

  14. Ultrashort microwave pulsed thermoacoustic imaging for tumor localization over whole breast

    NASA Astrophysics Data System (ADS)

    Ji, Zhong; Fu, Yong; Lou, Cunguang

    2014-09-01

    Microwave-induced thermoacoustic imaging (TAI) has attracted considerable interest as a promising imaging modality. Previous studies show that TAI has great potential for use in breast tumor detection with high contrast and high spatial resolution, nevertheless it requires high energy density and possesses small field of view (FOV). In this paper, a ultrashort microwave pulse (USMP) TAI system was employed for quality imaging with much less energy density required , and simultaneously, large enough FOV was obtained to cover the whole breast. The experimental results clearly demonstrate that the new USMP TAI system can be used for three-dimensional (3-D) localization of deep breast tumors with low microwave radiation dose over the whole breast.

  15. Breast tumor oxygenation in response to carbogen intervention assessed simultaneously by three oxygen-sensitive parameters

    NASA Astrophysics Data System (ADS)

    Gu, Yueqing; Bourke, Vincent; Kim, Jae Gwan; Xia, Mengna; Constantinescu, Anca; Mason, Ralph P.; Liu, Hanli

    2003-07-01

    Three oxygen-sensitive parameters (arterial hemoglobin oxygen saturation SaO2, tumor vascular oxygenated hemoglobin concentration [HbO2], and tumor oxygen tension pO2) were measured simultaneously by three different optical techniques (pulse oximeter, near infrared spectroscopy, and FOXY) to evaluate dynamic responses of breast tumors to carbogen (5% CO2 and 95% O2) intervention. All three parameters displayed similar trends in dynamic response to carbogen challenge, but with different response times. These response times were quantified by the time constants of the exponential fitting curves, revealing the immediate and the fastest response from the arterial SaO2, followed by changes in global tumor vascular [HbO2], and delayed responses for pO2. The consistency of the three oxygen-sensitive parameters demonstrated the ability of NIRS to monitor therapeutic interventions for rat breast tumors in-vivo in real time.

  16. p16 overexpression and 9p21 deletion are linked to unfavorable tumor phenotype in breast cancer.

    PubMed

    Lebok, Patrick; Roming, Magdalena; Kluth, Martina; Koop, Christina; Özden, Cansu; Taskin, Berivan; Hussein, Khakan; Lebeau, Annette; Witzel, Isabell; Wölber, Linn; Geist, Stefan; Paluchowski, Peter; Wilke, Christian; Heilenkötter, Uwe; Müller, Volkmar; Schmalfeldt, Barbara; Simon, Ronald; Sauter, Guido; Terracciano, Luigi; Krech, Rainer Horst; von der Assen, Albert; Burandt, Eike

    2016-12-06

    Overexpression of the p16 tumor suppressor, but also deletion of its gene locus 9p21, is linked to unfavorable tumor phenotype and poor prognosis in breast cancer. To better understand these contradictory observations, and to clarify the prognostic impact of p16 expression and 9p21 deletion, a tissue microarray (TMA) with 2,197 breast cancers was analyzed by fluorescence in-situ hybridization and immunohistochemistry (FISH) for 9p21 deletion and p16 expression. p16 immunostaining was weak in 25.6%, moderate in 7.1%, and strong in 12.7% of 1,684 evaluable cancers. Strong p16 staining was linked to advanced tumor stage (p = 0.0003), high-grade (p < 0.0001), high tumor cell proliferation (p < 0.0001), negative hormone receptor (ER/PR) status (p < 0.0001 each), and shorter overall survival (p = 0.0038). 9p21 deletion was found in 15.3% of 1,089 analyzable breast cancers, including 1.7% homozygous and 13.6% heterozygous deletions. 9p21 deletion was linked to adverse tumor features, including high-grade (p < 0.0001) and nodal positive cancers (p = 0.0063), high cell proliferation (p < 0.0001), negative hormone receptor (ER/PR) status (p ≤ 0.0006), and HER2 amplification (p = 0.0078). Patient outcome was worse in 9p21 deleted than in undeleted cancers (p = 0.0720). p16 expression was absent in cancers harboring homozygous 9p21 deletions, but no difference in p16 expression was found between cancers with (59.2% p16 positive) and without heterozygous 9p21 deletion (51.3% p16 positive, p = 0.0256). In summary, p16 expression is unrelated to partial 9p21 deletion, but both alterations are linked to aggressive breast cancer phenotype. High-level p16 expression is a strong predictor of unfavorable disease course in breast cancer.

  17. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast.

    PubMed

    Gatalica, Zoran; Vranic, Semir; Ghazalpour, Anatole; Xiu, Joanne; Ocal, Idris Tolgay; McGill, John; Bender, Ryan P; Discianno, Erin; Schlum, Aaron; Sanati, Souzan; Palazzo, Juan; Reddy, Sandeep; Pockaj, Barbara

    2016-01-12

    Malignant phyllodes tumor is a rare breast malignancy with sarcomatous overgrowth and with limited effective treatment options for recurrent and metastatic cases. Recent clinical trials indicated a potential for anti-angiogenic, anti-EGFR and immunotherapeutic approaches for patients with sarcomas, which led us to investigate these and other targetable pathways in malignant phyllodes tumor of the breast. Thirty-six malignant phyllodes tumors (including 8 metastatic tumors with two cases having matched primary and metastatic tumors) were profiled using gene sequencing, gene copy number analysis, whole genome expression, and protein expression. Whole genome expression analysis demonstrated consistent over-expression of genes involved in angiogenesis including VEGFA, Angiopoietin-2, VCAM1, PDGFRA, and PTTG1. EGFR protein overexpression was observed in 26/27 (96%) of cases with amplification of the EGFR gene in 8/24 (33%) cases. Two EGFR mutations were identified including EGFRvIII and a presumed pathogenic V774M mutation, respectively. The most common pathogenic mutations included TP53 (50%) and PIK3CA (15%). Cases with matched primary and metastatic tumors harbored identical mutations in both sites (PIK3CA/KRAS and RB1 gene mutations, respectively). Tumor expression of PD-L1 immunoregulatory protein was observed in 3/22 (14%) of cases. Overexpression of molecular biomarkers of increased angiogenesis, EGFR and immune checkpoints provides novel targeted therapy options in malignant phyllodes tumors of the breast.

  18. Mammary adipocytes stimulate breast cancer invasion through metabolic remodeling of tumor cells

    PubMed Central

    Wang, Yuan Yuan; Attané, Camille; Milhas, Delphine; Dirat, Béatrice; Dauvillier, Stéphanie; Guerard, Adrien; Gilhodes, Julia; Lazar, Ikrame; Alet, Nathalie; Laurent, Victor; Le Gonidec, Sophie; Hervé, Caroline; Bost, Frédéric; Ren, Guo Sheng; Bono, Françoise; Escourrou, Ghislaine; Prentki, Marc; Nieto, Laurence; Valet, Philippe

    2017-01-01

    In breast cancer, a key feature of peritumoral adipocytes is their loss of lipid content observed both in vitro and in human tumors. The free fatty acids (FFAs), released by adipocytes after lipolysis induced by tumor secretions, are transferred and stored in tumor cells as triglycerides in lipid droplets. In tumor cell lines, we demonstrate that FFAs can be released over time from lipid droplets through an adipose triglyceride lipase–dependent (ATGL-dependent) lipolytic pathway. In vivo, ATGL is expressed in human tumors where its expression correlates with tumor aggressiveness and is upregulated by contact with adipocytes. The released FFAs are then used for fatty acid β-oxidation (FAO), an active process in cancer but not normal breast epithelial cells, and regulated by coculture with adipocytes. However, in cocultivated cells, FAO is uncoupled from ATP production, leading to AMPK/acetyl-CoA carboxylase activation, a circle that maintains this state of metabolic remodeling. The increased invasive capacities of tumor cells induced by coculture are completely abrogated by inhibition of the coupled ATGL-dependent lipolysis/FAO pathways. These results show a complex metabolic symbiosis between tumor-surrounding adipocytes and cancer cells that stimulate their invasiveness, highlighting ATGL as a potential therapeutic target to impede breast cancer progression. PMID:28239646

  19. Cancer associated fibroblasts express pro-inflammatory factors in human breast and ovarian tumors.

    PubMed

    Erez, Neta; Glanz, Sarah; Raz, Yael; Avivi, Camilla; Barshack, Iris

    2013-08-02

    Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  20. Modulation of the Proliferation and Metastasis of Human Breast Tumor Cells by SLUG (IDEA)

    DTIC Science & Technology

    2007-04-01

    E-cadherin preserved tumors is related to prognosis in patients with esophageal squamous cell carcinoma, Clin. Cancer Res. 11 (2005) 1174–1180. [2] A... human breast cells . 15. SUBJECT TERMS Breast cancer , SLUG, transcriptional silencing, molecular decoys, metastasis 16. SECURITY CLASSIFICATION OF: 17...SLUG activity and to evaluate the effects of this ablation on the proliferation, invasiveness and metastasis of these cancer cells in 3D-tissue culture

  1. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    SciTech Connect

    Erez, Neta; Glanz, Sarah; Raz, Yael; Avivi, Camilla; Barshack, Iris

    2013-08-02

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  2. Discrimination of Breast Tumors in Ultrasonic Images by Classifier Ensemble Trained with AdaBoost

    NASA Astrophysics Data System (ADS)

    Takemura, Atsushi; Shimizu, Akinobu; Hamamoto, Kazuhiko

    In this paper, we propose a novel method for acurate automated discrimination of breast tumors (carcinoma, fibroadenoma, and cyst). We defined 199 features related to diagnositic observations noticed when a doctor judges breast tumors, such as internal echo, shape, and boundary echo. These features included novel features based on a parameter of log-compressed K distribution, which reflect physical characteristics of ultrasonic B-mode imaging. Furthermore, we propose a discrimination method of breast tumors by using an ensemble classifier based on the multi-class AdaBoost algorithm with effective features selection. Verification by analyzing 200 carcinomas, 30 fibroadenomas and 30 cycts showed the usefulness of the newly defined features and the effectiveness of the discrimination by using an ensemble classifier trained by AdaBoost.

  3. Ossifying fibromyxoid tumor of the breast mimicking fibroadenoma: a case report and differential diagnoses.

    PubMed

    Asirvatham, Jaya Ruth; Shah, Anand; Carreon, Chrystalle Katte; Bhuiya, Tawfiqul A; Kahn, Leonard B; Kostroff, Karen; Morgenstern, Nora J

    2014-08-01

    An 80-year-old woman presented with a palpable mass in the right breast. Mammographic findings were consistent with calcified fibroadenoma. An ultrasound was performed that showed a solid nodule with peripheral calcification. A core biopsy was obtained that revealed a spindle cell proliferation with a shell of mature bone. The histologic features, in combination with immunohistochemical studies, were those of an ossifying fibromyxoid tumor. Complete excision of the specimen further confirmed the diagnosis. To the best of our knowledge, this is the first reported case of ossifying fibromyxoid tumor occurring in the breast. We review the current literature on ossifying fibromyxoid tumor and discuss the differential diagnoses when confronted with bland spindle cells on a core biopsy of the breast.

  4. [INVITED] Time reversal optical tomography: Detecting and locating tumors in an ex vivo model human breast

    NASA Astrophysics Data System (ADS)

    Wu, Binlin; Alrubaiee, Mohammad; Gayen, S. K.

    2016-03-01

    Time reversal optical tomography (TROT), a recently introduced diffuse optical imaging approach, is used to detect, locate, and obtain cross-section images of tumors inside a "model human breast." The model cancerous breast is assembled as a semi-cylindrical slab of uniform thickness using ex vivo human breast tissues with two pieces of tumors embedded in it. The experimental arrangement used a 750-nm light beam from a Ti:sapphire laser to illuminate an end face (source plane) of the sample in a multi-source probing scheme. A multi-detector signal acquisition scheme measured transmitted light intensity distribution on the other end face (detector plane). The perturbations in light intensity distribution in the detector plane were analyzed using TROT to obtain locations of the tumor pieces in three dimensions and estimate their cross sections. The estimated locations and dimensions of targets are in good agreement with the results of a corroborating magnetic resonance imaging experiment.

  5. Period-2: a tumor suppressor gene in breast cancer

    PubMed Central

    Xiang, Shulin; Coffelt, Seth B; Mao, Lulu; Yuan, Lin; Cheng, Qi; Hill, Steven M

    2008-01-01

    Previous reports have suggested that the ablation of the Period 2 gene (Per 2) leads to enhanced development of lymphoma and leukemia in mice. Employing immunoblot analyses, we have demonstrated that PER 2 is endogenously expressed in human breast epithelial cell lines but is not expressed or is expressed at significantly reduced level in human breast cancer cell lines. Expression of PER 2 in MCF-7 breast cancer cells significantly inhibited the growth of MCF-7 human breast cancer cells, and, when PER 2 was co-expressed with the Crytochrome 2 (Cry 2) gene, an even greater growth-inhibitory effect was observed. The inhibitory effect of PER 2 on breast cancer cells was also demonstrated by its suppression of the anchorage-independent growth of MCF-7 cells as evidenced by the reduced number and size of colonies. A corresponding blockade of MCF-7 cells in the G1 phase of the cell cycle was also observed in response to the expression of PER 2 alone or in combination with CRY 2. Expression of PER 2 also induced apoptosis of MCF-7 breast cancer cells as demonstrated by an increase in PARP [poly (ADP-ribose) polymerase] cleavage. Finally, our studies demonstrate that PER 2 expression in MCF-7 breast cancer cells is associated with a significant decrease in the expression of cyclin D1 and an up-regulation of p53 levels. PMID:18334030

  6. Period-2: a tumor suppressor gene in breast cancer.

    PubMed

    Xiang, Shulin; Coffelt, Seth B; Mao, Lulu; Yuan, Lin; Cheng, Qi; Hill, Steven M

    2008-03-11

    Previous reports have suggested that the ablation of the Period 2 gene (Per 2) leads to enhanced development of lymphoma and leukemia in mice. Employing immunoblot analyses, we have demonstrated that PER 2 is endogenously expressed in human breast epithelial cell lines but is not expressed or is expressed at significantly reduced level in human breast cancer cell lines. Expression of PER 2 in MCF-7 breast cancer cells significantly inhibited the growth of MCF-7 human breast cancer cells, and, when PER 2 was co-expressed with the Crytochrome 2 (Cry 2) gene, an even greater growth-inhibitory effect was observed. The inhibitory effect of PER 2 on breast cancer cells was also demonstrated by its suppression of the anchorage-independent growth of MCF-7 cells as evidenced by the reduced number and size of colonies. A corresponding blockade of MCF-7 cells in the G1 phase of the cell cycle was also observed in response to the expression of PER 2 alone or in combination with CRY 2. Expression of PER 2 also induced apoptosis of MCF-7 breast cancer cells as demonstrated by an increase in PARP [poly (ADP-ribose) polymerase] cleavage. Finally, our studies demonstrate that PER 2 expression in MCF-7 breast cancer cells is associated with a significant decrease in the expression of cyclin D1 and an up-regulation of p53 levels.

  7. NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas

    PubMed Central

    Yu, Yinhua; Xu, Fengji; Peng, Hongqi; Fang, Xianjun; Zhao, Shulei; Li, Yang; Cuevas, Bruce; Kuo, Wen-Lin; Gray, Joe W.; Siciliano, Michael; Mills, Gordon B.; Bast, Robert C.

    1999-01-01

    Using differential display PCR, we have identified a gene [NOEY2, ARHI (designation by the Human Gene Nomenclature Committee)] with high homology to ras and rap that is expressed consistently in normal ovarian and breast epithelial cells but not in ovarian and breast cancers. Reexpression of NOEY2 through transfection suppresses clonogenic growth of breast and ovarian cancer cells. Growth suppression was associated with down-regulation of the cyclin D1 promoter activity and induction of p21WAF1/CIP1. In an effort to identify mechanisms leading to NOEY2 silencing in cancer, we found that the gene is expressed monoallelically and is imprinted maternally. Loss of heterozygosity of the gene was detected in 41% of ovarian and breast cancers. In most of cancer samples with loss of heterozygosity, the nonimprinted functional allele was deleted. Thus, NOEY2 appears to be a putative imprinted tumor suppressor gene whose function is abrogated in ovarian and breast cancers. PMID:9874798

  8. Circulating tumor cell enumeration by the CellSearch system: the clinician's guide to breast cancer treatment?

    PubMed

    Beije, Nick; Jager, Agnes; Sleijfer, Stefan

    2015-02-01

    Circulating tumor cells (CTCs) are cancer cells that are present in the blood of patients with solid cancers and are shed from existing tumor lesions into the blood stream. The enumeration of CTCs has long been considered to hold great promise in guiding treatment decision-making in breast cancer patients. However, guidelines on how to use CTC enumeration in clinical decision-making in primary breast cancer and metastatic breast cancer are lacking. Here, we set out to review the most relevant literature to date, to ultimately come to general recommendations regarding the use of CTC enumeration in primary breast cancer and metastatic breast cancer.

  9. Endothelial Robo4 suppresses breast cancer growth and metastasis through regulation of tumor angiogenesis.

    PubMed

    Zhao, Helong; Ahirwar, Dinesh K; Oghumu, Steve; Wilkie, Tasha; Powell, Catherine A; Nasser, Mohd W; Satoskar, Abhay R; Li, Dean Y; Ganju, Ramesh K

    2016-02-01

    Targeting tumor angiogenesis is a promising alternative strategy for improvement of breast cancer therapy. Robo4 (roundabout homolog 4) signaling has been shown to protect endothelial integrity during sepsis shock and arthritis, and inhibit Vascular Endothelial Growth Factor (VEGF) signaling during pathological angiogenesis of retinopathy, which indicates that Robo4 might be a potential target for angiogenesis in breast cancer. In this study, we used immune competent Robo4 knockout mouse model to show that endothelial Robo4 is important for suppressing breast cancer growth and metastasis. And this effect does not involve the function of Robo4 on hematopoietic stem cells. Robo4 inhibits breast cancer growth and metastasis by regulating tumor angiogenesis, endothelial leakage and tight junction protein zonula occludens protein-1 (ZO-1) downregulation. Treatment with SecinH3, a small molecule drug which deactivates ARF6 downstream of Robo4, can enhance Robo4 signaling and thus inhibit breast cancer growth and metastasis. SecinH3 mediated its effect by reducing tumor angiogenesis rather than directly affecting cancer cell proliferation. In conclusion, endothelial Robo4 signaling is important for suppressing breast cancer growth and metastasis, and it can be targeted (enhanced) by administrating a small molecular drug.

  10. Continuation Study of Entinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2017-02-24

    Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Digestive System Neoplasms; Endocrine Gland Neoplasms; Carcinoma, Non-Small-Cell Lung; Lung Diseases; Breast Diseases; Renal Neoplasm; Solid Tumors

  11. Chemotherapy in Treating Patients With Refractory Advanced Solid Tumors or Hematologic Cancer

    ClinicalTrials.gov

    2013-06-20

    Bladder Cancer; Breast Cancer; Colorectal Cancer; Gastric Cancer; Head and Neck Cancer; Kidney Cancer; Leukemia; Lung Cancer; Melanoma (Skin); Ovarian Cancer; Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  12. Associations of Breast Cancer Risk Factors With Tumor Subtypes: A Pooled Analysis From the Breast Cancer Association Consortium Studies

    PubMed Central

    Chang-Claude, Jenny; Goode, Ellen L.; Couch, Fergus J.; Nevanlinna, Heli; Milne, Roger L.; Gaudet, Mia; Schmidt, Marjanka K.; Broeks, Annegien; Cox, Angela; Fasching, Peter A.; Hein, Rebecca; Spurdle, Amanda B.; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomäki, Kristiina; Heikkilä, Päivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van ‘t Veer, Laura J.; van Leeuwen, Flora E.; Andrulis, Irene L.; Glendon, Gord; Knight, Julia A.; Mulligan, Anna Marie; O’Malley, Frances P.; Weerasooriya, Nayana; John, Esther M.; Beckmann, Matthias W.; Hartmann, Arndt; Weihbrecht, Sebastian B.; Wachter, David L.; Jud, Sebastian M.; Loehberg, Christian R.; Baglietto, Laura; English, Dallas R.; Giles, Graham G.; McLean, Catriona A.; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E.; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E.; Connley, Daniel; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W. R.; Dörk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H.; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Pérez, Jose Ignacio; Rodríguez, Primitiva Menéndez; Zamora, Pilar; Benítez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Brüning, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M.; Tapper, William J.; Gerty, Sue M.; Sawyer, Elinor J.; Tomlinson, Ian P.; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A.; Henderson, Brian E.; Le Marchand, Loic; Kolonel, Laurence N.; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubiński, Jan; Huzarski, Tomasz; Byrski, Tomasz; Górski, Bohdan; Gronwald, Jacek; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M. A.; Collée, Margriet; Wang-Gohrke, Shan; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Päivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E.; Dynnes Ørsted, David; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Børge G.; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E.; Hunter, David J.; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; McKay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P.E.A.; Tollenaar, RAEM.; Seynaeve, C.; Dite, Gillian S.; Apicella, Carmel; Hopper, John L.; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D.; Southey, Melissa C.; Humphreys, Manjeet K.; Easton, Douglas; Pharoah, Paul; Sherman, Mark E.; Garcia-Closas, Montserrat

    2011-01-01

    Background Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. Methods We pooled tumor marker and epidemiological risk factor data from 35 568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case–case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case–control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided. Results In case–case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR− than PR+ tumors (P = .001). Nulliparity (P = 3 × 10−6) and increasing age at first birth (P = 2 × 10−9) were less frequent in ER− than in ER+ tumors. Obesity (body mass index [BMI] ≥ 30 kg/m2) in younger women (≤50 years) was more frequent in ER−/PR− than in ER+/PR+ tumors (P = 1 × 10−7), whereas obesity in older women (>50 years) was less frequent in PR− than in PR+ tumors (P = 6 × 10−4). The triple-negative (ER−/PR−/HER2−) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6+ and/or epidermal growth factor receptor [EGFR]+) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case–control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER+ or PR+ tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95

  13. Should the hyperechogenic halo around malignant breast lesions be included in the measurement of tumor size?

    PubMed

    Joekel, Judith; Eggemann, Holm; Costa, Serban Dan; Ignatov, Atanas

    2016-04-01

    The estimation of tumor size is important for treatment strategies of breast cancer. The hyperechogenic zone around breast cancer is a recognized criterion for malignancy, but its impact on preoperative tumor size estimations has been poorly investigated. Data of prospectively maintained database of 513 patients with primary breast tumors were analyzed retrospectively. A total of 196 patients with complete datasets including preoperative ultrasound (US) were eligible for analysis. The median age of the patients was 58.5 years (range 33-87). With all of the 196 patients, US has been performed. In 170 of 196 (86.7 %) cases, an echogenic halo was detected. We use two ways to measure tumor size with US: without (US-0) and with (US-1) echogenic halo. Mammography (MG) was used as standard. Tumor size measured by US and MG was compared with the actual histopathological (HP) tumor size. Mean differences between the sizing obtained by US-0, US-1, and MG and the HP sizing were -6.5, -1.5, and -1.8 mm, respectively. All three methods tend to underestimate the tumor size. The US-1 measurement was the closest to the HP size in comparison to the MG and US-0 measurements and the match was higher in tumors <2 cm. The estimated Pearson correlation coefficients (r) were 0.72, 0.68, and 0.61 for US-1, US-0, and MG, respectively. Moreover, the predictive value of US-1 regarding tumor size was not influenced by histological type and grade of the tumor, receptor status, and presence of intraductal component. Estimation of tumor size by US should include the hyperechogenic zone around the tumor.

