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Sample records for breast cancer epidermal

  1. Epidermal Growth Factor Receptor Overexpression as a Target for Auger Electron Radiotherapy of Breast Cancer

    DTIC Science & Technology

    1999-08-01

    proportion of estrogen receptor-negative and hormone-resistant breast cancers. Our objective is to construct a human epidermal growth factor (hEGF...61 5 INTRODUCTION Overexpression of the epidermal growth factor receptor (EGFR) occurs in a high proportion of estrogen receptor-negative and...Lac Iq promotor induced by isopropyl-b- D -thiogalactopyranoside (IPTG). The DNA sequence of the final hEGF-CH1 construct was confirmed (FUi. 2). BamHJ

  2. Radiosensitizing effect of lapatinib in human epidermal growth factor receptor 2-positive breast cancer cells

    PubMed Central

    Park, Ji Min; Kim, Dan Hyo; Kim, In Ah

    2016-01-01

    Trastuzumab has been widely used for the treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer, however, it cannot easily cross the blood-brain barrier (BBB) and is known to increase the incidence of brain metastases. In contrast, lapatinib has a low molecular weight and can cross the BBB and it could be useful to treat brain metastases in patients with HER2-positive breast cancer. To explore the impact of lapatinib on radiation response, we conducted an in vitro experiment using SKBR3 and BT474 breast carcinoma cells exhibiting HER2/neu amplification. Lapatinib down-regulated phosphorylated (p)-HER2, p-epidermal growth factor receptor, p-AKT, and p-extracellular signal-regulated kinase. Pretreatment of lapatinib increased the radiosensitivity of SKBR3 (sensitizer enhancement ratio [SER]: 1.21 at a surviving fraction of 0.5) and BT474 (SER: 1.26 at a surviving fraction of 0.5) cells and hindered the repair of DNA damage, as suggested by the prolongation of radiation-induced γH2AX foci and the down-regulation of phosphorylated DNA-dependent protein kinase, catalytic subunit (p-DNAPKcs). Increases in radiation-induced apoptosis and senescence were suggested to be the major modes of cell death induced by the combination of lapatinib and radiation. Furthermore, lapatinib did not radiosensitize a HER2- negative breast cancer cell line or normal human astrocytes. These findings suggest that lapatinib can potentiate radiation-induced cell death in HER2-overexpressing breast cancer cells and may increase the efficacy of radiotherapy. A phase II clinical trial using lapatinib concurrently with whole-brain radiation therapy (WBRT) is currently being conducted. PMID:27738326

  3. Molecular Mechanisms and Translational Therapies for Human Epidermal Receptor 2 Positive Breast Cancer

    PubMed Central

    Lv, Quanxia; Meng, Ziyuan; Yu, Yuanyuan; Jiang, Feng; Guan, Daogang; Liang, Chao; Zhou, Junwei; Lu, Aiping; Zhang, Ge

    2016-01-01

    Breast cancer is the second leading cause of cancer death among women. Human epidermal receptor 2 (HER2) positive breast cancer (HER2+ BC) is the most aggressive subtype of breast cancer, with poor prognosis and a high rate of recurrence. About one third of breast cancer is HER2+ BC with significantly high expression level of HER2 protein compared to other subtypes. Therefore, HER2 is an important biomarker and an ideal target for developing therapeutic strategies for the treatment HER2+ BC. In this review, HER2 structure and physiological and pathological roles in HER2+ BC are discussed. Two diagnostic tests, immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH), for evaluating HER2 expression levels are briefly introduced. The current mainstay targeted therapies for HER2+ BC include monoclonal antibodies, small molecule tyrosine kinase inhibitors, antibody–drug conjugates (ADC) and other emerging anti-HER2 agents. In clinical practice, combination therapies are commonly adopted in order to achieve synergistic drug response. This review will help to better understand the molecular mechanism of HER2+ BC and further facilitate the development of more effective therapeutic strategies against HER2+ BC. PMID:27983617

  4. An Immunotherapeutic Approach to the Treatment and Prevention of Breast Cancer, Based on Epidermal Growth Factor Receptor Variant, Type III

    DTIC Science & Technology

    1999-05-01

    H. (1996). Pulmonary metastases neutralization and tumor rejection by in vivo administration of B glucan and bispecific antibody. Int. J. Cancer 65...AD GRANT NUMBER DAMD17-96-1-6016 Title: An Immunotherapeutic Approach to the Treatment and Prevention of Breast Cancer , Based on Epidermal Growth...Leave blank) 2. REPORT DATE May 1999 4. TITLE AND SUBTITLE An Immunotherapeutic Approach to the Treatment and Prevention of Breast Cancer

  5. Targeting Epidermal Growth Factor Receptor in triple negative breast cancer: New discoveries and practical insights for drug development.

    PubMed

    Costa, Ricardo; Shah, Ami N; Santa-Maria, Cesar A; Cruz, Marcelo R; Mahalingam, Devalingam; Carneiro, Benedito A; Chae, Young Kwang; Cristofanilli, Massimo; Gradishar, William J; Giles, Francis J

    2017-02-01

    Triple negative breast cancer (TNBC) accounts for 10-20% of cases in breast cancer. Despite recent advances in the treatment of hormonal receptor+ and HER2+ breast cancers, there are no targeted therapies available for TNBC. Evidence supports that most patients with TNBC express the transmembrane Epidermal Growth Factor Receptor (EGFR). However, early phase clinical trials failed to demonstrate significant activity of EGFR-targeted monoclonal antibodies and/or tyrosine kinase inhibitors. Here, we review the recent discoveries related to the underlying biology of the EGFR pathway in TNBC, clinical progress to date and suggest rational future approaches for investigational therapies in TNBC.

  6. Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment

    PubMed Central

    Koo, Taeryool

    2016-01-01

    Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents. PMID:27104161

  7. Trastuzumab Emtansine in Treating Older Patients With Human Epidermal Growth Factor Receptor 2-Positive Stage I-III Breast Cancer

    ClinicalTrials.gov

    2017-02-03

    Estrogen Receptor Negative; HER2 Positive Breast Carcinoma; Progesterone Receptor Negative; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIC Breast Cancer

  8. Parabens and Human Epidermal Growth Factor Receptor Ligand Cross-Talk in Breast Cancer Cells

    PubMed Central

    Pan, Shawn; Yuan, Chaoshen; Tagmount, Abderrahmane; Rudel, Ruthann A.; Ackerman, Janet M.; Yaswen, Paul; Vulpe, Chris D.; Leitman, Dale C.

    2015-01-01

    Background: Xenoestrogens are synthetic compounds that mimic endogenous estrogens by binding to and activating estrogen receptors. Exposure to estrogens and to some xenoestrogens has been associated with cell proliferation and an increased risk of breast cancer. Despite evidence of estrogenicity, parabens are among the most widely used xenoestrogens in cosmetics and personal-care products and are generally considered safe. However, previous cell-based studies with parabens do not take into account the signaling cross-talk between estrogen receptor α (ERα) and the human epidermal growth factor receptor (HER) family. Objectives: We investigated the hypothesis that the potency of parabens can be increased with HER ligands, such as heregulin (HRG). Methods: The effects of HER ligands on paraben activation of c-Myc expression and cell proliferation were determined by real-time polymerase chain reaction, Western blots, flow cytometry, and chromatin immunoprecipitation assays in ERα- and HER2-positive human BT-474 breast cancer cells. Results: Butylparaben (BP) and HRG produced a synergistic increase in c-Myc mRNA and protein levels in BT-474 cells. Estrogen receptor antagonists blocked the synergistic increase in c-Myc protein levels. The combination of BP and HRG also stimulated proliferation of BT-474 cells compared with the effects of BP alone. HRG decreased the dose required for BP-mediated stimulation of c-Myc mRNA expression and cell proliferation. HRG caused the phosphorylation of serine 167 in ERα. BP and HRG produced a synergistic increase in ERα recruitment to the c-Myc gene. Conclusion: Our results show that HER ligands enhanced the potency of BP to stimulate oncogene expression and breast cancer cell proliferation in vitro via ERα, suggesting that parabens might be active at exposure levels not previously considered toxicologically relevant from studies testing their effects in isolation. Citation: Pan S, Yuan C, Tagmount A, Rudel RA, Ackerman JM

  9. Parabens and Human Epidermal Growth Factor Receptor Ligand Cross-Talk in Breast Cancer Cells.

    PubMed

    Pan, Shawn; Yuan, Chaoshen; Tagmount, Abderrahmane; Rudel, Ruthann A; Ackerman, Janet M; Yaswen, Paul; Vulpe, Chris D; Leitman, Dale C

    2016-05-01

    Xenoestrogens are synthetic compounds that mimic endogenous estrogens by binding to and activating estrogen receptors. Exposure to estrogens and to some xenoestrogens has been associated with cell proliferation and an increased risk of breast cancer. Despite evidence of estrogenicity, parabens are among the most widely used xenoestrogens in cosmetics and personal-care products and are generally considered safe. However, previous cell-based studies with parabens do not take into account the signaling cross-talk between estrogen receptor α (ERα) and the human epidermal growth factor receptor (HER) family. We investigated the hypothesis that the potency of parabens can be increased with HER ligands, such as heregulin (HRG). The effects of HER ligands on paraben activation of c-Myc expression and cell proliferation were determined by real-time polymerase chain reaction, Western blots, flow cytometry, and chromatin immunoprecipitation assays in ERα- and HER2-positive human BT-474 breast cancer cells. Butylparaben (BP) and HRG produced a synergistic increase in c-Myc mRNA and protein levels in BT-474 cells. Estrogen receptor antagonists blocked the synergistic increase in c-Myc protein levels. The combination of BP and HRG also stimulated proliferation of BT-474 cells compared with the effects of BP alone. HRG decreased the dose required for BP-mediated stimulation of c-Myc mRNA expression and cell proliferation. HRG caused the phosphorylation of serine 167 in ERα. BP and HRG produced a synergistic increase in ERα recruitment to the c-Myc gene. Our results show that HER ligands enhanced the potency of BP to stimulate oncogene expression and breast cancer cell proliferation in vitro via ERα, suggesting that parabens might be active at exposure levels not previously considered toxicologically relevant from studies testing their effects in isolation. Pan S, Yuan C, Tagmount A, Rudel RA, Ackerman JM, Yaswen P, Vulpe CD, Leitman DC. 2016. Parabens and human epidermal

  10. Designed ankyrin repeat proteins: a novel tool for testing epidermal growth factor receptor 2 expression in breast cancer.

    PubMed

    Theurillat, Jean-Philippe; Dreier, Birgit; Nagy-Davidescu, Gabriela; Seifert, Burkhardt; Behnke, Silvia; Zürrer-Härdi, Ursina; Ingold, Fabienne; Plückthun, Andreas; Moch, Holger

    2010-09-01

    Designed ankyrin repeat proteins are a novel class of specific binding molecules, which display increased thermodynamic stability, smaller size and at least equal target affinity compared to immunoglobulins, making them potentially powerful tools in diagnostic pathology and therapeutic oncology. Here, we investigated whether designed ankyrin repeat proteins can reliably identify the amplification status of the epidermal growth factor receptor 2 in breast cancer. Designed ankyrin repeat proteins specific for epidermal growth factor receptor 2 were tested in paraffin-embedded tissue sections. Detection using enzymatic biotinylation proved to be most specific and sensitive. The affinity of the designed ankyrin repeat proteins was found crucial, but for a picomolar binder no further gain was found by making it multivalent. The best designed ankyrin repeat protein, G3 (K(D) 90 pM) was compared on breast cancer tissue microarrays (n=792) to an FDA-approved rabbit monoclonal antibody against epidermal growth factor receptor 2 (clone 4B5; Ventana Medical Systems) and correlated with corresponding epidermal growth factor receptor 2 amplification status measured by fluorescent in situ hybridization. Amplification status and epidermal growth factor receptor 2 expression measured by designed ankyrin repeat protein and antibody correlated strongly with each other (P<0.0001 each), the correlation between designed ankyrin repeat protein and amplification status being the strongest (0.87 compared to 0.77 for the antibody, Kendall's tau-beta). Using a modified scoring system for the designed ankyrin repeat protein, we show that the designed ankyrin repeat protein detects a positive epidermal growth factor receptor 2 amplification status with similar sensitivity and significantly higher specificity than the antibody (P=0.0005). This study suggests that designed ankyrin repeat proteins provide a valuable alternative to antibodies for the detection of epidermal growth factor receptor

  11. Nuclear Epidermal Growth Factor Receptor is a Functional Molecular Target in Triple-Negative Breast Cancer

    PubMed Central

    Brand, Toni M.; Iida, Mari; Luthar, Neha; Kostopoulos, Kellie T.; Corrigan, Kelsey L.; Wleklinski, Matthew J.; Yang, David; Wisinski, Kari B.; Salgia, Ravi; Wheeler, Deric L.

    2014-01-01

    Triple-negative breast cancer (TNBC) is a subclass of breast cancers (i.e. estrogen receptor negative, progesterone receptor negative, and HER2 negative) that have poor prognosis and very few identified molecular targets. Strikingly, a high percentage of TNBC’s overexpress the epidermal growth factor receptor (EGFR), yet EGFR inhibition has yielded little clinical benefit. Over the last decade, advances in EGFR biology have established that EGFR functions in two distinct signaling pathways: 1) classical membrane-bound signaling, and 2) nuclear signaling. Previous studies have demonstrated that nuclear EGFR (nEGFR) can enhance resistance to anti-EGFR therapies and is correlated with poor overall survival in breast cancer. Based on these findings we hypothesized that nEGFR may promote intrinsic resistance to cetuximab in TNBC. To examine this question, a battery of TNBC cell lines and human tumors were screened and found to express nEGFR. Knockdown of EGFR expression demonstrated that TNBC cell lines retained dependency on EGFR for proliferation, yet all cell lines were resistant to cetuximab. Further, Src Family Kinases (SFKs) influenced nEGFR translocation in TNBC cell lines and in vivo tumor models, where inhibition of SFK activity led to potent reductions in nEGFR expression. Inhibition of nEGFR translocation led to a subsequent accumulation of EGFR on the plasma membrane, which greatly enhanced sensitivity of TNBC cells to cetuximab. Collectively, these data suggest that targeting both the nEGFR signaling pathway, through the inhibition of its nuclear transport, and the classical EGFR signaling pathway with cetuximab may be a viable approach for the treatment of TNBC patients. PMID:24634415

  12. Cost-Effectiveness of Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer.

    PubMed

    Durkee, Ben Y; Qian, Yushen; Pollom, Erqi L; King, Martin T; Dudley, Sara A; Shaffer, Jenny L; Chang, Daniel T; Gibbs, Iris C; Goldhaber-Fiebert, Jeremy D; Horst, Kathleen C

    2016-03-20

    The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study showed a 15.7-month survival benefit with the addition of pertuzumab to docetaxel and trastuzumab (THP) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2) -overexpressing metastatic breast cancer. We performed a cost-effectiveness analysis to assess the value of adding pertuzumab. We developed a decision-analytic Markov model to evaluate the cost effectiveness of docetaxel plus trastuzumab (TH) with or without pertuzumab in US patients with metastatic breast cancer. The model followed patients weekly over their remaining lifetimes. Health states included stable disease, progressing disease, hospice, and death. Transition probabilities were based on the CLEOPATRA study. Costs reflected the 2014 Medicare rates. Health state utilities were the same as those used in other recent cost-effectiveness studies of trastuzumab and pertuzumab. Outcomes included health benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost effectiveness expressed as an incremental cost-effectiveness ratio. One- and multiway deterministic and probabilistic sensitivity analyses explored the effects of specific assumptions. Modeled median survival was 39.4 months for TH and 56.9 months for THP. The addition of pertuzumab resulted in an additional 1.81 life-years gained, or 0.62 QALYs, at a cost of $472,668 per QALY gained. Deterministic sensitivity analysis showed that THP is unlikely to be cost effective even under the most favorable assumptions, and probabilistic sensitivity analysis predicted 0% chance of cost effectiveness at a willingness to pay of $100,000 per QALY gained. THP in patients with metastatic HER2-positive breast cancer is unlikely to be cost effective in the United States. © 2015 by American Society of Clinical Oncology.

  13. Modulation of estrogen and epidermal growth factor receptors by rosemary extract in breast cancer cells.

    PubMed

    González-Vallinas, Margarita; Molina, Susana; Vicente, Gonzalo; Sánchez-Martínez, Ruth; Vargas, Teodoro; García-Risco, Mónica R; Fornari, Tiziana; Reglero, Guillermo; Ramírez de Molina, Ana

    2014-06-01

    Breast cancer is the leading cause of cancer-related mortality among females worldwide, and therefore the development of new therapeutic approaches is still needed. Rosemary (Rosmarinus officinalis L.) extract possesses antitumor properties against tumor cells from several organs, including breast. However, in order to apply it as a complementary therapeutic agent in breast cancer, more information is needed regarding the sensitivity of the different breast tumor subtypes and its effect in combination with the currently used chemotherapy. Here, we analyzed the antitumor activities of a supercritical fluid rosemary extract (SFRE) in different breast cancer cells, and used a genomic approach to explore its effect on the modulation of ER-α and HER2 signaling pathways, the most important mitogen pathways related to breast cancer progression. We found that SFRE exerts antitumor activity against breast cancer cells from different tumor subtypes and the downregulation of ER-α and HER2 receptors by SFRE might be involved in its antitumor effect against estrogen-dependent (ER+) and HER2 overexpressing (HER2+) breast cancer subtypes. Moreover, SFRE significantly enhanced the effect of breast cancer chemotherapy (tamoxifen, trastuzumab, and paclitaxel). Overall, our results support the potential utility of SFRE as a complementary approach in breast cancer therapy.

  14. Human epidermal growth factor receptor 2 overexpression in breast cancer of patients with anti-Yo--associated paraneoplastic cerebellar degeneration.

    PubMed

    Rojas-Marcos, Iñigo; Picard, Geraldine; Chinchón, David; Gelpi, Ellen; Psimaras, Dimitri; Giometto, Bruno; Delattre, J Y; Honnorat, J; Graus, F

    2012-04-01

    Isolated case reports suggest that breast tumors from patients with paraneoplastic cerebellar degeneration (PCD) and Yo antibodies overexpress human epidermal growth factor receptor 2 (HER2). HER2 overexpression is present in 15%-25% of breast cancers and is associated with poor prognosis. We retrospectively analyzed the status of HER2 in breast tumors of 27 patients with anti-Yo-associated PCD to evaluate whether HER2 overexpression in this group of patients is higher than expected. In addition, we analyzed HER2 status of 19 breast tumors from patients with paraneoplastic neurological syndromes and Ri antibodies to see whether HER2 was specifically related to anti-Yo-associated PCD. We also assessed cdr2 expression (the onconeural antigen recognized by Yo antibodies) in 21 HER2-positive breast tumors from patients without paraneoplastic neurological syndromes. HER2 was overexpressed in 26 patients (96.3%) with anti-Yo-associated PCD but only in 2 patients (10.5%) with paraneoplastic neurological syndromes associated with Ri antibodies (P< .0001). Only 5 (23.8%) of the 21 HER2-positive breast tumors showed cdr2 immunoreactivity. This study shows a very high frequency of HER2 overexpression in breast cancers in patients with anti-Yo-associated PCD but not in those from patients with Ri antibodies. Although the expression of cdr2 onconeural antigen is not high in HER2-positive breast cancers, HER2 overexpression seems to be an important requirement to develop an anti-Yo-associated PCD.

  15. Anti-epidermal growth factor receptor conjugated mesoporous zinc oxide nanofibers for breast cancer diagnostics

    NASA Astrophysics Data System (ADS)

    Ali, Md. Azahar; Mondal, Kunal; Singh, Chandan; Dhar Malhotra, Bansi; Sharma, Ashutosh

    2015-04-01

    We report the fabrication of an efficient, label-free, selective and highly reproducible immunosensor with unprecedented sensitivity (femto-molar) to detect a breast cancer biomarker for early diagnostics. Mesoporous zinc oxide nanofibers (ZnOnFs) are synthesized by electrospinning technique with a fiber diameter in the range of 50-150 nm. Fragments of ZnOnFs are electrophoretically deposited on an indium tin oxide glass substrate and conjugated via covalent or electrostatic interactions with a biomarker (anti-ErbB2; epidermal growth factor receptor 2). Oxygen plasma treatment of the carbon doped ZnOnFs generates functional groups (-COOH, -OH, etc.) that are effective for the conjugation of anti-ErbB2. ZnOnFs without plasma treatment that conjugate via electrostatic interactions were also tested for comparison. Label-free detection of the breast cancer biomarker by this point-of-care device is achieved by an electrochemical impedance technique that has high sensitivity (7.76 kΩ μM-1) and can detect 1 fM (4.34 × 10-5 ng mL-1) concentration. The excellent impedimetric response of this immunosensor provides a fast detection (128 s) in a wide detection test range (1.0 fM-0.5 μM). The oxy-plasma treated ZnOnF immunoelectrode shows a higher association constant (404.8 kM-1 s-1) indicating a higher affinity towards the ErbB2 antigen compared to the untreated ZnOnF immunoelectrode (165.6 kM-1 s-1). This sensor is about an order of magnitude more sensitive than the best demonstrated in the literature based on different nanomaterials and about three orders of magnitude better than the ELISA standard for breast cancer biomarker detection. This proposed point-of-care cancer diagnostic offers several advantages, such as higher stability, rapid monitoring, simplicity, cost-effectiveness, etc., and should prove to be useful for the detection of other bio- and cancer markers.We report the fabrication of an efficient, label-free, selective and highly reproducible immunosensor

  16. Expression of T-Lymphocyte Markers in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer

    PubMed Central

    Lee, Changro; Kim, Joo Heung; Lim, Sung Mook; Park, Hyung Seok; Kim, Seung Il; Park, Byeong-Woo

    2016-01-01

    Purpose The present study aimed to examine the clinical implications of CD4, CD8, and FOXP3 expression on the prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer using a web-based database, and to compare the immunohistochemical expression of T-lymphocyte markers using primary and metastatic HER2-positive tumor tissues before and after HER2-targeted therapy. Methods Using the cBioPortal for Cancer Genomics and Kaplan-Meier plotter, the mRNA expression, association between T-lymphocyte markers, and survival in HER2-positive cancers were investigated according to various cutoff levels. Immunohistochemistry analysis was performed using paired primary and metastatic tissues of 29 HER2-positive tumors treated with systemic chemotherapy and HER2-directed therapy. Results HER2 mRNA was mutually exclusive of T-lymphocyte markers, and a significant correlation between T-cell markers was observed in the cBioPortal for Cancer Genomics. According to analysis of the Kaplan-Meier plotter, the impact of T-lymphocyte marker expression on survival was statistically insignificant in clinical HER2-positive tumors, irrespective of the cutoff levels. However, in the intrinsic HER2-positive subtype, the individual analyses of T-cell markers except for FOXP3 and combined analysis showed significantly favorable survival irrespective of cutoff points. Although the small clinical sample size made it difficult to show the statistical relevance of immunohistochemistry findings, good responses to neoadjuvant treatments might be associated with positive expression of combined T-lymphocyte markers, and approximately half of the samples showed discordance of combined markers between baseline and resistant tumors. Conclusion T-lymphocyte markers could be favorable prognostic factors in HER2-positive breast cancers; however, a consensus on patient section criteria, detection methods, and cutoff value could not be reached. The resistance to HER2-directed therapy might

  17. Development of novel epidermal growth receptor-basedradiopharmaceuticals: Imaging agents for breast cancer

    SciTech Connect

    Van Brocklin, Henry F.

    2001-09-25

    The goal of this research was to develop epidermal growthfactor receptor (EGFR) nuclear medicine breast cancer imaging agents. Ourapproach was to synthesize small molecule inhibitors of the EGFR tyrosinekinase (tk) suitable for labeling with single photon or positron-emittingradioisotopes and evaluate the imaging potential of these new molecules.We have synthesized and fully characterized 22 quinazoline compounds. Allcompounds inhibit EGFR tk phosphorylation activity in the nanomolarrange. All compounds tested exhibited specificity for the EGFR tk versusthe ErbB2 and ErbB4 tyrosine kinases. A radiometric binding assay usingan iodine-125 labeled quinazoline was developed to determine the affinityof the quinazolines for the EGFR tk ATP binding site. The affinitiesranged from 0.4-51 nM. The octanol/water partition coefficients (Log P;lipophilicity) of the new compounds ranged from 2.2-5.5. Six compoundshave been labeled with fluorine-18. Biodistribution in EGFRoverexpressing tumor bearing mice demonstrated tumor uptake buthighlighted delivery and metabolism issues. The 2-fluoro quinazoline wasnot metabolized in an in vitro hepatocyte study. From this work a breadthof agent characteristics was created establishing the foundation forfuture research toward the optimal EGFR imaging agent.