  14. Observation of tumor microvessels that are controlled by blood flow in breast cancer

    NASA Astrophysics Data System (ADS)

    Ishida, H.; Andoh, T.; Akiguchi, S.; Kyoden, T.; Hachiga, T.

    2015-04-01

    We attempted to perform non-invasive breast cancer imaging using a reflection-type multipoint laser Doppler velocimeter to monitor blood flow. On day six, after transplantation of cancer cells into mouse breast, we found that blood flow velocity in a blood vessel that extended into the tumor was increased compared to that in normal skin. The effect of carcinogenesis on blood flow over such a short period was shown using blood flow velocity imaging. Although such imaging has not yet been adapted for use in humans, this study is an important step in reaching the ultimate goal, which is early detection of breast cancer.

  15. Monte Carlo simulation of breast tumor imaging properties with compact, discrete gamma cameras

    SciTech Connect

    Gruber, G.J.; Moses, W.W.; Derenzo, S.E.

    1999-12-01

    The authors describe Monte Carlo simulation results for breast tumor imaging using a compact, discrete gamma camera. The simulations were designed to analyze and optimize camera design, particularly collimator configuration and detector pixel size. Simulated planar images of 5--15 mm diameter tumors in a phantom patient (including a breast, torso, and heart) were generated for imaging distances of 5--55 mm, pixel sizes of 2 x 2--4 x 4 mm{sup 2}, and hexagonal and square hole collimators with sensitivities from 4,000 to 16,000 counts/mCi/sec. Other factors considered included T/B (tumor-to-background tissue uptake ratio) and detector energy resolution. Image properties were quantified by computing the observed tumor fwhm (full-width at half-maximum) and S/N (sum of detected tumor events divided by the statistical noise). Results suggest that hexagonal and square hole collimators perform comparably, that higher sensitivity collimators provide higher tumor S/N with little increase in the observed tumor fwhm, that smaller pixels only slightly improve tumor fwhm and S/N, and that improved detector energy resolution has little impact on either the observed tumor fwhm or the observed tumor S/N.

  16. Class I major histocompatibility complex antigens and tumor ploidy in breast and bronchogenic carcinomas.

    PubMed

    Redondo, M; Concha, A; Ruiz-Cabello, F; Morell, M; Esteban, F; Talavera, P; Garrido, F

    1997-01-01

    We determined the frequency of expression of the major histocompatibility complex antigens HLA-A,B,C in tumor cells from 207 primary tumor lesions of breast and bronchogenic carcinomas, to see if the expression of theses antigens was linked with several clinicopathological parameters associated with tumor aggressivity, such as abnormal cellular DNA content. We compared tumor tissues with nonneoplastic tissues and tissues from 15 benign breast lesions. HLA class I expressor and nonexpressor tumor cells were determined by using immunohistochemical stains (PAP and APAAP methods) and antibodies against these antigens. Reduction of HLA class I antigen was detected in 65 tumors (31.7%) and was significantly associated with poor tumor differentiation and abnormal cellular DNA content (p < 0.001). These characteristics might define a group of aggressive tumors in which the decrease of HLA class I antigens would enable tumor cells to avoid eliciting host immune responses. On the other hand, the altered regulatory mechanisms, of tumors with abnormal cellular DNA content, might modulate the expression of HLA class I molecules.

  17. Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats.

    PubMed

    Singh, Bhupendra; Mense, Sarah M; Bhat, Nimee K; Putty, Sandeep; Guthiel, William A; Remotti, Fabrizio; Bhat, Hari K

    2010-09-01

    Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17beta-estradiol (E(2)). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E(2)-induced breast cancer in vivo. Female ACI rats were given quercetin (2.5 g/kg food) for 8 months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E(2) pellets, co-exposure to quercetin did not protect rats from E(2)-induced breast tumor development with 100% of the animals developing breast tumors within 8 months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin+E(2)-treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin+E(2) group relative to those in the E(2) group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin-exposed mammary tissue. Analysis of 8-isoprostane F(2alpha) (8-iso-PGF(2alpha)) levels as a marker of oxidant stress showed that quercetin did not decrease E(2)-induced oxidant stress. These results indicate that quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E(2)-induced oxidant stress and may exacerbate breast carcinogenesis in E(2)-treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E(2) and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E(2) and chronic exposure to oxidant stress as a result of metabolic redox cycling to estrogen metabolites, and thus quercetin may exacerbate E(2

  18. Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats

    SciTech Connect

    Singh, Bhupendra; Mense, Sarah M.; Bhat, Nimee K.; Putty, Sandeep; Guthiel, William A.; Remotti, Fabrizio; Bhat, Hari K.

    2010-09-01

    Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17{beta}-estradiol (E{sub 2}). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E{sub 2}-induced breast cancer in vivo. Female ACI rats were given quercetin (2.5 g/kg food) for 8 months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E{sub 2} pellets, co-exposure to quercetin did not protect rats from E{sub 2}-induced breast tumor development with 100% of the animals developing breast tumors within 8 months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin + E{sub 2}-treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin + E{sub 2} group relative to those in the E{sub 2} group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin-exposed mammary tissue. Analysis of 8-isoprostane F{sub 2{alpha}} (8-iso-PGF{sub 2{alpha}}) levels as a marker of oxidant stress showed that quercetin did not decrease E{sub 2}-induced oxidant stress. These results indicate that quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E{sub 2}-induced oxidant stress and may exacerbate breast carcinogenesis in E{sub 2}-treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E{sub 2} and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E{sub 2} and chronic exposure to oxidant stress as a result of metabolic redox

  19. Tumor-Infiltrating Lymphocytes in Triple Negative Breast Cancer: The Future of Immune Targeting.

    PubMed

    García-Teijido, Paula; Cabal, María Luque; Fernández, Ignacio Peláez; Pérez, Yolanda Fernández

    2016-01-01

    Triple negative breast cancer (TNBC) is a highly heterogeneous tumor. There is increasing evidence of the role of tumor lymphocytic immune infiltrates in this subtype of breast cancer. Robust levels of tumor infiltrating lymphocytes (TILs) have been associated with improved disease-free and overall survival rates in TNBC patients with and without any treatment. Recent efforts have been made to develop a standardized methodology for evaluating TILs. The presence of TILs in the breast tumor microenvironment can also predict responses not only to neoadjuvant but also to adjuvant chemotherapy treatments. High numbers of TILs correlate with increased pathological complete responses (pCR) in TNBC. TILs are prognostic and predictive of response to standard therapies; thus, the immune system appears to play an active role in a subgroup of breast cancer. There is an increasing interest in directly targeting the immune system as part of breast cancer therapy, mainly in patients with TNBC. New immune modulatory agents, including immune checkpoints inhibitors, have shown promising activity in a subgroup of metastatic TNBC. Increased programmed cell death protein 1 ligand (PD-L1) expression on the surface of TNBC provides the rationale for implementing therapeutic strategies targeting the PD-1/PD-L1 axis in TNBC. The programmed cell death protein 1 (PD-1) inhibitor pembrolizumab, and the PD-L1 inhibitor atezolizumab have shown promising results in clinical trials.

  20. Yin-yang effect of tumor infiltrating B cells in breast cancer: From mechanism to immunotherapy.

    PubMed

    Zhang, Zhigang; Zhu, Ying; Wang, Zhen; Zhang, Ting; Wu, Pin; Huang, Jian

    2017-05-01

    Breast cancer cells secrete chemokines, such as CXCL13, and antigens or express high endothelial venules, attracting B cells to infiltrate into the tumor microenvironment and play a "yin-yang" effect. They not only enhance the anti-tumor immune effect via secreting antibodies and influencing the Fas/FasL, CXCR4/CXCL12 and perforin pathways but they also promote the tumor to form a suppressive milieu by producing immunomodulatory factors and cytokines or using cell-to-cell education to induce the generation of Tregs or myeloid-derived suppressor cells (MDSCs). Currently, most studies on breast cancer tissue have indicated that B cell infiltration could predict better survival and response to therapy, but two studies have reported opposite results. In a 4T1 tumor-bearing BALB/c mice model, B cell-based immunotherapies were administered, but the efficiency was unstable. Herein, we review the "yin-yang" effect of B cells in breast cancer and discuss B cell-based immunotherapy. B cells are complex aggregates, and breast cancer is a heterogeneous disease. Further studies are urgently required to define the B cell subsets and to discover ways to use B cell-based immunotherapy in breast cancer.

  1. Tumor-Infiltrating Lymphocytes in Triple Negative Breast Cancer: The Future of Immune Targeting

    PubMed Central

    García-Teijido, Paula; Cabal, María Luque; Fernández, Ignacio Peláez; Pérez, Yolanda Fernández

    2016-01-01

    Triple negative breast cancer (TNBC) is a highly heterogeneous tumor. There is increasing evidence of the role of tumor lymphocytic immune infiltrates in this subtype of breast cancer. Robust levels of tumor infiltrating lymphocytes (TILs) have been associated with improved disease-free and overall survival rates in TNBC patients with and without any treatment. Recent efforts have been made to develop a standardized methodology for evaluating TILs. The presence of TILs in the breast tumor microenvironment can also predict responses not only to neoadjuvant but also to adjuvant chemotherapy treatments. High numbers of TILs correlate with increased pathological complete responses (pCR) in TNBC. TILs are prognostic and predictive of response to standard therapies; thus, the immune system appears to play an active role in a subgroup of breast cancer. There is an increasing interest in directly targeting the immune system as part of breast cancer therapy, mainly in patients with TNBC. New immune modulatory agents, including immune checkpoints inhibitors, have shown promising activity in a subgroup of metastatic TNBC. Increased programmed cell death protein 1 ligand (PD-L1) expression on the surface of TNBC provides the rationale for implementing therapeutic strategies targeting the PD-1/PD-L1 axis in TNBC. The programmed cell death protein 1 (PD-1) inhibitor pembrolizumab, and the PD-L1 inhibitor atezolizumab have shown promising results in clinical trials. PMID:27081325

  2. Complement inhibitor CSMD1 acts as tumor suppressor in human breast cancer

    PubMed Central

    Escudero-Esparza, Astrid; Okroj, Marcin; Owen, Sioned; Jirström, Karin; Orimo, Akira; Jiang, Wen G.; Pietras, Kristian; Blom, Anna M.

    2016-01-01

    Human CUB and Sushi multiple domains 1 (CSMD1) is a membrane-bound complement inhibitor suggested to act as a putative tumor suppressor gene, since allelic loss of this region encompassing 8p23 including CSMD1 characterizes various malignancies. Here, we assessed the role of CSMD1 as a tumor suppressor gene in the development of breast cancer in vitro and in vivo. We found that human breast tumor tissues expressed CSMD1 at lower levels compared to that in normal mammary tissues. The decreased expression of CSMD1 was linked to a shorter overall survival of breast cancer patients. We also revealed that expression of CSMD1 in human breast cancer cells BT-20 and MDA-MB-231 significantly inhibited their malignant phenotypes, including migration, adhesion and invasion. Conversely, stable silencing of CSMD1 expression in T47D cells enhanced cancer cell migratory, adherent and clonogenic abilities. Moreover, expression of CSMD1 in the highly invasive MDA-MB-231 cells diminished their signaling potential as well as their stem cell-like properties as assessed by measurement of aldehyde dehydrogenase activity. In a xenograft model, expression of CSMD1 blocked the ability of cancer cells to metastasize to secondary sites in vivo, likely via inhibiting local invasion but not the extravasation into distant tissues. Taken together, these findings demonstrate the role of CSMD1 as a tumor suppressor gene in breast cancer. PMID:27764775

  3. Genistein induces breast cancer-associated aromatase and stimulates estrogen-dependent tumor cell growth in in vitro breast cancer model.

    PubMed

    van Duursen, M B M; Nijmeijer, S M; de Morree, E S; de Jong, P Chr; van den Berg, M

    2011-11-18

    In breast cancer, the interaction between estrogen-producing breast adipose fibroblasts (BAFs) and estrogen-dependent epithelial tumor cells is pivotal. Local estrogen production is catalyzed by aromatase, which is differentially regulated in disease-free and tumorigenic breast tissue. The use of aromatase inhibitors to block local estrogen production has proven effective in treatment of estrogen-dependent breast cancer. However, a major problem during breast cancer treatment is the sudden onset of menopause and many women seek for alternative medicines, such as the soy isoflavone genistein. In this study, we show that genistein can induce estrogen-dependent MCF-7 tumor cell growth and increase breast cancer-associated aromatase expression and activity in vitro. We have previously developed an in vitro breast cancer model where the positive feedback loop between primary BAFs and estrogen-dependent MCF-7 tumor cells is operational, thereby representing a more natural in vitro model for breast cancer. In this model, genistein could negate the growth inhibitory action of the aromatase inhibitor fadrozole at physiologically relevant concentrations. These data suggest that soy-based supplements might affect the efficacy of breast cancer treatment with aromatase inhibitors. Considering the high number of breast cancer patients using soy supplements to treat menopausal symptoms, the increasing risk for adverse interactions with breast cancer treatment is of major concern and should be considered with care.

  4. Mucinous micropapillary carcinoma of the breast: an aggressive counterpart to conventional pure mucinous tumors.

    PubMed

    Barbashina, Violetta; Corben, Adriana D; Akram, Muzaffar; Vallejo, Christina; Tan, Lee K

    2013-08-01

    Mucinous micropapillary carcinoma of the breast, also described as "pure mucinous carcinoma with micropapillary pattern," has recently come to attention as an unusual form of invasive breast cancer exhibiting dual mucinous and micropapillary differentiation. Despite increasing awareness of this morphologic variant, its clinical significance has not yet been elucidated. Here, we present 15 additional examples of these rare tumors to highlight some important differences between mucinous micropapillary carcinoma of the breast and ordinary pure mucinous carcinomas. The key features of mucinous micropapillary carcinoma of the breast included (a) largely or entirely mucinous appearance (>90% mucinous morphology), (b) distinctive micropapillary arrangement of the neoplastic cells, (c) intermediate to high nuclear grade, (d) "hobnail" cells, and (e) frequent psammomatous calcifications. In contrast to ordinary pure mucinous carcinomas, 20% of mucinous micropapillary carcinomas of the breast were characterized by human epidermal growth factor receptor 2 positivity, and 23% were p53 positive. More than half of mucinous micropapillary carcinomas of the breast (60%) demonstrated lymphovascular invasion, sometimes extensive. Synchronous axillary lymph node metastases were detected in 33% of patients and, on 2 occasions, involved more than 10 nodes. With a median follow-up of 4.5 years, we identified 1 patient (7%) with chest wall recurrence of mucinous micropapillary carcinoma of the breast after mastectomy. We conclude that mucinous micropapillary carcinomas of the breast constitute a clinically aggressive subset of mucin-producing breast carcinomas characterized by an increased capacity for lymphatic invasion and regional lymph node metastasis, reflective of their dual phenotype. Recognition of the morphologic and biologic heterogeneity within breast cancer subtypes should allow for a more accurate classification of the individual tumors and better patient stratification for

  5. Brain metastasis reirradiation in patients with advanced breast cancer

    PubMed Central

    Huang, Zhou; Sun, Bing; Shen, Ge; Cha, Lei; Meng, Xiangying; Wang, Junliang; Zhou, Zhenshan; Wu, Shikai

    2017-01-01

    The outcome of recurrent brain metastasis is dismal. This study aims to assess the clinical outcomes and toxicity of reirradiation as a salvage treatment for progressive brain metastasis in patients with advanced breast cancer. Between July 2005 and September 2014, the medical records of 56 patients with brain metastasis from breast cancer were retrospectively reviewed. Of these patients, 39 received whole-brain radiotherapy (WBRT) followed by stereotactic radiosurgery (SRS) reirradiation (Group 1), and 17 received SRS followed by WBRT reirradiation (Group 2). Overall survival (OS) and brain progression-free survival rates/times were calculated using the Kaplan–Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Change in neurologic function was also assessed. The median OS was 10.8 months (range, 1.3–56.8 months). In Group 1, the median PFS time (PFS-1) was 6.5 months and the OS time was 11.4 months. Multivariate analysis revealed that longer OS was significantly associated with a high Karnofsky performance score (KPS) (P = 0.004), controlled extracranial metastasis (P = 0.001) and a good response to reirradiation (P = 0.034). In Group 2, the median PFS time (PFS-2) after reirradiation was 8.5 months and the OS time was 10.8 months. Multivariate analysis revealed that longer OS was significantly associated with a high KPS (P = 0.018). The majority of the patients had improved or stable neurological function. Reirradiation is an effective and a safe treatment for patients with brain metastases from breast cancer. It might delay the progression of intracranial disease and improve neurological function. A suitable patient selection for reirradiation was suggested. PMID:27707842

  6. Time-Domain Optical Mammography: Initial Clinical Results on Detection and Characterization of Breast Tumors

    NASA Astrophysics Data System (ADS)

    Grosenick, Dirk; Moesta, K. Thomas; Wabnitz, Heidrun; Mucke, Jörg; Stroszczynski, Christian; MacDonald, Rainer; Schlag, Peter M.; Rinneberg, Herbert

    2003-06-01

    Mammograms of 35 patients suspected of breast cancer were taken along craniocaudal and mediolateral projections with a dual-wavelength scanning laser pulse mammograph measuring time-resolved transmittance. Among 26 tumors known from routine clinical diagnostics, 17 tumors were detected retrospectively in optical mammograms. Effective tumor optical properties derived from a homogeneous model were used to deduce physiological information. All tumors exhibited increased total hemoglobin concentration and decreased or unchanged blood oxygen saturation compared with surrounding healthy tissue. Scatter plots based on a pixelwise analysis of individual mammograms were introduced and applied to represent correlations between characteristic quantities derived from measured distributions of times of flight of photons.

  7. Hereditary breast and gynecological tumors: Italian legal issues.

    PubMed

    DI Vella, Giancarlo

    2016-10-01

    The availability of diagnostic and therapeutic procedures that lower the risk for developing hereditary family-related tumors is weighed against Italian ethical and legal provisions. The healthcare environment in which a professional works should require that he possess specific technical, relational and medical competencies based upon legal orientation in addition to scientific evidence. Particular emphasis is attributed to the doctor-patient relationship, with explicit reference to the following: 1) all of the information at hand that is required to achieve a "therapeutic alliance" that combines the best interests of the patient with treatment options; 2) the completeness and intelligibility of health records, as they are likely to explain the background logic and the following of scientific clinical procedure; 3) the observance of guidelines and protocols, and their relevance to the legal responsibility of the individual and health care companies; 4) the need of a multidisciplinary approach in the treatment of these patients and the obligation of the team to have malpractice insurance. Advances on "provisions concerning liability of health personnel", which is currently awaiting approval, allows the professional to protect the patient's health without the fear of being unnecessarily censured, and unjustified from a penal or civil point of view which can deteriorate the relationship of trust and cooperation established.

  8. The electromagnetic-trait imaging computation of traveling wave method in breast tumor microwave sensor system.

    PubMed

    Tao, Zhi-Fu; Han, Zhong-Ling; Yao, Meng

    2011-01-01

    Using the difference of dielectric constant between malignant tumor tissue and normal breast tissue, breast tumor microwave sensor system (BRATUMASS) determines the detected target of imaging electromagnetic trait by analyzing the properties of target tissue back wave obtained after near-field microwave radicalization (conelrad). The key of obtained target properties relationship and reconstructed detected space is to analyze the characteristics of the whole process from microwave transmission to back wave reception. Using traveling wave method, we derive spatial transmission properties and the relationship of the relation detected points distances, and valuate the properties of each unit by statistical valuation theory. This chapter gives the experimental data analysis results.

  9. Mapping of a Breast Carcinoma Tumor Suppressor Gene to Chromosome 11P15.5

    DTIC Science & Technology

    1997-07-01

    4. Fults, D., Petronio, J., Noblett, B. D., Pedone, C. A. Chromosome 11p15 deletions in human malignant astrocytomas and primitive neuroectodermal ...AD _ GRANT NUMBER DAMDI7-94-J-4175 TITLE: Mapping of a Breast Carcinoma Tumor Suppressor Gene to Chromosome 11P15.5 PRINCIPAL INVESTIGATOR: Tracey...FUNDING NUMBERS Mapping of a Breast Carcinoma Tumor Suppressor Gene to Chromosome llP15.5 DAMD17-94-J-4175 6. AUTHOR(S) Tracey Moore, Ph.D. 7

  10. Serum anti - TPO levels in benign and malignant breast tumors.

    PubMed

    Sabitha; Suneetha; Mohanty, Shruti; Rao, Pragna

    2009-07-01

    Breast cancer is a hormone dependent neoplasm. Conflicting results regarding the clinical correlation between breast cancer and thyroid diseases have been reported. The objective of this study was to determine the association of anti - TPO levels in patients having complaints of a lump in breast. Serum samples and Fine needle aspiration cytology (FNAC) samples were collected from 31 female patients with a lump in breast between the age group of 20-75 years. 31 age matched normal healthy controls were also examined for the same parameters. Serum samples were analyzed for its anti - TPO levels. FNAC reports confirmed patients as having duct cell carcinoma. They had raised serum anti - TPO levels compared to controls. FNAC results of others (n=26) were reported as fibroadenoma whose anti - TPO levels were less than the controls.

  11. Simultaneous Vascular Targeting and Tumor Targeting of Cerebral Breast Cancer Metastases Using a T-Cell Receptor Mimic Antibody

    DTIC Science & Technology

    2013-05-01

    Tumor Targeting of Cerebral Breast Cancer Metastases Using a T-Cell Receptor Mimic Antibody PRINCIPAL INVESTIGATOR: Ulrich Bickel...of Cerebral Breast Cancer Metastases Using a T-Cell Receptor Mimic Antibody 5b. GRANT NUMBER W81XWH-12-1-0184 5c. PROGRAM ELEMENT NUMBER 6...tumors using a brain selective cell line, 231-BR, derived from human breast cancer . Therefore, the experimental model to be used must be immune

  12. Epithelial derived CTGF promotes breast tumor progression via inducing EMT and collagen I fibers deposition

    PubMed Central

    Zhao, Zhen; Sheng, Jianting; Wang, Jiang; Liu, Jiyong; Cui, Kemi; Chang, Jenny; Zhao, Hong; Wong, Stephen

    2015-01-01

    Interactions among tumor cells, stromal cells, and extracellular matrix compositions are mediated through cytokines during tumor progression. Our analysis of 132 known cytokines and growth factors in published clinical breast cohorts and our 84 patient-derived xenograft models revealed that the elevated connective tissue growth factor (CTGF) in tumor epithelial cells significantly correlated with poor clinical prognosis and outcomes. CTGF was able to induce tumor cell epithelial-mesenchymal transition (EMT), and promote stroma deposition of collagen I fibers to stimulate tumor growth and metastasis. This process was mediated through CTGF-tumor necrosis factor receptor I (TNFR1)-IκB autocrine signaling. Drug treatments targeting CTGF, TNFR1, and IκB signaling each prohibited the EMT and tumor progression. PMID:26318291

  13. One-Carbon Metabolism and Methylation in Breast Tumors

    DTIC Science & Technology

    2007-06-01

    statistically non-significant association 18 disease , body mass index, total energy intake , and other factors known to increase the risk of breast cancer...implicated as a risk factor for cardiovascular disease (90), Down’s syndrome (91), and neural tube defects (89, 92). This polymorphism appears to be...et al.(50) reported a non-significant reduced breast cancer risk among women reporting the highest dietary folate intake (OR = 0.49, 95%CI: 0.20

  14. Breast tumor segmentation in high resolution x-ray phase contrast analyzer based computed tomography

    SciTech Connect

    Brun, E.; Grandl, S.; Sztrókay-Gaul, A.; Gasilov, S.; Barbone, G.; Mittone, A.; Coan, P.; Bravin, A.

    2014-11-01

    Purpose: Phase contrast computed tomography has emerged as an imaging method, which is able to outperform present day clinical mammography in breast tumor visualization while maintaining an equivalent average dose. To this day, no segmentation technique takes into account the specificity of the phase contrast signal. In this study, the authors propose a new mathematical framework for human-guided breast tumor segmentation. This method has been applied to high-resolution images of excised human organs, each of several gigabytes. Methods: The authors present a segmentation procedure based on the viscous watershed transform and demonstrate the efficacy of this method on analyzer based phase contrast images. The segmentation of tumors inside two full human breasts is then shown as an example of this procedure’s possible applications. Results: A correct and precise identification of the tumor boundaries was obtained and confirmed by manual contouring performed independently by four experienced radiologists. Conclusions: The authors demonstrate that applying the watershed viscous transform allows them to perform the segmentation of tumors in high-resolution x-ray analyzer based phase contrast breast computed tomography images. Combining the additional information provided by the segmentation procedure with the already high definition of morphological details and tissue boundaries offered by phase contrast imaging techniques, will represent a valuable multistep procedure to be used in future medical diagnostic applications.

  15. On metabolic reprogramming and tumor biology: A comprehensive survey of metabolism in breast cancer

    PubMed Central

    Penkert, Judith; Ripperger, Tim; Schieck, Maximilian; Schlegelberger, Brigitte; Steinemann, Doris; Illig, Thomas

    2016-01-01

    Altered metabolism in tumor cells has been a focus of cancer research for as long as a century but has remained controversial and vague due to an inhomogeneous overall picture. Accumulating genomic, metabolomic, and lastly panomic data as well as bioenergetics studies of the past few years enable a more comprehensive, systems-biologic approach promoting deeper insight into tumor biology and challenging hitherto existing models of cancer bioenergetics. Presenting a compendium on breast cancer-specific metabolome analyses performed thus far, we review and compile currently known aspects of breast cancer biology into a comprehensive network, elucidating previously dissonant issues of cancer metabolism. As such, some of the aspects critically discussed in this review include the dynamic interplay or metabolic coupling between cancer (stem) cells and cancer-associated fibroblasts, the intratumoral and intertumoral heterogeneity and plasticity of cancer cell metabolism, the existence of distinct metabolic tumor compartments in need of separate yet simultaneous therapeutic targeting, the reliance of cancer cells on oxidative metabolism and mitochondrial power, and the role of pro-inflammatory, pro-tumorigenic stromal conditioning. Comprising complex breast cancer signaling networks as well as combined metabolomic and genomic data, we address metabolic consequences of mutations in tumor suppressor genes and evaluate their contribution to breast cancer predisposition in a germline setting, reasoning for distinct personalized preventive and therapeutic measures. The review closes with a discussion on central root mechanisms of tumor cell metabolism and rate-limiting steps thereof, introducing essential strategies for therapeutic targeting. PMID:27590516

  16. Genomic and phenotypic profiles of two Brazilian breast cancer cell lines derived from primary human tumors

    PubMed Central

    CORRÊA, NATÁSSIA C.R.; KUASNE, HELLEN; FARIA, JERUSA A.Q.A.; SEIXAS, CIÇA C.S.; SANTOS, IRIA G.D.; ABREU, FRANCINE B.; NONOGAKI, SUELY; ROCHA, RAFAEL M.; SILVA, GERLUZA APARECIDA BORGES; GOBBI, HELENICE; ROGATTO, SILVIA R.; GOES, ALFREDO M.; GOMES, DAWIDSON A.

    2013-01-01

    Breast cancer is the most common type of cancer among women worldwide. Research using breast cancer cell lines derived from primary tumors may provide valuable additional knowledge regarding this type of cancer. Therefore, the aim of this study was to investigate the phenotypic profiles of MACL-1 and MGSO-3, the only Brazilian breast cancer cell lines available for comparative studies. We evaluated the presence of hormone receptors, proliferation, differentiation and stem cell markers, using immunohistochemical staining of the primary tumor, cultured cells and xenografts implanted in immunodeficient mice. We also investigated the ability of the cell lines to form colonies and copy number alterations by array comparative genomic hybridization. Histopathological analysis showed that the invasive primary tumor from which the MACL-1 cell line was derived, was a luminal A subtype carcinoma, while the ductal carcinoma in situ (DCIS) that gave rise to the MGSO-3 cell line was a HER2 subtype tumor, both showing different proliferation levels. The cell lines and the tumor xenografts in mice preserved their high proliferative potential, but did not maintain the expression of the other markers assessed. This shift in expression may be due to the selection of an ‘establishment’ phenotype in vitro. Whole-genome DNA evaluation showed a large amount of copy number alterations (CNAs) in the two cell lines. These findings render MACL-1 and MGSO-3 the first characterized Brazilian breast cancer cell lines to be potentially used for comparative research. PMID:23404580

  17. TRIM28 multi-domain protein regulates cancer stem cell population in breast tumor development

    PubMed Central

    Czerwińska, Patrycja; Shah, Parantu K.; Tomczak, Katarzyna; Klimczak, Marta; Mazurek, Sylwia; Sozańska, Barbara; Biecek, Przemysław; Korski, Konstanty; Filas, Violetta; Mackiewicz, Andrzej; Andersen, Jannik N.; Wiznerowicz, Maciej

    2017-01-01

    The expression of Tripartite motif-containing protein 28 (TRIM28)/Krüppel-associated box (KRAB)-associated protein 1 (KAP1), is elevated in at least 14 tumor types, including solid and hematopoietic tumors. High level of TRIM28 is associated with triple-negative subtype of breast cancer (TNBC), which shows higher aggressiveness and lower survival rates. Interestingly, TRIM28 is essential for maintaining the pluripotent phenotype in embryonic stem cells. Following on that finding, we evaluated the role of TRIM28 protein in the regulation of breast cancer stem cells (CSC) populations and tumorigenesis in vitro and in vivo. Downregulation of TRIM28 expression in xenografts led to deceased expression of pluripotency and mesenchymal markers, as well as inhibition of signaling pathways involved in the complex mechanism of CSC maintenance. Moreover, TRIM28 depletion reduced the ability of cancer cells to induce tumor growth when subcutaneously injected in limiting dilutions. Our data demonstrate that the downregulation of TRIM28 gene expression reduced the ability of CSCs to self-renew that resulted in significant reduction of tumor growth. Loss of function of TRIM28 leads to dysregulation of cell cycle, cellular response to stress, cancer cell metabolism, and inhibition of oxidative phosphorylation. All these mechanisms directly regulate maintenance of CSC population. Our original results revealed the role of the TRIM28 in regulating the CSC population in breast cancer. These findings may pave the way to novel and more effective therapies targeting cancer stem cells in breast tumors. PMID:27845900

  18. ADAM12 transmembrane and secreted isoforms promote breast tumor growth: a distinct role for ADAM12-S protein in tumor metastasis.

    PubMed

    Roy, Roopali; Rodig, Scott; Bielenberg, Diane; Zurakowski, David; Moses, Marsha A

    2011-06-10

    Increased levels of ADAM12 have been reported in a variety of human cancers. We have previously reported that urinary ADAM12 is predictive of disease status in breast cancer patients and that ADAM12 protein levels in urine increase with progression of disease. On the basis of these findings, the goal of this study was to elucidate the contribution of ADAM12 in breast tumor growth and progression. Overexpression of both the ADAM12-L (transmembrane) and ADAM12-S (secreted) isoforms in human breast tumor cells resulted in a significantly higher rate of tumor take and increased tumor size. Cells expressing the enzymatically inactive form of the secreted isoform, ADAM12-S, had tumor take rates and tumor volumes similar to those of wild-type cells, suggesting that the tumor-promoting activity of ADAM12-S was a function of its proteolytic activity. Of the two isoforms, only the secreted isoform, ADAM12-S, enhanced the ability of tumor cells to migrate and invade in vitro and resulted in a higher incidence of local and distant metastasis in vivo. This stimulatory effect of ADAM12-S on migration and invasion was dependent on its catalytic activity. Expression of both ADAM12 isoforms was found to be significantly elevated in human malignant breast tissue. Taken together, our results suggest that ADAM12 overexpression results in increased tumor take, tumor size, and metastasis in vivo. These findings suggest that ADAM12 may represent a potential therapeutic target in breast cancer.

  19. Determining whether excision of all fibroepithelial lesions of the breast is needed to exclude phyllodes tumor: upgrade rate of fibroepithelial lesions of the breast to phyllodes tumor.

    PubMed

    Van Osdol, Andrew D; Landercasper, Jeffrey; Andersen, Jeremiah J; Ellis, Richard L; Gensch, Erin M; Johnson, Jeanne M; De Maiffe, Brooke; Marcou, Kristen A; Al-Hamadani, Mohammed; Vang, Choua A

    2014-10-01

    Fibroepithelial lesions (FELs) are a common histologic finding on core needle biopsy (CNB) of the breast. Fibroepithelial lesions include fibroadenoma and phyllodes tumor, which can be difficult to distinguish with an initial CNB. An institutional experience was reviewed from February 12, 2001, to January 4, 2007, to determine the safety of selective rather than routine excision of FELs and to determine the factors associated with upgrading diagnosis of FELs to phyllodes tumors without definitive phyllodes tumor diagnosis by CNB. Of 313 patients, 261 (83%) with FELs diagnosed by CNB received observation with long-term follow-up (mean, 8 years). Of the observed patients, 3 (1%) were diagnosed with phyllodes tumor on follow-up. Eighteen of 52 patients (35%) who received excision had an upgrade of diagnosis to phyllodes tumor. Sensitivity and specificity of the pathologist's comment of concern for phyllodes tumor on a CNB demonstrating FELs without definitive phyllodes tumor diagnosis were 82% and 93%, respectively. Our policy of selective excision of FELs without definitive phyllodes tumor diagnosis resulted in safe avoidance of many surgical procedures.

  20. Evaluating mononuclear cells as nanoparticle delivery vehicles for the treatment of breast tumors

    NASA Astrophysics Data System (ADS)

    Murton, Jaclyn K.; Hu, Chelin; Ahmed, Mona M.; Hathaway, Helen J.; Nysus, Monique; Anderson Daniels, Tamara; Norenberg, Jeffrey P.; Adolphi, Natalie L.

    2015-08-01

    In breast cancer, certain types of circulating immune cells respond to long-range chemical signals from tumors by leaving the blood stream to actively infiltrate tumor tissue. The aim of this study was to evaluate whether immune cells could be used to deliver therapeutic nanoparticles into breast tumors in mice. Mononuclear splenocytes (MS) were harvested from donor mice, labeled with Indium-111, injected intravenously into immune-competent recipient mice (3 tumor-bearing and 3 control), and imaged longitudinally by SPECT/CT. For comparison, the biodistribution of bonemarrow derived macrophages (BMDM) in one pair of mice was also imaged. Quantitative analysis of the SPECT images demonstrates that, after 24 hours, the concentration of MS detected in mammary tumors is more than 3-fold higher than the concentration detected in normal mammary glands. The ratio of MS concentration in mammary tissue to MS concentration in non-target tissues (muscle, lung, heart, liver, spleen, and kidney) was enhanced in tumor-bearing mice (compared to controls), with statistical significance achieved for mammary/muscle (p<0.01), mammary/lung (p<0.05), and mammary/kidney (p<0.05). By contrast, BMDM did not show a different affinity for tumors relative to normal mammary tissue. MS were incubated with 100 nm red fluorescent nanoparticles, and flow cytometry demonstrated that ~35% of the MS population exhibited strong phagocytic uptake of the nanoparticles. After intravenous injection into tumor-bearing mice, fluorescence microscopy images of tumor sections show qualitatively that nanoparticle-loaded MS retain the ability to infiltrate mammary tumors. Taken together, these results suggest that MS carriers are capable of actively targeting therapeutic nanoparticles to breast tumors.

  1. Advances in Breast Cancer – Looking Back over the Year

    PubMed Central

    Lüftner, D.; Lux, M. P.; Maass, N.; Schütz, F.; Schwidde, I.; Fasching, P. A.; Fehm, T.; Janni, W.; Kümmel, S.; Kolberg, H.-C.

    2012-01-01

    Treatment options as well as the characteristics for therapeutic decisions in patients with primary and advanced breast cancer are increasing in number and variety. New targeted therapies in combination with established chemotherapy schemes are broadening the spectrum, yet not every new, promising combination achieves a better result. New data from the field of pharmacogenomics point to prognostic and predictive factors that take not only the properties of the tumour but also the genetic disposition of the patient into consideration. Current therapeutic decision-making is thus based on a combination of classical clinical and modern molecular biomarkers. Health-economic concerns are also being taken into consideration more frequently, meaning political decisions may also become a factor. This review presents the trends over the past year. PMID:26640285

  2. Caveolin-1 and Accelerated Host Aging in the Breast Tumor Microenvironment

    PubMed Central

    Mercier, Isabelle; Camacho, Jeanette; Titchen, Kanani; Gonzales, Donna M.; Quann, Kevin; Bryant, Kelly G.; Molchansky, Alexander; Milliman, Janet N.; Whitaker-Menezes, Diana; Sotgia, Federica; Jasmin, Jean-François; Schwarting, Roland; Pestell, Richard G.; Blagosklonny, Mikhail V.; Lisanti, Michael P.

    2013-01-01

    Increasing chronological age is the most significant risk factor for human cancer development. To examine the effects of host aging on mammary tumor growth, we used caveolin (Cav)-1 knockout mice as a bona fide model of accelerated host aging. Mammary tumor cells were orthotopically implanted into these distinct microenvironments (Cav-1+/+ versus Cav-1−/− age-matched young female mice). Mammary tumors grown in a Cav-1–deficient tumor microenvironment have an increased stromal content, with vimentin-positive myofibroblasts (a marker associated with oxidative stress) that are also positive for S6-kinase activation (a marker associated with aging). Mammary tumors grown in a Cav-1–deficient tumor microenvironment were more than fivefold larger than tumors grown in a wild-type microenvironment. Thus, a Cav-1–deficient tumor microenvironment provides a fertile soil for breast cancer tumor growth. Interestingly, the mammary tumor-promoting effects of a Cav-1–deficient microenvironment were estrogen and progesterone independent. In this context, chemoprevention was achieved by using the mammalian target of rapamycin (mTOR) inhibitor and anti-aging drug, rapamycin. Systemic rapamycin treatment of mammary tumors grown in a Cav-1–deficient microenvironment significantly inhibited their tumor growth, decreased their stromal content, and reduced the levels of both vimentin and phospho-S6 in Cav-1–deficient cancer-associated fibroblasts. Since stromal loss of Cav-1 is a marker of a lethal tumor microenvironment in breast tumors, these high-risk patients might benefit from treatment with mTOR inhibitors, such as rapamycin or other rapamycin-related compounds (rapalogues). PMID:22698676

  3. Leptin as a mediator of tumor-stromal interactions promotes breast cancer stem cell activity.

    PubMed

    Giordano, Cinzia; Chemi, Francesca; Panza, Salvatore; Barone, Ines; Bonofiglio, Daniela; Lanzino, Marilena; Cordella, Angela; Campana, Antonella; Hashim, Adnan; Rizza, Pietro; Leggio, Antonella; Győrffy, Balázs; Simões, Bruno M; Clarke, Robert B; Weisz, Alessandro; Catalano, Stefania; Andò, Sebastiano

    2016-01-12

    Breast cancer stem cells (BCSCs) play crucial roles in tumor initiation, metastasis and therapeutic resistance. A strict dependency between BCSCs and stromal cell components of tumor microenvironment exists. Thus, novel therapeutic strategies aimed to target the crosstalk between activated microenvironment and BCSCs have the potential to improve clinical outcome. Here, we investigated how leptin, as a mediator of tumor-stromal interactions, may affect BCSC activity using patient-derived samples (n = 16) and breast cancer cell lines, and determined the potential benefit of targeting leptin signaling in these model systems. Conditioned media (CM) from cancer-associated fibroblasts and breast adipocytes significantly increased mammosphere formation in breast cancer cells and depletion of leptin from CM completely abrogated this effect. Mammosphere cultures exhibited increased leptin receptor (OBR) expression and leptin exposure enhanced mammosphere formation. Microarray analyses revealed a similar expression profile of genes involved in stem cell biology among mammospheres treated with CM and leptin. Interestingly, leptin increased mammosphere formation in metastatic breast cancers and expression of OBR as well as HSP90, a target of leptin signaling, were directly correlated with mammosphere formation in metastatic samples (r = 0.68/p = 0.05; r = 0.71/p = 0.036, respectively). Kaplan-Meier survival curves indicated that OBR and HSP90 expression were associated with reduced overall survival in breast cancer patients (HR = 1.9/p = 0.022; HR = 2.2/p = 0.00017, respectively). Furthermore, blocking leptin signaling by using a full leptin receptor antagonist significantly reduced mammosphere formation in breast cancer cell lines and patient-derived samples. Our results suggest that leptin/leptin receptor signaling may represent a potential therapeutic target that can block the stromal-tumor interactions driving BCSC-mediated disease progression.

  4. Letrozole in advanced breast cancer: the PO25 trial

    PubMed Central

    2007-01-01

    Tamoxifen has been a standard first-line endocrine therapy for post-menopausal women with hormone-responsive advanced breast cancer, but more than half of patients fail to respond and time to progression is less than 12 months in responders. The third-generation aromatase inhibitors were developed to provide more effective alternatives to tamoxifen. In the Femara Study PO25, post-menopausal women with advanced breast cancer were randomized to receive letrozole 2.5 mg (n = 453) or tamoxifen 20 mg (n = 454) given orally daily until progressive disease occurred. Patients were permitted to cross over to the other treatment at progression. In the primary efficacy analysis, median time to progression (TTP) was significantly longer with letrozole than with tamoxifen (9.4 months vs. 6.0 months, respectively; P < 0.0001). The objective response rate (ORR) was significantly higher for letrozole than for tamoxifen (32% vs. 21%; P = 0.0002). Prospectively planned analyses of the intent-to-treat population showed that letrozole significantly improved overall survival (OS) compared with tamoxifen over the first 24 months of the trial. An exploratory analysis of patients, who did not cross over, indicated a median OS benefit of 14 months for letrozole compared with tamoxifen. Letrozole is the only third-generation aromatase inhibitor that has demonstrated significant improvements in ORR, TTP, and early OS. PMID:17333340

  5. Interface between breast cancer cells and the tumor microenvironment using platelet-rich plasma to promote tumor angiogenesis - influence of platelets and fibrin bundles on the behavior of breast tumor cells.

    PubMed

    Andrade, Sheila Siqueira; Sumikawa, Joana Tomomi; Castro, Eloísa Dognani; Batista, Fabricio Pereira; Paredes-Gamero, Edgar; Oliveira, Lilian Carolina; Guerra, Izabel Monastério; Peres, Giovani Bravin; Cavalheiro, Renan Pelluzzi; Juliano, Luiz; Nazário, Afonso Pinto; Facina, Gil; Tsai, Siu Mui; Oliva, Maria Luiza Vilela; Girão, Manoel João Batista Castello

    2017-02-07

    Cancer progression is associated with an evolving tissue interface of direct epithelial-tumor microenvironment interactions. In biopsies of human breast tumors, extensive alterations in molecular pathways are correlated with cancer staging on both sides of the tumor-stroma interface. These interactions provide a pivotal paracrine signaling to induce malignant phenotype transition, the epithelial-mesenchymal transition (EMT). We explored how the direct contact between platelets-fibrin bundles primes metastasis using platelet-rich plasma (PRP) as a source of growth factors and mimics the provisional fibrin matrix between actively growing breast cancer cells and the tumor stroma. We have demonstrated PRP functions, modulating cell proliferation that is tumor-subtype and cancer cell-type-specific. Epithelial and stromal primary cells were prepared from breast cancer biopsies from 21 women with different cancer subtypes. Cells supplemented with PRP were immunoblotted with anti-phospho and total Src-Tyr-416, FAK-Try-925, E-cadherin, N-cadherin, TGF-β, Smad2, and Snail monoclonal antibodies. Breast tumor cells from luminal B and HER2 subtypes showed the most malignant profiles and the expression of thrombin and other classes of proteases at levels that were detectable through FRET peptide libraries. The angiogenesis process was investigated in the interface obtained between platelet-fibrin-breast tumor cells co-cultured with HUVEC cells. Luminal B and HER2 cells showed robust endothelial cell capillary-like tubes ex vivo. The studied interface contributes to the attachment of endothelial cells, provides a source of growth factors, and is a solid substrate. Thus, replacement of FBS supplementation with PRP supplementation represents an efficient and simple approach for mimicking the real multifactorial tumor microenvironment.

  6. Decreased expression of ADAMTS-1 in human breast tumors stimulates migration and invasion

    PubMed Central

    2013-01-01

    Background ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motifs) is a member of the ADAMTS family of metalloproteases. Here, we investigated mRNA and protein levels of ADAMTS-1 in normal and neoplastic tissues using qPCR, immunohistochemistry and immunoblot analyses, and we addressed the role of ADAMTS-1 in regulating migration, invasion and invadopodia formation in breast tumor cell lines. Results In a series of primary breast tumors, we observed variable levels of ADAMTS-1 mRNA expression but lower levels of ADAMTS-1 protein expression in human breast cancers as compared to normal tissue, with a striking decrease observed in high-malignancy cases (triple-negative for estrogen, progesterone and Her-2). This result prompted us to analyze the effect of ADAMTS-1 knockdown in breast cancer cells in vitro. MDA-MB-231 cells with depleted ADAMTS-1 expression demonstrated increased migration, invasion and invadopodia formation. The regulatory mechanisms underlying the effects of ADAMTS-1 may be related to VEGF, a growth factor involved in migration and invasion. MDA-MB-231 cells with depleted ADAMTS-1 showed increased VEGF concentrations in conditioned medium capable of inducing human endothelial cells (HUVEC) tubulogenesis. Furthermore, expression of the VEGF receptor (VEGFR2) was increased in MDA-MB-231 cells as compared to MCF7 cells. To further determine the relationship between ADAMTS-1 and VEGF regulating breast cancer cells, MDA-MB-231 cells with reduced expression of ADAMTS-1 were pretreated with a function-blocking antibody against VEGF and then tested in migration and invasion assays; both were partially rescued to control levels. Conclusions ADAMTS-1 expression was decreased in human breast tumors, and ADAMTS-1 knockdown stimulated migration, invasion and invadopodia formation in breast cancer cells in vitro. Therefore, this series of experiments suggests that VEGF is involved in the effects mediated by ADAMTS-1 in breast cancer cells. PMID

  7. Decreased expression of SOX17 is associated with tumor progression and poor prognosis in breast cancer.

    PubMed

    Fu, De-Yuan; Tan, Hao-Sheng; Wei, Jin-Li; Zhu, Chang-Ren; Jiang, Ji-Xin; Zhu, Yu-Xiang; Cai, Feng-Lin; Chong, Mei-Hong; Ren, Chuan-Li

    2015-09-01

    The SOX17 (SRY-related HMG-box) transcription factor is involved in a variety of biological processes and is related to the tumorigenesis and progression of multiple tumors. However, the clinical application of SOX17 for breast cancer prognosis is currently limited. The aim of this study was to investigate the clinicopathologic and prognostic significance of SOX17 expression in human breast cancer. qPCR and western blot assays were performed to measure the expression of SOX17 in breast cancer cell lines and 30 matched pairs of breast cancer and corresponding noncancerous tissues. A SOX17 overexpression cell model was used to examine changes in cell growth in vitro. Immunohistochemical analyses were performed to retrospectively examine the prognostic impact of SOX17 expression in 187 additional breast cancer patients. Our results showed that SOX17 expression was decreased at both the messenger RNA (mRNA) and protein levels in the breast cancer cell lines and tissues, and that SOX17 overexpression could strongly suppress cell growth in vitro. Furthermore, the lack of SOX17 protein expression was strongly correlated with higher tumor grade (P = 0.002), lymph node metastasis (P < 0.001), and tumor node metastasis (TNM) stage (P = 0.001) and had poorer disease-free survival (DFS) and overall survival (OS) compared to normal SOX17 expression (P = 0.002 and 0.001, respectively). Univariate and multivariate analyses indicated that lower SOX17 expression was an independent prognostic factor for DFS (P = 0.007; HR = 2.854; 95 % CI 1.326-6.147) and OS (P = 0.005; HR = 5.035; 95 % CI 1.648-15.385) for breast cancer. Our findings indicate that SOX17 expression is a useful prognostic biomarker for breast cancer.