  18. Evaluation of human epidermal growth factor receptor 2 (HER2) single nucleotide polymorphisms (SNPs) in normal and breast tumor tissues and their link with breast cancer prognostic factors.

    PubMed

    Furrer, Daniela; Lemieux, Julie; Côté, Marc-André; Provencher, Louise; Laflamme, Christian; Barabé, Frédéric; Jacob, Simon; Michaud, Annick; Diorio, Caroline

    2016-12-01

    Amplification of the human epidermal growth factor receptor 2 (HER2) gene is associated with worse prognosis and decreased overall survival in breast cancer patients. The HER2 gene contains several polymorphisms; two of the best-characterized HER2 polymorphisms are Ile655Val and Ala1170Pro. The aim of this study was to evaluate the association between these two HER2 polymorphisms in normal breast and breast cancer tissues and known breast cancer prognostic factors in a retrospective cohort study of 73 women with non-metastatic HER2-positive breast cancer. HER2 polymorphisms were assessed in breast cancer tissue and normal breast tissue using TaqMan assay. Ala1170Pro polymorphism in normal breast tissue was associated with age at diagnosis (p = 0.007), tumor size (p = 0.004) and lymphovascular invasion (p = 0.06). Similar significant associations in cancer tissues were observed. No association between the Ile655Val polymorphism and prognostic factors were observed. However, we found significant differences in the distribution of Ile655Val (p = 0.03) and Ala1170Pro (p = 0.01) genotypes between normal breast and breast tumor tissues. This study demonstrates that only the Ala1170Pro polymorphism is associated with prognostic factors in HER2-positive breast cancer patients. Moreover, our results suggest that both HER2 polymorphisms could play a significant role in carcinogenesis in non-metastatic HER2-positive breast cancer women.

  19. Epidermal growth factor receptor gene polymorphisms are associated with prognostic features of breast cancer

    PubMed Central

    2014-01-01

    Background The epidermal growth factor receptor (EGFR) is differently expressed in breast cancer, and its presence may favor cancer progression. We hypothesized that two EGFR functional polymorphisms, a (CA)n repeat in intron 1, and a single nucleotide polymorphism, R497K, may affect EGFR expression and breast cancer clinical profile. Methods The study population consisted of 508 Brazilian women with unilateral breast cancer, and no distant metastases. Patients were genotyped for the (CA)n and R497K polymorphisms, and the associations between (CA)n polymorphism and EGFR transcript levels (n = 129), or between either polymorphism and histopathological features (n = 505) were evaluated. The REMARK criteria of tumor marker evaluation were followed. Results (CA)n lengths ranged from 14 to 24 repeats, comprehending 11 alleles and 37 genotypes. The most frequent allele was (CA)16 (0.43; 95% CI = 0.40–0.46), which was set as the cut-off length to define the Short allele. Variant (CA)n genotypes had no significant effect in tumoral EGFR mRNA levels, but patients with two (CA)n Long alleles showed lower chances of being negative for progesterone receptor (ORadjusted = 0.42; 95% CI = 0.19–0.91). The evaluation of R497K polymorphism indicated a frequency of 0.21 (95% CI = 0.19 – 0.24) for the variant (Lys) allele. Patients with variant R497K genotypes presented lower proportion of worse lymph node status (pN2 or pN3) when compared to the reference genotype Arg/Arg (ORadjusted = 0.32; 95% CI = 0.17–0.59), which resulted in lower tumor staging (ORadjusted = 0.34; 95% CI = 0.19-0.63), and lower estimated recurrence risk (OR = 0.50; 95% CI = 0.30-0.81). The combined presence of both EGFR polymorphisms (Lys allele of R497K and Long/Long (CA)n) resulted in lower TNM status (ORadjusted = 0.22; 95% CI = 0.07-0.75) and lower ERR (OR = 0.25; 95% CI = 0.09-0.71). When tumors were stratified according to biological

  20. Pertuzumab for the treatment of patients with human epidermal growth factor receptor 2-positive breast cancer in Japan.

    PubMed

    Osako, Tomofumi; Nishimura, Reiki; Nishiyama, Yasuyuki; Fujisue, Mamiko

    2015-11-01

    Pertuzumab, a novel anti-human epidermal growth factor receptor 2 (HER2) agent, is effective for metastatic HER2-positive breast cancer when used in combination with taxane and trastuzumab. The aim of the present study was to describe the use of pertuzumab in Japan. A phase I clinical trial of pertuzumab for HER2-positive metastatic breast cancer was first conducted in the United States in 2001 (study ID no. TOC2297g) and for HER2-positive solid cancers in Japan in 2004 (study ID no. JO17076). However, Japanese patients were not enrolled in a global phase II trial for metastatic breast cancer (study ID no. BO17929) and no phase II trial of pertuzumab for Japanese patients has yet been conducted. A phase III trial on pertuzumab for metastatic breast cancer (CLEOPATRA study), which included 53 Japanese patients, revealed that pertuzumab significantly prolonged progression-free and overall survival. However, the superiority of the pertuzumab group was not verified in the subgroup analysis of Japanese patients, which was not a preplanned analysis. Therefore, a postmarketing clinical trial for Japanese patients with HER2-positive metastatic breast cancer (COMACHI study) was initiated in November, 2013, to investigate the clinical effectiveness of pertuzumab in Japanese patients. As of December, 2014, global trials on pertuzumab in the metastatic and adjuvant settings are currently ongoing. These trials included Japanese patients with HER2-positive breast cancer. Pertuzumab was approved in Japan in August, 2013 due to the positive findings of the CLEOPATRA study. Unlike the United States and Europe, the Japanes Pharmaceutical and Medical Devices Agency approved the administration of pertuzumab as second- or later-line treatment for HER2-positive metastatic breast cancer, as well as first-line treatment. Furthermore, pertuzumab may be used in combination with other chemotherapeutic agents, with the exception of docetaxel. The approval of the expanded use of pertuzumab is

  1. Evolving landscape of human epidermal growth factor receptor 2-positive breast cancer treatment and the future of biosimilars.

    PubMed

    Jackisch, Christian; Lammers, Philip; Jacobs, Ira

    2017-04-01

    Human epidermal growth factor receptor 2-positive (HER2+) breast cancer comprises approximately 15%-20% of all breast cancers and is associated with a poor prognosis. The introduction of anti-HER2 therapy has significantly improved clinical outcomes for patients with HER2+ breast cancer, and multiple HER2-directed agents (ie, trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine [T-DM1]) are approved for clinical use in various settings. The treatment landscape for patients with HER2+ breast cancer is continuing to evolve. While novel agents and therapeutic strategies are emerging, biologic therapies, particularly trastuzumab, are likely to remain a mainstay of treatment. However, access issues create barriers to the use of biologics, and there is evidence for underuse of trastuzumab worldwide. A biosimilar is a biologic product that is highly similar to a licensed biologic in terms of product safety and effectiveness. Biosimilars of trastuzumab are in development and may soon become available. The introduction of biosimilars may improve access to anti-HER2 therapies by providing additional treatment options and lower-cost alternatives. Because HER2-targeted drugs may be administered for extended periods of time and in combination with other systemic therapies, biosimilars have the potential to result in significant savings for healthcare systems. Herein we review current and emerging treatment options for, and discuss the possible role of biosimilars in, treating patients with HER2+ breast cancer.

  2. Human epidermal growth factor receptor 2 status of breast cancer patients in Asia: Results from a large, multicountry study.

    PubMed

    Pathmanathan, Nirmala; Geng, Jing-Shu; Li, Wencai; Nie, Xiu; Veloso, Januario; Hill, Julie; McCloud, Philip; Bilous, Michael

    2016-12-01

    Current estimates of the human epidermal growth factor receptor 2 (HER2)-positivity rate in breast cancer are largely based on studies from the United States, Europe and Australia, and might not reflect the rate among breast cancer patients in Asia. The primary aim of this study was to conduct a clinical audit of laboratories across eight countries in Asia to determine the incidence of HER2-positive breast cancer in this region. Pathology laboratories submitted data on breast cancers consecutively tested for HER2 over a two-year period. The proportion of HER2-positive, -equivocal and -negative tumors was determined for each country and overall. HER2-positivity rate by age and histological grade was also determined. HER2 results from 30 179 breast cancers were submitted by 96 laboratories. The overall HER2-positivity rate was 23.5%; the rate between countries ranged from 19.7% to 44.2%, and from 4.4% to 51.6% between laboratories. An equivocal HER2 result was recorded in 18.2% of cases. Discrepancies between laboratories suggest that testing expertise contributes to variations seen in HER2 status across laboratories, as well as the generally higher rate of HER2-positivity that was recorded. In this study, the incidence of HER2-positive breast cancer diagnosed in Asian women was higher than published studies on women from Western countries. In addition, the study found that women in Asian countries presented with breast cancer at an earlier age, with a higher histological grade. This study serves to highlight the challenges with HER2 testing and data collection in a large multicenter Asian cohort. © 2016 The Authors. Asia-Pacific Journal of Clinical Oncology Published by John Wiley & Sons Australia, Ltd.

  3. Epidermal Growth Factor Receptor Overexpression as a Target for Auger Electron Radiotherapy of Breast Cancer

    DTIC Science & Technology

    2002-08-01

    perfused rat liver: ligand and receptor dynamics. J . Cell Biol. 1984; 98: 2148-2159. 5. Fisher DA, Salido EC, Barajas L. Epidermal growth factor and the...Appendices .................................... .................................------------------------------------------------------ 21 Preprint 1. Wang J ...tumor uptake. Cancer Biother. and Radiopharm. (in press) 2002. Reprint 2. Wang J , Chen P, Su Z-F et al. Amplified delivery of indium- 111 to EGFR

  4. Insulin-like growth factor and epidermal growth factor signaling in breast cancer cell growth: focus on endocrine resistant disease.

    PubMed

    Voudouri, Kallirroi; Berdiaki, Aikaterini; Tzardi, Maria; Tzanakakis, George N; Nikitovic, Dragana

    2015-01-01

    Breast cancer is the most common type of cancer for women worldwide with a lifetime risk amounting to a staggering total of 10%. It is well established that the endogenous synthesis of insulin-like growth factor (IGF) and epidermal growth factor (EGF) polypeptide growth factors are closely correlated to malignant transformation and all the steps of the breast cancer metastatic cascade. Numerous studies have demonstrated that both estrogens and growth factors stimulate the proliferation of steroid-dependent tumor cells, and that the interaction between these signaling pathways occurs at several levels. Importantly, the majority of breast cancer cases are estrogen receptor- (ER-) positive which have a more favorable prognosis and pattern of recurrence with endocrine therapy being the backbone of treatment. Unfortunately, the majority of patients progress to endocrine therapy resistant disease (acquired resistance) whereas a proportion of patients may fail to respond to initial therapy (de novo resistance). The IGF-I and EGF downstream signaling pathways are closely involved in the process of progression to therapy resistant disease. Modifications in the bioavailability of these growth factors contribute critically to disease progression. In the present review therefore, we will discuss in depth how IGF and EGF signaling participate in breast cancer pathogenesis and progression to endocrine resistant disease.

  5. 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

  6. Quantum dot-based quantitative immunofluorescence detection and spectrum analysis of epidermal growth factor receptor in breast cancer tissue arrays

    PubMed Central

    Yang, Xue-Qin; Chen, Chuang; Peng, Chun-Wei; Hou, Jin-Xuan; Liu, Shao-Ping; Qi, Chu-Bo; Gong, Yi-Ping; Zhu, Xiao-Bo; Pang, Dai-Wen; Li, Yan

    2011-01-01

    Background The epidermal growth factor receptor (EGFR) is a promising therapeutic target in cancer, but its clinical value in breast cancer remains controversial. Our previous studies have found that quantitative analysis of biomarkers with quantum dot-based nanotechnology had better detection performance than conventional immunohistochemistry. The present study was undertaken to investigate the prognostic value of EGFR in breast cancer using quantum dot-based quantitative spectral analysis. Methods EGFR expression in 65 breast cancer specimens was detected by immunohistochemistry and quantum dot-immunohistochemistry, and comparisons were made between the two methods. EGFR expression in tissue microarrays of 240 breast cancer patients was then detected by quantum dot-immunohistochemistry and spectral analysis. The prognostic value of EGFR immunofluorescence area (EGFR area) for five-year recurrence-free survival was investigated. Results The same antigen localization, high correlation of staining rates (r = 0.914), and high agreement of measurement (κ = 0.848) of EGFR expression in breast cancer were found by quantum dot-immunohistochemistry and immunohistochemistry. The EGFR area showed significant differences by tumor grade, lymph node status, HER2 status, and hormone receptor status (all P < 0.05). Patients in the large EGFR area (≥30.51) group had a significantly higher five-year recurrence rate (47.2% versus 27.4%, P = 0.002) and worse five-year recurrence-free survival (log-rank test, P = 0.0015) than those in the small EGFR area (<30.51) group. In the subgroups, EGFR area was an independent prognosticator in the HER2-positive and lymph node-positive subgroups. Conclusion Quantum dot-based quantitative detection demonstrates the prognostic value of EGFR area in the HER2-positive and lymph node-positive subgroups of invasive breast cancer. PMID:22072864

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

    PubMed

    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 addition

  8. Imaging of epidermal growth factor receptor on single breast cancer cells using surface-enhanced Raman spectroscopy.

    PubMed

    Xiao, Lifu; Harihar, Sitaram; Welch, Danny R; Zhou, Anhong

    2014-09-16

    Epidermal growth factor receptor (EGFR) is widely used as a biomarker for pathological grading and therapeutic targeting of human cancers. This study investigates expression, spatial distribution as well as the endocytosis of EGFR in single breast cancer cells using surface-enhanced Raman spectroscopy (SERS). By incubating anti-EGFR antibody conjugated SERS nanoprobes with an EGFR-over-expressing cancer cell line, A431, EGFR localization was measured over time and found to be located primarily at the cell surface. To further validate the constructed SERS probes, we applied this SERS probes to detect the EGFR expression on breast cancer cells (MDA-MB-435, MDA-MB-231) and their counterpart cell lines in which EGFR expression was down-regulated by breast cancer metastasis suppressor 1 (BRMS1). The results showed that SERS method not only confirms immunoblot data measuring EGFR levels, but also adds new insights regarding EGFR localization and internalization in living cells which is impossible in immunoblot method. Thus, SERS provides a powerful new tool to measure biomarkers in living cancer cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer

    PubMed Central

    Hu, YunLong; Chen, TingTing; Peng, BoYa; Gao, NingNing; Jin, ZhenChao; Jia, TieLiu; Zhang, Na; Wang, ZhuLin; Jin, GuangYi

    2016-01-01

    Prolonged treatment of breast cancer with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) often results in acquired resistance and a narrow therapeutic index. One strategy to improve the therapeutic effects of EGFR TKIs is to combine them with drugs used for other clinical indications. Ethacrynic acid (EA) is an FDA approved drug that may have antitumor effects and may enhance the cytotoxicity of chemotherapeutic agents by binding to glutathione and inhibiting WNT signaling. While the α,β-unsaturated-keto structure of EA is similar to that of irreversible TKIs, the mechanism of action of EA when combined with irreversible EGFR TKIs in breast cancer remains unknown. We therefore investigated the combination of irreversible EGFR TKIs and EA. We found that irreversible EGFR TKIs and EA synergistically inhibit breast cancer both in vitro and in vivo. The combination of EGFR TKIs and EA induces necrosis and cell cycle arrest and represses WNT/β-catenin signaling as well as MAPK-ERK1/2 signaling. We conclude that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer. PMID:27487128

  10. Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer.

    PubMed

    Liu, Bing; Huang, XinPing; Hu, YunLong; Chen, TingTing; Peng, BoYa; Gao, NingNing; Jin, ZhenChao; Jia, TieLiu; Zhang, Na; Wang, ZhuLin; Jin, GuangYi

    2016-09-06

    Prolonged treatment of breast cancer with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) often results in acquired resistance and a narrow therapeutic index. One strategy to improve the therapeutic effects of EGFR TKIs is to combine them with drugs used for other clinical indications. Ethacrynic acid (EA) is an FDA approved drug that may have antitumor effects and may enhance the cytotoxicity of chemotherapeutic agents by binding to glutathione and inhibiting WNT signaling. While the α,β-unsaturated-keto structure of EA is similar to that of irreversible TKIs, the mechanism of action of EA when combined with irreversible EGFR TKIs in breast cancer remains unknown. We therefore investigated the combination of irreversible EGFR TKIs and EA. We found that irreversible EGFR TKIs and EA synergistically inhibit breast cancer both in vitro and in vivo. The combination of EGFR TKIs and EA induces necrosis and cell cycle arrest and represses WNT/β-catenin signaling as well as MAPK-ERK1/2 signaling. We conclude that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer.

  11. Inverse relationship between estrogen receptor and epidermal growth factor receptor mRNA levels in human breast cancer cell lines.

    PubMed

    Lee, C S; Hall, R E; Alexander, I E; Koga, M; Shine, J; Sutherland, R L

    1990-01-01

    Epidermal growth factor receptors (EGF-R) are present in a number of human breast cancer cell lines and tumor biopsies. Furthermore, it has been suggested that EGF-R levels are higher in estrogen receptor negative (ER-) than in ER+ human breast tumors and that EGF-R status may be a prognostic indicator in breast cancer. The present study was undertaken to establish whether there is a quantitative relationship between EGF-R and ER mRNA concentrations in a series of 10 well-characterized human breast cancer cell lines. All cell lines expressed detectable quantities of EGF-R mRNA by Northern analysis but the relative abundance of EGF-R mRNA varied more than 50-fold. Two transcripts corresponding to the 10.5- and 5.8-kb mRNAs described in other cell types were present but in different relative proportions in different cell lines. When these lines were divided into an ER+ and an ER- group based on their ability to bind estradiol, ER- cell lines were shown to express significantly higher concentrations of EGF-R mRNA than did ER+ cell lines (p less than 0.005). Furthermore, linear-regression analysis revealed a significant inverse relationship between ER and EGF-R mRNA concentrations both within the group of 10 human breast cancer cell lines as a whole (r = 0.66) and within the 6 functionally ER + lines (r = 0.77). This demonstration of a significant (p less than 0.005) inverse relationship between the concentrations of ER and EGF-R mRNAs in ER + cell lines raises the possibility of reciprocal regulation of the expression of these genes in human breast cancer.

  12. Neo-adjuvant Therapy With Anastrozole Plus Pazopanib in Stage II and III ER+ Breast Cancer

    ClinicalTrials.gov

    2016-05-24

    Estrogen Receptor-positive Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Male Breast Cancer; Recurrent Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer

  13. Fulvestrant regulates epidermal growth factor (EGF) family ligands to activate EGF receptor (EGFR) signaling in breast cancer cells.

    PubMed

    Zhang, Xihong; Diaz, Michael R; Yee, Douglas

    2013-06-01

    Estrogen receptor-α (ER) targeted therapies are routinely used to treat breast cancer. However, patient responses are limited by resistance to endocrine therapy. Breast cancer cells resistant to the pure steroidal ER antagonist fulvestrant (fulv) demonstrate increased activation of epidermal growth factor receptor (EGFR) family members and downstream ERK signaling. In this study, we investigated the effects of fulv on EGFR signaling and ligand regulation in several breast cancer cell lines. EGFR/HER2/HER3 phosphorylation and ERK1,2 activation were seen after 24-48 h after fulvestrant treatment in ER-positive breast cancer cell lines. 4-Hydroxy-tamoxifen and estradiol did not cause EGFR activation. Fulvestrant did not affect EGFR expression. Cycloheximide abolished the ability of fulv to activate EGFR suggesting the autocrine production of EGFR ligands might be responsible for fulvestrant induced EGFR signaling. qRT-PCR results showed fulv differentially regulated EGFR ligands; HB-EGF mRNA was increased, while amphiregulin and epiregulin mRNAs were decreased. Fulvestrant induced EGFR activation and upregulation of EGFR ligands were ER dependent since fulv treatment in C4-12, an ER-negative cell line derivative of MCF-7 cells, did not result in EGFR activation or change in ligand mRNA levels. ER downregulation by siRNA induced similar EGFR activation and regulation of EGFR ligands as fulvestrant. Neutralizing HB-EGF antibody blocked fulv-induced EGFR activation. Combination of fulv and EGFR family tyrosine kinase inhibitors (erlotinib and lapatinib) significantly decreased EGFR signaling and cell survival. In conclusion, fulvestrant-activated EGFR family members accompanied by ER dependent upregulation of HB-EGF within 48 h. EGF receptor or ligand inhibition might enhance or prolong the therapeutic effects of targeting ER by fulvestrant in breast cancer.

  14. Human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer: how the latest results are improving therapeutic options.

    PubMed

    Jiang, Hanfang; Rugo, Hope S

    2015-11-01

    Human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (MBC) remains an incurable disease, and approximately 25% of patients with HER2+ early breast cancer still relapse after adjuvant trastuzumab-based treatment. HER2 is a validated therapeutic target that remains relevant throughout the disease process. Recently, a number of novel HER2 targeted agents have become available, including lapatinib (a small molecule tyrosine kinase inhibitor of both HER2 and the epidermal growth factor receptor), pertuzumab (a new anti-HER2 monoclonal antibody) and ado-trastuzumab emtansine (T-DM1, a novel antibody-drug conjugate), which provide additional treatment options for patients with HER2+ MBC. The latest clinical trials have demonstrated improved outcome with treatment including pertuzumab or T-DM1 compared with standard HER2 targeted therapy. Here we review the clinical development of approved and investigational targeted agents for the treatment of HER2+ MBC, summarize the latest results of important clinical trials supporting use of these agents in the treatment of HER2+ MBC, and discuss how these results impact therapeutic options in clinical practice.

  15. Conversion of epidermal growth factor receptor 2 and hormone receptor expression in breast cancer metastases to the brain

    PubMed Central

    2012-01-01

    Introduction We investigated the status of estrogen receptor alpha (ERα), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) in primary tumor and in the corresponding brain metastases in a consecutive series of breast cancer patients. Additionally, we studied factors potentially influencing conversion and evaluated its association with survival. Methods The study group included 120 breast cancer patients. ERα, PR, and HER2 status in primary tumors and in matched brain metastases was determined centrally by immunohistochemistry and/or fluorescence in situ hybridization. Results Using the Allred score of ≥ 3 as a threshold, conversion of ERα and PR in brain metastases occurred in 29% of cases for both receptors, mostly from positive to negative. Conversion of HER2 occurred in 14% of patients and was more balanced either way. Time to brain relapse and the use of chemotherapy or trastuzumab did not influence conversion, whereas endocrine therapy induced conversion of ERα (P = 0.021) and PR (P = 0.001), mainly towards their loss. Receptor conversion had no significant impact on survival. Conclusions Receptor conversion, particularly loss of hormone receptors, is a common event in brain metastases from breast cancer, and endocrine therapy may increase its incidence. Receptor conversion does not significantly affect survival. PMID:22898337

  16. Dichloroacetate potentiates tamoxifen-induced cell death in breast cancer cells via downregulation of the epidermal growth factor receptor

    PubMed Central

    Park, Yoonhwa; Kim, Eun-Kyu; Seong, Min-Ki; Kim, Hyun-Ah; Song, Jie-Young; Hwang, Sang-Gu; Lee, Jin Kyung; Noh, Woo Chul; Park, In-Chul

    2016-01-01

    Metabolic reprogramming in cancer cells has recently been recognized as an essential hallmark of neoplasia. In this context, metabolic alterations represent an attractive therapeutic target, and encouraging results with drugs targeting various metabolic processes have been obtained in preclinical studies. Recently, several studies have suggested that dichloroacetate (DCA), a specific pyruvate dehydrogenase kinase inhibitor, may be a potential anticancer drug in a large number of diverse tumors. However, the precise mechanism is not fully understood, which is important for the use of DCA in cancer treatment. In the present study, we found that DCA sensitized MCF7 breast cancer cells to tamoxifen-induced cell death by decreasing epidermal growth factor receptor (EGFR) expression. The downregulation of EGFR was caused by degradation of the protein. Furthermore, p38 mitogen-activated protein kinase played an important role in DCA/tamoxifen-induced EGFR degradation. Finally, DCA also promoted comparable tamoxifen-induced cell death in tamoxifen-resistant MCF7 cells, which were established by long-term treatment with tamoxifen. In summary, our results suggest that DCA is an attractive potential drug that sensitizes cells to tamoxifen-induced cell death and overcome tamoxifen resistance via downregulation of EGFR expression in breast cancer cells. PMID:27494858

  17. 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 ...

  18. From bench to bedside: What do we know about hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer?

    PubMed

    Wu, Victoria Shang; Kanaya, Noriko; Lo, Chiao; Mortimer, Joanne; Chen, Shiuan

    2015-09-01

    Breast cancer is a heterogeneous disease. Thanks to extensive efforts from research scientists and clinicians, treatment for breast cancer has advanced into the era of targeted medicine. With the use of several well-established biomarkers, such as hormone receptors (HRs) (i.e., estrogen receptor [ER] and progesterone receptor [PgR]) and human epidermal growth factor receptor-2 (HER2), breast cancer patients can be categorized into multiple subgroups with specific targeted treatment strategies. Although therapeutic strategies for HR-positive (HR+) HER2-negative (HER2-) breast cancer and HR-negative (HR-) HER2-positive (HER2+) breast cancer are well-defined, HR+ HER2+ breast cancer is still an overlooked subgroup without tailored therapeutic options. In this review, we have summarized the molecular characteristics, etiology, preclinical tools and therapeutic options for HR+ HER2+ breast cancer. We hope to raise the attention of both the research and the medical community on HR+ HER2+ breast cancer, and to advance patient care for this subtype of disease.

  19. From bench to bedside: what do we know about Hormone Receptor-positive and Human Epidermal Growth Factor Receptor 2-positive breast cancer?

    PubMed Central

    Wu, Victoria Shang; Kanaya, Noriko; Lo, Chiao; Mortimer, Joanne; Chen, Shiuan

    2015-01-01

    Breast cancer is a heterogeneous disease. Thanks to extensive efforts from research scientists and clinicians, treatment for breast cancer has advanced into the era of targeted medicine. With the use of several well-established biomarkers, such as hormone receptors (HRs) (i.e. estrogen receptor [ER] and progesterone receptor [PgR]) and Human Epidermal Growth Factor Receptor-2 (HER2), breast cancer patients can be categorized into multiple subgroups with specific targeted treatment strategies. Although therapeutic strategies for HR-positive (HR+) HER2-negative (HER2−) breast cancer and HR-negative (HR−) HER2-positive (HER2+) breast cancer are well-defined, HR+ HER2+ breast cancer is still an overlooked subgroup without tailored therapeutic options. In this review, we have summarized the molecular characteristics, etiology, preclinical tools and therapeutic options for HR+ HER2+ breast cancer. We hope to raise the attention of both the research and the medical community on HR+ HER2+ breast cancer, and to advance patient care for this subtype of disease. PMID:25998416

  20. Cost-Effectiveness of Pertuzumab in Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

    PubMed Central

    Qian, Yushen; Pollom, Erqi L.; King, Martin T.; Dudley, Sara A.; Shaffer, Jenny L.; Chang, Daniel T.; Gibbs, Iris C.; Goldhaber-Fiebert, Jeremy D.; Horst, Kathleen C.

    2016-01-01

    Purpose The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study showed a 15.7-month survival benefit with the addition of pertuzumab to docetaxel and trastuzumab (THP) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2) –overexpressing metastatic breast cancer. We performed a cost-effectiveness analysis to assess the value of adding pertuzumab. Patient and Methods We developed a decision-analytic Markov model to evaluate the cost effectiveness of docetaxel plus trastuzumab (TH) with or without pertuzumab in US patients with metastatic breast cancer. The model followed patients weekly over their remaining lifetimes. Health states included stable disease, progressing disease, hospice, and death. Transition probabilities were based on the CLEOPATRA study. Costs reflected the 2014 Medicare rates. Health state utilities were the same as those used in other recent cost-effectiveness studies of trastuzumab and pertuzumab. Outcomes included health benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost effectiveness expressed as an incremental cost-effectiveness ratio. One- and multiway deterministic and probabilistic sensitivity analyses explored the effects of specific assumptions. Results Modeled median survival was 39.4 months for TH and 56.9 months for THP. The addition of pertuzumab resulted in an additional 1.81 life-years gained, or 0.62 QALYs, at a cost of $472,668 per QALY gained. Deterministic sensitivity analysis showed that THP is unlikely to be cost effective even under the most favorable assumptions, and probabilistic sensitivity analysis predicted 0% chance of cost effectiveness at a willingness to pay of $100,000 per QALY gained. Conclusion THP in patients with metastatic HER2-positive breast cancer is unlikely to be cost effective in the United States. PMID:26351332

  1. Palbociclib in Combination With Tamoxifen as First Line Therapy for Metastatic Hormone Receptor Positive Breast Cancer

    ClinicalTrials.gov

    2017-03-28

    Hormone Receptor Positive Malignant Neoplasm of Breast; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Estrogen Receptor Positive Breast Cancer; Progesterone Receptor Positive Tumor; Metastatic Breast Cancer

  2. Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases.

    PubMed

    Freedman, Rachel A; Gelman, Rebecca S; Wefel, Jeffrey S; Melisko, Michelle E; Hess, Kenneth R; Connolly, Roisin M; Van Poznak, Catherine H; Niravath, Polly A; Puhalla, Shannon L; Ibrahim, Nuhad; Blackwell, Kimberly L; Moy, Beverly; Herold, Christina; Liu, Minetta C; Lowe, Alarice; Agar, Nathalie Y R; Ryabin, Nicole; Farooq, Sarah; Lawler, Elizabeth; Rimawi, Mothaffar F; Krop, Ian E; Wolff, Antonio C; Winer, Eric P; Lin, Nancy U

    2016-03-20

    Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. Eligible patients were those with HER2-positive brain metastases (≥ 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection. Patients received neratinib 240 mg orally once per day, and tumors were assessed every two cycles. The primary endpoint was composite CNS objective response rate (ORR), requiring all of the following: ≥ 50% reduction in volumetric sum of target CNS lesions and no progression of non-target lesions, new lesions, escalating corticosteroids, progressive neurologic signs/symptoms, or non-CNS progression--the threshold for success was five of 40 responders. Forty patients were enrolled between February 2012 and June 2013; 78% of patients had previous whole-brain radiotherapy. Three women achieved a partial response (CNS objective response rate, 8%; 95% CI, 2% to 22%). The median number of cycles received was two (range, one to seven cycles), with a median progression-free survival of 1.9 months. Five women received six or more cycles. The most common grade ≥ 3 event was diarrhea (occurring in 21% of patients taking prespecified loperamide prophylaxis and 28% of those without prophylaxis). Patients in the study experienced a decreased quality of life over time. Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies combining neratinib with chemotherapy in patients

  3. Clinical usefulness of human epidermal growth factor receptor-2 extracellular domain as a biomarker for monitoring cancer status and predicting the therapeutic efficacy in breast cancer

    PubMed Central

    Kontani, Keiichi; Kuroda, Noriyuki; Hashimoto, Shin-ichiro; Murazawa, Chisa; Norimura, Shoko; Tanaka, Hiroaki; Ohtani, Masahiro; Fujiwara-Honjo, Naomi; Kushida, Yoshio; Date, Manabu; Haba, Reiji; Houchi, Hitoshi; Yamauchi, Akira; Yokomise, Hiroyasu

    2013-01-01

    We assessed the clinical usefulness of human epidermal growth factor receptor-2 extracellular domain (HER2ECD) as a biomarker for detecting cancer and monitoring disease status and for predicting the efficacy of anticancer treatment in breast cancer. Five-hundred and eighty serum samples from 252 patients with breast cancer were examined for the concentration of HER2ECD to compare with conventional tumor markers (CEA, CA15-3, NCC-ST439 and BCA225). Also, in 19 patients with HER2-overexpressed advanced or recurrent breast cancer who were treated with trastuzumab, clinical outcomes were evaluated retrospectively to determine whether their serum HER2ECD levels predict clinical responses. The proportion of patients with elevated HER2ECD levels was 15.1%, which was compatible with those with elevated conventional marker levels. In patients with HER2-overexpressed breast cancer, the positive rate of HER2ECD was significantly higher (24.1%) than those of conventional markers (7.4–12.9%), suggesting the usefulness of HER2ECD for detecting cancer in this population. HER2-overexpressed patients responding to trastuzumab (12 of 19 patients) showed significantly higher serum HER2ECD level (p = 0.033) and longer time to progression (TTP) (p = 0.039) and overall survival (OS) (p = 0.031) than did patients not responding (seven patients). Furthermore, higher response rates were observed in patients with elevated HER2ECD levels than in patients without elevated HER2ECD levels (91.3% vs. 14.3%, p = 0.032), whereas there was no difference in survival between the two groups. The results suggest that HER2ECD is a useful biomarker not only for detecting breast cancer recurrence but also for predicting tumor responses to trastuzumab. PMID:23114645

  4. Enhanced Human Epidermal Growth Factor Receptor 2 Degradation in Breast Cancer Cells by Lysosome-Targeting Gold Nanoconstructs.

    PubMed

    Lee, Hyojin; Dam, Duncan Hieu M; Ha, Ji Won; Yue, Jun; Odom, Teri W

    2015-10-27

    This paper describes how gold nanoparticle nanoconstructs can enhance anticancer effects of lysosomal targeting aptamers in breast cancer cells. Nanoconstructs consisting of anti-HER2 aptamer (human epidermal growth factor receptor 2, HApt) densely grafted on gold nanostars (AuNS) first targeted HER2 and then were internalized via HER2-mediated endocytosis. As incubation time increased, the nanoconstruct complexes were found in vesicular structures, starting from early endosomes to lysosomes as visualized by confocal fluorescence and differential interference contrast microscopy. Within the target organelle, lysosomes, HER2 was degraded by enzymes at low pH, which resulted in apoptosis. At specific time points related to the doubling time of the cancer cells, we found that accumulation of HER2-HApt-AuNS complexes in lysosomes, lysosomal activity, and lysosomal degradation of HER2 were positively correlated. Increased HER2 degradation by HApt-AuNS triggered cell death and cell cycle arrest in the G0/G1 phase inhibition of cell proliferation. This work shows how a perceived disadvantage of nanoparticle-based therapeutics-the inability of nanoconstructs to escape from vesicles and thus induce a biological response-can be overcome by both targeting lysosomes and exploiting lysosomal degradation of the biomarkers.

  5. Treatment challenges for community oncologists treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

    PubMed Central

    Gradishar, William J

    2016-01-01

    Community-based oncologists are faced with challenges and opportunities when delivering quality patient care, including high patient volumes and diminished resources; however, there may be the potential to deliver increased patient education and subsequently improve outcomes. This review discusses the treatment of postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2- negative advanced breast cancer in order to illustrate considerations in the provision of pertinent quality education in the treatment of these patients and the management of therapy-related adverse events. An overview of endocrine-resistant breast cancer and subsequent treatment challenges is also provided. Approved treatment options for endocrine-resistant breast cancer include hormonal therapies and mammalian target of rapamycin inhibitors. Compounds under clinical investigation are also discussed. PMID:27468248

  6. Pattern of hormone receptors and human epidermal growth factor receptor 2 status in sub-Saharan breast cancer cases: Private practice experience.

    PubMed

    Nwafor, C C; Keshinro, S O

    2015-01-01

    Breast cancer is the most common cancer among women globally. With immunohistochemistry (IHC), breast cancer is classified into four groups based on IHC profile of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2/neu) expression, positive (+) and/or negative (-). The IHC classification correlates well with intrinsic gene expression microarray categorization. ER-positive tumors may benefit from being treated with selective ER modulators and aromatase inhibitors, whereas patients with HER2/neu positive tumors have been shown to experience a significant survival advantage when treated with humanized monoclonal antibodies against HER2/neu. To determine ER/PR, HER2/neu expression and their association with histological prognostic markers in female breast carcinomas seen in a private diagnostic laboratory based in Lagos. Immunohistochemistry reports of breast cancer patients, which were diagnosed by histopathology section of a private diagnostic laboratory based in Lagos, Nigeria from August 2009 to August 2014. About 18.7% of breast cancers had IHC (ER, PR and HER2) done on them and were all females. The mean age of all subjects was 49.5 years (standard deviation, 13.2; range, 29-78 years). Most (95.8%) of the breast cancers were of invasive ductal carcinoma type, with 77.4% of them been >5 cm. IHC pattern was as follows: ER/PR+, HER2-=19 (39.6%), ER/PR-, HER2- (triple negative [TN])=14 (29.2%), ER/PR+, HER2+=9 (18.8%), ER/PR-, HER2+=6 (12.5%), corresponding to Lumina A, TN/basal-like, Lumina B and HER2 over expressed respectively. Triple negative breast cancers are common in our environment and affect young females most and could be contributory to the poorer prognosis of breast cancer in our environment.

  7. GDC-0941 and Cisplatin in Treating Patients With Androgen Receptor-Negative Triple Negative Metastatic Breast Cancer

    ClinicalTrials.gov

    2015-08-17

    Estrogen Receptor Negative Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Triple Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

  8. Activity of ixabepilone in oestrogen receptor-negative and oestrogen receptor-progesterone receptor-human epidermal growth factor receptor 2-negative metastatic breast cancer.

    PubMed

    Pivot, Xavier B; Li, Rubi K; Thomas, Eva S; Chung, Hyun-Cheol; Fein, Luis E; Chan, Valorie F; Jassem, Jacek; de Mendoza, Fernando Hurtado; Mukhopadyay, Pralay; Roché, Henri H

    2009-11-01

    Oestrogen receptor (ER)-negative breast cancer, including oestrogen receptor-, progesterone receptor- and human epidermal growth factor receptor 2-negative (ER/PR/HER2-negative) breast cancer, is more aggressive than ER-positive disease. A major limitation in the treatment of ER-negative disease subtypes is the inherent insensitivity to hormonal agents (tamoxifen, aromatase inhibitors) that are widely used in the treatment of breast cancer. Thus, therapeutic options for poor prognosis patients with ER-negative breast cancer are limited to a handful of chemotherapeutic agents, and new agents are needed to improve the treatment of this disease. Ixabepilone, a novel epothilone B analogue with low susceptibility to cellular mechanisms that confer resistance to taxanes and other chemotherapeutic agents, has demonstrated potent preclinical antitumour activity in multiple models, including those with primary or acquired drug resistance. This review summarises the results of a prospective subset analysis from a phase III clinical trial evaluating ixabepilone for the treatment of metastatic breast cancer (MBC), in which efficacy and safety were evaluated in patients with ER-negative and ER/PR/HER2-negative disease.

  9. Characteristics and treatment of human epidermal growth factor receptor 2 positive breast cancer: 43,485 cases from the National Cancer Database treated in 2010 and 2011.

    PubMed

    Killelea, Brigid K; Chagpar, Anees B; Horowitz, Nina R; Lannin, Donald R

    2017-02-01

    Although identification of human epidermal growth factor receptor 2 (Her2) positive breast cancer represents one of the greatest advances over the past 3 decades, it has not been studied extensively on a national level. The National Cancer Database is a joint project of the American Cancer Society and the American College of Surgeons and contains data on about 70% of the cancer cases in the United States. Data on Her2 have been collected since 2010 and was used for this study. Of 298,937 cases of invasive breast cancer with known Her2 status diagnosed in 2010 and 2011, 43,485 (14.5%) were Her2 positive. Her2 positivity was greatest in Asian/Pacific Islanders and least in non-Hispanic Whites and was markedly more common in younger women. The incidence of Her2 positive tumors ranged from a low of 13.9% in the Mountain West region to a high of 16.0% in the West South Central region (P < .001). Compared with Her2 negative tumors, Her2 positive tumors were larger (2.6 vs 2.2 cm, P < .001), more likely to have positive nodes (39% vs 31% P < .001), have lymphovascular invasion (30% vs 20%, P < .001), and be high grade (56% vs 29%, P < .001). There were also differences by histology: invasive ductal 16.4%, invasive lobular 5.5%, tubular 2.3%, inflammatory 36%, and Paget's with invasion 59%. When adjusted for age, race, tumor size, and nodal status Her2 positive tumors were much more likely to receive chemotherapy (odds ratio = 5.5, confidence interval = 5.2 to 6.0) and somewhat less likely to undergo breast preservation (odds ratio = .78, confidence interval = .76 to .80). Her2 positive tumors have distinct epidemiologic, clinical, and treatment characteristics. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Obesity increases the incidence of distant metastases in oestrogen receptor-negative human epidermal growth factor receptor 2-positive breast cancer patients.

    PubMed

    Mazzarella, Luca; Disalvatore, Davide; Bagnardi, Vincenzo; Rotmensz, Nicole; Galbiati, Donata; Caputo, Sara; Curigliano, Giuseppe; Pelicci, Pier Giuseppe

    2013-11-01

    Obesity is a major negative determinant of breast cancer outcome. However, there are contrasting data on the differential impact of obesity on specific breast cancer subtypes. In particular, very little is known on human epidermal growth factor receptor 2-positive (HER2+) tumours. We assessed the prognostic role of increased body mass index (BMI) on a consecutive series of non-metastatic HER2+ patients treated at our institution before the introduction of adjuvant Trastuzumab. We separately analysed oestrogen receptor-positive (ER+) and -negative (ER-) HER2+ cases. In ER-/HER2+ tumours we observed a significantly worse overall survival (Hazard ratio (HR) 1.79, p-value 0.041) and cumulative incidence of distant metastases (HR 2.03, p-value 0.019) in obese (BMI>30) versus normal/underweight (BMI<25) patients. Local relapses appeared to be non-significantly reduced in obese patients, masking the overall effect on disease-free survival. Outcome in ER+ tumours, instead, was not significantly different between BMI groups. Obesity significantly correlates with worse overall survival and cumulative incidence of distant metastases in ER-/HER2 positive breast cancer. Differences in the biology of breast tumours may determine individual susceptibility to obesity. The biology of the underlying tumour should be taken into account in the design of dietary intervention trials in breast cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Factors affecting disease-free survival in patients with human epidermal growth factor receptor 2-positive breast cancer who receive adjuvant trastuzumab.

    PubMed

    Gündüz, Seyda; Göksu, Sema Sezgin; Arslan, Deniz; Tatli, Ali Murat; Uysal, Mükremin; Gündüz, Umut Riza; Sevinç, Mert Mahsuni; Coşkun, Hasan Senol; Bozcuk, Hakan; Mutlu, Hasan; Savas, Burhan

    2015-09-01

    Breast cancer is the most frequently diagnosed cancer in women worldwide and the second cause of cancer-related mortality. A total of 20-30% of patients with early-stage breast cancer develop recurrence within the first 5 years following diagnosis. Trastuzumab significantly improves overall survival and disease-free survival (DFS) in women with human epidermal growth factor receptor 2 (HER2)-positive early and locally advanced breast cancer. This study aimed to determine the factors that affect DFS following adjuvant transtuzumab therapy. A total of 62 patients treated with trastuzumab for early and locally advanced breast cancer were included in our study. Data, including pathology, treatment and treatment outcome, rate of recurrence and laboratory tests, were retrospectively collected. There was no significant association between DFS and age, menopausal status, disease stage and hormone receptor status. The median follow-up was 48.4 months. The median DFS of patients treated with adjuvant trastuzumab was 64.1 months. In addition, the median DFS was 44.3 vs. 66.8 months in patients with platelet-lymphocyte ratio (PLR) ≤200 vs. >200, respectively (log-rank test; P=0.001), and 70 vs. 45 months in patients with eosinophil count ≤70 vs. >70×10(3)/mm(3) (log-rank test; P=0.001). Our data revealed the prognostic relevance of a decrease in the peripheral blood eosinophil count and PLR value following trastuzumab therapy in breast cancer. PLR and eosinophil count measurements are cost-effective, readily available worldwide, non-invasive and safe. Combined with other markers, such as patient age, tumor stage and tumor histology, may be effectively used for patients with breast cancer.

  12. Factors affecting disease-free survival in patients with human epidermal growth factor receptor 2-positive breast cancer who receive adjuvant trastuzumab

    PubMed Central

    GÜNDÜZ, SEYDA; GÖKSU, SEMA SEZGIN; ARSLAN, DENIZ; TATLI, ALI MURAT; UYSAL, MÜKREMIN; GÜNDÜZ, UMUT RIZA; SEVINÇ, MERT MAHSUNI; COŞKUN, HASAN SENOL; BOZCUK, HAKAN; MUTLU, HASAN; SAVAS, BURHAN

    2015-01-01

    Breast cancer is the most frequently diagnosed cancer in women worldwide and the second cause of cancer-related mortality. A total of 20–30% of patients with early-stage breast cancer develop recurrence within the first 5 years following diagnosis. Trastuzumab significantly improves overall survival and disease-free survival (DFS) in women with human epidermal growth factor receptor 2 (HER2)-positive early and locally advanced breast cancer. This study aimed to determine the factors that affect DFS following adjuvant transtuzumab therapy. A total of 62 patients treated with trastuzumab for early and locally advanced breast cancer were included in our study. Data, including pathology, treatment and treatment outcome, rate of recurrence and laboratory tests, were retrospectively collected. There was no significant association between DFS and age, menopausal status, disease stage and hormone receptor status. The median follow-up was 48.4 months. The median DFS of patients treated with adjuvant trastuzumab was 64.1 months. In addition, the median DFS was 44.3 vs. 66.8 months in patients with platelet-lymphocyte ratio (PLR) ≤200 vs. >200, respectively (log-rank test; P=0.001), and 70 vs. 45 months in patients with eosinophil count ≤70 vs. >70×103/mm3 (log-rank test; P=0.001). Our data revealed the prognostic relevance of a decrease in the peripheral blood eosinophil count and PLR value following trastuzumab therapy in breast cancer. PLR and eosinophil count measurements are cost-effective, readily available worldwide, non-invasive and safe. Combined with other markers, such as patient age, tumor stage and tumor histology, may be effectively used for patients with breast cancer. PMID:26623060

  13. What Is Breast Cancer?

    MedlinePlus

    ... Research? Breast Cancer About Breast Cancer What Is Breast Cancer? Breast cancer starts when cells in the breast ... spread, see our section on Cancer Basics . Where breast cancer starts Breast cancers can start from different parts ...

  14. Breast Cancer

    MedlinePlus

    Breast cancer affects one in eight women during their lives. No one knows why some women get breast cancer, but there are many risk factors. Risks that ... age 35, and having dense breasts. Symptoms of breast cancer may include a lump in the breast, a ...

  15. Relationship between body mass index and the expression of hormone receptors or human epidermal growth factor receptor 2 with respect to breast cancer survival.

    PubMed

    Jeon, Ye Won; Kang, Su Hwan; Park, Min Ho; Lim, Woosung; Cho, Se Heun; Suh, Young Jin

    2015-11-06

    The association between body mass index (BMI) at the time of breast cancer diagnosis and the prognosis of breast cancer patients remains controversial. Furthermore, the association between BMI and prognosis with respect to different breast cancer subtypes is not clearly defined. We analyzed data from 41,021 invasive breast cancer patients between January 1988 and February 2008 from the Korean Breast Cancer Registry (KBCR) database. Overall survival (OS) and breast cancer-specific survival (BCSS) were analyzed using the Kaplan-Meier method and Cox's proportional hazard regression model among all patients and specific breast cancer subtypes with respect to BMI categories. A U-shaped association between BMI and mortality was observed in the total cohort. Underweight and obese individuals exhibited worse OS (hazard ratio, 1.23 [95 % confidence interval {CI}, 1.05 to 1.44] and 1.29 [1.13 to 1.48], respectively) and BCSS (1.26 [1.03 to 1.54] and 1.21 [1.02 to 1.43], respectively) than normal-weight individuals. In the estrogen receptor (ER) and/or progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2) - subgroup, obese individuals exhibited worse OS (1.48 [1.18 to 1.85]) and BCSS (1.31 [1.13 to 1.52]) than normal-weight individuals. Conversely, in the ER and PR-/HER2+ subgroup, underweight individuals exhibited worse OS (1.68 [1.12 to 2.47]) and BCSS (1.79 [1.11 to 2.90]) than normal-weight individuals. We observed a U-shaped relationship between BMI at diagnosis and poor OS and BCSS among all breast cancer patients. However, obesity in the ER and/or PR+/HER2- subgroup and underweight in the ER and PR-/HER2+ subgroup were poor prognostic factors. Therefore, BMI at diagnosis and breast cancer subtype should be considered simultaneously in various treatment decision processes and surveillance schedules.

  16. Outcome prediction values of soluble human epidermal growth factor receptor-2 extracellular domain in metastatic breast cancer.