  8. A phase II study of axitinib in advanced neuroendocrine tumors

    PubMed Central

    Strosberg, J R; Cives, M; Hwang, J; Weber, T; Nickerson, M; Atreya, C E; Venook, A; Kelley, R K; Valone, T; Morse, B; Coppola, D; Bergsland, E K

    2016-01-01

    Neuroendocrine tumors (NETs) are highly vascular neoplasms overexpressing vascular endothelial growth factor (VEGF) as well as VEGF receptors (VEGFR). Axitinib is a potent, selective inhibitor of VEGFR-1, -2 and -3, currently approved for the treatment of advanced renal cell carcinoma. We performed an open-label, two-stage design, phase II trial of axitinib 5 mg twice daily in patients with progressive unresectable/metastatic low-to-intermediate grade carcinoid tumors. The primary end points were progression-free survival (PFS) and 12-month PFS rate. The secondary end points included time to treatment failure (TTF), overall survival (OS), overall radiographic response rate (ORR), biochemical response rate and safety. A total of 30 patients were enrolled and assessable for toxicity; 22 patients were assessable for response. After a median follow-up of 29 months, we observed a median PFS of 26.7 months (95% CI, 11.4–35.1), with a 12-month PFS rate of 74.5% (±10.2). The median OS was 45.3 months (95% CI, 24.4–45.3), and the median TTF was 9.6 months (95% CI, 5.5–12). The best radiographic response was partial response (PR) in 1/30 (3%) and stable disease (SD) in 21/30 patients (70%); 8/30 patients (27%) were unevaluable due to early withdrawal due to toxicity. Hypertension was the most common toxicity that developed in 27 patients (90%). Grade 3/4 hypertension was recorded in 19 patients (63%), leading to treatment discontinuation in six patients (20%). Although axitinib appears to have an inhibitory effect on tumor growth in patients with advanced, progressive carcinoid tumors, the high rate of grade 3/4 hypertension may represent a potential impediment to its use in unselected patients. PMID:27080472

  9. Causal Therapy of Breast Cancer Irrelevant of Age, Tumor Stage and 
ER-Status: Stimulation of Estrogen Signaling Coupled With Breast 
Conserving Surgery

    PubMed Central

    Suba, Zsuzsanna

    2016-01-01

    Abstract: Background Results of long-term studies justify that the rate of breast cancer recurrence and tumor-related mortality remains quite unpredictable, regardless of the use of any current therapeutic measures. Objective Since the application of standard therapies, such as surgery, radiation, chemotherapy and antiestrogen administration does not work as might be expected; our therapeutic practice requires thorough rethinking. Method Published long-term therapeutic results on breast cancer cases were analyzed in correlation with stage at diagnosis, ER-status of tumors and patients’ age. The effectiveness of current therapeutic measures was also compared by estimating the rate of tumor-free survival, breast cancer recurrence and breast cancer-specific mortality. Results Diagnosis and treatment of breast cancer at an early stage cannot improve the rate of tumor-free survival. Poor differentiation of tumors, ER-negativity in particular, defines poor prognosis even after applying aggressive therapies. In patients treated with in situ breast cancer, the recurrence-rate of invasive tumor increased directly with ageing irrespective of tumor size or ER-status at diagnosis. Women who underwent lumpectomy without adjuvant radiation or chemotherapy exhibited significantly better overall and breast cancer specific survival rates than those receiving mastectomy, regardless of stage and ER-status of tumors. Antiestrogen treatment exhibited unforeseeable effectiveness even on targeted ER-positive tumors. Recent patents propose the detection of ESR1-gene amplification or restoration of ER-alpha expression for prediction of effective antiestrogen treatment, suggesting a crucial inhibitory role of estrogen-signaling against tumor-growth. Conclusion Estradiol-induced upregulation of estrogen signaling coupled with sparing of the estrogen-rich mammary fatpad are the most effective strategies against breast cancer. PMID:27087654

  10. Integrated Bioinformatics Approach Reveals Crosstalk Between Tumor Stroma and Peripheral Blood Mononuclear Cells in Breast Cancer.

    PubMed

    He, Lang; Wang, Dan; Wei, Na; Guo, Zheng

    2016-01-01

    Breast cancer is now the leading cause of cancer death in women worldwide. Cancer progression is driven not only by cancer cell intrinsic alterations and interactions with tumor microenvironment, but also by systemic effects. Integration of multiple profiling data may provide insights into the underlying molecular mechanisms of complex systemic processes. We performed a bioinformatic analysis of two public available microarray datasets for breast tumor stroma and peripheral blood mononuclear cells, featuring integrated transcriptomics data, protein-protein interactions (PPIs) and protein subcellular localization, to identify genes and biological pathways that contribute to dialogue between tumor stroma and the peripheral circulation. Genes of the integrin family as well as CXCR4 proved to be hub nodes of the crosstalk network and may play an important role in response to stroma-derived chemoattractants. This study pointed to potential for development of therapeutic strategies that target systemic signals travelling through the circulation and interdict tumor cell recruitment.

  11. A Rare Breast Tumor Confused with Ductal Carcinoma in Situ, Primary Solid Neuroendocrine Carcinoma

    PubMed Central

    Alıcı, Ömer; Aydoğdu, Serap Korkmaz

    2014-01-01

    The concept of pure neuroendocrine breast tumors was initially defined by Sapino et al. There are three sub-types of these tumors: solid, small cell/oat cell, and large cell neuroendocrine carcinomas. To diagnose neuroendocrine tumors, more than half of the tumor cells must have neuroendocrine differentiation. The possibility of metastatic neuroendocrine carcinoma must always be excluded in the differential diagnosis. In addition, it should be considered that solid neuroendocrine (NE) carcinomas can be confused with ductal carcinoma in situ due to their similar morphologic appearance. In this article, a patient with primary solid neuroendocrine breast cancer who had been diagnosed with ductal carcinoma in situ at another center was presented along with morphological and immunohistochemical features.

  12. Monitoring the response to neoadjuvant hormone therapy for locally advanced breast cancer using three-dimensional time-resolved optical mammography

    NASA Astrophysics Data System (ADS)

    Enfield, Louise; Cantanhede, Gabriel; Douek, Michael; Ramalingam, Vernie; Purushotham, Arnie; Hebden, Jem; Gibson, Adam

    2013-05-01

    Optical mammography is a functional imaging technique that uses near-infrared light to produce three-dimensional breast images of tissue oxygen saturation and hemoglobin concentration. It has been used to monitor the response to neoadjuvant chemotherapy in breast cancer patients. We present the first results on monitoring tumor response to hormone therapy using optical mammography. We present three case studies from postmenopausal women treated with neoadjuvant hormone therapy for locally advanced breast cancer. The women were scanned before starting treatment, once during treatment, and then before surgery. Changes in physiological and optical properties within the tumor and in the rest of the breast were evaluated. At the time of surgery, two patients partially responded to treatment and one did not respond. The patients that partially responded on ultrasound revealed a corresponding recovery to normal in the hemoglobin concentration images, whereas the nonresponder indicated an increase in hemoglobin concentration in the tumor compared to her pretreatment images. These case studies suggest that optical imaging of the breast during neoadjuvant hormone treatment can provide potentially valuable information, and that physiological changes within the tumor can be seen in response to treatment.

  13. Netrin-1 expression confers a selective advantage for tumor cell survival in metastatic breast cancer

    PubMed Central

    Fitamant, Julien; Guenebeaud, Céline; Coissieux, Marie-May; Guix, Catherine; Treilleux, Isabelle; Scoazec, Jean-Yves; Bachelot, Thomas; Bernet, Agnès; Mehlen, Patrick

    2008-01-01

    Netrin-1, an axon navigation cue was proposed to play a crucial role during colorectal tumorigenesis by regulating apoptosis. The netrin-1 receptors DCC and UNC5H were shown to belong to the family of dependence receptors that share the ability to induce apoptosis in the absence of their ligands. Such a trait confers on these receptors a tumor suppressor activity. Expression of one of these dependence receptors at the surface of a tumor cell is indeed speculated to render this cell dependent on ligand availability for its survival, hence inhibiting uncontrolled cell proliferation or metastasis. Consequently, it is a selective advantage for a tumor cell to lose this dependence receptor activity, as previously described with losses of DCC and UNC5H expression in human cancers. However, the model predicts that a similar advantage may be obtained by gaining autocrine expression of the ligand. We describe here that, unlike human nonmetastatic breast tumors, a large fraction of metastatic breast cancers overexpress netrin-1. Moreover, we show that netrin-1-expressing mammary metastatic tumor cell lines undergo apoptosis when netrin-1 expression is experimentally decreased or when decoy soluble receptor ectodomains are added. Such treatments prevent metastasis formation both in a syngenic mouse model of lung colonization of a mammary cancer cell line and in a model of spontaneous lung metastasis of xenografted human breast tumor. Thus, netrin-1 expression observed in a large fraction of human metastatic breast tumors confers a selective advantage for tumor cell survival and potentially represents a promising target for alternative anticancer therapeutic strategies. PMID:18353983

  14. Influence of the Tumor Microenvironment on Genomic Changes Conferring Chemoresistance in Breast Cancer

    DTIC Science & Technology

    2013-04-01

    tumor microenvironment on clonal selection using intravital microscopy Jae-Hyun Park 1 , Miriam R. Fein 1 , Mikala Egeblad 1 1 Cold Spring Harbor...used surgically implanted mammary imaging windows in immunocompetent mice and injected “brainbow” expressing, syngeneic 4T1 breast carcinoma cells...under the windows. This allowed us to acquire multiple time- lapse imaging series by spinning disk confocal microscopy of the same tumor, done about 3

  15. The fate of BRCA1-related germline mutations in triple-negative breast tumors.

    PubMed

    Kotoula, Vassiliki; Fostira, Florentia; Papadopoulou, Kyriaki; Apostolou, Paraskevi; Tsolaki, Eleftheria; Lazaridis, Georgios; Manoussou, Kyriaki; Zagouri, Flora; Pectasides, Dimitrios; Vlachos, Ioannis; Tikas, Ioannis; Lakis, Sotiris; Konstantopoulou, Irene; Pentheroudakis, George; Gogas, Helen; Papakostas, Pavlos; Christodoulou, Christos; Bafaloukos, Dimitrios; Razis, Evangelia; Karavasilis, Vasilios; Bamias, Christina; Yannoukakos, Drakoulis; Fountzilas, George

    2017-01-01

    The preservation of pathogenic BRCA1/2 germline mutations in tumor tissues is usually not questioned, while it remains unknown whether these interact with somatic genotypes for patient outcome. Herein we compared germline and tumor genotypes in operable triple-negative breast cancer (TNBC) and evaluated their combined effects on prognosis. We analyzed baseline germline and primary tumor genotype data obtained by Sanger and Next Generation Sequencing in 194 TNBC patients. We also performed multiple tests interrogating the preservation of germline mutations in matched tumors and breast tissue from carriers with available material. Patients had been treated within clinical trials with adjuvant anthracyclines-taxanes based chemotherapy. We identified 50 (26%) germline mutation carriers (78% in BRCA1) and 136 (71%) tumors with somatic mutations (83% in TP53). Tumor mutation patterns differed between carriers and non-carriers (P<0.001); PIK3CA mutations were exclusively present in non-carriers (P=0.007). Germline BRCA1/2 mutations were not detected in matched tumors and breast tissues from 14 out of 33 (42%) evaluable carriers. Microsatellite markers revealed tumor loss of the germline mutant allele in one case only. Tumors that had lost the germline mutation demonstrated a higher incidence of somatic TP53 mutations as compared to tumors with preserved germline mutations (P=0.036). Germline mutation status significantly interacted with tumor TP53 mutations for patient disease-free survival (interaction P=0.026): In non-carriers, tumor TP53 mutations did not affect outcome; In carriers, those with mutated TP53 tumors experienced more relapses compared to those with wild-type TP53 tumors (36% vs. 9% relapse rate, respectively). In conclusion, we show that loss of germline BRCA1/2 mutations is not a rare event in TNBC. This finding, the observed differences in tumor genotypes with respect to germline status and the prognostic interaction between germline BRCA1-related and

  16. The fate of BRCA1-related germline mutations in triple-negative breast tumors

    PubMed Central

    Kotoula, Vassiliki; Fostira, Florentia; Papadopoulou, Kyriaki; Apostolou, Paraskevi; Tsolaki, Eleftheria; Lazaridis, Georgios; Manoussou, Kyriaki; Zagouri, Flora; Pectasides, Dimitrios; Vlachos, Ioannis; Tikas, Ioannis; Lakis, Sotiris; Konstantopoulou, Irene; Pentheroudakis, George; Gogas, Helen; Papakostas, Pavlos; Christodoulou, Christos; Bafaloukos, Dimitrios; Razis, Evangelia; Karavasilis, Vasilios; Bamias, Christina; Yannoukakos, Drakoulis; Fountzilas, George

    2017-01-01

    The preservation of pathogenic BRCA1/2 germline mutations in tumor tissues is usually not questioned, while it remains unknown whether these interact with somatic genotypes for patient outcome. Herein we compared germline and tumor genotypes in operable triple-negative breast cancer (TNBC) and evaluated their combined effects on prognosis. We analyzed baseline germline and primary tumor genotype data obtained by Sanger and Next Generation Sequencing in 194 TNBC patients. We also performed multiple tests interrogating the preservation of germline mutations in matched tumors and breast tissue from carriers with available material. Patients had been treated within clinical trials with adjuvant anthracyclines-taxanes based chemotherapy. We identified 50 (26%) germline mutation carriers (78% in BRCA1) and 136 (71%) tumors with somatic mutations (83% in TP53). Tumor mutation patterns differed between carriers and non-carriers (P<0.001); PIK3CA mutations were exclusively present in non-carriers (P=0.007). Germline BRCA1/2 mutations were not detected in matched tumors and breast tissues from 14 out of 33 (42%) evaluable carriers. Microsatellite markers revealed tumor loss of the germline mutant allele in one case only. Tumors that had lost the germline mutation demonstrated a higher incidence of somatic TP53 mutations as compared to tumors with preserved germline mutations (P=0.036). Germline mutation status significantly interacted with tumor TP53 mutations for patient disease-free survival (interaction P=0.026): In non-carriers, tumor TP53 mutations did not affect outcome; In carriers, those with mutated TP53 tumors experienced more relapses compared to those with wild-type TP53 tumors (36% vs. 9% relapse rate, respectively). In conclusion, we show that loss of germline BRCA1/2 mutations is not a rare event in TNBC. This finding, the observed differences in tumor genotypes with respect to germline status and the prognostic interaction between germline BRCA1-related and

  17. Global H3K27 trimethylation and EZH2 abundance in breast tumor subtypes.

    PubMed

    Holm, Karolina; Grabau, Dorthe; Lövgren, Kristina; Aradottir, Steina; Gruvberger-Saal, Sofia; Howlin, Jillian; Saal, Lao H; Ethier, Stephen P; Bendahl, Pär-Ola; Stål, Olle; Malmström, Per; Fernö, Mårten; Rydén, Lisa; Hegardt, Cecilia; Borg, Åke; Ringnér, Markus

    2012-10-01

    Polycomb repressive complex 2 (PRC2) and its core member enhancer of zeste homolog 2 (EZH2) mediate the epigenetic gene silencing mark: trimethylation of lysine 27 on histone 3 (H3K27me3). H3K27me3 is characteristic of the chromatin at genes involved in developmental regulation in undifferentiated cells. Overexpression of EZH2 has been found in several cancer types such as breast, prostate, melanoma and bladder cancer. Moreover, overexpression is associated with highly proliferative and aggressive types of breast and prostate tumors. We have analyzed the abundance of EZH2 and H3K27me3 using immunohistochemistry in two large and well-characterized breast tumor data sets encompassing more than 400 tumors. The results have been analyzed in relation to the molecular subtypes of breast tumors (basal-like, luminal A, luminal B, HER2-enriched and normal-like), as well as in subtypes defined by clinical markers (triple negative, ER+/HER2-/Ki67low, ER+/HER2-/Ki67high and HER2+), and were validated in representative breast cancer cell lines by western blot. We found significantly different expression of both EZH2 and H3K27me3 across all subtypes with high abundance of EZH2 in basal-like, triple negative and HER2-enriched tumors, and high H3K27me3 in luminal A, HER2-enriched and normal-like tumors. Intriguingly, the two markers show an inverse correlation, particularly for the basal-like and triple negative tumors. Consequently, high expression of EZH2 was associated with poor distant disease-free survival whereas high expression of H3K27me3 was associated with better survival. Additionally, none of 182 breast tumors was found to carry a previously described EZH2 mutation affecting Tyr641. Our observation that increased expression of EZH2 does not necessarily correlate with increased abundance of H3K27me3 supports the idea that EZH2 can have effects beyond epigenetic silencing of target genes in breast cancer.

  18. Nav1.5 regulates breast tumor growth and metastatic dissemination in vivo.

    PubMed

    Nelson, Michaela; Yang, Ming; Millican-Slater, Rebecca; Brackenbury, William J

    2015-10-20

    Voltage-gated Na+ channels (VGSCs) mediate action potential firing and regulate adhesion and migration in excitable cells. VGSCs are also expressed in cancer cells. In metastatic breast cancer (BCa) cells, the Nav1.5 α subunit potentiates migration and invasion. In addition, the VGSC-inhibiting antiepileptic drug phenytoin inhibits tumor growth and metastasis. However, the functional activity of Nav1.5 and its specific contribution to tumor progression in vivo has not been delineated. Here, we found that Nav1.5 is up-regulated at the protein level in BCa compared with matched normal breast tissue. Na+ current, reversibly blocked by tetrodotoxin, was retained in cancer cells in tumor tissue slices, thus directly confirming functional VGSC activity in vivo. Stable down-regulation of Nav1.5 expression significantly reduced tumor growth, local invasion into surrounding tissue, and metastasis to liver, lungs and spleen in an orthotopic BCa model. Nav1.5 down-regulation had no effect on cell proliferation or angiogenesis within the in tumors, but increased apoptosis. In vitro, Nav1.5 down-regulation altered cell morphology and reduced CD44 expression, suggesting that VGSC activity may regulate cellular invasion via the CD44-src-cortactin signaling axis. We conclude that Nav1.5 is functionally active in cancer cells in breast tumors, enhancing growth and metastatic dissemination. These findings support the notion that compounds targeting Nav1.5 may be useful for reducing metastasis.

  19. Identification of Fat4 as a candidate tumor suppressor gene in breast cancers

    PubMed Central

    Qi, Chao; Zhu, Yiwei Tony; Hu, Liping; Zhu, Yi-Jun

    2009-01-01

    Fat, a candidate tumor suppressor in drosophila, is a component of Hippo signaling pathway involved in controlling organ size. We found that a ~3Mbp deletion in mouse chromosome 3 caused tumorigenesis of a non-tumorigenic mammary epithelial cell line. The expression of Fat4 gene, one member of the Fat family, in the deleted region was inactivated, which resulted from promoter methylation of another Fat4 allele following the deletion of one Fat4 allele. Re-expression of Fat4 in Fat4-deficient tumor cells suppressed the tumorigenecity while suppression of Fat4 expression in the non-tumorigenic mammary epithelial cell line induced tumorigenesis. We also found that Fat4 expression was lost in a large fraction of human breast tumor cell lines and primary tumors. Loss of Fat4 expression in breast tumors was associated with human Fat4 promoter methylation. Together, these findings suggest that Fat4 is a strong candidate for a breast tumor suppressor gene. PMID:19048595

  20. Overexpression of the protein tyrosine phosphatase PRL-2 correlates with breast tumor formation and progression.

    PubMed

    Hardy, Serge; Wong, Nau Nau; Muller, William J; Park, Morag; Tremblay, Michel L

    2010-11-01

    The PRL-1, PRL-2, and PRL-3 phosphatases are prenylated protein tyrosine phosphatases with oncogenic activity that are proposed to drive tumor metastasis. We found that PRL-2 mRNA is elevated in primary breast tumors relative to matched normal tissue, and also dramatically elevated in metastatic lymph nodes compared with primary tumors. PRL-2 knockdown in metastatic MDA-MB-231 breast cancer cells decreased anchorage-independent growth and cell migration, suggesting that the malignant phenotype of these cells is mediated at least in part through PRL-2 signaling. In different mouse mammary tumor-derived cell lines overexpressing PRL-2, we confirmed its role in anchorage-independent growth and cell migration. Furthermore, injection of PRL-2-overexpressing cells into the mouse mammary fat pad promoted extracellular signal-regulated kinase 1/2 activation and tumor formation. MMTV-PRL-2 transgenic mice engineered to overexpress the enzyme in mammary tissue did not exhibit spontaneous tumorigenesis, but they exhibited an accelerated development of mammary tumors initiated by introduction of an MMTV-ErbB2 transgene. Together, our results argue that PRL-2 plays a role in breast cancer progression.

  1. In vivo photoacoustic imaging of breast cancer tumor with HER2-targeted nanodiamonds

    NASA Astrophysics Data System (ADS)

    Zhang, Ti; Cui, Huizhong; Fang, Chia-Yi; Jo, Janggun; Yang, Xinmai; Chang, Huan-Cheng; Forrest, M. Laird

    2013-09-01

    Radiation-damaged nanodiamonds (NDs) are ideal optical contrast agents for photoacoustic (PA) imaging in biological tissues due to their good biocompatibility and high optical absorbance in the near-infrared (NIR) range. Acid treated NDs are oxidized to form carboxyl groups on the surface, functionalized with polyethylene glycol (PEG) and human epidermal growth factor receptor 2 (HER2) targeting ligand for breast cancer tumor imaging. Because of the specific binding of the ligand conjugated NDs to the HER2-overexpressing murine breast cancer cells (4T1.2 neu), the tumor tissues are significantly delineated from the surrounding normal tissue at wavelength of 820 nm under the PA imaging modality. Moreover, HER2 targeted NDs (HER2-PEG-NDs) result in higher accumulation in HER2 positive breast tumors as compared to non-targeted NDs after intravenous injection (i.v.). Longer retention time of HER-PEG-NDs is observed in HER2 overexpressing tumor model than that in negative tumor model (4T1.2). This demonstrates that targeting moiety conjugated NDs have great potential for the sensitive detection of cancer tumors and provide an attractive delivery strategy for anti-cancer drugs.

  2. Stepwise heterogeneity analysis of breast tumors in perfusion DCE-MRI datasets

    NASA Astrophysics Data System (ADS)

    Mohajer, Mojgan; Schmid, Volker J.; Engels, Nina A.; Noel, Peter B.; Rummeny, Ernst; Englmeier, Karl-Hans

    2012-03-01

    The signal curves in perfusion dynamic contrast enhanced MRI (DCE-MRI) of cancerous breast tissue reveal valuable information about tumor angiogenesis. Pathological studies have illustrated that breast tumors consist of different subregions, especially with more homogeneous properties during their growth. Differences should be identifiable in DCEMRI signal curves if the characteristics of these sub-regions are related to the perfusion and angiogenesis. We introduce a stepwise clustering method which in a first step uses a new similarity measure. The new similarity measure (PM) compares how parallel washout phases of two curves are. To distinguish the starting point of the washout phase, a linear regression method is partially fitted to the curves. In the next step, the minimum signal value of the washout phase is normalized to zero. Finally, PM is calculated according to maximal variation among the point wise differences during washout phases. In the second step of clustering the groups of signal curves with parallel washout are clustered using Euclidean distance. The introduced method is evaluated on 15 DCE-MRI breast datasets with different types of breast tumors. The use of our new heterogeneity analysis is feasible in single patient examination and improves breast MR diagnostics.