    PubMed

    Shao, Xiying; Wang, Xian; Xu, Xiaohong; Feng, Jianguo; Han, Mark; Zhang, Han; Chen, Zhan-Hong; Wang, Sheng; Zang, Yi-Min; Huang, Ping; Jin, Hongchuan; Wang, Xiaojia

    2014-01-01

    HER-2 overexpression is an independent predictor for poor prognosis of breast cancer patients. Recently, extracellular domain of HER-2 (ECD) was found detectable in the serum of breast cancer patients. In this prospective study, we wonder whether ECD levels predict the clinical outcome of metastatic breast cancer patients. ECD were measured in 190 women with metastatic breast cancer. Chi-square test was performed to determine the relationship between ECD status and clinical outcomes. Kaplan-Meier curves were applied for survival analysis. Elevated ECD levels were significantly associated with short-term response to Herceptin treatment. The median PFS was significantly longer in ECD-Low patients. The patients who remained low ECD levels or achieved low ECD levels after treatments have significantly longer PFS than those whose levels remained high or converted from low to high. Overall, our results support the clinical utility of measuring serum HER2 ECD levels in patients with advanced breast cancer. Baseline and serial measurements of serum ECD levels are reliably predictive of clinical outcome of breast cancer patients.

  17. PIK3CA Mutations Are Associated With Decreased Benefit to Neoadjuvant Human Epidermal Growth Factor Receptor 2–Targeted Therapies in Breast Cancer

    PubMed Central

    Majewski, Ian J.; Nuciforo, Paolo; Mittempergher, Lorenza; Bosma, Astrid J.; Eidtmann, Holger; Holmes, Eileen; Sotiriou, Christos; Fumagalli, Debora; Jimenez, Jose; Aura, Claudia; Prudkin, Ludmila; Díaz-Delgado, Maria Carmen; de la Peña, Lorena; Loi, Sherene; Ellis, Catherine; Schultz, Nikolaus; de Azambuja, Evandro; Harbeck, Nadia; Piccart-Gebhart, Martine; Bernards, René; Baselga, José

    2015-01-01

    Purpose We investigated whether mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) correlates with response to neoadjuvant human epidermal growth factor receptor 2 (HER2) –targeted therapies in patients with breast cancer. Patients and Methods Baseline tissue biopsies were available from patients with HER2-positive early breast cancer who were enrolled onto the Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial (NeoALTTO). Activating mutations in PIK3CA were identified using mass spectrometry–based genotyping. Results PIK3CA mutations were identified in 23% of HER2-positive breast tumors, and these mutations were associated with poorer outcome in all of the treatment arms. Patients treated with a combination of trastuzumab and lapatinib who had wild-type PIK3CA obtained a total pathologic complete response (pCR) rate of 53.1%, which decreased to 28.6% in patients with tumors that carried PIK3CA activating mutations (P = .012). Conclusion Activating mutations in PIK3CA predicted poor pCR in patients with HER2-positive breast cancer treated with neoadjuvant therapies that target HER2. Consequently, the combination of anti-HER2 agents and PI3K inhibitors is being investigated. PMID:25559818

  18. Breast cancer

    MedlinePlus

    ... idea of what to expect in the future. Breast cancer stages range from 0 to IV. The higher the ... is based on many factors, including: Type of breast cancer Stage of the cancer (staging is a tool your ...

  19. The epidermal growth factor receptor (EGFR / HER-1) gatekeeper mutation T790M is present in European patients with early breast cancer.

    PubMed

    Bemanian, Vahid; Sauer, Torill; Touma, Joel; Lindstedt, Bjørn Arne; Chen, Ying; Ødegård, Hilde Presterud; Vetvik, Katja Marjaana; Bukholm, Ida Rashida; Geisler, Jürgen

    2015-01-01

    The epidermal growth factor receptor (EGFR) is one of the major oncogenes identified in a variety of human malignancies including breast cancer (BC). EGFR-mutations have been studied in lung cancer for some years and are established as important markers in guiding therapy with tyrosine kinase inhibitors (TKIs). In contrast, EGFR-mutations have been reported to be rare if not absent in human BC, although recent evidence has suggested a significant worldwide variation in somatic EGFR-mutations. Therefore, we investigated the presence of EGFR-mutations in 131 norwegian patients diagnosed with early breast cancer using real-time PCR methods. In the present study we identified three patients with an EGFR-T790M-mutation. The PCR-findings were confirmed by direct Sanger sequencing. Two patients had triple-negative BC (TNBC) while the third was classified as luminal-A subtype. The difference in incidence of T790M mutations comparing the TNBC subgroup with the other BC subgroups was statistical significant (P = 0.023). No other EGFR mutations were identified in the entire cohort. Interestingly, none of the patients had received any previous cancer treatment. To our best knowledge, the EGFR-T790M-TKI-resistance mutation has not been previously detected in breast cancer patients. Our findings contrast with the observations made in lung cancer patients where the EGFR-T790M-mutation is classified as a typical "second mutation"causing resistance to TKI-therapy during ongoing anticancer therapy. In conclusion, we have demonstrated for the first time that the EGFR-T790M-mutation occurs in primary human breast cancer patients. In the present study the EGFR-T790M mutation was not accompanied by any simultaneous EGFR-activating mutation.

  20. Prognostic impact of human epidermal growth factor-like receptor 2 and hormone receptor status in inflammatory breast cancer (IBC): analysis of 2,014 IBC patient cases from the California Cancer Registry.

    PubMed

    Zell, Jason A; Tsang, Walter Y; Taylor, Thomas H; Mehta, Rita S; Anton-Culver, Hoda

    2009-01-01

    Inflammatory breast cancer (IBC) is an aggressive form of breast cancer associated with overexpression of Her2/Neu (human epidermal growth factor-like receptor 2 (HER2)) and poor survival. We investigated survival differences for IBC patient cases based on hormone receptor status and HER2 receptor status using data from the California Cancer Registry, as contrasted with locally advanced breast cancer (LABC), metastatic breast cancer (MBC) and non-T4 breast cancer. A case-only analysis of 80,099 incident female breast cancer patient cases in the California Cancer Registry during 1999 to 2003 was performed, with follow-up through March 2007. Overall survival (OS) and breast cancer-specific survival (BC-SS) were analyzed using Kaplan-Meier methods and Cox proportional hazards ratios. A total of 2,014 IBC, 1,268 LABC, 3,059 MBC, and 73,758 non-T4 breast cancer patient cases were identified. HER2+ was associated with advanced tumor stage (P < 0.0001). IBC patient cases were more likely to be HER2+ (40%) and less likely to be hormone receptor-positive (HmR+) (59%) compared with LABC (35% and 69%, respectively), MBC (35% and 74%), and non-T4 patient cases (22% and 82%). HmR+ status was associated with improved OS and BC-SS for each breast cancer subtype after adjustment for clinically relevant factors. In multivariate analysis, HER2+ (versus HER2-) status was associated with poor BC-SS for non-T4 patient cases (hazards ratio = 1.16, 95% confidence interval 1.05 to 1.28) and had a borderline significant association with improved BC-SS for IBC (hazards ratio = 0.82, 95% confidence interval = 0.68 to 0.99). Despite an association with advanced tumor stage, HER2+ status is not an independent adverse prognostic factor for survival among IBC patient cases.

  1. Epidermal growth factor regulates Mcl-1 expression through the MAPK-Elk-1 signalling pathway contributing to cell survival in breast cancer.

    PubMed

    Booy, E P; Henson, E S; Gibson, S B

    2011-05-19

    Myeloid cell leukaemia-1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 family that is elevated in a variety of tumour types including breast cancer. In breast tumours, increased Mcl-1 expression correlates with high tumour grade and poor patient survival. We have previously demonstrated that Her-2 levels correspond to increased Mcl-1 expression in breast tumours. Epidermal growth factor (EGF) receptor signalling is frequently deregulated in breast cancer and leads to increased proliferation and survival. Herein, we determined the critical downstream signals responsible for the EGF mediated increase of Mcl-1 and their role in cell survival. We found that both Mcl-1 mRNA and protein levels are rapidly induced upon stimulation with EGF. Promoter analysis revealed that an Elk-1 transcription factor-binding site is critical for EGF activation of the Mcl-1 promoter. Furthermore, we found that knockdown of Elk-1 or inhibition of the Erk signalling pathway was sufficient to block EGF upregulation of Mcl-1 and EGF mediated cell survival. Using chromatin immunoprecipitation and biotin labelled probes of the Mcl-1 promoter, we found that Elk-1 and serum response factor are bound to the promoter after EGF stimulation. To determine whether Mcl-1 confers a survival advantage, we found that knockdown of Mcl-1 expression increased apoptosis whereas overexpression of Mcl-1 inhibited drug induced cell death. In human breast tumours, we found a correlation between phosphorylated Elk-1 and Mcl-1 protein levels. These results indicate that the EGF induced activation of Elk-1 is an important mediator of Mcl-1 expression and cell survival and therefore a potential therapeutic target in breast cancer.

  2. Patterns of resource utilization and cost for postmenopausal women with hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer in Europe.

    PubMed

    Jerusalem, Guy; Neven, Patrick; Marinsek, Nina; Zhang, Jie; Degun, Ravi; Benelli, Giancarlo; Saletan, Stephen; Ricci, Jean-François; Andre, Fabrice

    2015-10-24

    Healthcare resource utilization in breast cancer varies by disease characteristics and treatment choices. However, lack of clarity in guidelines can result in varied interpretation and heterogeneous treatment management and costs. In Europe, the extent of this variability is unclear. Therefore, evaluation of chemotherapy use and costs versus hormone therapy across Europe is needed. This retrospective chart review (N = 355) examined primarily direct costs for chemotherapy versus hormone therapy in postmenopausal women with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer across 5 European countries (France, Germany, The Netherlands, Belgium, and Sweden). Total direct costs across the first 3 treatment lines were approximately €10,000 to €14,000 lower for an additional line of hormone therapy-based treatment versus switching to chemotherapy-based treatment. Direct cost difference between chemotherapy-based and hormone therapy-based regimens was approximately €1900 to €2500 per month. Chemotherapy-based regimens were associated with increased resource utilization (managing side effects; concomitant targeted therapy use; and increased frequencies of hospitalizations, provider visits, and monitoring tests). The proportion of patients taking sick leave doubled after switching from hormone therapy to chemotherapy. These results suggest chemotherapy is associated with increased direct costs and potentially with increased indirect costs (lower productivity of working patients) versus hormone therapy in HR+, HER2- advanced breast cancer.

  3. Eicosopentaneoic Acid and Other Free Fatty Acid Receptor Agonists Inhibit Lysophosphatidic Acid- and Epidermal Growth Factor-Induced Proliferation of Human Breast Cancer Cells.

    PubMed

    Hopkins, Mandi M; Zhang, Zhihong; Liu, Ze; Meier, Kathryn E

    2016-01-26

    Many key actions of ω-3 (n-3) fatty acids have recently been shown to be mediated by two G protein-coupled receptors (GPCRs) in the free fatty acid receptor (FFAR) family, FFA1 (GPR40) and FFA4 (GPR120). n-3 Fatty acids inhibit proliferation of human breast cancer cells in culture and in animals. In the current study, the roles of FFA1 and FFA4 were investigated. In addition, the role of cross-talk between GPCRs activated by lysophosphatidic acid (LPA), and the tyrosine kinase receptor activated by epidermal growth factor (EGF), was examined. In MCF-7 and MDA-MB-231 human breast cancer cell lines, both LPA and EGF stimulated proliferation, Erk activation, Akt activation, and CCN1 induction. LPA antagonists blocked effects of LPA and EGF on proliferation in MCF-7 and MDA-MB-231, and on cell migration in MCF-7. The n-3 fatty acid eicosopentaneoic acid inhibited LPA- and EGF-induced proliferation in both cell lines. Two synthetic FFAR agonists, GW9508 and TUG-891, likewise inhibited LPA- and EGF-induced proliferation. The data suggest a major role for FFA1, which was expressed by both cell lines. The results indicate that n-3 fatty acids inhibit breast cancer cell proliferation via FFARs, and suggest a mechanism involving negative cross-talk between FFARS, LPA receptors, and EGF receptor.

  4. Eicosopentaneoic Acid and Other Free Fatty Acid Receptor Agonists Inhibit Lysophosphatidic Acid- and Epidermal Growth Factor-Induced Proliferation of Human Breast Cancer Cells

    PubMed Central

    Hopkins, Mandi M.; Zhang, Zhihong; Liu, Ze; Meier, Kathryn E.

    2016-01-01

    Many key actions of ω-3 (n-3) fatty acids have recently been shown to be mediated by two G protein-coupled receptors (GPCRs) in the free fatty acid receptor (FFAR) family, FFA1 (GPR40) and FFA4 (GPR120). n-3 Fatty acids inhibit proliferation of human breast cancer cells in culture and in animals. In the current study, the roles of FFA1 and FFA4 were investigated. In addition, the role of cross-talk between GPCRs activated by lysophosphatidic acid (LPA), and the tyrosine kinase receptor activated by epidermal growth factor (EGF), was examined. In MCF-7 and MDA-MB-231 human breast cancer cell lines, both LPA and EGF stimulated proliferation, Erk activation, Akt activation, and CCN1 induction. LPA antagonists blocked effects of LPA and EGF on proliferation in MCF-7 and MDA-MB-231, and on cell migration in MCF-7. The n-3 fatty acid eicosopentaneoic acid inhibited LPA- and EGF-induced proliferation in both cell lines. Two synthetic FFAR agonists, GW9508 and TUG-891, likewise inhibited LPA- and EGF-induced proliferation. The data suggest a major role for FFA1, which was expressed by both cell lines. The results indicate that n-3 fatty acids inhibit breast cancer cell proliferation via FFARs, and suggest a mechanism involving negative cross-talk between FFARS, LPA receptors, and EGF receptor. PMID:26821052

  5. ARF6 promotes the formation of Rac1 and WAVE-dependent ventral F-actin rosettes in breast cancer cells in response to epidermal growth factor.

    PubMed

    Marchesin, Valentina; Montagnac, Guillaume; Chavrier, Philippe

    2015-01-01

    Coordination between actin cytoskeleton assembly and localized polarization of intracellular trafficking routes is crucial for cancer cell migration. ARF6 has been implicated in the endocytic recycling of surface receptors and membrane components and in actin cytoskeleton remodeling. Here we show that overexpression of an ARF6 fast-cycling mutant in MDA-MB-231 breast cancer-derived cells to mimick ARF6 hyperactivation observed in invasive breast tumors induced a striking rearrangement of the actin cytoskeleton at the ventral cell surface. This phenotype consisted in the formation of dynamic actin-based podosome rosette-like structures expanding outward as wave positive for F-actin and actin cytoskeleton regulatory components including cortactin, Arp2/3 and SCAR/WAVE complexes and upstream Rac1 regulator. Ventral rosette-like structures were similarly induced in MDA-MB-231 cells in response to epidermal growth factor (EGF) stimulation and to Rac1 hyperactivation. In addition, interference with ARF6 expression attenuated activation and plasma membrane targeting of Rac1 in response to EGF treatment. Our data suggest a role for ARF6 in linking EGF-receptor signaling to Rac1 recruitment and activation at the plasma membrane to promote breast cancer cell directed migration.

  6. Human epidermal growth factor receptor 2 testing in primary breast cancer in the era of standardized testing: a Canadian prospective study.

    PubMed

    Hanna, Wedad M; Barnes, Penny J; Chang, Martin C; Gilks, C Blake; Magliocco, Anthony M; Rees, Henrike; Quenneville, Louise; Robertson, Susan J; SenGupta, Sandip K; Nofech-Mozes, Sharon

    2014-12-10

    Therapies that target overexpression of human epidermal growth factor receptor 2 (HER2) rely on accurate and timely assessment of all patients with new diagnoses. This study examines HER2 testing of primary breast cancer tissue when performed with immunohistochemistry (IHC) and additional in situ hybridization (ISH) for negative cases (IHC 0/1+). The analysis focuses on the rate of false-negative HER2 tests, defined as IHC 0/1+ with an ISH ratio ≥ 2.0, in eight pathology centers across Canada. Whole sections of surgical resections or tissue microarrays (TMAs) from invasive breast carcinoma tissue were tested by both IHC and ISH using standardized local methods. Samples were scored by the local breast pathologist, and consecutive HER2-negative IHC results (IHC 0/1+) were compared with the corresponding fluorescence or silver ISH result. Overall, 711 surgical excisions of primary breast cancer were analyzed by IHC and ISH; HER2 and chromosome 17 centromere (CEP17) counts were available in all cases. The overall rate of false-negative samples was 0.84% (six of 711 samples). Interpretable IHC and ISH scores were available in 1,212 cases from TMAs, and the overall rate of false-negative cases was 1.6% (16 of 978 cases). Our observation confirms that IHC is an adequate test to predict negative HER2 status in primary breast cancer in surgical excision specimens, even when different antibodies and IHC platforms are used. The study supports the American Society of Clinical Oncology/College of American Pathologists and Canadian testing algorithms of using IHC followed by ISH for equivocal cases. © 2014 by American Society of Clinical Oncology.

  7. Relationship between cyclooxygenase-2 and human epidermal growth factor receptor 2 in vascular endothelial growth factor C up-regulation and lymphangiogenesis in human breast cancer.

    PubMed

    Bhattacharjee, Rabindra N; Timoshenko, Alexander V; Cai, Jing; Lala, Peeyush K

    2010-09-01

    Both cyclooxygenase (COX)-2 and human epidermal growth factor receptor (HER)-2 promote breast cancer progression; however, the relationship between the two molecules remains unclear. We utilized human breast cancer tissues and cell lines to examine whether COX-2 and HER-2 played independent or interdependent roles in vascular endothelial growth factor (VEGF)-C up-regulation and lymphangiogenesis. A paired correlation of immunodetectable levels of COX-2, VEGF-C, and HER-2 proteins and lymphovascular density (LVD; D2-40-immunolabeled) in 55 breast cancer specimens revealed a positive correlation between COX-2 and HER-2 irrespective of clinicopathological status. However COX-2 alone positively correlated with LVD. In 10 independent specimens, mRNA levels showed a positive correlation between HER-2 and COX-2 or VEGF-C but not LYVE-1 (lymphovascular endothelial marker). These findings implicate COX-2, but not HER-2, in breast cancer-associated lymphangiogenesis. Manipulation of the COX-2 or HER-2 genes in breast cancer cell lines varying widely in COX-2 and HER-2 expression revealed a direct role of COX-2 and an indirect COX-2 dependent role of HER-2 in VEGF-C up-regulation: (i) high VEGF-C expression in high COX-2/low HER-2 expressing MDA-MB-231 cells was reduced by siRNA-mediated down-regulation of COX-2, but not HER-2; (ii) integration of HER-2 in these cells simultaneously up-regulated COX-2 protein as well as VEGF-C secretion; and (iii) low VEGF-C secretion by high HER-2/low COX-2 expressing SK-BR-3 cells was stimulated by COX-2 overexpression. These findings of the primary role of COX-2 and the COX-2-dependent role of HER-2, if any, in VEGF-C up-regulation and lymphangiogenesis suggest that COX-2 inhibitors may abrogate lymphatic metastasis in breast cancer irrespective of HER-2 status. © 2010 Japanese Cancer Association.

  8. Reduced annexin A6 expression promotes the degradation of activated epidermal growth factor receptor and sensitizes invasive breast cancer cells to EGFR-targeted tyrosine kinase inhibitors

    PubMed Central

    2013-01-01

    Background The expression of annexin A6 (AnxA6) in AnxA6-deficient non-invasive tumor cells has been shown to terminate epidermal growth factor receptor (EGFR) activation and downstream signaling. However, as a scaffolding protein, AnxA6 may stabilize activated cell-surface receptors to promote cellular processes such as tumor cell motility and invasiveness. In this study, we investigated the contribution of AnxA6 in the activity of EGFR in invasive breast cancer cells and examined whether the expression status of AnxA6 influences the response of these cells to EGFR-targeted tyrosine kinase inhibitors (TKIs) and/or patient survival. Results We demonstrate that in invasive BT-549 breast cancer cells AnxA6 expression is required for sustained membrane localization of activated (phosho-Y1068) EGFR and consequently, persistent activation of MAP kinase ERK1/2 and phosphoinositide 3-kinase/Akt pathways. Depletion of AnxA6 in these cells was accompanied by rapid degradation of activated EGFR, attenuated downstream signaling and as expected enhanced anchorage-independent growth. Besides inhibition of cell motility and invasiveness, AnxA6-depleted cells were also more sensitive to the EGFR-targeted TKIs lapatinib and PD153035. We also provide evidence suggesting that reduced AnxA6 expression is associated with a better relapse-free survival but poorer distant metastasis-free and overall survival of basal-like breast cancer patients. Conclusions Together this demonstrates that the rapid degradation of activated EGFR in AnxA6-depleted invasive tumor cells underlies their sensitivity to EGFR-targeted TKIs and reduced motility. These data also suggest that AnxA6 expression status may be useful for the prediction of the survival and likelihood of basal-like breast cancer patients to respond to EGFR-targeted therapies. PMID:24354805

  9. Racially restricted contribution of immunoglobulin Fcγ and Fcγ receptor genotypes to humoral immunity to human epidermal growth factor receptor 2 in breast cancer.

    PubMed

    Pandey, J P; Namboodiri, A M; Kistner-Griffin, E; Iwasaki, M; Kasuga, Y; Hamada, G S; Tsugane, S

    2013-03-01

    Tumour-associated antigen human epidermal growth factor receptor 2 (HER2) is over-expressed in 25-30% of breast cancer patients and is associated with poor prognosis. Naturally occurring anti-HER2 antibody responses have been described in patients with HER2 over-expressing tumours. There is significant interindividual variability in antibody responsiveness, but the host genetic factors responsible for this variability are poorly understood. The aim of the present investigation was to determine whether immunoglobulin genetic markers [GM (genetic determinants of γ chains)] and Fcγ receptor (FcγR) alleles contribute to the magnitude of natural antibody responsiveness to HER2 in patients with breast cancer. A total of 855 breast cancer patients from Japan and Brazil were genotyped for several GM and FcγR alleles. They were also characterized for immunoglobulin (Ig)G antibodies to HER2. In white subjects (n = 263), GM 23-carriers had higher levels of anti-HER2 antibodies than non-carriers of this allele (p = 0·004). At the GM 5/21 locus, the homozygotes for the GM 5 allele had higher levels of anti-HER2 antibodies than the other two genotypes (P = 0·0067). In black subjects (n = 42), FcγRIIa-histidine/histidine homozygotes and FcγRIIIa-phenylalanine/valine heterozygotes were associated with high antibody responses (P = 0·0071 and 0·0275, respectively). FcγR genotypes in white subjects and GM genotypes in black subjects were not associated with anti-HER2 antibody responses. No significant associations were found in other study groups. These racially restricted contributions of GM and FcγR genotypes to humoral immunity to HER2 have potential implications for immunotherapy of breast cancer.

  10. Adding hormonal therapy to chemotherapy and trastuzumab improves prognosis in patients with hormone receptor-positive and human epidermal growth factor receptor 2-positive primary breast cancer.

    PubMed

    Hayashi, Naoki; Niikura, Naoki; Yamauchi, Hideko; Nakamura, Seigo; Ueno, Naoto T

    2013-01-01

    Adjuvant hormonal therapy for hormone receptor (HR)-positive primary breast cancer patients and a human epidermal growth factor receptor 2 (HER2)-targeted agent for HER2-positive primary breast cancer patients are standard treatment. However, it is not well known whether adding hormonal therapy to the combination of preoperative or postoperative chemotherapy and HER2-targeted agent contributes any additional clinical benefit in patients with HR-positive/HER2-positive primary breast cancer regardless of cross-talk between HR and HER2. We retrospectively reviewed records from 897 patients with HR-positive/HER2-positive primary breast cancer with clinical stage I-III disease who underwent surgery between 1988 and 2009. We determined the overall survival (OS) and disease-free survival (DFS) rates according to whether they received hormonal therapy or not and according to the type of hormonal therapy, tamoxifen and aromatase inhibitor, they received. The median followup time was 52.8 months (range 1-294.6 months). Patients who received hormonal therapy with chemotherapy and trastuzumab (n = 128) had significantly higher OS and DFS rates than did those who received only chemotherapy and trastuzumab (n = 46) in log-rank analysis (OS 96.1 vs. 87.0 %, p = 0.023, DFS 86.7 vs. 78.3 %, p = 0.029). There was no statistical difference in OS or DFS between those given an aromatase inhibitor and those given tamoxifen. In multivariate analysis, receiving hormonal therapy in addition to the combination of chemotherapy and trastuzumab was the sole independent prognostic factor for DFS (hazard ratio 0.446; 95 % CI 0.200-0.992; p = 0.048), and there was a similar trend in OS. Our study supported that hormonal therapy, whether in the form of an aromatase inhibitor or tamoxifen, confers a survival benefit when added to chemotherapy and trastuzumab in patients with HR-positive/HER2-positive primary breast cancer. Adjuvant treatment without hormonal therapy is inferior for this patient

  11. Breast Cancer Prevention

    MedlinePlus

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Prevention (PDQ®)–Patient Version What is prevention? Go ... from starting. Risk-reducing surgery . General Information About Breast Cancer Key Points Breast cancer is a disease in ...