  3. Pit-1 inhibits BRCA1 and sensitizes human breast tumors to cisplatin and vitamin D treatment

    PubMed Central

    Seoane, Samuel; Arias, Efigenia; Sigueiro, Rita; Sendon-Lago, Juan; Martinez-Ordoñez, Anxo; Castelao, Esteban; Eiró, Noemí; Garcia-Caballero, Tomás; Macia, Manuel; Lopez-Lopez, Rafael; Maestro, Miguel; Vizoso, Francisco; Mouriño, Antonio; Perez-Fernandez, Roman

    2015-01-01

    The POU class 1 homeobox 1 (POU1F1, also known as Pit-1), pertaining to the Pit-Oct-Unc (POU) family of transcription factors, has been related to tumor growth and metastasis in breast. However, its role in response to breast cancer therapy is unknown. We found that Pit-1 down-regulated DNA-damage and repair genes, and specifically inhibited BRCA1 gene expression, sensitizing breast cancer cells to DNA-damage agents. Administration of 1α, 25-dihydroxy-3-epi-vitamin D3 (3-Epi, an endogenous low calcemic vitamin D metabolite) reduced Pit-1 expression, and synergized with cisplatin, thus, decreasing cell proliferation and apoptosis in vitro, and reducing tumor growth in vivo. In addition, fifteen primary cultures of human breast tumors showed significantly decreased proliferation when treated with 3-Epi+cisplatin, compared to cisplatin alone. This response positively correlated with Pit-1 levels. Our findings demonstrate that high levels of Pit-1 and reduced BRCA1 levels increase breast cancer cell susceptibility to 3-Epi+cisplatin therapy. PMID:25992773

  4. Tumor suppressor ING4 inhibits estrogen receptor activity in breast cancer cells

    PubMed Central

    Keenen, Madeline M; Kim, Suwon

    2016-01-01

    Resistance to antiestrogen therapy remains a significant problem in breast cancer. Low expression of inhibitor of growth 4 (ING4) in primary tumors has been correlated with increased rates of recurrence in estrogen receptor-positive (ER+) breast cancer patients, suggesting a role for ING4 in ER signaling. This study provides evidence that ING4 inhibits ER activity. ING4 overexpression increased the sensitivity of T47D and MCF7 ER+ breast cancer cells to hormone deprivation. ING4 attenuated maximal estrogen-dependent cell growth without affecting the dose–response of estrogen. These results indicated that ING4 functions as a noncompetitive inhibitor of estrogen signaling and may inhibit estrogen-independent ER activity. Supportive of this, treatment with fulvestrant but not tamoxifen rendered T47D cells sensitive to hormone deprivation as did ING4 overexpression. ING4 did not affect nuclear ERα protein expression, but repressed selective ER-target gene transcription. Taken together, these results demonstrated that ING4 inhibited estrogen-independent ER activity, suggesting that ING4-low breast tumors recur faster due to estrogen-independent ER activity that renders tamoxifen less effective. This study puts forth fulvestrant as a proposed therapy choice for patients with ING4-low ER+ breast tumors. PMID:27895513

  5. Tumor Genomic Profiling in Breast Cancer Patients Using Targeted Massively Parallel Sequencing

    DTIC Science & Technology

    2015-04-30

    exome sequencing to identify genomic mechanisms of therapeutic resistance The goal of this aim is perfotm whole exome sequencing in breast cancer...identify novel resistance mechanisms . Of the 72 patients described above, we have been able to obtain matched pre-treatment primary tissues from 28...advanced breast cancer, and novel strategies to overcome resistance mechanisms . If widely deployed, implementation of this approach may open new

  6. The Role of ADAM9 in Tumor-Stromal Interactions in Breast Cancer

    DTIC Science & Technology

    2010-04-01

    ADAM family members in cancer. ADAM12 is expressed in carcinoma and promotes breast cancer progression by inducing the apoptosis of surrounding...stromal cells (13). Consequently, ADAM12 protein levels correlate with advanced breast cancer (14, 15). In contrast, the disintegrin domain of ADAM15...subgroup of ADAMs that also contains ADAM12 and ADAM15 (18). The ADAM9 metalloprotease activity cleaves heparin-binding epidermal growth factor (HB

  7. True Recurrence Versus New Primary: An Analysis of Ipsilateral Breast Tumor Recurrences After Breast-Conserving Therapy

    SciTech Connect

    Panet-Raymond, Valerie; Truong, Pauline T.; McDonald, Rachel E.; Alexander, Cheryl; Ross, Louetta; Ryhorchuk, Aleata; Watson, Peter H.

    2011-10-01

    Purpose: Ipsilateral breast tumor recurrence (IBTR) can occur in 5-20% of women with early-stage breast cancer treated with breast-conserving therapy. Two entities of IBTR have been described: true recurrence (TR), suggested to be regrowth of disease at the tumor bed, and new primary (NP), distinct from the index lesion in histology and location. This study compared survival outcomes between two patient cohorts classified clinically as having either TR or NP. Methods and Materials: Between 1989 and 1999, 6,020 women were referred to the BC Cancer Agency with newly diagnosed pT1-2, N0-1, M0 invasive breast cancer, treated with breast-conserving surgery. Of these, 289 patients had pathologically confirmed IBTR. Retrospective analysis was performed, and a set of decision rules was applied to classify cases as TR or NP based on change in histology, grade, hormone receptor status, and tumor location. Of 289 patients, 129 (45%) were classified as having TR and 139 (48%) as having NP; 21 (7%) were unclassified. Results: The distributions of age at diagnosis, age at recurrence, and histopathologic factors were similar in the TR and NP cohorts (all p > 0.05). The mean time to recurrence was shorter in TR patients than in NP patients (4.8 years vs. 6.3 years, p = 0.001). Treatment of the IBTR did not differ between the two groups. In the TR and NP cohorts, breast cancer-specific survival was 55.7% vs. 61.3% (p = 0.93), and overall survival was 43.7% vs. 54.8% (p = 0.53). Conclusions: Time to recurrence is significantly shorter in patients with IBTR classified as true recurrence compared to new primary. Non-statistically significant trends for less favorable survival were observed for patients with TR. Further investigation of the hypothesis that TR and NP tumors are distinct entities with different survival prognoses will require standardized pathology review and molecular analyses.

  8. In vitro quantitative analysis of Salmonella typhimurium preference for amino acids secreted by human breast tumor

    NASA Astrophysics Data System (ADS)

    Choi, Eunpyo; Maeng, Bohee; Lee, Jae-hun; Chang, Hyung-kwan; Park, Jungyul

    2016-12-01

    Bacterial therapies have been paid significant attentions by their ability to penetrate deep into the solid tumor tissue and its propensity to naturally accumulate in tumors of living animals. Understanding the actual mechanism for bacteria to target the tumor is therapeutically crucial but is poorly understood. We hypothesized that amino acids released from the specific tumors induced bacteria to those tumors and the experiments for chemotactic response of bacteria toward the cancer secreting amino acids was then performed by using the diffusion based multiple chemical gradient generator constructed by in situ self-assembly of microspheres. The quantitative analysis was carried out by comparison of intensity using green fluorescent protein (GFP) tagged Salmonella typhimurium ( S. typhimurium) in the gradient generator, which showed the clear preference to the released amino acids, especially from breast cancer patients. The understanding chemotaxis toward the cancer secreting amino acids is essential for controlling S. typhimurium targeting in tumors and will allow for the development of bacterial therapies.

  9. Potentiated DNA Damage Response in Circulating Breast Tumor Cells Confers Resistance to Chemotherapy*

    PubMed Central

    Gong, Chang; Liu, Bodu; Yao, Yandan; Qu, Shaohua; Luo, Wei; Tan, Weige; Liu, Qiang; Yao, Herui; Zou, Lee; Su, Fengxi; Song, Erwei

    2015-01-01

    Circulating tumor cells (CTCs) are seeds for cancer metastasis and are predictive of poor prognosis in breast cancer patients. Whether CTCs and primary tumor cells (PTCs) respond to chemotherapy differently is not known. Here, we show that CTCs of breast cancer are more resistant to chemotherapy than PTCs because of potentiated DNA repair. Surprisingly, the chemoresistance of CTCs was recapitulated in PTCs when they were detached from the extracellular matrix. Detachment of PTCs increased the levels of reactive oxygen species and partially activated the DNA damage checkpoint, converting PTCs to a CTC-like state. Inhibition of checkpoint kinases Chk1 and Chk2 in CTCs reduces the basal checkpoint response and sensitizes CTCs to DNA damage in vitro and in mouse xenografts. Our results suggest that DNA damage checkpoint inhibitors may benefit the chemotherapy of breast cancer patients by suppressing the chemoresistance of CTCs and reducing the risk of cancer metastasis. PMID:25897074

  10. Potentiated DNA Damage Response in Circulating Breast Tumor Cells Confers Resistance to Chemotherapy.

    PubMed

    Gong, Chang; Liu, Bodu; Yao, Yandan; Qu, Shaohua; Luo, Wei; Tan, Weige; Liu, Qiang; Yao, Herui; Zou, Lee; Su, Fengxi; Song, Erwei

    2015-06-12

    Circulating tumor cells (CTCs) are seeds for cancer metastasis and are predictive of poor prognosis in breast cancer patients. Whether CTCs and primary tumor cells (PTCs) respond to chemotherapy differently is not known. Here, we show that CTCs of breast cancer are more resistant to chemotherapy than PTCs because of potentiated DNA repair. Surprisingly, the chemoresistance of CTCs was recapitulated in PTCs when they were detached from the extracellular matrix. Detachment of PTCs increased the levels of reactive oxygen species and partially activated the DNA damage checkpoint, converting PTCs to a CTC-like state. Inhibition of checkpoint kinases Chk1 and Chk2 in CTCs reduces the basal checkpoint response and sensitizes CTCs to DNA damage in vitro and in mouse xenografts. Our results suggest that DNA damage checkpoint inhibitors may benefit the chemotherapy of breast cancer patients by suppressing the chemoresistance of CTCs and reducing the risk of cancer metastasis.

  11. The nuclear corepressor 1 and the thyroid hormone receptor β suppress breast tumor lymphangiogenesis.

    PubMed

    Martínez-Iglesias, Olaia; Olmeda, David; Alonso-Merino, Elvira; Gómez-Rey, Sara; González-López, Ana M; Luengo, Enrique; Soengas, María S; Palacios, José; Regadera, Javier; Aranda, Ana

    2016-11-29

    Vascular Endotelial Growth Factors C and D (VEGF-C and VEGF-D) are crucial regulators of lymphangiogenesis, a main event in the metastatic spread of breast cancer tumors. Although inhibition of lymphangiogenic gene expression might be a useful therapeutic strategy to restrict the progression of cancer, the factors involved in the transcriptional repression of these genes are still unknown. We have previously shown that Nuclear Receptor Corepressor 1 (NCoR) and the thyroid hormone receptor β1 (TRβ) inhibit tumor invasion. Here we show that these molecules repress VEGF-C and VEGF-D gene transcription in breast cancer cells, reducing lymphatic vessel density and sentinel lymph node invasion in tumor xenografts. The clinical significance of these results is stressed by the finding that NCoR and TRβ transcripts correlate negatively with those of the lymphangiogenic genes and the lymphatic vessel marker LYVE-1 in human breast tumors. Our results point to the use of NCoR and TRβ as potential biomarkers for diagnosis or prognosis in breast cancer and suggest that further studies of these molecules as potential targets for anti-lymphangiogenic therapy are warranted.

  12. Prognostic Relevance of Circulating Tumor Cells in Molecular Subtypes of Breast Cancer

    PubMed Central

    Banys-Paluchowski, M.; Schneck, H.; Blassl, C.; Schultz, S.; Meier-Stiegen, F.; Niederacher, D.; Krawczyk, N.; Ruckhaeberle, E.; Fehm, T.; Neubauer, H.

    2015-01-01

    Circulating tumor cells (CTCs) can be detected in the peripheral blood of breast cancer patients with early and metastatic disease. Recent data suggest that immune pathologic characteristics between the primary tumor, metastatic colonies and CTCs are discordant and that CTCs possess an independent phenotype that is associated with prognosis and treatment efficacy. Large scale gene expression analysis has provided the possibility to stratify breast cancer according to the gene expression fingerprint of primary tumor tissue into five intrinsic molecular subtypes which can be associated with different clinical outcome. As a consequence of the different prognostic power of primary tumorsʼ characteristics and CTCs several groups have started to investigate if CTCs might be disseminated differentially within these breast cancer subtypes. They determined the CTC number in immunohistochemical subtypes to validate if CTCs may provide differential and more specific prognostic information within each subtype. This review provides an overview of the outcome of some recently published data gathered from early and metastatic breast cancer. PMID:25914415

  13. A comparative study of four serological tumor markers for the detection of breast cancer.

    PubMed

    Clinton, Shawn R; Beason, Kevin L; Bryant, Sabrina; Johnson, James T; Jackson, Margaret; Wilson, Cynthia; Holifield, Kay; Vincent, Charlton; Hall, Margot

    2003-01-01

    Breast cancer is currently the third most common cause of cancer in the world. Circulating tumor antigens are often used as a minimally invasive tool for noting breast cancer progression. The objective of this study was to compare four tumor antigens (CA 15-3, CA 27.29, alpha-fetoprotein [AFP], and carcinoembryonic antigen [CEA]) for their diagnostic efficacy in breast cancer patients. It was hypothesized that CA 15-3 would proved to be superior to CA 27.29, CEA, and AFP in assay performance. Tumor marker assays were performed according to the manufacturers' directions. Assays used in this study were CA 15-3 and CA 27.29 (Fujirebio Diagnostics/Centocor Inc.), AFP (Abbott Inc.), and CEA (Hybritech Inc.). A total of 554 patient samples were obtained from an area hospital, plus 200 healthy adult samples which were used for the determination of normal reference intervals. The patients included patients with no disease (184), with non-malignant disease (11), with breast cancer (87), and with other types of cancer (272). Diagnostic percent sensitivities for each marker were: CA 15-3 (63%), CA 27.29 (39%), CEA (22%), and AFP (22%). Diagnostic specificities for each marker were comparable, ranging from 80-88%. Analytical parameters were evaluated for the assays and compared favorably. We concluded that CA 15-3 was the best tumor antigen for use as a diagnostic aid and monitoring agent.

  14. Simultaneous Monitoring of Vascular Oxygenation and Tissue Oxygen Tension of Breast Tumors under Hyperbaric Oxygen Exposure

    DTIC Science & Technology

    2006-04-01

    FOXY system, on various rat breast tumor size (months 14- 30). Instead of single-channel NIRS, steady-state diffuse reflectance spectroscopy (SSDRS...combination of normobaric and hyperbaric oxygen interventions) simultaneously monitored by steady-state diffuse reflectance spectroscopy (SSDRS) and...simultaneously by steady-state diffuse reflectance spectroscopy (SSDRS) and FOXY oxygen sensor in response to normobaric and hyperbaric oxygen

  15. The Influence of Neuronal Activity on Breast Tumor Metastasis to the Brain

    DTIC Science & Technology

    2009-09-01

    drugs to alter brain activity: caffeine, methylphenidate and modafinil . While the smallest effect may be expected from caffeine which is not as potent...caffeine, we have initiated experiments to test the effects of modafinil on breast tumor metastasis to the brain in our model. Unfortunately, we have had

  16. The nuclear corepressor 1 and the thyroid hormone receptor β suppress breast tumor lymphangiogenesis

    PubMed Central

    Martínez-Iglesias, Olaia; Olmeda, David; Alonso-Merino, Elvira; Gómez-Rey, Sara; González-López, Ana M.; Luengo, Enrique; Soengas, María S.; Palacios, José; Regadera, Javier; Aranda, Ana

    2016-01-01

    Vascular Endotelial Growth Factors C and D (VEGF-C and VEGF-D) are crucial regulators of lymphangiogenesis, a main event in the metastatic spread of breast cancer tumors. Although inhibition of lymphangiogenic gene expression might be a useful therapeutic strategy to restrict the progression of cancer, the factors involved in the transcriptional repression of these genes are still unknown. We have previously shown that Nuclear Receptor Corepressor 1 (NCoR) and the thyroid hormone receptor β1 (TRβ) inhibit tumor invasion. Here we show that these molecules repress VEGF-C and VEGF-D gene transcription in breast cancer cells, reducing lymphatic vessel density and sentinel lymph node invasion in tumor xenografts. The clinical significance of these results is stressed by the finding that NCoR and TRβ transcripts correlate negatively with those of the lymphangiogenic genes and the lymphatic vessel marker LYVE-1 in human breast tumors. Our results point to the use of NCoR and TRβ as potential biomarkers for diagnosis or prognosis in breast cancer and suggest that further studies of these molecules as potential targets for anti-lymphangiogenic therapy are warranted. PMID:27806339

  17. Recent Advances in the Molecular Characterization of Circulating Tumor Cells

    PubMed Central

    Lowes, Lori E.; Allan, Alison L.

    2014-01-01

    Although circulating tumor cells (CTCs) were first observed over a century ago, lack of sensitive methodology precluded detailed study of these cells until recently. However, technological advances have now facilitated the identification, enumeration, and characterization of CTCs using a variety of methods. The majority of evidence supporting the use of CTCs in clinical decision-making has been related to enumeration using the CellSearch® system and correlation with prognosis. Growing evidence also suggests that CTC monitoring can provide an early indication of patient treatment response based on comparison of CTC levels before and after therapy. However, perhaps the greatest potential that CTCs hold for oncology lies at the level of molecular characterization. Clinical treatment decisions may be more effective if they are based on molecular characteristics of metastatic cells rather than on those of the primary tumor alone. Molecular characterization of CTCs (which can be repeatedly isolated in a minimally invasive fashion) provides the opportunity for a “real-time liquid biopsy” that allows assessment of genetic drift, investigation of molecular disease evolution, and identification of actionable genomic characteristics. This review focuses on recent advances in this area, including approaches involving immunophenotyping, fluorescence in situ hybridization (FISH), multiplex RT-PCR, microarray, and genomic sequencing. PMID:24633084

  18. Autoantibodies against Muscarinic Receptors in Breast Cancer: Their Role in Tumor Angiogenesis

    PubMed Central

    Lombardi, María Gabriela; Negroni, María Pía; Pelegrina, Laura Tatiana; Castro, María Ester; Fiszman, Gabriel L.; Azar, María Eugenia; Morgado, Carlos Cresta; Sales, María Elena

    2013-01-01

    The presence of autoantibodies in cancer has become relevant in recent years. We demonstrated that autoantibodies purified from the sera of breast cancer patients activate muscarinic acetylcholine receptors in tumor cells. Immunoglobulin G (IgG) from breast cancer patients in T1N0Mx stage (tumor size≤2 cm, without lymph node metastasis) mimics the action of the muscarinic agonist carbachol stimulating MCF-7 cell proliferation, migration and invasion. Angiogenesis is a central step in tumor progression because it promotes tumor invasion and metastatic spread. Vascular endothelial growth factor-A (VEGF-A) is the main angiogenic mediator, and its levels have been correlated with poor prognosis in cancer. The aim of the present work was to investigate the effect of T1N0Mx-IgG on the expression of VEGF-A, and the in vivo neovascular response triggered by MCF-7 cells, via muscarinic receptor activation. We demonstrated that T1N0Mx-IgG (10−8 M) and carbachol (10−9 M) increased the constitutive expression of VEGF-A in tumor cells, effect that was reverted by the muscarinic antagonist atropine. We also observed that T1N0Mx-IgG and carbachol enhanced the neovascular response produced by MCF-7 cells in the skin of NUDE mice. The action of IgG or carbachol was reduced in the presence of atropine. In conclusion, T1N0Mx-IgG and carbachol may promote VEGF-A production and neovascularization induced by breast tumor cells via muscarinic receptors activation. These effects may be accelerating breast tumor progression. PMID:23460876

  19. Autoantibodies against muscarinic receptors in breast cancer: their role in tumor angiogenesis.

    PubMed

    Lombardi, María Gabriela; Negroni, María Pía; Pelegrina, Laura Tatiana; Castro, María Ester; Fiszman, Gabriel L; Azar, María Eugenia; Morgado, Carlos Cresta; Sales, María Elena

    2013-01-01

    The presence of autoantibodies in cancer has become relevant in recent years. We demonstrated that autoantibodies purified from the sera of breast cancer patients activate muscarinic acetylcholine receptors in tumor cells. Immunoglobulin G (IgG) from breast cancer patients in T1N0Mx stage (tumor size≤2 cm, without lymph node metastasis) mimics the action of the muscarinic agonist carbachol stimulating MCF-7 cell proliferation, migration and invasion. Angiogenesis is a central step in tumor progression because it promotes tumor invasion and metastatic spread. Vascular endothelial growth factor-A (VEGF-A) is the main angiogenic mediator, and its levels have been correlated with poor prognosis in cancer. The aim of the present work was to investigate the effect of T1N0Mx-IgG on the expression of VEGF-A, and the in vivo neovascular response triggered by MCF-7 cells, via muscarinic receptor activation. We demonstrated that T1N0Mx-IgG (10(-8) M) and carbachol (10(-9) M) increased the constitutive expression of VEGF-A in tumor cells, effect that was reverted by the muscarinic antagonist atropine. We also observed that T1N0Mx-IgG and carbachol enhanced the neovascular response produced by MCF-7 cells in the skin of NUDE mice. The action of IgG or carbachol was reduced in the presence of atropine. In conclusion, T1N0Mx-IgG and carbachol may promote VEGF-A production and neovascularization induced by breast tumor cells via muscarinic receptors activation. These effects may be accelerating breast tumor progression.

  20. Hypercholesterolemia Induces Angiogenesis and Accelerates Growth of Breast Tumors in Vivo

    PubMed Central

    Pelton, Kristine; Coticchia, Christine M.; Curatolo, Adam S.; Schaffner, Carl P.; Zurakowski, David; Solomon, Keith R.; Moses, Marsha A.