  12. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline.

    PubMed

    Ramakrishna, Naren; Temin, Sarah; Chandarlapaty, Sarat; Crews, Jennie R; Davidson, Nancy E; Esteva, Francisco J; Giordano, Sharon H; Gonzalez-Angulo, Ana M; Kirshner, Jeffrey J; Krop, Ian; Levinson, Jennifer; Modi, Shanu; Patt, Debra A; Perez, Edith A; Perlmutter, Jane; Winer, Eric P; Lin, Nancy U

    2014-07-01

    To provide formal expert consensus-based recommendations to practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer. The American Society of Clinical Oncology (ASCO) convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic review of the literature. When that failed to yield sufficiently strong quality evidence, the Expert Panel undertook a formal expert consensus-based process to produce these recommendations. ASCO used a modified Delphi process. The panel members drafted recommendations, and a group of other experts joined them for two rounds of formal ratings of the recommendations. No studies or existing guidelines met the systematic review criteria; therefore, ASCO conducted a formal expert consensus-based process. Patients with brain metastases should receive appropriate local therapy and systemic therapy, if indicated. Local therapies include surgery, whole-brain radiotherapy, and stereotactic radiosurgery. Treatments depend on factors such as patient prognosis, presence of symptoms, resectability, number and size of metastases, prior therapy, and whether metastases are diffuse. Other options include systemic therapy, best supportive care, enrollment onto a clinical trial, and/or palliative care. Clinicians should not perform routine magnetic resonance imaging (MRI) to screen for brain metastases, but rather should have a low threshold for MRI of the brain because of the high incidence of brain metastases among patients with HER2-positive advanced breast cancer. © 2014 by American Society of Clinical Oncology.

  13. Delaying Chemotherapy in the Treatment of Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer

    PubMed Central

    Brufsky, Adam M.

    2015-01-01

    Global guidelines for the management of locally advanced or metastatic hormone receptor–positive (HR-positive), human epidermal growth factor 2–negative (HER2-negative) breast cancer recommend endocrine therapy as first-line treatment for all patients, regardless of age or postmenopausal status. However, current practice patterns in the United States and Europe suggest that these modes of therapy are not being used as recommended, and many patients with advanced HR-positive, HER2-negative disease are being treated first-line with chemotherapy or switched to chemotherapy after a single endocrine therapy. Given that chemotherapy is associated with increased toxicity and reduced quality of life (QOL) compared with endocrine therapy, prolonging the duration of response obtained with endocrine therapy may help delay chemotherapy and its attendant toxicities. Several strategies to delay or overcome endocrine resistance and thereby postpone chemotherapy have been explored, including the use of second-line endocrine agents with different mechanisms of action, adding targeted agents that inhibit specific resistance pathways, and adding agents that act in complementary or synergistic ways to inhibit tumor cell proliferation. This review analyzes the different therapy options available to HR-positive, HER2-negative patients with advanced breast cancer that can be used to delay chemotherapy and enhance QOL. PMID:26793013

  14. Effects of the microtubule-disturbing agents docetaxel (Taxotere), vinblastine and vincristine on epidermal growth factor-receptor binding of human breast cancer cell lines in vitro.

    PubMed

    Hanauske, A R; Depenbrock, H; Shirvani, D; Rastetter, J

    1994-01-01

    Epidermal growth factor (EGF) is a mitogenic peptide that binds to surface membrane receptors (EGFR) of breast cancer cells. After binding, secondary transmitter molecules are activated by tyrosine phosphorylation of the intracellular receptor domaine. The activity of the EGF/EGFR system can be modulated by a variety of chemically unrelated compounds including cytostatic agents. The purpose of our present study was to determine the effects of mitotic inhibitors on EGF receptor binding on human breast cancer cells. We found that MDA-231 and MDA-468 cells bind substantially more [125I]EGF after preincubation with docetaxel, vinblastine and vincristine. This effect was concentration- and time-dependent, reaching a maximum at 3000 ng/ml and 48 h incubation for docetaxel, and 100 ng/ml and 48 h incubation for vinca alcaloids. Subsequent experiments showed an increase in the rate of EGF binding as well as maximal binding capacity. Scatchard analysis of binding experiments under equilibrium conditions indicated that this was due to an increase in the number of apparent EGF binding sites. Modulation of EGF receptor binding by docetaxel, vinblastine, and vincristine was not detectable when isolated membranes were used, indicating that intact cytoplasmatic mechanisms are required for the upregulation of EGF receptors.

  15. Concordance between core needle biopsy and surgical specimen for oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status in breast cancer

    PubMed Central

    Asogan, Aravind Barathi; Hong, Ga Sze; Prabhakaran, Subash Kumar Arni

    2017-01-01

    INTRODUCTION This study aimed to analyse the concordance rate, sensitivity, specificity, positive predictive value (PPV) and negative predictive value of core needle biopsy (CNB) and subsequent surgical specimen (SS) in assessing levels of oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2/neu). It also evaluated the revised American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines for ER/PgR positivity. METHODS We analysed the breast cancer database of KK Women’s and Children’s Hospital, Singapore, from 1 June 2005 to 30 December 2012. Invasive breast cancer patients who had CNB and subsequent SS were included. RESULTS A total of 560 patients were included. The concordance of ER, PgR and HER2/neu positivity between CNB and SS was 96.1%, 89.1% and 96.8%, respectively. When the ‘ER ≥ 10% positive’ group was compared with the ‘ER ≥ 1% positive’ group, specificity increased from 79.7% to 92.5% and PPV increased from 93.9% to 97.5%. When the ‘PgR ≥ 10% positive’ group was compared with the ‘PgR ≥ 1% positive’ group, specificity increased from 84.2% to 89.3% and PPV improved from 89.7% to 92.9%. The revised ASCO/CAP guidelines decreased discordant results by > 50% for ER and by 18.2% for PgR. CONCLUSION CNB has high concordance with SS in the evaluation of the molecular profile of invasive breast cancer. Thus, molecular evaluation does not need to be repeated with SS except for ER-, PgR- and HER2/neu-negative CNB results. The revised ASCO/CAP guidelines resulted in more precise ER and PgR status on CNB. PMID:27029805

  16. [Immunohistochemical hormonal mismatch and human epidermal growth factor type 2 [HER2] phenotype of brain metastases in breast cancer carcinoma compared to primary tumors].

    PubMed

    Joubert, C; Boissonneau, S; Fina, F; Figarella-Branger, D; Ouafik, L; Fuentes, S; Dufour, H; Gonçalves, A; Charaffe-Jauffret, E; Metellus, P

    2016-06-01

    Phenotype changes between primary tumor and the corresponding brain metastases are recent reported data. Breast cancer, with biological markers predicting prognosis and guiding therapeutic strategy remains an interesting model to observe and evaluate theses changes. The objective of our study was to compare molecular features (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor type 2, [HER2]) between brain metastases and its primary tumor in patients presenting with pathologically confirmed breast cancer. This retrospective study was based on the immunohistochemical analysis of the brain metastases paraffin embedded samples stored in our institutional tumor bank, after surgical resection. The level of expression of hormonal receptors and HER2 on brain metastases were centrally reviewed and compared to the expression status in primary breast cancer from medical records. Forty-four samples of brain metastases were available for analysis. Hormonal receptor modification status was observed in 11/44 brain metastases (25%) for ER and 6/44 (13.6%) for PR. A modification of HER2 overexpression was observed in brain metastases in 6/44 (13.6%). Molecular subtype modification was shown in 17 cases (38.6%). A significant difference was demonstrated between time to develop brain metastases in cases without status modification (HER2, ER and PR) (med=49.5months [7.8-236.4]) and in cases in which brain metastases status differs from primary tumor (med=27.5months [0-197.3]), (P=0.0244, IC95=3.09-51.62, Mann and Whitney test). the main interest of this study was to focus on the molecular feature changes between primary tumor and their brain metastases. Time to develop brain metastases was correlated to phenotypic changes in brain metastases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update.

    PubMed

    Wolff, Antonio C; Hammond, M Elizabeth H; Hicks, David G; Dowsett, Mitch; McShane, Lisa M; Allison, Kimberly H; Allred, Donald C; Bartlett, John M S; Bilous, Michael; Fitzgibbons, Patrick; Hanna, Wedad; Jenkins, Robert B; Mangu, Pamela B; Paik, Soonmyung; Perez, Edith A; Press, Michael F; Spears, Patricia A; Vance, Gail H; Viale, Giuseppe; Hayes, Daniel F

    2014-02-01

    To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer. ASCO/CAP convened an Update Committee that included coauthors of the 2007 guideline to conduct a systematic literature review and update recommendations for optimal HER2 testing. The Update Committee identified criteria and areas requiring clarification to improve the accuracy of HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The guideline was reviewed and approved by both organizations. The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive). Testing criteria define HER2-positive status when (on observing within an area of tumor that amounts to >10% of contiguous and homogeneous tumor cells) there is evidence of protein overexpression (IHC) or gene amplification (HER2 copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within the area). If results are equivocal (revised criteria), reflex testing should be performed using an alternative assay (IHC or ISH). Repeat testing should be considered if results seem discordant with other histopathologic findings. Laboratories should demonstrate high concordance with a validated HER2 test on a sufficiently large and representative set of specimens. Testing must be performed in a laboratory accredited by CAP or another accrediting entity. The Update Committee urges providers and health systems to cooperate to ensure the highest quality testing.

  18. Breast cancer.

    PubMed

    Pearce, Lynne

    2016-08-17

    Essential facts Breast cancer is the most common cancer in the UK, with around 60,000 new cases diagnosed each year, according to the charity Breast Cancer Care. Over a lifetime, women have a one in eight risk of developing it.

  19. Intrathecal trastuzumab for leptomeningeal carcinomatosis in patients with human epidermal growth factor receptor 2 positive breast cancer

    PubMed Central

    Gulia, Seema; Gupta, Sudeep; Singh, Ashish

    2016-01-01

    There has been recent increase in incidence of leptomeningeal carcinomatosis, possibly due to widespread use of adjuvant trastuzumab and its known poor CNS penetration. Currently there are limited therapeutic options for these patients and outcome is poor. We report two cases of women with HER2 positive breast cancer who developed leptomeningeal carcinomatosis for which they were treated with intrathecal trastuzumab in combination with systemic therapy. Both patients had rapid symptomatic benefit and radiological response and remained progression free for at least seven months. Intrathecal trastuzumab can be considered a reasonable therapeutic option for these difficult to treat patients. PMID:27688614

  20. Breast cancer screening

    MedlinePlus

    Mammogram - breast cancer screening; Breast exam - breast cancer screening; MRI - breast cancer screening ... is performed to screen women to detect early breast cancer when it is more likely to be cured. ...

  1. Absolute Benefit of Adjuvant Endocrine Therapies for Premenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer: TEXT and SOFT Trials.

    PubMed

    Regan, Meredith M; Francis, Prudence A; Pagani, Olivia; Fleming, Gini F; Walley, Barbara A; Viale, Giuseppe; Colleoni, Marco; Láng, István; Gómez, Henry L; Tondini, Carlo; Pinotti, Graziella; Price, Karen N; Coates, Alan S; Goldhirsch, Aron; Gelber, Richard D

    2016-07-01

    Risk of recurrence is the primary consideration in breast cancer adjuvant therapy recommendations. The TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor-positive breast cancer, testing exemestane plus ovarian function suppression (OFS), tamoxifen plus OFS, and tamoxifen alone. We examined absolute treatment effect across a continuum of recurrence risk to individualize endocrine therapy decision making for premenopausal women with human epidermal growth factor receptor 2 (HER2) -negative disease. The TEXT and SOFT hormone receptor-positive, HER2-negative analysis population included 4,891 women. The end point was breast cancer-free interval (BCFI), defined as time from random assignment to first occurrence of invasive locoregional, distant, or contralateral breast cancer. A continuous, composite measure of recurrence risk for each patient was determined from a Cox model incorporating age, nodal status, tumor size and grade, and estrogen receptor, progesterone receptor, and Ki-67 expression levels. Subpopulation treatment effect pattern plot methodology revealed differential treatment effects on 5-year BCFI according to composite risk. SOFT patients who remained premenopausal after chemotherapy experienced absolute improvement of 5% or more in 5-year BCFI with exemestane plus OFS versus tamoxifen plus OFS or tamoxifen alone, reaching 10% to 15% at intermediate to high composite risk; the benefit of tamoxifen plus OFS versus tamoxifen alone was apparent at the highest composite risk. The SOFT no-chemotherapy cohort-for whom composite risk was lowest on average-did well with all endocrine therapies. For TEXT patients, the benefit of exemestane plus OFS versus tamoxifen plus OFS in 5-year BCFI ranged from 5% to 15%; patients not receiving chemotherapy and with lowest composite risk did well with both treatments. Premenopausal women with

  2. Endoscopic Breast Surgery in Treating Patients With Breast Cancer

    ClinicalTrials.gov

    2014-02-05

    Male Breast Cancer; Recurrent Breast 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

  3. Breast Cancer In Women

    Cancer.gov

    This infographic shows the Breast Cancer Subtypes in Women. It’s important for guiding treatment and predicting survival. Know the Science: HR = Hormone receptor. HR+ means tumor cells have receptors for the hormones estrogen or progesterone, which can promote the growth of HR+ tumors. Hormone therapies like tamoxifen can be used to treat HR+ tumors. HER2 = Human epidermal growth Factor receptor, HER2+ means tumor cells overexpress (make high levels of) a protein, called HE2/neu, which has been shown to be associated with certain aggressive types of breast cancer. Trastuzumab and some other therapies can target cells that overexpress HER2. HR+/HER2, aka “LuminalA”. 73% of all breast cancer cases: best prognosis, most common subtype for every race, age, and poverty level. HR-/HER2, aka “Triple Negative”: 13% of all breast cancer cases, Worst prognosis, Non-Hispanic blacks have the highest rate of this subtype at every age and poverty level. HR+/HER2+, aka “Luminal B”, 10% of all breast cancer cases, little geographic variation by state. HR-/HER2+, aka”HER2-enriched”, 5% of all breast cancer cases, lowest rates for all races and ethnicities. www.cancer.gov Source: Special section of the Annual Report to the Nation on the Status of Cancer, 1975-2011.

  4. Transforming growth factor-β1 induces EMT by the transactivation of epidermal growth factor signaling through HA/CD44 in lung and breast cancer cells

    PubMed Central

    LI, LINGMEI; QI, LISHA; LIANG, ZHIJIE; SONG, WANGZHAO; LIU, YANXUE; WANG, YALEI; SUN, BAOCUN; ZHANG, BIN; CAO, WENFENG

    2015-01-01

    Epithelial-mesenchymal transition (EMT), a process closely related to tumor development, is regulated by a variety of signaling pathways and growth factors, such as transforming growth factor-β1 (TGF-β1) and epidermal growth factor (EGF). Hyaluronan (HA) has been shown to induce EMT through either TGF-β1 or EGF signaling and to be a regulator of the crosstalk between these two pathways in fibroblasts. In this study, in order to clarify whether HA has the same effect in tumor cells, we utilized the lung cancer cell line, A549, and the breast cancer cell line, MCF-7, and found that the effects of stimulation with TGF-β1 were more potent than those of EGF in regulating the expression of EMT-associated proteins and in enhancing cell migration and invasion. In addition, we observed that TGF-β1 activated EGF receptor (EGFR) and its downstream AKT and extracellular signal-regulated kinase (ERK) pathways. Furthermore, we found that TGF-β1 upregulated the expression of hyaluronan synthases (HAS1, HAS2 and HAS3) and promoted the expression of CD44, a cell surface receptor for HA, which interacts with EGFR, resulting in the activation of the downstream AKT and ERK pathways. Conversely, treatment with 4-methylumbelliferone (4-MU; an inhibitor of HAS) prior to stimulation with TGF-β1, inhibited the expression of CD44 and EGFR, abolished the interaction between CD44 and EGFR. Furthermore, the use of shRNA targeting CD44 impaired the expression of EGFR, deactivated the AKT and ERK pathways, reversed EMT and decreased the migration and invasion ability of cells. In conclusion, our data demonstrate that TGF-β1 induces EMT by the transactivation of EGF signaling through HA/CD44 in lung and breast cancer cells. PMID:26005723

  5. Augmentation of tissue transglutaminase expression and activation by epidermal growth factor inhibit doxorubicin-induced apoptosis in human breast cancer cells.

    PubMed

    Antonyak, Marc A; Miller, Allison M; Jansen, Jaclyn M; Boehm, Jason E; Balkman, Cheryl E; Wakshlag, Joseph J; Page, Rodney L; Cerione, Richard A

    2004-10-01

    Tissue transglutaminase (TGase) exhibits both a GTP binding/hydrolytic capability and an enzymatic transamidation activity. Increases in TGase expression and activation often occur in response to stimuli that promote cellular differentiation and apoptosis, yet the signaling mechanisms used by these stimuli to regulate TGase expression and activation and the role of TGase in these cellular processes are not well understood. Retinoic acid (RA) consistently induces TGase expression and activation, and it was shown recently that RA-induced TGase expression was inhibited in NIH3T3 mouse fibroblasts co-stimulated with epidermal growth factor (EGF). Here we investigate whether EGF also antagonized RA-induced TGase expression in breast cancer cells. We found that EGF stimulation affected TGase expression and activation very differently in these cancer cells. Not only did EGF fail to block RA-induced TGase expression, but also EGF alone was sufficient to potently up-regulate TGase expression and activation in SKBR3 cells, as well as MDAMB468 and BT-20 cells. Inhibiting phosphoinositide 3-kinase activity severely diminished the ability of EGF and RA to increase TGase protein levels, whereas a constitutively active form of phosphoinositide 3-kinase potentiated the induction of TGase expression by EGF in SKBR3 cells. Because EGF is an established antiapoptotic factor, we examined whether the protection afforded by EGF was dependent on its ability to up-regulate TGase activity in SKBR3 and BT-20 cells. Exposure of cells to a TGase inhibitor or expression of a dominant-negative form of TGase potently inhibited EGF-mediated protection from doxorubicin-induced apoptosis. Moreover, expression of exogenous TGase in SKBR3 cells mimicked the survival advantage of EGF, suggesting that TGase activation is necessary and sufficient for the antiapoptotic properties of EGF. These findings indicate for the first time that EGF can induce TGase expression and activation in human breast cancer

  6. Epidermal growth factor receptor and AKT1 gene copy numbers by multi-gene fluorescence in situ hybridization impact on prognosis in breast cancer.

    PubMed

    Li, Jiao; Su, Wei; Zhang, Sheng; Hu, Yunhui; Liu, Jingjing; Zhang, Xiaobei; Bai, Jingchao; Yuan, Weiping; Hu, Linping; Cheng, Tao; Zetterberg, Anders; Lei, Zhenmin; Zhang, Jin

    2015-05-01

    The epidermal growth factor receptor (EGFR)/PI3K/AKT signaling pathway aberrations play significant roles in breast cancer occurrence and development. However, the status of EGFR and AKT1 gene copy numbers remains unclear. In this study, we showed that the rates of EGFR and AKT1 gene copy number alterations were associated with the prognosis of breast cancer. Among 205 patients, high EGFR and AKT1 gene copy numbers were observed in 34.6% and 27.8% of cases by multi-gene fluorescence in situ hybridization, respectively. Co-heightened EGFR/AKT1 gene copy numbers were identified in 11.7% cases. No changes were found in 49.3% of patients. Although changes in EGFR and AKT1 gene copy numbers had no correlation with patients' age, tumor stage, histological grade and the expression status of other molecular makers, high EGFR (P = 0.0002) but not AKT1 (P = 0.1177) gene copy numbers correlated with poor 5-year overall survival. The patients with co-heightened EGFR/AKT1 gene copy numbers displayed a poorer prognosis than those with tumors with only high EGFR gene copy numbers (P = 0.0383). Both Univariate (U) and COX multivariate (C) analyses revealed that high EGFR and AKT1 gene copy numbers (P = 0.000 [U], P = 0.0001 [C]), similar to histological grade (P = 0.001 [U], P = 0.012 [C]) and lymph node metastasis (P = 0.046 [U], P = 0.158 [C]), were independent prognostic indicators of 5-year overall survival. These results indicate that high EGFR and AKT1 gene copy numbers were relatively frequent in breast cancer. Co-heightened EGFR/AKT1 gene copy numbers had a worse outcome than those with only high EGFR gene copy numbers, suggesting that evaluation of these two genes together may be useful for selecting patients for anti-EGFR-targeted therapy or anti-EGFR/AKT1-targeted therapy and for predicting outcomes. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  7. Breast Cancer: Treatment Options

    MedlinePlus

    ... Breast Cancer > Breast Cancer: Treatment Options Request Permissions Breast Cancer: Treatment Options Approved by the Cancer.Net Editorial ... recommendations for ovarian ablation . Hormonal therapy for metastatic breast cancer Hormonal therapies are also commonly used to treat ...

  8. A Study Evaluating INIPARIB in Combination With Chemotherapy to Treat Triple Negative Breast Cancer Brain Metastasis

    ClinicalTrials.gov

    2016-02-17

    Estrogen Receptor Negative (ER-Negative) Breast Cancer; Progesterone Receptor Negative (PR-Negative) Breast Cancer; Human Epidermal Growth Factor Receptor 2 Negative (HER2-Negative) Breast Cancer; Brain Metastases

  9. Circulating-free DNA Mutation Associated with Response of Targeted Therapy in Human Epidermal Growth Factor Receptor 2-positive Metastatic Breast Cancer

    PubMed Central

    Ye, Qing; Qi, Fan; Bian, Li; Zhang, Shao-Hua; Wang, Tao; Jiang, Ze-Fei

    2017-01-01

    Background: The addition of anti-human epidermal growth factor receptor 2 (HER2)-targeted drugs, such as trastuzumab, lapatinib, and trastuzumab emtansine (T-DM1), to chemotherapy significantly improved prognosis of HER2-positive breast cancer patients. However, it was confused that metastatic patients vary in the response of targeted drug. Therefore, methods of accurately predicting drug response were really needed. To overcome the spatial and temporal limitations of biopsies, we aimed to develop a more sensitive and less invasive method of detecting mutations associated with anti-HER2 therapeutic response through circulating-free DNA (cfDNA). Methods: From March 6, 2014 to December 10, 2014, 24 plasma samples from 20 patients with HER2-positive metastatic breast cancer who received systemic therapy were eligible. We used a panel for detection of hot-spot mutations from 50 oncogenes and tumor suppressor genes, and then used targeted next-generation sequencing (NGS) to identify somatic mutation of these samples in those 50 genes. Samples taken before their first trastuzumab administration and subsequently proven with clinical benefit were grouped into sensitive group. The others were collected after disease progression of the trastuzumab-based therapy and were grouped into the resistant group. Results: A total of 486 single-nucleotide variants from 46 genes were detected. Of these 46 genes, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), proto-oncogene c-Kit (KIT), and tumor protein p53 (TP53) were the most common mutated genes. Seven genes, including epidermal growth factor receptor (EGFR), G protein subunit alpha S (GNAS), HRas proto-oncogene (HRAS), mutL homolog 1 (MLH1), cadherin 1 (CDH1), neuroblastoma RAS viral oncogene homolog (NRAS), and NOTCH1, that only occurred mutations in the resistant group were associated with the resistance of targeted therapy. In addition, we detected a HER2 S855I mutation in two patients who had

  10. Activation of the Na+/H+ antiport is not required for epidermal growth factor-dependent gene expression, growth inhibition or proliferation in human breast cancer cells.

    PubMed Central

    Church, J G; Mills, G B; Buick, R N

    1989-01-01

    Mitogen interaction with specific receptors in many cell types leads to activation of the Na+/H+ antiport and a resultant cytoplasmic alkalinization. Since amiloride inhibits both Na+/H+ exchange and cell proliferation, it has been hypothesized that activation of the antiport is an obligatory requirement for mitogenesis. However, concentrations of amiloride which inhibit the antiport also inhibit other cellular processes, including protein synthesis and phosphorylation. We have used an epidermal growth factor (EGF) receptor gene-amplified human breast cancer cell line, the growth of which is inhibited by high levels of EGF in culture (MDA-468) and a variant, the growth of which is stimulated by EGF (MDA-468-S4), along with two potent amiloride analogues to examine whether activation of the Na+/H+ antiport and cytoplasmic alkalinization is necessary for both EGF-dependent effects to occur. At concentrations of the amiloride analogues which block Na+/H+ exchange in both cell types by 76-98%, the EGF-dependent alterations in [3H]thymidine incorporation or induction in c-myc or c-fos gene transcription were unaltered. These results were confirmed by a lack of effect of the amiloride analogues on both the growth-stimulatory and growth-inhibitory effects on EGF in an anchorage-independent growth assay. Similarly, in pH-altered media that prevented normal cytoplasmic alkalinization, the response of both MDA-468 and MDA-468-S4 to EGF activation was unaltered. In addition, activation of the Na+/H+ antiport alone was not sufficient to induce c-myc and c-fos transcription in either cell type. Taken together, these data suggest that neither the Na+/H+ antiport nor cytoplasmic alkalinization are necessary or sufficient for either EGF-dependent growth stimulation or growth inhibition in MDA-468 human breast cancer cells. Images Fig. 3. PMID:2537620

  11. Heart remodeling induced by adjuvant trastuzumab-containing chemotherapy for breast cancer overexpressing human epidermal growth factor receptor type 2: a prospective study.

    PubMed

    Piotrowski, Grzegorz; Gawor, Rafał; Bourge, Robert C; Stasiak, Arkadiusz; Potemski, Piotr; Gawor, Zenon; Nanda, Navin C; Banach, Maciej

    2013-12-01

    We aimed to investigate the cardiac changes in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with trastuzumab in an adjuvant setting. Two hundred and fifty-three women with HER2-positive breast cancer were included. The assessment of cardiovascular system and echocardiography were performed and compared at baseline, at the termination of trastuzumab therapy and 6 months latter. Left heart remodeling was defined arbitrary as the change in at least one of the analyzed echocardiographic parameters of ≥standard deviation (SD) (in model I) or ≥2×SD (in model II) after 6-month follow-up. After 6-month follow-up 39 (31.7%), 27 (22%), 14 (11.4%), 10 (8.1%), 5 (4.1%) and 1 (0.8%), women had at least one parameter with a change exceeding mean difference ≥SD, respectively; and 30 (24.4%), 9 (7.5%), 3 (2.4%), 2 (1.6%) 1 (0.8%) exceeding mean difference ≥2SD. In stepwise multivariate regression analysis sedentary life style (OR16.7, p=0.003), positive cardiovascular family history (OR 6,9; p=0.013) and left ventricular ejection fraction change after 3 months (OR 1.2; p=0.007) were independent predictors of left heart remodeling in model I, whereas hypertension (OR 5.6; p=0.06) and positive cardiovascular family history (OR 3.9; p=0.032) were independent predictors of heart remodeling in model II. In conclusion, trastuzumab induces LV and left atrial cavity dilatation together with LV systolic function impairment.

  12. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update.

    PubMed

    Wolff, Antonio C; Hammond, M Elizabeth H; Hicks, David G; Dowsett, Mitch; McShane, Lisa M; Allison, Kimberly H; Allred, Donald C; Bartlett, John M S; Bilous, Michael; Fitzgibbons, Patrick; Hanna, Wedad; Jenkins, Robert B; Mangu, Pamela B; Paik, Soonmyung; Perez, Edith A; Press, Michael F; Spears, Patricia A; Vance, Gail H; Viale, Giuseppe; Hayes, Daniel F

    2013-11-01

    To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer. ASCO/CAP convened an Update Committee that included coauthors of the 2007 guideline to conduct a systematic literature review and update recommendations for optimal HER2 testing. The Update Committee identified criteria and areas requiring clarification to improve the accuracy of HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The guideline was reviewed and approved by both organizations. The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive). Testing criteria define HER2-positive status when (on observing within an area of tumor that amounts to > 10% of contiguous and homogeneous tumor cells) there is evidence of protein overexpression (IHC) or gene amplification (HER2 copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within the area). If results are equivocal (revised criteria), reflex testing should be performed using an alternative assay (IHC or ISH). Repeat testing should be considered if results seem discordant with other histopathologic findings. Laboratories should demonstrate high concordance with a validated HER2 test on a sufficiently large and representative set of specimens. Testing must be performed in a laboratory accredited by CAP or another accrediting entity. The Update Committee urges providers and health systems to cooperate to ensure the highest quality testing. This guideline was developed through a collaboration between the American Society of Clinical Oncology and the College of American Pathologists and

  13. Breast Cancer

    MedlinePlus

    ... how early the cancer was diagnosed. Left untreated, breast cancer can spread to other parts of the body, including internal organs. This could cause serious health problems or be fatal. It is very important to get treatment as soon as possible.Living with cancer during ...

  14. Learning about Breast Cancer

    MedlinePlus

    ... genetic terms used on this page Learning About Breast Cancer What do we know about heredity and breast ... Cancer What do we know about heredity and breast cancer? Breast cancer is a common disease. Each year, ...

  15. Surgery for Breast Cancer

    MedlinePlus

    ... Oncology . 5th ed. Philadelphia, Pa: Elsevier; 2014. Last Medical Review: June 1, 2016 Last Revised: August 18, 2016 Breast Cancer Treatment Surgery for Breast Cancer Radiation for Breast Cancer Chemotherapy for Breast Cancer Hormone ...

  16. Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases

    PubMed Central

    Gelman, Rebecca S.; Wefel, Jeffrey S.; Melisko, Michelle E.; Hess, Kenneth R.; Connolly, Roisin M.; Van Poznak, Catherine H.; Niravath, Polly A.; Puhalla, Shannon L.; Ibrahim, Nuhad; Blackwell, Kimberly L.; Moy, Beverly; Herold, Christina; Liu, Minetta C.; Lowe, Alarice; Agar, Nathalie Y.R.; Ryabin, Nicole; Farooq, Sarah; Lawler, Elizabeth; Rimawi, Mothaffar F.; Krop, Ian E.; Wolff, Antonio C.; Winer, Eric P.; Lin, Nancy U.

    2016-01-01

    Purpose Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)–positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. Patients and Methods Eligible patients were those with HER2-positive brain metastases (≥ 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection. Patients received neratinib 240 mg orally once per day, and tumors were assessed every two cycles. The primary endpoint was composite CNS objective response rate (ORR), requiring all of the following: ≥50% reduction in volumetric sum of target CNS lesions and no progression of non-target lesions, new lesions, escalating corticosteroids, progressive neurologic signs/symptoms, or non-CNS progression—the threshold for success was five of 40 responders. Results Forty patients were enrolled between February 2012 and June 2013; 78% of patients had previous whole-brain radiotherapy. Three women achieved a partial response (CNS objective response rate, 8%; 95% CI, 2% to 22%). The median number of cycles received was two (range, one to seven cycles), with a median progression-free survival of 1.9 months. Five women received six or more cycles. The most common grade ≥ 3 event was diarrhea (occurring in 21% of patients taking prespecified loperamide prophylaxis and 28% of those without prophylaxis). Patients in the study experienced a decreased quality of life over time. Conclusion Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies

  17. 6 Common Cancers - Breast Cancer

    MedlinePlus

    ... Home Current Issue Past Issues 6 Common Cancers - Breast Cancer Past Issues / Spring 2007 Table of Contents For ... slow her down. Photo: AP Photo/Brett Flashnick Breast Cancer Breast cancer is a malignant (cancerous) growth that ...

  18. Resistance to therapy in estrogen receptor positive and human epidermal growth factor 2 positive breast cancers: progress with latest therapeutic strategies

    PubMed Central

    Lousberg, Laurence; Collignon, Joëlle; Jerusalem, Guy

    2016-01-01

    In this article, we focus on the subtype of estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-positive breast cancer (BC). Preclinical and clinical data indicate a complex molecular bidirectional crosstalk between the ER and HER2 pathways. This crosstalk probably constitutes one of the key mechanisms of drug resistance in this subclass of BC. Delaying or even reversing drug resistance seems possible by targeting pathways implicated in this crosstalk. High-risk patients currently receive anti-HER2 therapy, chemotherapy and endocrine therapy in the adjuvant setting. In metastatic cases, most patients receive a combination of anti-HER2 therapy and chemotherapy. Only selected patients presenting more indolent disease are candidates for combinations of anti-HER2 therapy and endocrine therapy. However, relative improvements in progression-free survival by chemotherapy-based regimens are usually lower in ER-positive patients than the ER-negative and HER2-positive subgroup. Consequently, new approaches aiming to overcome endocrine therapy resistance by adding targeted therapies to endocrine therapy based regimens are currently explored. In addition, dual blockade of HER2 or the combination of trastuzumab and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOP) inhibitors targeting the downstream pathway are strategies to overcome resistance to trastuzumab. This may lead in the near future to the less frequent use of chemotherapy-based treatment options in ER-positive, HER2-positive BC. PMID:27800032

  19. Resistance to therapy in estrogen receptor positive and human epidermal growth factor 2 positive breast cancers: progress with latest therapeutic strategies.

    PubMed

    Lousberg, Laurence; Collignon, Joëlle; Jerusalem, Guy

    2016-11-01

    In this article, we focus on the subtype of estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-positive breast cancer (BC). Preclinical and clinical data indicate a complex molecular bidirectional crosstalk between the ER and HER2 pathways. This crosstalk probably constitutes one of the key mechanisms of drug resistance in this subclass of BC. Delaying or even reversing drug resistance seems possible by targeting pathways implicated in this crosstalk. High-risk patients currently receive anti-HER2 therapy, chemotherapy and endocrine therapy in the adjuvant setting. In metastatic cases, most patients receive a combination of anti-HER2 therapy and chemotherapy. Only selected patients presenting more indolent disease are candidates for combinations of anti-HER2 therapy and endocrine therapy. However, relative improvements in progression-free survival by chemotherapy-based regimens are usually lower in ER-positive patients than the ER-negative and HER2-positive subgroup. Consequently, new approaches aiming to overcome endocrine therapy resistance by adding targeted therapies to endocrine therapy based regimens are currently explored. In addition, dual blockade of HER2 or the combination of trastuzumab and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOP) inhibitors targeting the downstream pathway are strategies to overcome resistance to trastuzumab. This may lead in the near future to the less frequent use of chemotherapy-based treatment options in ER-positive, HER2-positive BC.

  20. Real world cost of human epidermal receptor 2-positive metastatic breast cancer patients: a longitudinal incidence-based observational costing study in the Netherlands and Belgium.

    PubMed

    Frederix, G W J; Severens, J L; Hövels, A M; van Hasselt, J G C; Hooiveld, M J J; Neven, P; Raaijmakers, J A M; Schellens, J H M

    2015-05-01

    Currently, no country-specific metastatic breast cancer (MBC) observational costing data are available for the Netherlands and Belgium. Our aim is to describe country-specific resource use and costs of human epidermal receptor 2 (HER-2)-positive MBC in the Netherlands and Belgium, making use of real-world data. The eligibility period for patient selection was from April 2004 to April 2010. Inclusion and retrospective data collection begins at the time of first diagnosis of HER-2-positive MBC during the eligibility period and ends 24 months post-index diagnosis of MBC or at patient death. We identified 88 eligible patients in the Netherlands and 44 patients in Belgium. The total costs of medical treatment and other resource use utilisation per patient was €48,301 in the Netherlands and €37,431 in Belgium. Majority of costs was related to the use of trastuzumab in both countries, which was 50% of the total costs in the Netherlands and 56% in Belgium respectively. Our study provides estimates of resource use and costs for HER-2-positive MBC in the Netherlands and Belgium. We noticed various differences in resource use patterns between both countries demonstrating caution is needed when transferring cost estimates between countries. © 2014 John Wiley & Sons Ltd.

  1. Risks of Breast Cancer Screening

    MedlinePlus

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Screening (PDQ®)–Patient Version What is screening? Go ... cancer screening: Cancer Screening Overview General Information About Breast Cancer Key Points Breast cancer is a disease in ...

  2. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer.

    PubMed

    Wolff, Antonio C; Hammond, M Elizabeth H; Schwartz, Jared N; Hagerty, Karen L; Allred, D Craig; Cote, Richard J; Dowsett, Mitchell; Fitzgibbons, Patrick L; Hanna, Wedad M; Langer, Amy; McShane, Lisa M; Paik, Soonmyung; Pegram, Mark D; Perez, Edith A; Press, Michael F; Rhodes, Anthony; Sturgeon, Catharine; Taube, Sheila E; Tubbs, Raymond; Vance, Gail H; van de Vijver, Marc; Wheeler, Thomas M; Hayes, Daniel F

    2007-01-01

    To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2 (HER2) testing in invasive breast cancer and its utility as a predictive marker. The American Society of Clinical Oncology and the College of American Pathologists convened an expert panel, which conducted a systematic review of the literature and developed recommendations for optimal HER2 testing performance. The guideline was reviewed by selected experts and approved by the board of directors for both organizations. Approximately 20% of current HER2 testing may be inaccurate. When carefully validated testing is performed, available data do not clearly demonstrate the superiority of either immunohistochemistry (IHC) or in situ hybridization (ISH) as a predictor of benefit from anti-HER2 therapy. The panel recommends that HER2 status should be determined for all invasive breast cancer. A testing algorithm that relies on accurate, reproducible assay performance, including newly available types of brightfield ISH, is proposed. Elements to reliably reduce assay variation (for example, specimen handling, assay exclusion, and reporting criteria) are specified. An algorithm defining positive, equivocal, and negative values for both HER2 protein expression and gene amplification is recommended: a positive HER2 result is IHC staining of 3+ (uniform, intense membrane staining of > 30% of invasive tumor cells), a fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or a FISH ratio (HER2 gene signals to chromosome 17 signals) of more than 2.2; a negative result is an IHC staining of 0 or 1+, a FISH result of less than 4.0 HER2 gene copies per nucleus, or FISH ratio of less than 1.8. Equivocal results require additional action for final determination. It is recommended that to perform HER2 testing, laboratories show 95% concordance with another validated test for positive and negative assay values. The panel strongly recommends validation of

  3. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer.

    PubMed

    Wolff, Antonio C; Hammond, M Elizabeth H; Schwartz, Jared N; Hagerty, Karen L; Allred, D Craig; Cote, Richard J; Dowsett, Mitchell; Fitzgibbons, Patrick L; Hanna, Wedad M; Langer, Amy; McShane, Lisa M; Paik, Soonmyung; Pegram, Mark D; Perez, Edith A; Press, Michael F; Rhodes, Anthony; Sturgeon, Catharine; Taube, Sheila E; Tubbs, Raymond; Vance, Gail H; van de Vijver, Marc; Wheeler, Thomas M; Hayes, Daniel F

    2007-01-01

    To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2(HER2) testing in invasive breast cancer and its utility as a predictive marker. The American Society of Clinical Oncology and the College of American Pathologists convened an expert panel, which conducted a systematic review of the literature and developed recommendations for optimal HER2 testing performance. The guideline was reviewed by selected experts and approved by the board of directors for both organizations. Approximately 20% of current HER2 testing may be inaccurate. When carefully validated testing is performed, available data do not clearly demonstrate the superiority of either immunohistochemistry(IHC) or in situ hybridization (ISH) as a predictor of benefit from anti-HER2 therapy. The panel recommends that HER2 status should be determined for all invasive breast cancer. A testing algorithm that relies on accurate, reproducible assay performance, including newly available types of brightfield ISH, is proposed. Elements to reliably reduce assay variation (for example, specimen handling, assay exclusion, and reporting criteria) are specified. An algorithm defining positive, equivocal, and negative values for both HER2 protein expression and gene amplification is recommended: a positive HER2 result is IHC staining of 3 + (uniform, intense membrane staining of 30% of invasive tumor cells), a fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or a FISH ratio (HER2 gene signals to chromosome 17 signals) of more than 2.2; a negative result is an IHC staining of 0 or 1 +, a FISH result of less than 4.0 HER2 gene copies per nucleus, or FISH ratio of less than 1.8. Equivocal results require additional action for final determination. It is recommended that to perform HER2 testing, laboratories show 95% concordance with another validated test for positive and negative assay values. The panel strongly recommends validation of

  4. Second-line single-agent chemotherapy in human epidermal growth factor receptor 2-negative metastatic breast cancer: A systematic review.

    PubMed

    Puglisi, Fabio; Rea, Daniel; Kroes, Michel A; Pronzato, Paolo

    2016-02-01

    No 'gold standard' exists for single-agent chemotherapy of human epidermal growth factor receptor 2-negative (HER2-negative) metastatic breast cancer (MBC) in the second-line. The objective of this systematic review is to identify and appraise overall survival (OS), progression-free survival (PFS), time to progression (TTP) and Grade ≥3 adverse event evidence for single-agent chemotherapy in this setting. MEDLINE, Embase and the Cochrane Library were searched to October 2013, and PubMed October 2013 to November 2014. Electronic database searches were supplemented with hand searching of reference lists and conferences. Eligible randomised controlled trials (RCTs) employed at least one single-agent chemotherapy treatment, enrolled HER2-negative or unselected MBC patients who had progressed following first-line chemotherapy within the metastatic setting, and reported outcomes of interest for the second-line setting. Fifty-three RCTs were included in total, with most containing mixed populations by HER2 status and treatment line. Fourteen studies reported data specifically for second- and later-line treatment within the metastatic setting. Median overall survival (OS) in most trials was 8-13 months. Only one trial reported a significant difference between studied interventions in the second-line metastatic setting: nab-paclitaxel (n=131) conferred a statistically significant OS advantage vs. three-weekly paclitaxel (n=136) (median OS 13.0 vs. 10.7 months, respectively; hazard ratio 0.73, p=0.024) and improved overall safety. One RCT demonstrated significant benefit in this setting in confirmed HER2-negative MBC alongside favourable safety. Treatment line terminology was imprecise. To reliably inform patient treatment decisions, quality-of-life data are needed and precise OS estimation according to underlying patient characteristics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Recurrent Breast Cancer

    MedlinePlus

    ... you may have received after your first breast cancer diagnosis was intended to kill any cancer cells that ... 35 at the time of their original breast cancer diagnosis, face a higher risk of recurrent breast cancer. ...

  6. Understanding a Breast Cancer Diagnosis

    MedlinePlus

    ... Category Cancer A-Z Breast Cancer Understanding a Breast Cancer Diagnosis If you’ve been diagnosed with breast ... cancer or how fast it’s growing. Types of Breast Cancer There are several types of breast cancer. The ...

  7. Promoter methylation of BRCA1 is associated with estrogen, progesterone and human epidermal growth factor receptor-negative tumors and the prognosis of breast cancer: A meta-analysis.

    PubMed

    Guo, Taiyan; Ren, Yongyong; Wang, Boyuan; Huang, Yingze; Jia, Shuting; Tang, Wenru; Luo, Ying

    2015-11-01

    Aberrant methylation of the breast cancer susceptibility gene 1 (BRCA1) promoter is a mechanism for its functional inactivation. It may potentially be used as a prognostic marker in studies for patients with breast cancer and plays an important role in tumorigenesis. Numerous studies have suggested that the methylation of the BRCA1 promoter is associated with the prognosis of breast cancer. However, the prognosis of BRCA1 promoter methylation in breast cancer patients of different ethnicities remains ambiguous. The present meta-analysis was performed to adjust and augment a previously published study, which estimated the correlations between promoter methylation of BRCA1 and the clinical outcomes of breast cancer patients. These results indicated that BRCA1 methylation was significantly correlated with a poor prognosis of breast cancer, particularly for Asian patients, but the correlation was over-estimated in the previous study. The combined hazard ratios (HRs) in the present study were 1.76 (1.15-2.68) and 1.97 (1.12-3.44) for univariate and multivariate analysis of overall survival, which were different from 2.02 (1.35-3.03) and 1.38 (1.04-1.84) in the previous study. For studies of disease-free survival, the univariate and multivariate analyses also have different pooled HRs: 2.89 (1.73-4.83) and 3.92 (1.49-10.32) in the previously published study and 1.28 (0.68-2.43) and 1.64 (0.64-4.19) in the present study. In addition, the BRCA1 promoter regions used to detect the hypermethylation were different. All the studies using the Baldwin's primer reported that breast cancer patients with BRCA1 promoter methylation had a better prognosis. There were also correlations between BRCA1 promoter methylation and receptor-negativity of the estrogen receptors, progesterone receptor, human epidermal growth factor receptor 2 and a triple-negative status. Patients with the estrogen, progesterone and epidermal growth factor-related receptor-negative status were more likely to be

  8. Breast cancer statistics and markers.

    PubMed

    Donepudi, Mallika Siva; Kondapalli, Kasturi; Amos, Seelam Jeevan; Venkanteshan, Pavithra

    2014-01-01

    Breast cancer is one of the familiar diseases in women. Incidence and mortality due to cancer, particularly breast cancer has been increasing for last 50 years, even though there is a lacuna in the diagnosis of breast cancer at early stages. According to World Health Organization (WHO) 2012 reports, breast cancer is the leading cause of death in women, accounting 23% of all cancer deaths. In Asia, one in every three women faces the risk of breast cancer in their lifetime as per reports of WHO 2012. Here, the review is been focused on different breast cancer markers, that is, tissue markers (hormone receptors, human epidermal growth factor-2, urokinase plasminogen activator, plasminogen activator inhibitor, p53 and cathepsin D), genetic markers (BRAC1 and 2 and gene expression microarray technique, etc.), and serum markers (CA 15.3, BR 27.29, MCA, CA 549, carcinoembryonic antigen, oncoproteins, and cytokeratins) used in present diagnosis, but none of the mentioned markers can diagnose breast cancer at an early stage. There is a disquieting need for the identification of best diagnosing marker, which can be able to diagnose even in early stage of breast carcinogenesis.

  9. Breast Cancer -- Male

    MedlinePlus

    ... Home > Types of Cancer > Breast Cancer in Men Breast Cancer in Men This is Cancer.Net’s Guide to Breast Cancer in Men. Use the menu below to choose ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer in Men Introduction Statistics Risk Factors and Prevention ...

  10. Breast Cancer Overview

    MedlinePlus

    ... are here Home > Types of Cancer > Breast Cancer Breast Cancer This is Cancer.Net’s Guide to Breast Cancer. Use the menu below to choose the Overview/ ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer Introduction Statistics Medical Illustrations Risk Factors and Prevention ...

  11. Breast Cancer (For Kids)

    MedlinePlus

    ... de los dientes Video: Getting an X-ray Breast Cancer KidsHealth > For Kids > Breast Cancer Print A A ... for it when they are older. What Is Breast Cancer? The human body is made of tiny building ...

  12. Male Breast Cancer

    MedlinePlus

    Although breast cancer is much more common in women, men can get it too. It happens most often to men ... usually aren't cancer. However, most men with breast cancer have lumps. Other breast symptoms can include Dimpled ...

  13. Breast Cancer Trends

    MedlinePlus

    ... Breast Cancer Funding: Young Breast Cancer Survivors Funding: Breast Cancer Genomics Statistics Rates by Race and Ethnicity Rates by State Risk by Age Trends What CDC Is Doing Research African American Women and Mass Media Campaign Public Service Announcements Print ...

  14. Glut1 promotes cell proliferation, migration and invasion by regulating epidermal growth factor receptor and integrin signaling in triple-negative breast cancer cells.

    PubMed

    Oh, Sunhwa; Kim, Hyungjoo; Nam, KeeSoo; Shin, Incheol

    2017-03-01

    Elevated glucose levels in cancer cells can be attributed to increased levels of glucose transporter (GLUT) proteins. Glut1 expression is increased in human malignant cells. To investigate alternative roles of Glut1 in breast cancer, we silenced Glut1 in triple-negative breast-cancer cell lines using a short hairpin RNA (shRNA) system. Glut1 silencing was verified by Western blotting and qRT-PCR. Knockdown of Glut1 resulted in decreased cell proliferation, glucose uptake, migration, and invasion through modulation of the EGFR/ MAPK signaling pathway and integrin β1/Src/FAK signaling pathways. These results suggest that Glut1 not only plays a role as a glucose transporter, but also acts as a regulator of signaling cascades in the tumorigenesis of breast cancer. [BMB Reports 2017; 50(3): 132-137].

  15. Breast Cancer Surgery

    MedlinePlus

    FACTS FOR LIFE Breast Cancer Surgery The goal of breast cancer surgery is to remove the whole tumor from the breast. Some lymph nodes ... might still be in the body. Types of breast cancer surgery There are two types of breast cancer ...

  16. Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: Final Results of NCIC CTG MA.31.