    2015-01-01

    Obesity and metabolic syndrome are linked to an increased prevalence of breast cancer among postmenopausal women. A common feature of obesity, metabolic syndrome, and a Western diet rich in saturated fat is a high level of circulating cholesterol. Epidemiological reports investigating the relationship between high circulating cholesterol levels, cholesterol-lowering drugs, and breast cancer are conflicting. Here, we modeled this complex condition in a well-controlled, preclinical animal model using innovative isocaloric diets. Female severe combined immunodeficient mice were fed a low-fat/no-cholesterol diet and then randomized to four isocaloric diet groups: low-fat/no-cholesterol diet, with or without ezetimibe (cholesterol-lowering drug), and high-fat/high-cholesterol diet, with or without ezetimibe. Mice were implanted orthotopically with MDA-MB-231 cells. Breast tumors from animals fed the high-fat/high-cholesterol diet exhibited the fastest progression. Significant differences in serum cholesterol level between groups were achieved and maintained throughout the study; however, no differences were observed in intratumoral cholesterol levels. To determine the mechanism of cholesterol-induced tumor progression, we analyzed tumor proliferation, apoptosis, and angiogenesis and found a significantly greater percentage of proliferating cells from mice fed the high-fat/high-cholesterol diet. Tumors from hypercholesterolemic animals displayed significantly less apoptosis compared with the other groups. Tumors from high-fat/high-cholesterol mice had significantly higher microvessel density compared with tumors from the other groups. These results demonstrate that hypercholesterolemia induces angiogenesis and accelerates breast tumor growth in vivo. PMID:24952430

  1. Tumor suppressor berberine binds VASP to inhibit cell migration in basal-like breast cancer

    PubMed Central

    Wang, Xiaolan; Kuang, Changchun; Xiang, Qingmin; Yang, Fang; Xiang, Jin; Zhu, Shan; Wei, Lei; Zhang, Jingwei

    2016-01-01

    Berberine is a plant-derived compound used in traditional Chinese medicine, which has been shown to inhibit cell proliferation and migration in breast cancer. On the other hand, vasodilator-stimulated phosphoprotein (VASP) promotes actin filament elongation and cell migration. We previously showed that VASP is overexpressed in high-motility breast cancer cells. Here we investigated whether the anti-tumorigenic effects of berberine are mediated by binding VASP in basal-like breast cancer. Our results show that berberine suppresses proliferation and migration of MDA-MB-231 cells as well as tumor growth in MDA-MB-231 nude mouse xenografts. We also show that berberine binds to VASP, inducing changes in its secondary structure and inhibits actin polymerization. Our study reveals the mechanism underlying berberine's inhibition of cell proliferation and migration in basal-like breast cancer, highlighting the use of berberine as a potential adjuvant therapeutic agent. PMID:27322681

  2. Regulator of G protein signaling 6 is a novel suppressor of breast tumor initiation and progression

    PubMed Central

    Fisher, Rory A.

    2013-01-01

    Breast cancer is a large global health burden and the most frequently diagnosed malignancy in women worldwide. Here, we utilize RGS6− /− mice to interrogate the role of regulator of G protein signaling 6 (RGS6), localized to the ductal epithelium in mouse and human breast, as a novel tumor suppressor in vivo. RGS6− /− mice exhibit accelerated 7,12-dimethylbenza[α]anthracene (DMBA)-induced tumor initiation and progression, as well as decreased overall survival. Analysis of carcinogenic aberrations in the mammary glands of DMBA-treated mice revealed a failure of the DNA damage response concurrent with augmented oncogenesis in RGS6−/− animals. Furthermore, RGS6 suppressed cell growth induced by either human epidermal growth factor receptor 2 or estrogen receptor activation in both MCF-7 breast cancer cells and mammary epithelial cells (MECs). MECs isolated from RGS6−/− mice also showed a deficit in DMBA-induced ATM/p53 activation, reactive oxygen species generation and apoptosis confirming that RGS6 is required for effective activation of the DNA damage response in these cells, a critical countermeasure against carcinogen-mediated genotoxic stress. The ability of RGS6 to simultaneously enhance DNA-damage-induced apoptotic signaling and suppress oncogenic cell growth likely underlie the accelerated tumorigenesis and cellular transformation observed in DMBA-treated RGS6−/− mice and isolated MECs, respectively. Unsurprisingly, spontaneous tumor formation was also seen in old female RGS6−/− but not in wild-type mice. Our finding that RGS6 is downregulated in all human breast cancer subtypes independent of their molecular classification indicates that obtaining a means to restore the growth suppressive and pro-apoptotic actions of RGS6 in breast might be a viable means to treat a large spectrum of breast tumors. PMID:23598467

  3. Regulator of G protein signaling 6 is a novel suppressor of breast tumor initiation and progression.

    PubMed

    Maity, Biswanath; Stewart, Adele; O'Malley, Yunxia; Askeland, Ryan W; Sugg, Sonia L; Fisher, Rory A

    2013-08-01

    Breast cancer is a large global health burden and the most frequently diagnosed malignancy in women worldwide. Here, we utilize RGS6(-/-) mice to interrogate the role of regulator of G protein signaling 6 (RGS6), localized to the ductal epithelium in mouse and human breast, as a novel tumor suppressor in vivo. RGS6(-/-) mice exhibit accelerated 7,12-dimethylbenza[α]anthracene (DMBA)-induced tumor initiation and progression, as well as decreased overall survival. Analysis of carcinogenic aberrations in the mammary glands of DMBA-treated mice revealed a failure of the DNA damage response concurrent with augmented oncogenesis in RGS6(-/-) animals. Furthermore, RGS6 suppressed cell growth induced by either human epidermal growth factor receptor 2 or estrogen receptor activation in both MCF-7 breast cancer cells and mammary epithelial cells (MECs). MECs isolated from RGS6(-/-) mice also showed a deficit in DMBA-induced ATM/p53 activation, reactive oxygen species generation and apoptosis confirming that RGS6 is required for effective activation of the DNA damage response in these cells, a critical countermeasure against carcinogen-mediated genotoxic stress. The ability of RGS6 to simultaneously enhance DNA-damage-induced apoptotic signaling and suppress oncogenic cell growth likely underlie the accelerated tumorigenesis and cellular transformation observed in DMBA-treated RGS6(-/-) mice and isolated MECs, respectively. Unsurprisingly, spontaneous tumor formation was also seen in old female RGS6(-/-) but not in wild-type mice. Our finding that RGS6 is downregulated in all human breast cancer subtypes independent of their molecular classification indicates that obtaining a means to restore the growth suppressive and pro-apoptotic actions of RGS6 in breast might be a viable means to treat a large spectrum of breast tumors.

  4. Bone marrow-derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors

    PubMed Central

    2013-01-01

    Introduction Mesenchymal stem cells (MSCs) are known to migrate to tumor tissues. This behavior of MSCs has been exploited as a tumor-targeting strategy for cell-based cancer therapy. However, the effects of MSCs on tumor growth are controversial. This study was designed to determine the effect of MSCs on the growth of breast and prostate tumors. Methods Bone marrow-derived MSCs (BM-MSCs) were isolated and characterized. Effects of BM-MSCs on tumor cell proliferation were analyzed in a co-culture system with mouse breast cancer cell 4T1 or human prostate cancer cell DU145. Tumor cells were injected into nude mice subcutaneously either alone or coupled with BM-MSCs. The expression of cell proliferation and angiogenesis-related proteins in tumor tissues were immunofluorescence analyzed. The angiogenic effect of BM-MSCs was detected using a tube formation assay. The effects of the crosstalk between tumor cells and BM-MSCs on expression of angiogenesis related markers were examined by immunofluorescence and real-time PCR. Results Both co-culturing with mice BM-MSCs (mBM-MSCs) and treatment with mBM-MSC-conditioned medium enhanced the growth of 4T1 cells. Co-injection of 4T1 cells and mBM-MSCs into nude mice led to increased tumor size compared with injection of 4T1 cells alone. Similar experiments using DU145 cells and human BM-MSCs (hBM-MSCs) instead of 4T1 cells and mBM-MSCs obtained consistent results. Compared with tumors induced by injection of tumor cells alone, the blood vessel area was greater in tumors from co-injection of tumor cells with BM-MSCs, which correlated with decreased central tumor necrosis and increased tumor cell proliferation. Furthermore, both conditioned medium from hBM-MSCs alone and co-cultures of hBM-MSCs with DU145 cells were able to promote tube formation ability of human umbilical vein endothelial cells. When hBM-MSCs are exposed to the DU145 cell environment, the expression of markers associated with neovascularization (macrophage

  5. Quantification of tumor changes during neoadjuvant chemotherapy with longitudinal breast DCE-MRI registration

    NASA Astrophysics Data System (ADS)

    Wu, Jia; Ou, Yangming; Weinstein, Susan P.; Conant, Emily F.; Yu, Ning; Hoshmand, Vahid; Keller, Brad; Ashraf, Ahmed B.; Rosen, Mark; DeMichele, Angela; Davatzikos, Christos; Kontos, Despina

    2015-03-01

    Imaging plays a central role in the evaluation of breast tumor response to neoadjuvant chemotherapy. Image-based assessment of tumor change via deformable registration is a powerful, quantitative method potentially to explore novel information of tumor heterogeneity, structure, function, and treatment response. In this study, we continued a previous pilot study to further validate the feasibility of an open source deformable registration algorithm DRAMMS developed within our group as a means to analyze spatio-temporal tumor changes for a set of 14 patients with DCE-MR imaging. Two experienced breast imaging radiologists marked landmarks according to their anatomical meaning on image sets acquired before and during chemotherapy. Yet, chemotherapy remarkably changed the anatomical structure of both tumor and normal breast tissue, leading to significant discrepancies between both raters for landmarks in certain areas. Therefore, we proposed a novel method to grade the manually denoted landmarks into different challenge levels based on the inter-rater agreement, where a high level indicates significant discrepancies and considerable amounts of anatomical structure changes, which would indeed impose giant problem for the following registration algorithm. It is interesting to observe that DRAMMS performed in a similar manner as the human raters: landmark errors increased as inter-rater differences rose. Among all selected six deformable registration algorithms, DRAMMS achieves the highest overall accuracy, which is around 5.5 mm, while the average difference between human raters is 3 mm. Moreover, DRAMMS performed consistently well within both tumor and normal tissue regions. Lastly, we comprehensively tuned the fundamental parameters of DRAMMS to better understand DRAMMS to guide similar works in the future. Overall, we further validated that DRAMMS is a powerful registration tool to accurately quantify tumor changes and potentially predict early tumor response to

  6. StrandAdvantage test for early-line and advanced-stage treatment decisions in solid tumors.

    PubMed

    Sen, Manimala; Katragadda, Shanmukh; Ravichandran, Aarthi; Deshpande, Gouri; Parulekar, Minothi; Nayanala, Swetha; Vittal, Vikram; Shen, Weiming; Phooi Nee Yong, Melanie; Jacob, Jemima; Parchuru, Sravanthi; Dhanuskodi, Kalpana; Eyring, Kenneth; Agrawal, Pooja; Agarwal, Smita; Shanmugam, Ashwini; Gupta, Satish; Vishwanath, Divya; Kumari, Kiran; Hariharan, Arun K; Balaji, Sai A; Liang, Qiaoling; Robolledo, Belen; Gauribidanur Raghavendrachar, Vijayashree; Oomer Farooque, Mohammed; Buresh, Cary J; Ramamoorthy, Preveen; Bahadur, Urvashi; Subramanian, Kalyanasundaram; Hariharan, Ramesh; Veeramachaneni, Vamsi; Sankaran, Satish; Gupta, Vaijayanti

    2017-04-03

    Comprehensive genetic profiling of tumors using next-generation sequencing (NGS) is gaining acceptance for guiding treatment decisions in cancer care. We designed a cancer profiling test combining both deep sequencing and immunohistochemistry (IHC) of relevant cancer targets to aid therapy choices in both standard-of-care (SOC) and advanced-stage treatments for solid tumors. The SOC report is provided in a short turnaround time for four tumors, namely lung, breast, colon, and melanoma, followed by an investigational report. For other tumor types, an investigational report is provided. The NGS assay reports single-nucleotide variants (SNVs), copy number variations (CNVs), and translocations in 152 cancer-related genes. The tissue-specific IHC tests include routine and less common markers associated with drugs used in SOC settings. We describe the standardization, validation, and clinical utility of the StrandAdvantage test (SA test) using more than 250 solid tumor formalin-fixed paraffin-embedded (FFPE) samples and control cell line samples. The NGS test showed high reproducibility and accuracy of >99%. The test provided relevant clinical information for SOC treatment as well as more information related to investigational options and clinical trials for >95% of advanced-stage patients. In conclusion, the SA test comprising a robust and accurate NGS assay combined with clinically relevant IHC tests can detect somatic changes of clinical significance for strategic cancer management in all the stages.

  7. Detection and identification of mouse mammary tumor virus-like DNA sequences in blood and breast tissues of breast cancer patients.

    PubMed

    Naushad, Wasifa; Bin Rahat, Talha; Gomez, Miriam Kathleen; Ashiq, Muhammad Taimoor; Younas, Muhammad; Sadia, Hajra

    2014-08-01

    Mouse mammary tumor virus (MMTV) is a well-known cause of mammary tumors in mice transmitted as endogenous proviruses or exogenously as infectious virions. The hypothesis that a retrovirus homologous to MMTV is involved in human breast cancers has resulted in renewed interest in the etiology of human breast cancer. Therefore, the detection of MMTV-like exogenous sequences in 30-40 % of invasive breast cancer has increased attention towards this hypothesis. To detect the prevalence of MMTV in Pakistani population, 666-bp-long MMTV envelop and 630-bp LTR sequences were amplified from breast cancer patient samples (tissue biopsies and peripheral blood) using mouse with mammary tumor as control. MMTV-like virus env and LTR DNA sequences were detected in 20 and 26 % of breast tumor samples, respectively, from the total of 80 breast cancer patients' blood and tissue samples. No significant association was observed between age, grade of disease, and lymph node involvement with the prevalence of MMTV-like sequences. Our data add to the growing number of studies implicating MMTV-like virus in human breast cancer, but still clear causal association of MMTV to breast cancer remains to be reputable.

  8. Development of array piezoelectric fingers towards in vivo breast tumor detection

    NASA Astrophysics Data System (ADS)

    Xu, Xin; Chung, Youngsoo; Brooks, Ari D.; Shih, Wei-Heng; Shih, Wan Y.

    2016-12-01

    We have investigated the development of a handheld 4 × 1 piezoelectric finger (PEF) array breast tumor detector system towards in vivo patient testing, particularly, on how the duration of the DC applied voltage, the depression depth of the handheld unit, and breast density affect the PEF detection sensitivity on 40 patients. The tests were blinded and carried out in four phases: with DC voltage durations 5, 3, 2, to 0.8 s corresponding to scanning a quadrant, a half, a whole breast, and both breasts within 30 min, respectively. The results showed that PEF detection sensitivity was unaffected by shortening the applied voltage duration from 5 to 0.8 s nor was it affected by increasing the depression depth from 2 to 6 mm. Over the 40 patients, PEF detected 46 of the 48 lesions (46/48)—with the smallest lesion detected being 5 mm in size. Of 28 patients (some have more than one lesion) with mammography records, PEF detected 31/33 of all lesions (94%) and 14/15 of malignant lesions (93%), while mammography detected 30/33 of all lesions (91%) and 12/15 of malignant lesions (80%), indicating that PEF could detect malignant lesions not detectable by mammography without significantly increasing false positives. PEF's detection sensitivity is also shown to be independent of breast density, suggesting that PEF could be a potential tool for detecting breast cancer in young women and women with dense breasts.

  9. A novel thermal treatment modality for controlling breast tumor growth and progression.

    PubMed

    Xie, Yifan; Liu, Ping; Xu, Lisa X

    2012-01-01

    The new concept of keeping primary tumor under control in situ to suppress distant foci sheds light on the novel treatment of metastatic tumor. Hyperthermia is considered as one of the means for controlling tumor growth. In this study, a novel thermal modality was built to introduce hyperthermia effect on tumor to suppress its growth and progression using 4T1 murine mammary carcinoma, a common animal model of metastatic breast cancer. A mildly raised temperature (i.e.39°C) was imposed on the skin surface of the implanted tumor using a thermal heating pad. Periodic heating (12 hours per day) was carried out for 3 days, 7 days, 14 days, and 21 days, respectively. The tumor growth rate was found significantly decreased in comparison to the control without hyperthermia. Biological evidences associated with tumor angiogenesis and metastasis were examined using histological analyses. Accordingly, the effect of mild hyperthermia on immune cell infiltration into tumors was also investigated. It was demonstrated that a delayed tumor growth and malignancy progression was achieved by mediating tumor cell apoptosis, vascular injury, degrading metastasis potential and as well as inhibiting the immunosuppressive cell myeloid derived suppressor cells (MDSCs) recruitment. Further mechanistic studies will be performed to explore the quantitative relationship between tumor progression and thermal dose in the near future.

  10. Combination Chemotherapy in Treating Young Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2013-05-01

    Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Unspecified Childhood Solid Tumor, Protocol Specific

  11. [Correlation of size of the primary tumor and axillary node status with the p53 tumor suppressor gene in carcinoma of the breast].

    PubMed

    Topić, Brano; Stanković, N; Savjak, D; Grbić, S

    2002-01-01

    Correlation of standard pathomorphological prognostic parameters, primary tumor size and axillary nodal status with new prognostic factor in breast carcinoma: tumor suppressor gene p53 was analyzed. The studied sample included 65 women who underwent surgery for breast carcinoma at the Surgical Clinic of Clinical Center Banja Luka, from January 1st 1997 till January 1st 1999. Statistical data analysis was performed and correlation of prognostic factors was determined. The majority of authors in this field agree that the primary tumor size and axillary nodal status are the two most important prognostic factors. These factors are the best predictors of prognosis and survival of women who had the tumor and were operated on. Tumor markers were immunohistochemically determined in the last ten years and, according to the majority of authors, are still considered the additional or relative prognostic factors in breast carcinoma. Their prognostic value and significance increase almost daily. Most frequently determined tumor markers are bcl-2, pS2, Ki-67 and p53. There was a positive, directly proportional relationship between primary tumor size and tumor suppressor gene p53, but there was no positive correlation between the axillary nodal status and tumor suppressor gene p53. Significance of determination of new tumor markers as the prognostic factors was emphasized. These markers represent a powerful tool in the early detection and prevention of breast carcinoma.

  12. Radio-Photothermal Therapy Mediated by a Single Compartment Nanoplatform Depletes Tumor Initiating Cells and Reduces Lung Metastasis in Orthotopic 4T1 Breast Tumor Model

    PubMed Central

    Zhou, Min; Zhao, Jun; Tian, Mei; Song, Shaoli; Zhang, Rui; Gupta, Sanjay; Tan, Dongfeng; Shen, Haifa; Ferrari, Mauro; Li, Chun

    2016-01-01

    Tumor Initiating Cells (TICs) are resistant to radiotherapy and chemotherapy, and are believed to be responsible for tumor recurrence and metastasis. Combination therapies can overcome the limitation of conventional cancer treatments, and has demonstrated promising application in clinic. Here, we show that dual modality radiotherapy (RT) and photothermal therapy (PTT) mediated by a single compartment nanosystem copper-64-labeled copper sulfide nanoparticles ([64Cu]CuS NPs) could suppress breast tumor metastasis through eradication of TICs. Positron electron tomography (PET) imaging and biodistribution studies showed that more than 90% of [64Cu]CuS NPs was retained in subcutaneously grown BT474 breast tumor 24 h after intratumoral (i.t.) injection, indicating the NPs is suitable for the combination therapy. Combined RT/PTT therapy resulted in significant tumor growth delay in subcutaneous BT474 breast cancer model. Moreover, RT/PTT treatment significantly prolonged the survival of mice bearing orthotopic 4T1 breast tumors compared to no treatment, RT alone, or PTT alone. The RT/PTT combination therapy significantly reduced the number of tumor nodules in the lung and the formation of tumor mammospheres from treated 4T1 tumors. No obvious side effects of the CuS NPs were noted in the treated mice in a pilot toxicity study. Taken together, our data support the feasibility of a therapeutic approach for suppression of tumor metastasis through localized RT/PTT therapy. PMID:26376843

  13. Alteration of the MT1 melatonin receptor gene and its expression in primary human breast tumors and breast cancer cell lines.

    PubMed

    Lai, Ling; Yuan, Lin; Cheng, Qi; Dong, Chunmin; Mao, Lulu; Hill, Steven Marc

    2009-11-01

    The MT1 melatonin receptor is bound and activated by the pineal hormone melatonin. This G protein-coupled melatonin receptor is expressed in human breast tumor cell lines, and when activated, mediates the growth-suppressive and steroid hormone/nuclear receptor modulatory actions of melatonin on breast tumor cells. In the current studies, we have examined the expression of the MT1 receptor in breast cancer cell lines and primary human breast tumors and correlated MT1 receptor expression with the deletion, rearrangement and amplification of the MT1 gene and established markers of breast cancer such as tumor size, stage, estrogen receptor alpha (ERalpha) and progesterone receptor (PR) expression. Theses studies suggest amplification of the MT1 gene in some breast tumors and an inverse correlation with ERalpha, PR and MT1 protein expression. Furthermore, these approaches employing immunohistochemical and immunofluorescent/confocal microscopic studies demonstrate that the MT1 receptor is localized to the caveoli and that MT1 expression in MCF-7 breast cancer cells can be repressed by estradiol and melatonin.

  14. Sonoelastomics for Breast Tumor Classification: A Radiomics Approach with Clustering-Based Feature Selection on Sonoelastography.

    PubMed

    Zhang, Qi; Xiao, Yang; Suo, Jingfeng; Shi, Jun; Yu, Jinhua; Guo, Yi; Wang, Yuanyuan; Zheng, Hairong

    2017-02-20

    A radiomics approach to sonoelastography, called "sonoelastomics," is proposed for classification of benign and malignant breast tumors. From sonoelastograms of breast tumors, a high-throughput 364-dimensional feature set was calculated consisting of shape features, intensity statistics, gray-level co-occurrence matrix texture features and contourlet texture features, which quantified the shape, hardness and hardness heterogeneity of a tumor. The high-throughput features were then selected for feature reduction using hierarchical clustering and three-feature selection metrics. For a data set containing 42 malignant and 75 benign tumors from 117 patients, seven selected sonoelastomic features achieved an area under the receiver operating characteristic curve of 0.917, an accuracy of 88.0%, a sensitivity of 85.7% and a specificity of 89.3% in a validation set via the leave-one-out cross-validation, revealing superiority over the principal component analysis, deep polynomial networks and manually selected features. The sonoelastomic features are valuable in breast tumor differentiation.

  15. A novel microchannel-based device to capture and analyze circulating tumor cells (CTCs) of breast cancer

    PubMed Central

    RIAHI, REZA; GOGOI, PRIYADARSHINI; SEPEHRI, SAEDEH; ZHOU, YI; HANDIQUE, KALYAN; GODSEY, JIM; WANG, YIXIN

    2014-01-01

    Circulating tumor cells (CTCs) have been shown in many studies as a possible biomarker for metastasis and may be instrumental for the spread of the disease. Despite advances in CTC capturing technologies, the low frequency of CTCs in cancer patients and the heterogeneity of the CTCs have limited the wide application of the technology in clinic. In this study, we investigated a novel microfluidic technology that uses a size- and deformability-based capture system to characterize CTCs. This unique platform not only allows flexibility in the selection of antibody markers but also segregates the CTCs in their own chambers, thus, enabling morphological, immunological and genetic characterization of each CTC at the single cell level. In this study, different breast cancer cell lines including MCF7, MDA-MB-231 and SKBR3, as well as a panel of breast cancer biomarkers were used to test the device. The technology can capture a wide range of cells with high reproducibility. The capturing efficiency of the cells is greater than 80%. In addition, the background of leukocytes is minimized because individual cells are segregated in their own chambers. The device captured both epithelial cancer cells such as MCF7 and SKBR3 and mesenchymal cells such as MDA-MB-231. Immunostaining of the captured cells on the microchannel device suggests that a panel of breast cancer biomarkers can be used to further characterize differential expression of the captured cells. PMID:24676558

  16. A Rare Tumor that Mimicked Metastasis in a Patient with Breast Cancer: Epithelioid Hemangioendothelioma

    PubMed Central

    Çabuk, Fatmagül Kuşku; Aktepe, Fatma; İlgün, Ahmet Serkan; Sarsenov, Dauren; Elbüken, Filiz; Özmen, Vahit

    2016-01-01

    A woman aged 50 years was diagnosed as having an invasive ductal carcinoma in the right breast and ductal carcinoma in situ in the left breast and underwent bilateral mastectomy eight years ago. A mass was identified during follow-up in positron-emission tomography (PET) image in the left infraclavicular region, indicating metastasis. Histopathologic examination showed a mass of 1.9 × 1 × 0.7 cm in dimensions characterized by spindle or round nuclei cells that formed island or cords in hyaline and myxoid ground and intracytoplasmic vacuoles containing erythrocytes. In the immunohistochemical analysis, tumor cells were widespread with diffuse positivity with CD34 and vimentin. These findings redirected us from a diagnosis of metastatic carcinoma to epithelioid hemangioendothelioma, a rare tumor of intermediate vascular tumor groups. In this respect, confirmation through biopsy from considered cases of metastasis is important in making a definite pathologic differential diagnosis.