    PubMed

    Gelmon, Karen A; Boyle, Frances M; Kaufman, Bella; Huntsman, David G; Manikhas, Alexey; Di Leo, Angelo; Martin, Miguel; Schwartzberg, Lee S; Lemieux, Julie; Aparicio, Samuel; Shepherd, Lois E; Dent, Susan; Ellard, Susan L; Tonkin, Katia; Pritchard, Kathleen I; Whelan, Timothy J; Nomikos, Dora; Nusch, Arnd; Coleman, Robert E; Mukai, Hirofumi; Tjulandin, Sergei; Khasanov, Rustem; Rizel, Shulamith; Connor, Anne P; Santillana, Sergio L; Chapman, Judith-Anne W; Parulekar, Wendy R

    2015-05-10

    The efficacy of lapatinib versus trastuzumab combined with taxanes in the first-line setting of human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (BC) is unknown. The MA.31 trial compared a combination of first-line anti-HER2 therapy (lapatinib or trastuzumab) and taxane therapy for 24 weeks, followed by the same anti-HER2 monotherapy until progression. Stratification was by prior (neo)adjuvant anti-HER2 therapy, prior (neo)adjuvant taxane, planned taxane, and liver metastases. The primary end point was intention-to-treat (ITT) progression-free survival (PFS), defined as time from random assignment to progression by RECIST (version 1.0) criteria, or death for patients with locally assessed HER2-positive tumors. The primary test statistic was a stratified log-rank test for noninferiority. PFS was also assessed for patients with centrally confirmed HER2-positive tumors. From July 17, 2008, to December 1, 2011, 652 patients were accrued from 21 countries, resulting in 537 patients with centrally confirmed HER2-positive tumors. Median follow-up was 21.5 months. Median ITT PFS was 9.0 months with lapatinib and 11.3 months with trastuzumab. By ITT analysis, PFS was inferior for lapatinib compared with trastuzumab, with a stratified hazard ratio (HR) of 1.37 (95% CI, 1.13 to 1.65; P = .001). In patients with centrally confirmed HER2-positive tumors, median PFS was 9.1 months with lapatinib and 13.6 months with trastuzumab (HR, 1.48; 95% CI, 1.20 to 1.83; P < .001). More grade 3 or 4 diarrhea and rash were observed with lapatinib (P < .001). PFS results were supported by the secondary end point of overall survival, with an ITT HR of 1.28 (95% CI, 0.95 to 1.72; P = .11); in patients with centrally confirmed HER2-positive tumors, the HR was 1.47 (95% CI, 1.03 to 2.09; P = .03). As first-line therapy for HER2-positive metastatic BC, lapatinib combined with taxane was associated with shorter PFS and more toxicity compared with trastuzumab

  17. Budget impact analysis of everolimus for the treatment of hormone receptor positive, human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer in the United States.

    PubMed

    Xie, Jipan; Diener, Melissa; De, Gourab; Yang, Hongbo; Wu, Eric Q; Namjoshi, Madhav

    2013-01-01

    To estimate the budget impact of everolimus as the first and second treatment option after letrozole or anastrozole (L/A) failure for post-menopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer (ABC). Pharmacy and medical budget impacts (2011 USD) were estimated over the first year of everolimus use in HR+, HER2- ABC from a US payer perspective. Epidemiology data were used to estimate target population size. Pre-everolimus entry treatment options included exemestane, fulvestrant, and tamoxifen. Pre- and post-everolimus entry market shares were estimated based on market research and assumptions. Drug costs were based on wholesale acquisition cost. Patients were assumed to be on treatment until progression or death. Annual medical costs were calculated as the average of pre- and post-progression medical costs weighted by the time in each period, adjusted for survival. One-way and two-way sensitivity analyses were conducted to assess the model robustness. In a hypothetical 1,000,000 member plan, 72 and 159 patients were expected to be candidates for everolimus treatment as first and second treatment option, respectively, after L/A failure. The total budget impact for the first year post-everolimus entry was $0.044 per member per month [PMPM] (pharmacy budget: $0.058 PMPM; medical budget: -$0.014 PMPM), assuming 10% of the target population would receive everolimus. The total budget impacts for the first and second treatment options after L/A failure were $0.014 PMPM (pharmacy budget: $0.018; medical budget: -$0.004) and $0.030 PMPM (pharmacy budget: $0.040; medical budget: -$0.010), respectively. Results remained robust in sensitivity analyses. Assumptions about some model input parameters were necessary and may impact results. Increased pharmacy costs for HR+, HER2- ABC following everolimus entry are expected to be partially offset by reduced medical service costs. Pharmacy and total

  18. Breast Cancer In Women Infographic

    Cancer.gov

    This infographic shows the Breast Cancer Subtypes in Women. It’s important for guiding treatment and predicting survival. Know the Science: HR = Hormone receptor. HR+ means tumor cells have receptors for the hormones estrogen or progesterone, which can promote the growth of HR+ tumors. Hormone therapies like tamoxifen can be used to treat HR+ tumors. HER2 = Human epidermal growth Factor receptor, HER2+ means tumor cells overexpress (make high levels of) a protein, called HE2/neu, which has been shown to be associated with certain aggressive types of breast cancer. Trastuzumab and some other therapies can target cells that overexpress HER2. HR+/HER2, aka “LuminalA”. 73% of all breast cancer cases: best prognosis, most common subtype for every race, age, and poverty level. HR-/HER2, aka “Triple Negative”: 13% of all breast cancer cases, Worst prognosis, Non-Hispanic blacks have the highest rate of this subtype at every age and poverty level. HR+/HER2+, aka “Luminal B”, 10% of all breast cancer cases, little geographic variation by state. HR-/HER2+, aka”HER2-enriched”, 5% of all breast cancer cases, lowest rates for all races and ethnicities. www.cancer.gov Source: Special section of the Annual Report to the Nation on the Status of Cancer, 1975-2011.

  19. Preclinical pharmacokinetic, biodistribution, toxicology, and dosimetry studies of 111In-DTPA-human epidermal growth factor: an auger electron-emitting radiotherapeutic agent for epidermal growth factor receptor-positive breast cancer.

    PubMed

    Reilly, Raymond M; Chen, Paul; Wang, Judy; Scollard, Deborah; Cameron, Ross; Vallis, Katherine A

    2006-06-01

    by light microscopy in any of 19 tissues sampled. Minor morphologic changes in the liver were observed by electron microscopy. The projected whole-body dose in humans was 0.19 mSv.MBq(-1). The projected doses to the liver, kidneys, and lower large intestine were 0.76, 1.82, and 1.12 mSv.MBq(-1), respectively. (111)In-DTPA-hEGF was safely administered to mice and rabbits at multiples of the maximum dose planned for a phase I trial in breast cancer patients.

  20. Breast Cancer Disparities

    MedlinePlus

    ... 2.65 MB] Read the MMWR Science Clips Breast Cancer Black Women Have Higher Death Rates from Breast ... of Page U.S. State Info Number of Additional Breast Cancer Deaths Among Black Women, By State SOURCE: National ...

  1. Breast cancer in men

    MedlinePlus

    ... in situ - male; Intraductal carcinoma - male; Inflammatory breast cancer - male; Paget disease of the nipple - male; Breast cancer - male ... The cause of breast cancer in men is not clear. But there are risk factors that make breast cancer more likely in men: Exposure to ...

  2. Urinary epidermal growth factor (hEGF) levels in patients with carcinomas of the breast, colon and rectum.

    PubMed Central

    Sweetenham, J. W.; Davies, D. E.; Warnes, S.; Alexander, P.

    1990-01-01

    A specific two-site ELISA for human epidermal growth factor (hEGF) has been used to measure urinary hEGF/creatinine ratios in 30 normal subjects, 30 hospital in-patients with breast cancer and 30 hospital in-patients with colonic or rectal cancer. There was no significant difference between patients with breast cancer and controls. Although a statistically significant difference between patients with colorectal cancer and controls was observed, the biological significance of this observation is doubtful. No clear effect of the presence of breast or colorectal carcinoma on the urinary excretion of hEGF has been observed. PMID:2206955

  3. Epidermal growth factor-like proteins in breast fluid and human milk.

    PubMed

    Connolly, J M; Rose, D P

    1988-01-01

    Epidermal growth factor (EGF), and the transforming growth factor-alpha (TGF-alpha) family of proteins, which also bind to the EGF receptor, have been associated with human breast cancer. The total EGF-like proteins were determined by a radioreceptor assay, and TGF-alpha by radioimmunoassay, in human milk and breast fluid samples. The breast fluids were collected by nipple aspiration from healthy premenopausal women. Both the 24 milks and 18 breast fluids assayed contained EGF-like proteins, at concentrations ranging from 32-600 ng/ml (median, 140 ng/ml), and 62-654 ng/ml (median, 205 ng/ml) respectively. Immunoreactive TGF-alpha proteins were detected at higher levels in 21 breast fluids (range, 0-50.0; median 5.1 ng/ml) than in 24 milk samples (range, 0-8.4; median, 0.8 ng/ml).

  4. P53 mutations in triple negative breast cancer upregulate endosomal recycling of epidermal growth factor receptor (EGFR) increasing its oncogenic potency.

    PubMed

    Shapira, Iuliana; Lee, Annette; Vora, Reena; Budman, Daniel R

    2013-11-01

    There is no available targeted therapy for triple-negative or its more aggressive subtype, basal-like breast cancer. Multiple therapeutic strategies based on translational knowledge have not improved the treatment options for triple negative patients. As understanding of molecular pathways that drive tumor development is rapidly increasing, it is imperative to adapt our treatment strategies to perturbations in molecular pathways driving the malignant process. Basal-like breast cancers over-express EGFR (without mutations or EGFR gene amplifications) and have p53 mutations. While EGFR drives the malignant behavior in triple negative breast cancer (TNBC), anti-EGFR therapies have fallen short of the expected results in clinical trials. Here we bring evidence that the less than optimal results of the anti-EGFR therapies may be explained in part by the increased potency of the EGFR signaling due to increased endosomal recycling. The functional connection between EGFR and endosomal trafficking in TNBC is mutant p53 found in the most aggressive forms of TNBC. Mutant p53 acquires oncogenic functions and binds p63 protein, a member of p53 family with tumor suppressor activities. In the absence of functional p63 there is an upregulation of endosomal recycling EGFR and integrin to the membrane with increased proinvasive abilities of cancer cells. Blocking endosomal trafficking combined with anti-EGFR treatments may result in better clinical outcomes in TNBC.

  5. Cell surface interaction of annexin A2 and galectin-3 modulates epidermal growth factor receptor signaling in Her-2 negative breast cancer cells.

    PubMed

    Shetty, Praveenkumar; Bargale, Anil; Patil, Basavraj R; Mohan, Rajashekar; Dinesh, U S; Vishwanatha, Jamboor K; Gai, Pramod B; Patil, Vidya S; Amsavardani, T S

    2016-01-01

    Overexpression and activation of tyrosine kinase receptors like EGFR and Src regulate the progression and metastasis of Her-2 negative breast cancer. Recently we have reported the role of cell membrane interaction of phospholipid-binding protein annexin A2 (AnxA2) and EGFR in regulating cellular signaling in the activation of angiogenesis, matrix degradation, invasion, and cancer metastasis. Beta-galactoside-specific animal lectin galectin-3 is an apoptosis inhibitor, and cell surface-associated extracellular galectin-3 also has a role in cell migration, cancer progression, and metastasis. Similar expression pattern and membrane co-localization of these two proteins made us to hypothesize in the current study that galectin-3 and AnxA2 interaction is critical for Her-2 negative breast cancer progression. By various experimental analyses, we confirm that glycosylated AnxA2 at the membrane surface interacts with galectin-3. N-linked glycosylation inhibitor tunicamycin treatment convincingly blocked AnxA2 membrane translocation and its association with galectin-3. To analyze whether this interaction has any functional relevance, we tried to dissociate this interaction with purified plant lectin from chickpea (Cicer arietinum agglutinin). This highly specific 30 kDa plant lectin could dissociate AnxA2 from endogenous lectin galectin-3 interaction at the cell surface. This dissociation could down-regulate Bcl-2 family proteins, cell proliferation, and migration simultaneously triggering cell apoptosis. Targeting this interaction of membrane surface glycoprotein and its animal lectin in Her-2 negative breast cancer may be of therapeutic value.

  6. Impact of estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER2) co-expression on breast cancer disease characteristics: implications for tumor biology and research.

    PubMed

    Alqaisi, Abeer; Chen, Li; Romond, Edward; Chambers, Mara; Stevens, Mark; Pasley, Grace; Awasthi, Mukta; Massarweh, Suleiman

    2014-11-01

    ER and HER2 are critical drivers of breast cancer biology and can interact when co-expressed, but less data describe the impact of ER/HER2 co-expression on clinical disease characteristics. We studied the impact of ER and HER2 (co)-expression in a cohort of 1,187 patients with invasive breast cancer and compared disease characteristics among different groups according to ER and HER2 status. Age, tumor size, grade, nodal status, TNM stage, and metastatic sites were compared and significance determined using the appropriate t tests. All p values were two-tailed. Compared to ER-negative/HER2-negative disease as the control group, ER expression was associated with older age, smaller tumors, lower grade, earlier TNM stage, and increased bone involvement in de novo metastasis, while HER2 had no significant impact on these characteristics. ER and HER2 co-expression was associated with lower grade and higher bone involvement in de novo metastasis, reflecting a retained impact for ER. HER2 impact on ER-positive disease was reflected by younger age, higher grade and TNM stage, and increased frequency of visceral involvement in de novo metastasis. Within the ER-positive/HER2-positive group, triple positive breast cancer (ER+/PgR+/HER2+) was associated with younger age compared to ER+/PgR-/HER2+ disease (mean age of 50.8 vs. 56 years, p = 0.0226). PgR was also associated with younger age in ER+/HER2- disease with a mean age of 57.6 years in ER+/PgR+/HER2- disease vs. 63.4 years in ER+/PgR-/HER2- disease (p < 0.0001). In conclusion, ER has a profound impact on breast cancer characteristics, including a retained impact when co-expressed with HER2. Similarly, HER2 dramatically modulates ER-positive breast cancer making it more aggressive. PgR association with young age may be related to hormonal levels of the premenopausal state, with HER2 providing an earlier growth advantage in triple positive disease, suggesting a specific dependence for this subset on high estrogen

  7. Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial

    PubMed Central

    Holmes, Eileen; Baselga, José; de Azambuja, Evandro; Dueck, Amylou C.; Viale, Giuseppe; Zujewski, Jo Anne; Goldhirsch, Aron; Armour, Alison; Pritchard, Kathleen I.; McCullough, Ann E.; Dolci, Stella; McFadden, Eleanor; Holmes, Andrew P.; Tonghua, Liu; Eidtmann, Holger; Dinh, Phuong; Di Cosimo, Serena; Harbeck, Nadia; Tjulandin, Sergei; Im, Young-Hyuck; Huang, Chiun-Sheng; Diéras, Véronique; Hillman, David W.; Wolff, Antonio C.; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Suter, Thomas; Gelber, Richard D.; Perez, Edith A.

    2016-01-01

    Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2–positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2–positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. PMID:26598744

  8. Genomic profiling of breast cancers.

    PubMed

    Curtis, Christina

    2015-02-01

    To describe recent advances in the application of advanced genomic technologies towards the identification of biomarkers of prognosis and treatment response in breast cancer. Advances in high-throughput genomic profiling such as massively parallel sequencing have enabled researchers to catalogue the spectrum of somatic alterations in breast cancers. These tools also hold promise for precision medicine through accurate patient prognostication, stratification, and the dynamic monitoring of treatment response. For example, recent efforts have defined robust molecular subgroups of breast cancer and novel subtype-specific oncogenes. In addition, previously unappreciated activating mutations in human epidermal growth factor receptor 2 have been reported, suggesting new therapeutic opportunities. Genomic profiling of cell-free tumor DNA and circulating tumor cells has been used to monitor disease burden and the emergence of resistance, and such 'liquid biopsy' approaches may facilitate the early, noninvasive detection of aggressive disease. Finally, single-cell genomics is coming of age and will contribute to an understanding of breast cancer evolutionary dynamics. Here, we highlight recent studies that employ high-throughput genomic technologies in an effort to elucidate breast cancer biology, discover new therapeutic targets, improve prognostication and stratification, and discuss the implications for precision cancer medicine.

  9. The SystHERs registry: an observational cohort study of treatment patterns and outcomes in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer

    PubMed Central

    2014-01-01

    Background Amplification of the human epidermal growth factor receptor 2 (HER2) gene occurs in approximately 20% of invasive breast cancer cases and is associated with a more aggressive disease course than HER2-negative breast cancer. HER2-targeted therapies have altered the natural history of HER2-positive breast cancer, a trend that will likely further improve with the recent approval of new agents. A prospective, observational cohort study was designed and initiated to provide real-world insights into current treatment patterns, long-term survival, and patients’ experiences with initial and subsequent treatments for HER2-positive metastatic breast cancer (MBC). Methods/Design The Systematic Therapies for HER2-positive Metastatic Breast Cancer Study (SystHERs) is a US-based prospective observational cohort study enrolling patients ≥18 years of age with recently diagnosed HER2-positive MBC not previously treated with systemic therapy in the metastatic setting. The primary objective of the study is to identify treatment patterns and clinical outcomes in recently diagnosed patients in a variety of practice settings. Secondary objectives include comparative efficacy, safety, and patient-reported outcomes (PROs). Healthcare resource utilization is an exploratory end point. Tumor tissue and blood sample collection is optional. The SystHERs registry will enroll approximately 1000 patients over a 3-year period, after which the study will continue for ≥5 years, allowing for a maximum follow-up of 8 years. The treating physician will determine all care and the frequency of visits. PRO measures will be completed at study enrollment and every 90 days. Clinical data will be abstracted quarterly from patient records. The first patient was enrolled in June 2012, and preliminary descriptive data based on 25% to 30% of the final study population are expected at the end of 2013, and as of April 25, 2014, 386 patients are enrolled. Discussion SystHERs is expected to

  10. Impact of Diabetes, Insulin, and Metformin Use on the Outcome of Patients With Human Epidermal Growth Factor Receptor 2-Positive Primary Breast Cancer: Analysis From the ALTTO Phase III Randomized Trial.

    PubMed

    Sonnenblick, Amir; Agbor-Tarh, Dominique; Bradbury, Ian; Di Cosimo, Serena; Azim, Hatem A; Fumagalli, Debora; Sarp, Severine; Wolff, Antonio C; Andersson, Michael; Kroep, Judith; Cufer, Tanja; Simon, Sergio D; Salman, Pamela; Toi, Masakazu; Harris, Lyndsay; Gralow, Julie; Keane, Maccon; Moreno-Aspitia, Alvaro; Piccart-Gebhart, Martine; de Azambuja, Evandro

    2017-05-01

    Purpose Previous studies have suggested an association between metformin use and improved outcome in patients with diabetes and breast cancer. In the current study, we aimed to explore this association in human epidermal growth factor receptor 2 (HER2 ) -positive primary breast cancer in the context of a large, phase III adjuvant trial. Patients and Methods The ALTTO trial randomly assigned patients with HER2-positive breast cancer to receive 1 year of either trastuzumab alone, lapatinib alone, their sequence, or their combination. In this substudy, we evaluated whether patients with diabetes at study entry-with or without metformin treatment-were associated with different disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) compared with patients without diabetes. Results A total of 8,381 patients were included in the current analysis: 7,935 patients (94.7%) had no history of diabetes at diagnosis, 186 patients (2.2%) had diabetes with no metformin treatment, and 260 patients (3.1%) were diabetic and had been treated with metformin. Median follow-up was 4.5 years (0.16 to 6.31 years), at which 1,205 (14.38%), 929 (11.08%), and 528 (6.3%) patients experienced DFS, DDFS, and OS events, respectively. Patients with diabetes who had not been treated with metformin experienced worse DFS (multivariable hazard ratio [HR], 1.40; 95% CI, 1.01 to 1.94; P = .043), DDFS (multivariable HR, 1.56; 95% CI, 1.10 to 2.22; P = .013), and OS (multivariable HR, 1.87; 95% CI, 1.23 to 2.85; P = .004). This effect was limited to hormone receptor-positive patients. Whereas insulin treatment was associated with a detrimental effect, metformin had a salutary effect in patients with diabetes who had HER2-positive and hormone receptor-positive breast cancer. Conclusion Metformin may improve the worse prognosis that is associated with diabetes and insulin treatment, mainly in patients with primary HER2-positive and hormone receptor-positive breast cancer.

  11. Lapatinib and trastuzumab in combination with an aromatase inhibitor for the first-line treatment of metastatic hormone receptor-positive breast cancer which over-expresses human epidermal growth factor 2 (HER2): a systematic review and economic analysis.

    PubMed

    Fleeman, N; Bagust, A; Boland, A; Dickson, R; Dundar, Y; Moonan, M; Oyee, J; Blundell, M; Davis, H; Armstrong, A; Thorp, N

    2011-01-01

    Breast cancer is the uncontrolled, abnormal growth of malignant breast tissue affecting predominantly women. Metastatic breast cancer (mBC) is an advanced stage of the disease when the disease has spread beyond the original organ. Hormone receptor status and human epidermal growth factor 2 (HER2) status are two predictive factors that are taken into consideration when estimating the prognosis of patients with breast cancer. To review the clinical effectiveness and cost-effectiveness evidence base for lapatinib (LAP) in combination with an aromatase inhibitor (AI) and trastuzumab (TRA) in combination with an AI for the first-line treatment of patients who have hormone receptor-positive (HR+)/human epidermal growth factor 2-positive (HER2+) mBC. Relevant electronic databases and websites, including MEDLINE, EMBASE and the Cochrane Library, were searched until May 2010. Further data were derived from the manufacturers' submissions for LAP + AI and TRA + AI. A systematic review of the clinical effectiveness and cost-effectiveness of LAP + AI and TRA + AI was undertaken. As it was deemed inappropriate to compare LAP + AI with TRA + AI, two separate assessments of cost-effectiveness versus AIs alone were undertaken. Three trials were included in the systematic review [the patient populations of the efficacy and safety of lapatinib combined with letrozole (EGF30008) trial, the efficacy and safety of trastuzumab combined with anastrozole (TAnDEM) trial and the efficacy and safety of letrozole combined with trastuzumab (eLEcTRA) trial]. As a result of differences in the exclusion criteria and because one trial was halted prematurely, comparisons across trials were believed to be inappropriate and meta-analysis was not possible. Individually, however, the findings from the trials all suggest that LAP + AI or TRA + AI results in improved progression-free survival and/or time to progression when compared with AIs alone. The trials do not show a statistically significant

  12. Metastatic human epidermal growth factor 2 (HER2/neu) amplified breast cancer with acute fulminant hepatitis responding to trastuzumab, pertuzumab and carboplatin

    PubMed Central

    Macias, Mariela N; Shin, Daniel Sanghoon; Ledezma, Blanca; Sadeghi, Saeed

    2014-01-01

    A 30-year-old woman presented to an outside hospital with pain in the right upper abdomen. Imaging revealed over 100 liver lesions, the largest measuring 74 mm×71 mm, and multiple lytic bone lesions. An outpatient liver biopsy showed a poorly differentiated adenocarcinoma favouring a breast primary. The tumour was oestrogen and progesterone receptor negative, but human epidermal growth factor 2 (HER2/neu) amplified. In her second clinic visit she had decompensated liver failure manifested by new-onset ascites and jaundice. Initially, the chemotherapy plan was for docetaxel, pertuzumab and trastuzumab, but given her severe liver dysfunction we used a combination of carboplatin, pertuzumab and trastuzumab as an inpatient. She was hospitalised for 14 days and eventually discharged with a marked improvement of her symptoms and liver tests. She subsequently completed five outpatient chemotherapy cycles. We showed that carboplatin is a possible alternative to docetaxel when severe liver dysfunction precludes docetaxel's use in combination with pertuzumab and trastuzumab. PMID:24899001

  13. Metastatic human epidermal growth factor 2 (HER2/neu) amplified breast cancer with acute fulminant hepatitis responding to trastuzumab, pertuzumab and carboplatin.

    PubMed

    Macias, Mariela N; Shin, Daniel Sanghoon; Ledezma, Blanca; Sadeghi, Saeed

    2014-06-04

    A 30-year-old woman presented to an outside hospital with pain in the right upper abdomen. Imaging revealed over 100 liver lesions, the largest measuring 74 mm×71 mm, and multiple lytic bone lesions. An outpatient liver biopsy showed a poorly differentiated adenocarcinoma favouring a breast primary. The tumour was oestrogen and progesterone receptor negative, but human epidermal growth factor 2 (HER2/neu) amplified. In her second clinic visit she had decompensated liver failure manifested by new-onset ascites and jaundice. Initially, the chemotherapy plan was for docetaxel, pertuzumab and trastuzumab, but given her severe liver dysfunction we used a combination of carboplatin, pertuzumab and trastuzumab as an inpatient. She was hospitalised for 14 days and eventually discharged with a marked improvement of her symptoms and liver tests. She subsequently completed five outpatient chemotherapy cycles. We showed that carboplatin is a possible alternative to docetaxel when severe liver dysfunction precludes docetaxel's use in combination with pertuzumab and trastuzumab.