  17. Data mining with decision trees for diagnosis of breast tumor in medical ultrasonic images.

    PubMed

    Kuo, W J; Chang, R F; Chen, D R; Lee, C C

    2001-03-01

    To increase the ability of ultrasonographic (US) technology for the differential diagnosis of solid breast tumors, we describe a novel computer-aided diagnosis (CADx) system using data mining with decision tree for classification of breast tumor to increase the levels of diagnostic confidence and to provide the immediate second opinion for physicians. Cooperating with the texture information extracted from the region of interest (ROI) image, a decision tree model generated from the training data in a top-down, general-to-specific direction with 24 co-variance texture features is used to classify the tumors as benign or malignant. In the experiments, accuracy rates for a experienced physician and the proposed CADx are 86.67% (78/90) and 95.50% (86/90), respectively.

  18. PRC2/EED-EZH2 Complex Is Up-Regulated in Breast Cancer Lymph Node Metastasis Compared to Primary Tumor and Correlates with Tumor Proliferation In Situ

    PubMed Central

    Yu, Hongxiang; Simons, Diana L.; Segall, Ilana; Carcamo-Cavazos, Valeria; Schwartz, Erich J.; Yan, Ning; Zuckerman, Neta S.; Dirbas, Frederick M.; Johnson, Denise L.; Holmes, Susan P.; Lee, Peter P.

    2012-01-01

    Background Lymph node metastasis is a key event in the progression of breast cancer. Therefore it is important to understand the underlying mechanisms which facilitate regional lymph node metastatic progression. Methodology/Principal Findings We performed gene expression profiling of purified tumor cells from human breast tumor and lymph node metastasis. By microarray network analysis, we found an increased expression of polycomb repression complex 2 (PRC2) core subunits EED and EZH2 in lymph node metastatic tumor cells over primary tumor cells which were validated through real-time PCR. Additionally, immunohistochemical (IHC) staining and quantitative image analysis of whole tissue sections showed a significant increase of EZH2 expressing tumor cells in lymph nodes over paired primary breast tumors, which strongly correlated with tumor cell proliferation in situ. We further explored the mechanisms of PRC2 gene up-regulation in metastatic tumor cells and found up-regulation of E2F genes, MYC targets and down-regulation of tumor suppressor gene E-cadherin targets in lymph node metastasis through GSEA analyses. Using IHC, the expression of potential EZH2 target, E-cadherin was examined in paired primary/lymph node samples and was found to be significantly decreased in lymph node metastases over paired primary tumors. Conclusions/Significance This study identified an over expression of the epigenetic silencing complex PRC2/EED-EZH2 in breast cancer lymph node metastasis as compared to primary tumor and its positive association with tumor cell proliferation in situ. Concurrently, PRC2 target protein E-cadherin was significant decreased in lymph node metastases, suggesting PRC2 promotes epithelial mesenchymal transition (EMT) in lymph node metastatic process through repression of E-cadherin. These results indicate that epigenetic regulation mediated by PRC2 proteins may provide additional advantage for the outgrowth of metastatic tumor cells in lymph nodes. This opens

  19. Tumor-infiltrating lymphocytes and breast cancer: Beyond the prognostic and predictive utility.

    PubMed

    Ravelli, Andrea; Roviello, Giandomenico; Cretella, Daniele; Cavazzoni, Andrea; Biondi, Alessandra; Cappelletti, Maria Rosa; Zanotti, Laura; Ferrero, Giuseppina; Ungari, Marco; Zanconati, Fabrizio; Bottini, Alberto; Alfieri, Roberta; Petronini, Pier Giorgio; Generali, Daniele

    2017-04-01

    The importance of the immune system as a potent anti-tumor defense has been consolidated in recent times, and novel immune-related therapies are today demonstrating a strong clinical benefit in the setting of several solid neoplasms. Tumor-infiltrating lymphocytes reflect the attempt of the host to eradicate malignancies, and during the last decades, they have been shown to possess an interesting prognostic utility for breast cancer, especially in case of HER2 positive and triple-negative molecular subtypes. In parallel, the clinical evaluation of tumor-infiltrating lymphocytes has been shown to effectively predict treatment outcomes in both neoadjuvant and adjuvant settings. Currently, tumor-infiltrating lymphocytes are promising further predictive utility in view of novel immune-related therapeutic strategies which are coming into the clinical setting launching a solid rationale for the future next-generation treatment options. In this scenario, tumor-infiltrating lymphocytes might represent an important resource for the selection of the most appropriate therapeutic strategy, as well as further evaluations of the molecular mechanisms underlying tumor-infiltrating lymphocytes and the immunoediting process would eventually provide new insights to augment therapeutic success. Considering these perspectives, we review the potential utility of tumor-infiltrating lymphocytes in the definition of breast cancer prognosis and in the prediction of treatment outcomes, along with the new promising molecular-based therapeutic discoveries.

  20. Breast tumor and stromal cell responses to TGF-β and hypoxia in matrix deposition

    PubMed Central

    Curran, Colleen S.; Keely, Patricia J

    2012-01-01

    The components that comprise the extracellular matrix (ECM) are integral to normal tissue homeostasis as well as the development and progression of breast tumors. The secretion, construction, and remodeling of the ECM are each regulated by a complex interplay between tumor cells, fibroblasts and macrophages. Transforming growth factor-β (TGF-β) is an essential molecule in regulating the cellular production of ECM molecules and the adhesive interactions of cells with the ECM. Additionally, hypoxic cell signals, initiated by oxygen deprivation, additional metabolic factors or receptor activation, are associated with ECM formation and the progression of breast cancer. Both TGF-β and hypoxic cell signals are implicated in the functional and morphological changes of cancer-associated-fibroblasts and tumor-associated-macrophages. Moreover, the enhanced recruitment of tumor and stromal cells in response to hypoxia-induced chemokines leads to increased ECM deposition and remodeling, increased blood vessel formation, and enhanced tumor migration. Thus, elucidation of the collaborative networks between tumor and stromal cells in response to the combined signals of TGF-β and hypoxia may yield insight into treatment parameters that target both tumor and stromal cells. PMID:23262216

  1. Inhibiting the HSP90 chaperone destabilizes macrophage migration inhibitory factor and thereby inhibits breast tumor progression

    PubMed Central

    Schulz, Ramona; Marchenko, Natalia D.; Holembowski, Lena; Fingerle-Rowson, Günter; Pesic, Marina; Zender, Lars; Dobbelstein, Matthias

    2012-01-01

    Intracellular macrophage migration inhibitory factor (MIF) often becomes stabilized in human cancer cells. MIF can promote tumor cell survival, and elevated MIF protein correlates with tumor aggressiveness and poor prognosis. However, the molecular mechanism facilitating MIF stabilization in tumors is not understood. We show that the tumor-activated HSP90 chaperone complex protects MIF from degradation. Pharmacological inhibition of HSP90 activity, or siRNA-mediated knockdown of HSP90 or HDAC6, destabilizes MIF in a variety of human cancer cells. The HSP90-associated E3 ubiquitin ligase CHIP mediates the ensuing proteasome-dependent MIF degradation. Cancer cells contain constitutive endogenous MIF–HSP90 complexes. siRNA-mediated MIF knockdown inhibits proliferation and triggers apoptosis of cultured human cancer cells, whereas HSP90 inhibitor-induced apoptosis is overridden by ectopic MIF expression. In the ErbB2 transgenic model of human HER2-positive breast cancer, genetic ablation of MIF delays tumor progression and prolongs overall survival of mice. Systemic treatment with the HSP90 inhibitor 17AAG reduces MIF expression and blocks growth of MIF-expressing, but not MIF-deficient, tumors. Together, these findings identify MIF as a novel HSP90 client and suggest that HSP90 inhibitors inhibit ErbB2-driven breast tumor growth at least in part by destabilizing MIF. PMID:22271573

  2. HER4 selectively coregulates estrogen stimulated genes associated with breast tumor cell proliferation

    SciTech Connect

    Han, Wen; Jones, Frank E.

    2014-01-10

    Highlights: •HER4/4ICD is an obligate coactivator for 37% of estrogen regulated genes. •HER4/4ICD coactivated genes selectively regulate estrogen stimulated proliferation. •Estrogen stimulated tumor cell migration occurs independent of HER4/4ICD. •Disrupting HER4/4ICD and ER coactivated gene expression may suppress breast cancer. -- Abstract: The EGFR-family member HER4 undergoes regulated intramembrane proteolysis (RIP) to generate an intracellular domain (4ICD) that functions as a transcriptional coactivator. Accordingly, 4ICD coactivates the estrogen receptor (ER) and associates with ER at target gene promoters in breast tumor cells. However, the extent of 4ICD coactivation of ER and the functional significance of the 4ICD/ER transcriptional complex is unclear. To identify 4ICD coactivated genes we performed a microarray gene expression analysis of β-estradiol treated cells comparing control MCF-7 breast cancer cells to MCF-7 cells where HER4 expression was stably suppressed using a shRNA. In the MCF-7 cell line, β-estradiol significantly stimulated or repressed by 2-fold or more 726 or 53 genes, respectively. Significantly, HER4/4ICD was an obligate coactivator for 277 or 38% of the β-estradiol stimulated genes. Ingenuity Pathway Analysis of β-estradiol regulated genes identified significant associations with multiple cellular functions regulating cellular growth and proliferation, cell cycle progression, cancer metastasis, decreased hypoplasia, tumor cell migration, apoptotic resistance of tumor cells, and increased transcription. Genes coactivated by 4ICD displayed functional specificity by only significantly contributing to cellular growth and proliferation, cell cycle progression, and decreased hypoplasia. In direct concordance with these in situ results we show that HER4 knockdown in MCF-7 cells results in a loss of estrogen stimulated tumor cell proliferation and cell cycle progression, whereas, estrogen stimulated tumor cell migration was

  3. Inhibition of autophagy stimulate molecular iodine-induced apoptosis in hormone independent breast tumors

    SciTech Connect

    Singh, Preeti; Godbole, Madan; Rao, Geeta; Annarao, Sanjay; Mitra, Kalyan; Roy, Raja; Ingle, Arvind; Agarwal, Gaurav; Tiwari, Swasti

    2011-11-11

    Highlights: Black-Right-Pointing-Pointer Molecular iodine (I{sub 2}) causes non-apoptotic cell death in MDA-MB231 breast tumor cells. Black-Right-Pointing-Pointer Autophagy is activated as a survival mechanism in response to I{sub 2} in MDA-MB231. Black-Right-Pointing-Pointer Autophagy inhibition sensitizes tumor cells to I{sub 2}-induced apoptotic cell death. Black-Right-Pointing-Pointer Autophagy inhibitor potentiates apoptosis and tumor regressive effects of I{sub 2} in mice. -- Abstract: Estrogen receptor negative (ER{sup -ve}) and p53 mutant breast tumors are highly aggressive and have fewer treatment options. Previously, we showed that molecular Iodine (I{sub 2}) induces apoptosis in hormone responsive MCF-7 breast cancer cells, and non-apoptotic cell death in ER{sup -ve}-p53 mutant MDA-MB231 cells (Shrivastava, 2006). Here we show that I{sub 2} (3 {mu}M) treatment enhanced the features of autophagy in MDA-MB231 cells. Since autophagy is a cell survival response to most anti-cancer therapies, we used both in vitro and in vivo systems to determine whether ER{sup -ve} mammary tumors could be sensitized to I{sub 2}-induced apoptosis by inhibiting autophagy. Autophagy inhibition with chloroquine (CQ) and inhibitors for PI3K (3MA, LY294002) and H+/ATPase (baflomycin) resulted in enhanced cell death in I{sub 2} treated MDA-MB231 cells. Further, CQ (20 {mu}M) in combination with I{sub 2}, showed apoptotic features such as increased sub-G1 fraction ({approx}5-fold), expression of cleaved caspase-9 and -3 compared to I{sub 2} treatment alone. Flowcytometry of I{sub 2} and CQ co-treated cells revealed increase in mitochondrial membrane permeability (p < 0.01) and translocation of cathepsin D activity to cytosol relative to I{sub 2} treatment. For in vivo studies ICRC mice were transplanted subcutaneously with MMTV-induced mammary tumors. A significant reduction in tumor volumes, as measured by MRI, was found in I{sub 2} and CQ co-treated mice relative to I{sub 2} or

  4. Effect of Melatonin on Tumor Growth and Angiogenesis in Xenograft Model of Breast Cancer

    PubMed Central

    Jardim-Perassi, Bruna Victorasso; Arbab, Ali S.; Ferreira, Lívia Carvalho; Borin, Thaiz Ferraz; Varma, Nadimpalli R. S.; Iskander, A. S. M.; Shankar, Adarsh; Ali, Meser M.; de Campos Zuccari, Debora Aparecida Pires

    2014-01-01

    As neovascularization is essential for tumor growth and metastasis, controlling angiogenesis is a promising tactic in limiting cancer progression. Melatonin has been studied for their inhibitory properties on angiogenesis in cancer. We performed an in vivo study to evaluate the effects of melatonin treatment on angiogenesis in breast cancer. Cell viability was measured by MTT assay after melatonin treatment in triple-negative breast cancer cells (MDA-MB-231). After, cells were implanted in athymic nude mice and treated with melatonin or vehicle daily, administered intraperitoneally 1 hour before turning the room light off. Volume of the tumors was measured weekly with a digital caliper and at the end of treatments animals underwent single photon emission computed tomography (SPECT) with Technetium-99m tagged vascular endothelial growth factor (VEGF) C to detect in vivo angiogenesis. In addition, expression of pro-angiogenic/growth factors in the tumor extracts was evaluated by membrane antibody array and collected tumor tissues were analyzed with histochemical staining. Melatonin in vitro treatment (1 mM) decreased cell viability (p<0.05). The breast cancer xenografts nude mice treated with melatonin showed reduced tumor size and cell proliferation (Ki-67) compared to control animals after 21 days of treatment (p<0.05). Expression of VEGF receptor 2 decreased significantly in the treated animals compared to that of control when determined by immunohistochemistry (p<0.05) but the changes were not significant on SPECT (p>0.05) images. In addition, there was a decrease of micro-vessel density (Von Willebrand Factor) in melatonin treated mice (p<0.05). However, semiquantitative densitometry analysis of membrane array indicated increased expression of epidermal growth factor receptor and insulin-like growth factor 1 in treated tumors compared to vehicle treated tumors (p<0.05). In conclusion, melatonin treatment showed effectiveness in reducing tumor growth and cell

  5. IDENTIFYING AND TARGETING TUMOR-INITIATING CELLS IN THE TREATMENT OF BREAST CANCER

    PubMed Central

    Wei, Wei; Lewis, Michael T.

    2015-01-01

    Breast cancer is the most common cancer in women (exclusive of skin cancer), and is the second leading cause of cancer-related deaths. Although conventional and targeted therapies have improved survival rates, there are still considerable challenges in treating breast cancer, including treatment resistance, disease recurrence, and metastasis. Treatment resistance can be either de novo - due to traits that tumor cells possess prior to treatment, or acquired, - due to traits that tumor cells gain in response to treatment. A recently proposed mechanism of de novo resistance invokes existence of a specialized subset of cancer cells defined as tumor-initiating cells (TICs), or cancer stem cells (CSC). TICs have the capacity to self-renew and regenerate new tumors that consist of all clonally-derived cell types present in the parental tumor. There are data to suggest that TICs are resistant to many conventional cancer therapies, and survive treatment in spite of dramatic shrinkage of the tumor. Residual TICs can then eventually regrow resulting in disease relapse. It is also hypothesized that TIC may be responsible for metastatic disease. If these hypotheses are correct, targeting TICs may be imperative to achieve cure. In this review, we discuss evidence for breast TICs and their apparent resistance to conventional chemotherapy and radiotherapy, as well as to various targeted therapies. We also address the potential impact of breast TIC plasticity and metastatic potential on therapeutic strategies. Finally, we describe several genes and signaling pathways that appear important for TIC function that may represent promising therapeutic targets. PMID:25876646

  6. Cytokines secreted by macrophages isolated from tumor microenvironment of inflammatory breast cancer patients possess chemotactic properties

    PubMed Central

    Mohamed, Mona M.; El-Ghonaimy, Eslam A.; Nouh, Mohamed A.; Schneider, Robert J.; Sloane, Bonnie F.; El-Shinawi, Mohamed

    2014-01-01

    Although there is a growing literature describing the role of macrophages in breast cancer, the role of macrophages in inflammatory breast cancer (IBC) is unclear. The aim of present study was to isolate and characterize tumor associated macrophages of IBC and non-IBC patients and define their role in IBC. Tumor infiltrating monocytes/macrophages (CD14+ and CD68+) were measured by immunohistochem-istry using specific monoclonal antibodies. Blood drained from axillary vein tributaries was collected during breast cancer surgery and the percentage of CD14+ in the total isolated leukocytes was assessed by flow cytometric analysis. CD14+ cells were separated from total leukocytes by immuno-magnetic beads technique and were cultured overnight. Media conditioned by CD14+ were collected and subjected to cytokine profiling using cytokine antibody array. Wound healing and invasion assays were used to test whether cytokines highly secreted by tumor drained macrophages induce motility and invasion of breast cancer cells. We found that macrophages highly infiltrate into carcinoma tissues of IBC patients. In addition blood collected from axillary tributaries of IBC patients is highly enriched with CD14+ cells as compared to blood collected from non-IBC patients. Cytokine profiling of CD14+ cells isolated from IBC patients revealed a significant increase in secretion of tumor necrosis factor-α; monocyte chemoat-tractant protein-1/CC-chemokine ligand 2; interleukin-8 and interleukin-10 as compared to CD14+ cells isolated from non-IBC patients. Tumor necrosis factor-a, interleukin-8 and interleukin-10 significantly increased motility and invasion of IBC cells in vitro. In conclusion, macrophages isolated from the tumor microenvironment of IBC patients secrete chemotactic cytokines that may augment dissemination and metastasis of IBC carcinoma cells. PMID:24291763

  7. Cytokines secreted by macrophages isolated from tumor microenvironment of inflammatory breast cancer patients possess chemotactic properties.

    PubMed

    Mohamed, Mona M; El-Ghonaimy, Eslam A; Nouh, Mohamed A; Schneider, Robert J; Sloane, Bonnie F; El-Shinawi, Mohamed

    2014-01-01

    Although there is a growing literature describing the role of macrophages in breast cancer, the role of macrophages in inflammatory breast cancer (IBC) is unclear. The aim of present study was to isolate and characterize tumor associated macrophages of IBC and non-IBC patients and define their role in IBC. Tumor infiltrating monocytes/macrophages (CD14+ and CD68+) were measured by immunohistochemistry using specific monoclonal antibodies. Blood drained from axillary vein tributaries was collected during breast cancer surgery and the percentage of CD14+ in the total isolated leukocytes was assessed by flow cytometric analysis. CD14+ cells were separated from total leukocytes by immuno-magnetic beads technique and were cultured overnight. Media conditioned by CD14+ were collected and subjected to cytokine profiling using cytokine antibody array. Wound healing and invasion assays were used to test whether cytokines highly secreted by tumor drained macrophages induce motility and invasion of breast cancer cells. We found that macrophages highly infiltrate into carcinoma tissues of IBC patients. In addition blood collected from axillary tributaries of IBC patients is highly enriched with CD14+ cells as compared to blood collected from non-IBC patients. Cytokine profiling of CD14+ cells isolated from IBC patients revealed a significant increase in secretion of tumor necrosis factor-α; monocyte chemoattractant protein-1/CC-chemokine ligand 2; interleukin-8 and interleukin-10 as compared to CD14+ cells isolated from non-IBC patients. Tumor necrosis factor-α, interleukin-8 and interleukin-10 significantly increased motility and invasion of IBC cells in vitro. In conclusion, macrophages isolated from the tumor microenvironment of IBC patients secrete chemotactic cytokines that may augment dissemination and metastasis of IBC carcinoma cells.

  8. Early impact of social isolation and breast tumor progression in mice.

    PubMed

    Madden, Kelley S; Szpunar, Mercedes J; Brown, Edward B

    2013-03-01

    Evidence from cancer patients and animal models of cancer indicates that exposure to psychosocial stress can promote tumor growth and metastasis, but the pathways underlying stress-induced cancer pathogenesis are not fully understood. Social isolation has been shown to promote tumor progression. We examined the impact of social isolation on breast cancer pathogenesis in adult female severe combined immunodeficiency (SCID) mice using the human breast cancer cell line, MDA-MB-231, a high β-adrenergic receptor (AR) expressing line. When group-adapted mice were transferred into single housing (social isolation) one week prior to MB-231 tumor cell injection into a mammary fat pad (orthotopic), no alterations in tumor growth or metastasis were detected compared to group-housed mice. When social isolation was delayed until tumors were palpable, tumor growth was transiently increased in singly-housed mice. To determine if sympathetic nervous system activation was associated with increased tumor growth, spleen and tumor norepinephrine (NE) was measured after social isolation, in conjunction with tumor-promoting macrophage populations. Three days after transfer to single housing, spleen weight was transiently increased in tumor-bearing and non-tumor-bearing mice in conjunction with reduced splenic NE concentration and elevated CD11b+Gr-1+ macrophages. At day 10 after social isolation, no changes in spleen CD11b+ populations or NE were detected in singly-housed mice. In the tumors, social isolation increased CD11b+Gr-1+, CD11b+Gr-1-, and F4/80+ macrophage populations, with no change in tumor NE. The results indicate that a psychological stressor, social isolation, elicits dynamic but transient effects on macrophage populations that may facilitate tumor growth. The transiency of the changes in peripheral NE suggest that homeostatic mechanisms may mitigate the impact of social isolation over time. Studies are underway to define the neuroendocrine mechanisms underlying the

  9. Use of non-selective β-blockers is associated with decreased tumor proliferative indices in early stage breast cancer.

    PubMed

    Montoya, Alexa; Amaya, Clarissa N; Belmont, Andres; Diab, Nabih; Trevino, Richard; Villanueva, Geri; Rains, Steven; Sanchez, Luis A; Badri, Nabeel; Otoukesh, Salman; Khammanivong, Ali; Liss, Danielle; Baca, Sarah T; Aguilera, Renato J; Dickerson, Erin B; Torabi, Alireza; Dwivedi, Alok K; Abbas, Aamer; Chambers, Karinn; Bryan, Brad A; Nahleh, Zeina

    2017-01-24

    Previous studies suggest beta-adrenergic receptor (β-AR) antagonists (β-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of β1-AR and β3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% (p < 0.0001) in early stage breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of β-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective β-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3β. In conclusion, use of non-selective β-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation.

  10. Use of non-selective β-blockers is associated with decreased tumor proliferative indices in early stage breast cancer

    PubMed Central

    Diab, Nabih; Trevino, Richard; Villanueva, Geri; Rains, Steven; Sanchez, Luis A.; Badri, Nabeel; Otoukesh, Salman; Khammanivong, Ali; Liss, Danielle; Baca, Sarah T.; Aguilera, Renato J.; Dickerson, Erin B.; Torabi, Alireza; Dwivedi, Alok K.; Abbas, Aamer; Chambers, Karinn; Bryan, Brad A.; Nahleh, Zeina

    2017-01-01

    Previous studies suggest beta-adrenergic receptor (β-AR) antagonists (β-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of β1-AR and β3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% (p < 0.0001) in early stage breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of β-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective β-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3β. In conclusion, use of non-selective β-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation. PMID:28031536

  11. Clinical application of circulating tumor cells in breast cancer: overview of the current interventional trials.

    PubMed

    Bidard, François-Clément; Fehm, Tanja; Ignatiadis, Michail; Smerage, Jeffrey B; Alix-Panabières, Catherine; Janni, Wolfgang; Messina, Carlo; Paoletti, Costanza; Müller, Volkmar; Hayes, Daniel F; Piccart, Martine; Pierga, Jean-Yves

    2013-06-01

    In 2004, circulating tumor cells (CTC) enumeration by the CellSearch® technique at baseline and during treatment was reported to be associated with prognosis in metastatic breast cancer patients. In 2008, the first evidence of the impact of CTC detection by this technique on survival of cM0(i+) patients were reported. These findings were confirmed by other non-interventional studies, whereas CTC were also investigated as a surrogate for tumor biology, mainly for HER2 expression/amplification. The aim of this report is to present the current prospective large interventional studies that have been specifically designed to demonstrate that CTC enumeration/characterization may improve the management of breast cancer patients: STIC CTC METABREAST (France) and Endocrine Therapy Index (USA) assess the CTC-guided hormone therapy vs chemotherapy decision in M1 patients; SWOG0500 (USA) and CirCe01 (France) assess the CTC count changes during treatment in metastatic patients; DETECT III (M1 patients, Germany) and Treat CTC (cM0(i+) patients, European Organization for Research and Treatment of Cancer/Breast International Group) assess the use of anti-HER2 treatments in HER2-negative breast cancer patients selected on the basis of CTC detection/characterization. These trials have different designs in various patient populations but are expected to be the pivotal trials for CTC implementation in the routine management of breast cancer patients.

  12. A Nonpalpable Nodule in Ectopic Axillary Breast Tissue: Consider Phyllodes Tumor

    PubMed Central

    Bautista-Piña, Verónica; Ramírez-Bollas, Julio; Espejo-Fonseca, Ruby; Rodríguez-Cuevas, Sergio

    2016-01-01

    Benign and malignant pathology can develop in ectopic axillary breast tissue, such as fibroadenomas, phyllodes tumors, and breast cancer. We present a rare case of an asymptomatic 43-year-old woman with an axillary nodule which was identified during screening mammography within ectopic axillary breast tissue, initially considered as a suspicious lymph node. Radiologic studies were considered as Breast Imaging-Reporting Data System (BI-RADS) 4. A hyperdense, lobular, and well-circumscribed nodule was identified in mammogram while the nodule by ultrasound (US) was hypoechoic with indistinct microlobular margins, without vascularity by Doppler, and measuring 1.26 × 1 cm. Core-needle biopsy reported a fibroepithelial neoplasm. The patient was submitted to local wide-needle excision located in intraoperative radiography of the surgical specimen and margin evaluation. Final histopathological study reported a 1.8 × 1.2 cm benign phyllodes tumor, with irregular, pushing, and clear wide margins within normal ectopic breast tissue. The patient without surgical complications continued annual screening without recurrence during a follow-up that took place 24 months later. PMID:28105378

  13. Maximizing Immune Response to Carbohydrate Antigens on Breast Tumors

    DTIC Science & Technology

    2004-08-01

    means to eradicate tumor cells would therefore be an advantage in vaccine development (manuscript #2 submitted). Choice of peptide mimotope Arrays of...peptide mimotopes of carbohydrate antigens formulated as multiple antigen peptides or as DNA vaccines can elicit carbohydrate reactive IgM serum...specific CTL. Immunity 1999; 10:51-61. 1. Kieber-Emmons T, Luo P, Qiu J, et al. Vaccination with carbohydrate peptide mimotopes promotes anti-tumor

  14. Tumor-Host Interaction in Breast Cancer Bone Metastasis

    DTIC Science & Technology

    2006-01-01

    of America. Twenty percent of women with early stage, node- negative breast cancer may subsequently develop metastatic disease , while as many as 90...the prolonged course of a disease with such complications as bone pain and pathological fractures severely reduces a patient’s quality of life, and...to the high incidence of bone metastases of this disease . One observation is the correlation between expression of parathyroid hormone related

  15. Tumor response estimation in radar-based microwave breast cancer detection.

    PubMed

    Kurrant, Douglas J; Fear, Elise C; Westwick, David T

    2008-12-01

    Radar-based microwave imaging techniques have been proposed for early stage breast cancer detection. A considerable challenge for the successful implementation of these techniques is the reduction of clutter, or components of the signal originating from objects other than the tumor. In particular, the reduction of clutter from the late-time scattered fields is required in order to detect small (subcentimeter diameter) tumors. In this paper, a method to estimate the tumor response contained in the late-time scattered fields is presented. The method uses a parametric function to model the tumor response. A maximum a posteriori estimation approach is used to evaluate the optimal values for the estimates of the parameters. A pattern classification technique is then used to validate the estimation. The ability of the algorithm to estimate a tumor response is demonstrated by using both experimental and simulated data obtained with a tissue sensing adaptive radar system.

  16. Photoacoustic imaging of breast tumor vascularization: a comparison with MRI and histopathology

    NASA Astrophysics Data System (ADS)

    Heijblom, Michelle; Piras, Daniele; van den Engh, Frank M.; Klaase, Joost M.; Brinkhuis, Mariël.; Steenbergen, Wiendelt; Manohar, Srirang

    2013-06-01

    Breast cancer is the most common form of cancer and the leading cause of cancer death among females. Early diagnosis improves the survival chances for the disease and that is why there is an ongoing search for improved methods for visualizing breast cancer. One of the hallmarks of breast cancer is the increase in tumor vascularization that is associated with angiogenesis: a crucial factor for survival of malignancies. Photoacoustic imaging can visualize the malignancyassociated increased hemoglobin concentration with optical contrast and ultrasound resolution, without the use of ionizing radiation or contrast agents and is therefore theoretically an ideal method for breast imaging. Previous clinical studies using the Twente Photoacoustic Mammoscope (PAM), which works in forward mode using a single wavelength (1064 nm), showed that malignancies can indeed be identified in the photoacoustic imaging volume as high contrast areas. However, the specific appearance of the malignancies led to questions about the contrast mechanism in relation to tumor vascularization. In this study, the photoacoustic lesion appearance obtained with an updated version of PAM is compared with the lesion appearance on Magnetic Resonance Imaging (MRI), both in general (19 patients) and on an individual basis (7 patients). Further, in 3 patients an extended histopathology protocol is being performed in which malignancies are stained for vascularity using an endothelial antibody: CD31. The correspondence between PAM and MRI and between PAM and histopathology makes it likely that the high photoacoustic contrast at 1064 nm is indeed largely the consequence of the increased tumor vascularization.

  17. miR-195 inhibits tumor growth and angiogenesis through modulating IRS1 in breast cancer.

    PubMed

    Wang, Yilin; Zhang, Xiaolong; Zou, Chao; Kung, Hsiang-Fu; Lin, Marie C; Dress, Andreas; Wardle, Fiona; Jiang, Bing-Hua; Lai, Lihui

    2016-05-01

    Angiogenesis has been found as an attractive target for drug therapy as it is necessary for tumor growth. Accumulating evidences show that microRNAs (miRNAs), which are a group of highly conserved, single-stranded, short non-coding RNAs, play important roles through directly targeting angiogenic factors and protein kinases. The purpose of this study is to investigate the role of miR-195 in breast cancer development and angiogenesis through targeting IRS1. We show that miR-195 is inversely related with Insulin receptor substrate 1 (IRS1) in both breast cancer cells and breast cancer tissues. Induction of miR-195 could suppress IRS1 protein expression through binding to its 3'UTR regions either by transfection with miR-195 oligo or by infection with lentivirus encoding miR-195 gene. Moreover, re-expression of IRS1 reverses miR-195-mediated repression of tumor cell growth and miR-195 inhibits tumor angiogenesis through suppressing IRS1-VEGF axis. These data suggest that miR-195 mimics are potential therapeutic agents for breast cancer diagnose.

  18. Automatic Detection and Classification of Breast Tumors in Ultrasonic Images Using Texture and Morphological Features

    PubMed Central

    Su, Yanni; Wang, Yuanyuan; Jiao, Jing; Guo, Yi

    2011-01-01

    Due to severe presence of speckle noise, poor image contrast and irregular lesion shape, it is challenging to build a fully automatic detection and classification system for breast ultrasonic images. In this paper, a novel and effective computer-aided method including generation of a region of interest (ROI), segmentation and classification of breast tumor is proposed without any manual intervention. By incorporating local features of texture and position, a ROI is firstly detected using a self-organizing map neural network. Then a modified Normalized Cut approach considering the weighted neighborhood gray values is proposed to partition the ROI into clusters and get the initial boundary. In addition, a regional-fitting active contour model is used to adjust the few inaccurate initial boundaries for the final segmentation. Finally, three textures and five morphologic features are extracted from each breast tumor; whereby a highly efficient Affinity Propagation clustering is used to fulfill the malignancy and benign classification for an existing database without any training process. The proposed system is validated by 132 cases (67 benignancies and 65 malignancies) with its performance compared to traditional methods such as level set segmentation, artificial neural network classifiers, and so forth. Experiment results show that the proposed system, which needs no training procedure or manual interference, performs best in detection and classification of ultrasonic breast tumors, while having the lowest computation complexity. PMID:21892371

  19. Role of Erbin in ErbB2-dependent breast tumor growth

    PubMed Central

    Tao, Yanmei; Shen, Chengyong; Luo, Shiwen; Traoré, Wilfried; Marchetto, Sylvie; Santoni, Marie-Josée; Xu, Linlin; Wu, Biao; Shi, Chao; Mei, Jinghong; Bates, Ryan; Liu, Xihui; Zhao, Kai; Xiong, Wen-Cheng; Borg, Jean-Paul; Mei, Lin

    2014-01-01

    ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), a receptor tyrosine kinase of the ErbB family, is overexpressed in around 25% of breast cancers. In addition to forming a heterodimer with other ErbB receptors in response to ligand stimulation, ErbB2 can be activated in a ligand-independent manner. We report here that Erbin, an ErbB2-interacting protein that was thought to act as an antitumor factor, is specifically expressed in mammary luminal epithelial cells and facilitates ErbB2-dependent proliferation of breast cancer cells and tumorigenesis in MMTV-neu transgenic mice. Disruption of their interaction decreases ErbB2-dependent proliferation, and deletion of the PDZ domain in Erbin hinders ErbB2-dependent tumor development in MMTV-neu mice. Mechanistically, Erbin forms a complex with ErbB2, promotes its interaction with the chaperon protein HSP90, and thus prevents its degradation. Finally, ErbB2 and Erbin expression correlates in human breast tumor tissues. Together, these observations establish Erbin as an ErbB2 regulator for breast tumor formation and progression. PMID:25288731

  20. Role of Erbin in ErbB2-dependent breast tumor growth.

    PubMed

    Tao, Yanmei; Shen, Chengyong; Luo, Shiwen; Traoré, Wilfried; Marchetto, Sylvie; Santoni, Marie-Josée; Xu, Linlin; Wu, Biao; Shi, Chao; Mei, Jinghong; Bates, Ryan; Liu, Xihui; Zhao, Kai; Xiong, Wen-Cheng; Borg, Jean-Paul; Mei, Lin

    2014-10-21

    ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), a receptor tyrosine kinase of the ErbB family, is overexpressed in around 25% of breast cancers. In addition to forming a heterodimer with other ErbB receptors in response to ligand stimulation, ErbB2 can be activated in a ligand-independent manner. We report here that Erbin, an ErbB2-interacting protein that was thought to act as an antitumor factor, is specifically expressed in mammary luminal epithelial cells and facilitates ErbB2-dependent proliferation of breast cancer cells and tumorigenesis in MMTV-neu transgenic mice. Disruption of their interaction decreases ErbB2-dependent proliferation, and deletion of the PDZ domain in Erbin hinders ErbB2-dependent tumor development in MMTV-neu mice. Mechanistically, Erbin forms a complex with ErbB2, promotes its interaction with the chaperon protein HSP90, and thus prevents its degradation. Finally, ErbB2 and Erbin expression correlates in human breast tumor tissues. Together, these observations establish Erbin as an ErbB2 regulator for breast tumor formation and progression.

  1. The a3 isoform of subunit a of the vacuolar ATPase localizes to the plasma membrane of invasive breast tumor cells and is overexpressed in human breast cancer

    PubMed Central

    Cotter, Kristina; Liberman, Rachel; Sun-Wada, GeHong; Wada, Yoh; Sgroi, Dennis; Naber, Stephen; Brown, Dennis; Breton, Sylvie; Forgac, Michael

    2016-01-01

    The vacuolar (H+)-ATPases (V-ATPases) are a family of ATP-driven proton pumps that acidify intracellular compartments and transport protons across the plasma membrane. Previous work has demonstrated that plasma membrane V-ATPases are important for breast cancer invasion in vitro and that the V-ATPase subunit a isoform a3 is upregulated in and critical for MDA-MB231 and MCF10CA1a breast cancer cell invasion. It has been proposed that subunit a3 is present on the plasma membrane of invasive breast cancer cells and is overexpressed in human breast cancer. To test this, we used an a3-specific antibody to assess localization in breast cancer cells. Subunit a3 localizes to the leading edge of migrating breast cancer cells, but not the plasma membrane of normal breast epithelial cells. Furthermore, invasive breast cancer cells express a3 throughout all intracellular compartments tested, including endosomes, the Golgi, and lysosomes. Moreover, subunit a3 knockdown in MB231 breast cancer cells reduces in vitro migration. This reduction is not enhanced upon addition of a V-ATPase inhibitor, suggesting that a3-containing V-ATPases are critical for breast cancer migration. Finally, we have tested a3 expression in human breast cancer tissue and mRNA prepared from normal and cancerous breast tissue. a3 mRNA was upregulated 2.5-47 fold in all breast tumor cDNA samples tested relative to normal tissue, with expression generally correlated to cancer stage. Furthermore, a3 protein expression was increased in invasive breast cancer tissue relative to noninvasive cancer and normal breast tissue. These studies suggest that subunit a3 plays an important role in invasive human breast cancer. PMID:27323815

  2. [Right Hemi-Colectomy for a Metastatic Transverse Colon Tumor from Breast Cancer Following Bilateral Breast Cancer Resection - A Case Report].

    PubMed

    Okamura, Shu; Yanagisawa, Tetsu; Ohishi, Kazuhito; Murata, Kohei; Nushijima, Yoichiro; Hamano, Rie; Fukuchi, Nariaki; Ebisui, Chikara; Yokouchi, Hideoki; Kinuta, Masakatsu

    2016-11-01

    We herein report the case of a 75-year-old female patient who underwent 4 surgeries for bilateral breast cancer and its recurrence. When she presented at a clinic with an irritable colon, a fist-sized tumor was palpated in the right upper abdomen at her first medical examination. Abdominal CT scan at the clinic revealed a tumor with a maximum diameter of 10 cm on the right side of the transverse colon and multiple swollen mesenteric lymph nodes. Therefore, the patient was referred to our hospital for surgery. Colonoscopy revealed stenosis of the same lesion with an edematous mucosa and sclerosis. Using immunohistochemistry, a biopsy specimen from the lesion tested positive for CK AE1+AE3, and negative for CD20(-)and CD3 (-). As a result, the tumor was diagnosed as a poorly differentiated adenocarcinoma. We performed right hemicolectomy to avoid her intestinal obstruction. Tumor cells were mainly present at the subserosa, according to HEstaining. Using immunostaining, the cells were tested for the following markers: CDX2(-), GCDFP15(weakly positive), CK7(strongly positive), CD20(partially positive), E R(+), PgR(-), and HER2(1+), characterizing the tumor as metastasis of breast cancer. Although gastro-intestinal metastasis from breast cancer is rare, and colon metastasis is even rarer, it might be necessary to rule out the possibility of a metastatic colon tumor from breast cancer when treating patients with a colon tumor who have undergone surgery for breast cancer.

  3. CCL18 from tumor-associated macrophages promotes angiogenesis in breast cancer.

    PubMed

    Lin, Ling; Chen, Yong-Song; Yao, Yan-Dan; Chen, Jing-Qi; Chen, Jia-Ning; Huang, Song-Yin; Zeng, Yun-Jie; Yao, He-Rui; Zeng, Si-Hai; Fu, Yong-Shui; Song, Er-Wei

    2015-10-27

    The infiltration of tumor-associated macrophages (TAMs) is associated with extensive angiogenesis, which contributes to a poor prognosis in breast cancer. However, anti-angiogenic therapy with VEGF-specific monotherapy has been unsuccessful in treating breast cancer, and the molecular mechanisms associated with chemoresistance remain unclear. Here, we investigated whether CCL18, a chemokine produced by TAMs, can stimulate angiogenesis in breast cancer, as well as the underlying mechanisms. Double immunohistochemical staining for CCL18 and CD34/CD31/vWF was performed in 80 breast cancer samples to study the correlation between CCL18+ TAMs and microvascular density (MVD). Cocultures of TAMs with human umbilical vein endothelial cells (HUVECs) were used to model the inflammatory microenvironment, and CCL18-induced angiogenesis was evaluated both in vitro and in vivo. We demonstrated that CCL18+ TAM infiltration positively associated with MVD in breast cancer samples, which was correlated with tumor metastasis and poor prognosis. We confirmed, both in vitro and in vivo, that CCL18 and VEGF synergistically promoted endothelial cell migration and angiogenesis. Conversely, blocking CCL18 or VEGF with neutralizing antibodies synergistically inhibited the promigratory effects of TAMs. Silencing PITPNM3, a putative CCL18 receptor, on the surface of HUVECs abrogated CCL18-mediated promigration and the enhancement of HUVEC tube formation, independently of VEGFR signaling. Moreover, CCL18 exposure induced the endothelial-mesenchymal transformation and activated ERK and Akt/GSK-3β/Snail signaling in HUVECs, thereby contributing to its pro-angiogenic effects. In conclusion, our findings suggest that CCL18 released from TAMs promotes angiogenesis and tumor progression in breast cancer; thus, CCL18 may serve as a novel target for anti-angiogenic therapies.

  4. Activation of PI3K/Akt/mTOR signaling in the tumor stroma drives endocrine therapy-dependent breast tumor regression

    PubMed Central

    Polo, María Laura; Riggio, Marina; May, María; Rodríguez, María Jimena; Perrone, María Cecilia; Stallings-Mann, Melody; Kaen, Diego; Frost, Marlene; Goetz, Matthew; Boughey, Judy; Lanari, Claudia; Radisky, Derek; Novaro, Virginia

    2015-01-01

    Improved efficacy of neoadjuvant endocrine-targeting therapies in luminal breast carcinomas could be achieved with optimal use of pathway targeting agents. In a mouse model of ductal breast carcinoma we identify a tumor regressive stromal reaction that is induced by neoadjuvant endocrine therapy. This reparative reaction is characterized by tumor neovascularization accompanied by infiltration of immune cells and carcinoma-associated fibroblasts that stain for phosphorylated ribosomal protein S6 (pS6), downstream the PI3K/Akt/mTOR pathway. While tumor variants with higher PI3K/Akt/mTOR activity respond well to a combination of endocrine and PI3K/Akt/mTOR inhibitors, tumor variants with lower PI3K/Akt/mTOR activity respond more poorly to the combination therapy than to the endocrine therapy alone, associated with inhibition of stromal pS6 and the reparative reaction. In human breast cancer xenografts we confirm that such differential sensitivity to therapy is primarily determined by the level of PI3K/Akt/mTOR in tumor cells. We further show that the clinical response of breast cancer patients undergoing neoadjuvant endocrine therapy is associated with the reparative stromal reaction. We conclude that tumor level and localization of pS6 are associated with therapeutic response in breast cancer and represent biomarkers to distinguish which tumors will benefit from the incorporation of PI3K/Akt/mTOR inhibitors with neoadjuvant endocrine therapy. PMID:26098779

  5. Surface-enhanced Raman spectroscopy of saliva proteins for the noninvasive differentiation of benign and malignant breast tumors.

    PubMed

    Feng, Shangyuan; Huang, Shaohua; Lin, Duo; Chen, Guannan; Xu, Yuanji; Li, Yongzeng; Huang, Zufang; Pan, Jianji; Chen, Rong; Zeng, Haishan

    2015-01-01

    The capability of saliva protein analysis, based on membrane protein purification and surface-enhanced Raman spectroscopy (SERS), for detecting benign and malignant breast tumors is presented in this paper. A total of 97 SERS spectra from purified saliva proteins were acquired from samples obtained from three groups: 33 healthy subjects; 33 patients with benign breast tumors; and 31 patients with malignant breast tumors. Subtle but discernible changes in the mean SERS spectra of the three groups were observed. Tentative assignments of the saliva protein SERS spectra demonstrated that benign and malignant breast tumors led to several specific biomolecular changes of the saliva proteins. Multiclass partial least squares-discriminant analysis was utilized to analyze and classify the saliva protein SERS spectra from healthy subjects, benign breast tumor patients, and malignant breast tumor patients, yielding diagnostic sensitivities of 75.75%, 72.73%, and 74.19%, as well as specificities of 93.75%, 81.25%, and 86.36%, respectively. The results from this exploratory work demonstrate that saliva protein SERS analysis combined with partial least squares-discriminant analysis diagnostic algorithms has great potential for the noninvasive and label-free detection of breast cancer.

  6. Advanced research on anti-tumor effects of amygdalin.

    PubMed

    Song, Zuoqing; Xu, Xiaohong

    2014-08-01

    Malignant tumors are the major disease that cause serious damage to human health, and have been listed as the premier diseases which seriously threatened human health by World Health Organization (WHO). In recent years the development of antitumor drugs has been gradually transformed from cytotoxic drugs to improving the selectivity of drugs, overcoming multidrug resistance, development of new targeted drugs and low toxicity with high specificity drugs. Amygdalin is a natural product that owns antitumor activity, less side effects, widely sourced and relatively low priced. All these features make the amygdalin a promising antitumor drugs, if combined with conditional chemotherapy drugs, which can produce synergistic effect. In this paper, we summarized the pharmacological activity, toxicity and antitumor activity of amygdalin, mainly focused on the advanced research of amygdalin on its antitumor effects in recent years, providing new insights for the development of new anticancer drugs, new targets searching and natural antitumor mechanism investigations.

  7. Pseudoangio-matous stromal hyperplasia: A rare tumor of the breast.

    PubMed

    Shahi, Kedar Singh; Bhandari, Geeta; Gupta, Rakesh Kumar; Sawai, Malvika

    2015-01-01

    Pseudoangiomatous stromal hyperplasia (PASH) is a benign breast entity described first by Vuitch et al., in 1986. PASH is a benign stromal lesion containing complex anastomosing channels lined by slender spindle cells. It can be mistaken with fibroadenoma on ultrasound examination and histologically with low-grade angiosarcoma and phyllodes tumor. Here, presented is a case report of a 30-year-old female who presented with huge palpable lump in left breast. Ultrasonography revealed the lesion as giant fibroadenoma and fine needle aspiration cytology report was suggestive of cystosarcoma phyllodes. Excision and reduction mammoplasty was done and histopathology report was suggestive of PASH.

  8. Promotion of Tumor-Initiating Cells in Primary and Recurrent Breast Tumors

    DTIC Science & Technology

    2014-10-01

    Moreover, we have demonstrated that the EMT transcription factor, Snail , is markedly upregulated in recurrent mammary tumors, and that forced expression of... Snail in primary tumors is sufficient to promote mammary tumor recurrence. We have also obtained evidence indicating that the NF-κB and TGFβ

  9. Tumor Selective Cytotoxic Action of a Thiomorpholin Hydroxamate Inhibitor (TMI-1) in Breast Cancer

    PubMed Central

    Mezil, Lynda; Berruyer-Pouyet, Carole; Caba