  14. Targeted Therapy for Breast Cancer Prevention

    PubMed Central

    den Hollander, Petra; Savage, Michelle I.; Brown, Powel H.

    2013-01-01

    With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer. PMID:24069582

  15. Estrogen Signaling via a Linear Pathway Involving Insulin-Like Growth Factor I Receptor, Matrix Metalloproteinases, and Epidermal Growth Factor Receptor to Activate Mitogen-Activated Protein Kinase in MCF-7 Breast Cancer Cells

    PubMed Central

    Song, Robert X.-D.; Zhang, Zhenguo; Chen, Yucai; Bao, Yongde; Santen, Richard J.

    2009-01-01

    We present an integrated model of an extranuclear, estrogen receptor-α (ERα)-mediated, rapid MAPK activation pathway in breast cancer cells. In noncancer cells, IGF-I initiates a linear process involving activation of the IGF-I receptor (IGF-IR) and matrix metalloproteinases (MMP), release of heparin-binding epidermal growth factor (HB-EGF), and activation of EGF receptor (EGFR)-dependent MAPK. 17β-Estradiol (E2) rapidly activates IGF-IR in breast cancer cells. We hypothesize that E2 induces a similar linear pathway involving IGF-IR, MMP, HB-EGF, EGFR, and MAPK. Using MCF-7 breast cancer cells, we for the first time demonstrated that a sequential activation of IGF-IR, MMP, and EGFR existed in E2 and IGF-I actions, which was supported by evidence that the selective inhibitors of IGF-IR and MMP or knockdown of IGF-IR all inhibited E2- or IGF-I-induced EGFR phosphorylation. Using the inhibitors and small inhibitoryRNA strategies,we also demonstrated that the same sequential activation of the receptors occurred in E2-, IGF-I-, but not EGF-induced MAPK phosphorylation. Additionally, a HB-EGF neutralizing antibody significantly blocked E2-induced MAPK activation, further supporting our hypothesis. The biological effects of sequential activation of IGF-IR and EGFR on E2 stimulation of cell proliferation were also investigated. Knockdown or blockade of IGF-IR significantly inhibited E2- or IGF-I-stimulated but not EGF-induced cell growth. Knockdown or blockade of EGFR abrogated cell growth induced by E2, IGF-I, and EGF, indicating that EGFR is a downstream molecule of IGF-IR in E2 and IGF-I action. Together, our data support the novel view that E2 can activate a linear pathway involving the sequential activation of IGF-IR, MMP, HB-EGF, EGFR, and MAPK. PMID:17525128

  16. Patient-reported outcomes from EMILIA, a randomized phase 3 study of trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2-positive locally advanced or metastatic breast cancer.

    PubMed

    Welslau, Manfred; Diéras, Veronique; Sohn, Joo-Hyuk; Hurvitz, Sara A; Lalla, Deepa; Fang, Liang; Althaus, Betsy; Guardino, Ellie; Miles, David

    2014-03-01

    This report describes the results of an analysis of patient-reported outcomes from EMILIA (TDM4370g/BO21977), a randomized phase 3 study of the antibody-drug conjugate trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer. A secondary endpoint of the EMILIA study was time to symptom worsening (time from randomization to the first documentation of a ≥ 5-point decrease from baseline) as measured by the Trial Outcome Index Physical/Functional/Breast (TOI-PFB) subset of the Functional Assessment of Cancer Therapy-Breast questionnaire. Predefined exploratory patient-reported outcome endpoints included proportion of patients with a clinically significant improvement in symptoms (per TOI-PFB) and proportion of patients with diarrhea symptoms (per Diarrhea Assessment Scale). In the T-DM1 arm, 450 of 495 patients had a baseline and ≥ 1 postbaseline TOI-PFB score versus 445 of 496 patients in the capecitabine-plus-lapatinib arm. Time to symptom worsening was delayed in the T-DM1 arm versus the capecitabine-plus-lapatinib arm (7.1 months versus 4.6 months, respectively; hazard ratio = 0.796; P = .0121). In the T-DM1 arm, 55.3% of patients developed clinically significant improvement in symptoms from baseline versus 49.4% in the capecitabine-plus-lapatinib arm (P = .0842). Although similar at baseline, the number of patients reporting diarrhea symptoms increased 1.5- to 2-fold during treatment with capecitabine and lapatinib but remained near baseline levels in the T-DM1 arm. Together with the EMILIA primary data, these results support the concept that T-DM1 has greater efficacy and tolerability than capecitabine plus lapatinib, which may translate into improvements in health-related quality of life. © 2013 American Cancer Society.

  17. Genetics Home Reference: breast cancer

    MedlinePlus

    ... cancers . A small percentage of all breast cancers cluster in families. These cancers are described as hereditary ... will develop breast cancer . Some breast cancers that cluster in families are associated with inherited mutations in ...

  18. Human epidermal growth factor receptor 4 (HER4) is a favorable prognostic marker of breast cancer: a systematic review and meta-analysis

    PubMed Central

    Wang, Jue; Yin, Jun; Yang, Qing; Ding, Feng; Chen, Xiao; Li, Bingjie; Tian, Xingsong

    2016-01-01

    Based on a large cohort of clinical studies involving a total of 8024 patients and reporting the effects of HER4 on breast cancer prognosis, we conducted the first meta-analysis and review of this type. We identified 26 studies published between 1985 and 2016 and assessed the prognostic value of HER4 in breast cancer by either real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR, for mRNA levels) or immunohistochemistry (IHC, for protein levels). Elevated expression of HER4 was significantly associated with longer relapse-free survival (RFS) (HR = 0.63; CI: 0.48−0.83; P = 0.001, random effects). Further subgroup analysis showed that our results were stable irrespective of subtype [Luminal: HR = 0.40, CI: 0.30−0.53, P < 0.001, fixed effects; triple negative breast cancer (TNBC): HR = 0.49, CI: 0.26−0.90, P = 0.02, fixed effects; and HER2-positive: HR = 0.53, CI: 0.40−0.71, P < 0.001, fixed effects]. Cytoplasmic HER4 was more effective than nuclear HER4 (HR = 0.74, CI: 0.60−0.92, P = 0.007, fixed effects) for predicting RFS. HER4 was also found to be a favorable prognostic marker for overall survival (OS) among patients with non-TNBC in the subgroup analysis (Luminal: HR = 0.71, CI: 0.52−0.95, P = 0.023, fixed effects; HER2-positive: HR = 0.48, CI: 0.26−0.89, P = 0.020, fixed effects). PMID:27736797

  19. Male Breast Cancer

    MedlinePlus

    ... or to other parts of the body. Where breast cancer begins in men Everyone is born with a ... skin around the nipple. Inherited genes that increase breast cancer risk Some men inherit abnormal (mutated) genes from ...

  20. Breast cancer staging

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000911.htm Breast cancer staging To use the sharing features on this ... Once your health care team knows you have breast cancer , they will do more tests to stage it. ...

  1. Breast Cancer Early Detection and Diagnosis

    MedlinePlus

    ... En Español Category Cancer A-Z Breast Cancer Breast Cancer Early Detection and Diagnosis Breast cancer is sometimes ... cancer screening is so important. Learn more. Can Breast Cancer Be Found Early? Breast cancer is sometimes found ...

  2. AR Signaling in Breast Cancer

    PubMed Central

    Rahim, Bilal; O’Regan, Ruth

    2017-01-01

    Androgen receptor (AR, a member of the steroid hormone receptor family) status has become increasingly important as both a prognostic marker and potential therapeutic target in breast cancer. AR is expressed in up to 90% of estrogen receptor (ER) positive breast cancer, and to a lesser degree, human epidermal growth factor 2 (HER2) amplified tumors. In the former, AR signaling has been correlated with a better prognosis given its inhibitory activity in estrogen dependent disease, though conversely has also been shown to increase resistance to anti-estrogen therapies such as tamoxifen. AR blockade can mitigate this resistance, and thus serves as a potential target in ER-positive breast cancer. In HER2 amplified breast cancer, studies are somewhat conflicting, though most show either no effect or are associated with poorer survival. Much of the available data on AR signaling is in triple-negative breast cancer (TNBC), which is an aggressive disease with inferior outcomes comparative to other breast cancer subtypes. At present, there are no approved targeted therapies in TNBC, making study of the AR signaling pathway compelling. Gene expression profiling studies have also identified a luminal androgen receptor (LAR) subtype that is dependent on AR signaling in TNBC. Regardless, there seems to be an association between AR expression and improved outcomes in TNBC. Despite lower pathologic complete response (pCR) rates with neoadjuvant therapy, patients with AR-expressing TNBC have been shown to have a better prognosis than those that are AR-negative. Clinical studies targeting AR have shown somewhat promising results. In this paper we review the literature on the biology of AR in breast cancer and its prognostic and predictive roles. We also present our thoughts on therapeutic strategies. PMID:28245550

  3. AR Signaling in Breast Cancer.

    PubMed

    Rahim, Bilal; O'Regan, Ruth

    2017-02-24

    Androgen receptor (AR, a member of the steroid hormone receptor family) status has become increasingly important as both a prognostic marker and potential therapeutic target in breast cancer. AR is expressed in up to 90% of estrogen receptor (ER) positive breast cancer, and to a lesser degree, human epidermal growth factor 2 (HER2) amplified tumors. In the former, AR signaling has been correlated with a better prognosis given its inhibitory activity in estrogen dependent disease, though conversely has also been shown to increase resistance to anti-estrogen therapies such as tamoxifen. AR blockade can mitigate this resistance, and thus serves as a potential target in ER-positive breast cancer. In HER2 amplified breast cancer, studies are somewhat conflicting, though most show either no effect or are associated with poorer survival. Much of the available data on AR signaling is in triple-negative breast cancer (TNBC), which is an aggressive disease with inferior outcomes comparative to other breast cancer subtypes. At present, there are no approved targeted therapies in TNBC, making study of the AR signaling pathway compelling. Gene expression profiling studies have also identified a luminal androgen receptor (LAR) subtype that is dependent on AR signaling in TNBC. Regardless, there seems to be an association between AR expression and improved outcomes in TNBC. Despite lower pathologic complete response (pCR) rates with neoadjuvant therapy, patients with AR-expressing TNBC have been shown to have a better prognosis than those that are AR-negative. Clinical studies targeting AR have shown somewhat promising results. In this paper we review the literature on the biology of AR in breast cancer and its prognostic and predictive roles. We also present our thoughts on therapeutic strategies.

  4. Immunophenotyping of male breast cancer.

    PubMed

    Kornegoor, Robert; Verschuur-Maes, Anoek H J; Buerger, Horst; Hogenes, Marieke C; de Bruin, Peter C; Oudejans, Joost J; Hinrichs, Bernd; van Diest, Paul J

    2012-12-01

    Male breast cancer is a rare disease, and knowledge of carcinogenesis is limited. Conflicting results, based on small series, have been reported for clinically relevant biomarkers. One hundred and thirty-four cases of male breast cancer were immunohistochemically stained on tissue microarrays for oestrogen receptor (ER), progesterone receptor (PR), androgen receptor, human epidermal growth factor receptor 2 (HER2), BRST2, cyclin D1, bcl-2, p53, p16, p21, Ki67, cytokeratin (CK) 5/6, CK14, and epidermal growth factor receptor. Data were correlated with clinicopathological features and patient outcome. High mitotic count and high grade were correlated with high Ki67, HER2 amplification/overexpression, p53 accumulation, high p21 expression, low PR expression, and low bcl-2 expression. PR negativity (P=0.009) and p53 accumulation (P=0.042) were correlated with decreased 5-year survival and were independent markers for patient outcome in Cox regression. In unsupervised hierarchical clustering, four groups were identified that were correlated with distinctive clinicopathological features. The hormone negative/ER-positive/high-grade cluster was significantly associated with decreased survival (P=0.011) and was an independent prognostic factor in Cox regression. Several tissue biomarkers are associated with an aggressive phenotype in male breast cancer. PR and p53 are the most promising individual prognostic markers. On the basis of immunophenotype, four distinctive and prognostically relevant male breast cancer groups were identified, indicating that protein expression profiling may be clinically useful in male breast cancer. © 2012 Blackwell Publishing Limited.

  5. Breast Cancer (For Kids)

    MedlinePlus

    ... With Breast Cancer Breast Cancer Prevention en español Cáncer de mama You may have heard about special events, like walks or races, to raise money for breast cancer research. Or maybe you've seen people wear ...

  6. Activating PIK3CA Mutations Induce an Epidermal Growth Factor Receptor (EGFR)/Extracellular Signal-regulated Kinase (ERK) Paracrine Signaling Axis in Basal-like Breast Cancer*

    PubMed Central

    Young, Christian D.; Zimmerman, Lisa J.; Hoshino, Daisuke; Formisano, Luigi; Hanker, Ariella B.; Gatza, Michael L.; Morrison, Meghan M.; Moore, Preston D.; Whitwell, Corbin A.; Dave, Bhuvanesh; Stricker, Thomas; Bhola, Neil E.; Silva, Grace O.; Patel, Premal; Brantley-Sieders, Dana M.; Levin, Maren; Horiates, Marina; Palma, Norma A.; Wang, Kai; Stephens, Philip J.; Perou, Charles M.; Weaver, Alissa M.; O'Shaughnessy, Joyce A.; Chang, Jenny C.; Park, Ben Ho; Liebler, Daniel C.; Cook, Rebecca S.; Arteaga, Carlos L.

    2015-01-01

    Mutations in PIK3CA, the gene encoding the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K) have been shown to transform human mammary epithelial cells (MECs). These mutations are present in all breast cancer subtypes, including basal-like breast cancer (BLBC). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 72 protein expression changes in human basal-like MECs with knock-in E545K or H1047R PIK3CA mutations versus isogenic MECs with wild-type PIK3CA. Several of these were secreted proteins, cell surface receptors or ECM interacting molecules and were required for growth of PIK3CA mutant cells as well as adjacent cells with wild-type PIK3CA. The proteins identified by MS were enriched among human BLBC cell lines and pointed to a PI3K-dependent amphiregulin/EGFR/ERK signaling axis that is activated in BLBC. Proteins induced by PIK3CA mutations correlated with EGFR signaling and reduced relapse-free survival in BLBC. Treatment with EGFR inhibitors reduced growth of PIK3CA mutant BLBC cell lines and murine mammary tumors driven by a PIK3CA mutant transgene, all together suggesting that PIK3CA mutations promote tumor growth in part by inducing protein changes that activate EGFR. PMID:25953087

  7. Activating PIK3CA Mutations Induce an Epidermal Growth Factor Receptor (EGFR)/Extracellular Signal-regulated Kinase (ERK) Paracrine Signaling Axis in Basal-like Breast Cancer.

    PubMed

    Young, Christian D; Zimmerman, Lisa J; Hoshino, Daisuke; Formisano, Luigi; Hanker, Ariella B; Gatza, Michael L; Morrison, Meghan M; Moore, Preston D; Whitwell, Corbin A; Dave, Bhuvanesh; Stricker, Thomas; Bhola, Neil E; Silva, Grace O; Patel, Premal; Brantley-Sieders, Dana M; Levin, Maren; Horiates, Marina; Palma, Norma A; Wang, Kai; Stephens, Philip J; Perou, Charles M; Weaver, Alissa M; O'Shaughnessy, Joyce A; Chang, Jenny C; Park, Ben Ho; Liebler, Daniel C; Cook, Rebecca S; Arteaga, Carlos L

    2015-07-01

    Mutations in PIK3CA, the gene encoding the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K) have been shown to transform human mammary epithelial cells (MECs). These mutations are present in all breast cancer subtypes, including basal-like breast cancer (BLBC). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 72 protein expression changes in human basal-like MECs with knock-in E545K or H1047R PIK3CA mutations versus isogenic MECs with wild-type PIK3CA. Several of these were secreted proteins, cell surface receptors or ECM interacting molecules and were required for growth of PIK3CA mutant cells as well as adjacent cells with wild-type PIK3CA. The proteins identified by MS were enriched among human BLBC cell lines and pointed to a PI3K-dependent amphiregulin/EGFR/ERK signaling axis that is activated in BLBC. Proteins induced by PIK3CA mutations correlated with EGFR signaling and reduced relapse-free survival in BLBC. Treatment with EGFR inhibitors reduced growth of PIK3CA mutant BLBC cell lines and murine mammary tumors driven by a PIK3CA mutant transgene, all together suggesting that PIK3CA mutations promote tumor growth in part by inducing protein changes that activate EGFR. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Differential sensitivities of trastuzumab (Herceptin)-resistant human breast cancer cells to phosphoinositide-3 kinase (PI-3K) and epidermal growth factor receptor (EGFR) kinase inhibitors.

    PubMed

    Chan, Carmel T; Metz, Marianne Z; Kane, Susan E

    2005-05-01

    Her2 (erbB2/neu) is overexpressed in 25-30% of human breast cancers. Herceptin is a recombinant humanized Her2 antibody used to treat breast cancer patients with Her2 overexpression. Over a 5-month selection process, we isolated clones of BT474 (BT) human breast carcinoma cells (BT/Her(R)) that were resistant to Herceptin in vitro. In BT/Her(R) subclones, cell-surface, phosphorylated and total cellular Her2 protein remained high in the continuous presence of Herceptin. Likewise, the levels of cell-surface, phosphorylated, and total cellular Her3 and EGFR were either unchanged or only slightly elevated in BT/Her(R) subclones relative to BT cells. One BT/Her(R) subclone had substantially upregulated cell-surface EGFR, but this did not correlate with a higher relative resistance to Herceptin. In looking at the downstream PI-3K/Akt signaling pathway, phosphorylated and total Akt levels and Akt kinase activities were all sustained in BT/Her(R) subclones in the presence of Herceptin, but significantly downregulated in BT cells exposed to Herceptin. Whereas BT cells lost sensitivity to the PI-3K inhibitor LY294002 in the presence of Herceptin, BT/Her(R) subclones were equally sensitive to this agent in the presence and absence of Herceptin. This suggests that BT/Her(R) subclones acquired a Herceptin-resistant mechanism of PI-3K signaling. BT/Her(R) subclones were also sensitive to the EGFR kinase inhibitor AG1478 in the presence of Herceptin, to the same extent as BT cells. The BT/Her(R) subclones provide new insights into mechanisms of Herceptin resistance and suggest new treatment strategies in combination with other inhibitors targeted to signal transduction pathways.

  9. Breast Cancer Rates by State

    MedlinePlus

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Breast Cancer Rates by State Language: English Español (Spanish) Recommend ... from breast cancer each year. Rates of Getting Breast Cancer by State The number of people who get ...

  10. Pembrolizumab in Treating Patients With Triple-Negative Breast Cancer

    ClinicalTrials.gov

    2017-10-12

    Estrogen Receptor Negative; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

  11. Absolute Benefit of Adjuvant Endocrine Therapies for Premenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Early Breast Cancer: TEXT and SOFT Trials

    PubMed Central

    Francis, Prudence A.; Pagani, Olivia; Fleming, Gini F.; Walley, Barbara A.; Viale, Giuseppe; Colleoni, Marco; Láng, István; Gómez, Henry L.; Tondini, Carlo; Pinotti, Graziella; Price, Karen N.; Coates, Alan S.; Goldhirsch, Aron; Gelber, Richard D.

    2016-01-01

    Purpose Risk of recurrence is the primary consideration in breast cancer adjuvant therapy recommendations. The TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor–positive breast cancer, testing exemestane plus ovarian function suppression (OFS), tamoxifen plus OFS, and tamoxifen alone. We examined absolute treatment effect across a continuum of recurrence risk to individualize endocrine therapy decision making for premenopausal women with human epidermal growth factor receptor 2 (HER2) –negative disease. Patients and Methods The TEXT and SOFT hormone receptor–positive, HER2-negative analysis population included 4,891 women. The end point was breast cancer–free interval (BCFI), defined as time from random assignment to first occurrence of invasive locoregional, distant, or contralateral breast cancer. A continuous, composite measure of recurrence risk for each patient was determined from a Cox model incorporating age, nodal status, tumor size and grade, and estrogen receptor, progesterone receptor, and Ki-67 expression levels. Subpopulation treatment effect pattern plot methodology revealed differential treatment effects on 5-year BCFI according to composite risk. Results SOFT patients who remained premenopausal after chemotherapy experienced absolute improvement of 5% or more in 5-year BCFI with exemestane plus OFS versus tamoxifen plus OFS or tamoxifen alone, reaching 10% to 15% at intermediate to high composite risk; the benefit of tamoxifen plus OFS versus tamoxifen alone was apparent at the highest composite risk. The SOFT no-chemotherapy cohort—for whom composite risk was lowest on average—did well with all endocrine therapies. For TEXT patients, the benefit of exemestane plus OFS versus tamoxifen plus OFS in 5-year BCFI ranged from 5% to 15%; patients not receiving chemotherapy and with lowest composite risk did well

  12. Curcumin in Treating Breast Cancer: A Review.

    PubMed

    Wang, Yiwei; Yu, Jiayi; Cui, Ran; Lin, Jinjin; Ding, Xianting

    2016-12-01

    Breast cancer is among the most common malignant tumors. It is the second leading cause of cancer mortality among women in the United States. Curcumin, an active derivative from turmeric, has been reported to have anticancer and chemoprevention effects on breast cancer. Curcumin exerts its anticancer effect through a complicated molecular signaling network, involving proliferation, estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2) pathways. Experimental evidence has shown that curcumin also regulates apoptosis and cell phase-related genes and microRNA in breast cancer cells. Herein, we review the recent research efforts in understanding the molecular targets and anticancer mechanisms of curcumin in breast cancer. © 2016 Society for Laboratory Automation and Screening.

  13. Male Breast Cancer

    PubMed Central

    Yalaza, Metin; İnan, Aydın; Bozer, Mikdat

    2016-01-01

    Male breast cancer (MBC) is a rare disease, accounting for less than 1% of all breast cancer diagnoses worldwide. Although breast carcinomas share certain characteristics in both genders, there are notable differences. Most studies on men with breast cancer are very small. Thus, most data on male breast cancer are derived from studies on females. However, when a number of these small studies are grouped together, we can learn more from them. This review emphasizes the incidence, etiology, clinical features, diagnosis, treatment, pathology, survival, and prognostic factors related to MBC.

  14. Clinical effects of prior trastuzumab on combination eribulin mesylate plus trastuzumab as first-line treatment for human epidermal growth factor receptor 2 positive locally recurrent or metastatic breast cancer: results from a Phase II, single-arm, multicenter study

    PubMed Central

    Puhalla, Shannon; Wilks, Sharon; Brufsky, Adam M; O’Shaughnessy, Joyce; Schwartzberg, Lee S; Berrak, Erhan; Song, James; Vahdat, Linda

    2016-01-01

    Eribulin mesylate, a novel nontaxane microtubule dynamics inhibitor in the halichondrin class of antineoplastic drugs, is indicated for the treatment of patients with metastatic breast cancer who previously received ≥2 chemotherapy regimens in the metastatic setting. Primary data from a Phase II trial for the first-line combination of eribulin plus trastuzumab in human epidermal growth factor receptor 2 positive patients showed a 71% objective response rate and tolerability consistent with the known profile of these agents. Here, we present prespecified analyses of efficacy of this combination based on prior trastuzumab use. Patients received eribulin mesylate 1.4 mg/m2 (equivalent to 1.23 mg/m2 eribulin [expressed as free base]) intravenously on days 1 and 8 plus trastuzumab (8 mg/kg intravenously/cycle 1, then 6 mg/kg) on day 1 of each 21-day cycle. Objective response rates, progression-free survival, and tolerability were assessed in patients who had and had not received prior adjuvant or neoadjuvant (neo/adjuvant) trastuzumab treatment. Fifty-two patients (median age: 59.5 years) received eribulin/trastuzumab for a median treatment duration of ~31 weeks; 40.4% (n=21) had been previously treated with neo/adjuvant trastuzumab prior to treatment with eribulin plus trastuzumab for metastatic disease (median time between neo/adjuvant and study treatment: 23 months). In trastuzumab-naïve patients (n=31) compared with those who had received prior trastuzumab, objective response rate was 77.4% versus 61.9%, respectively; duration of response was 11.8 versus 9.5 months, respectively; clinical benefit rate was 87.1% versus 81.0%, respectively; and median progression-free survival was 12.2 versus 11.5 months, respectively. The most common grade 3/4 treatment-emergent adverse events (occuring in ≥5% of patients) in patients who received prior trastuzumab versus trastuzumab naïve patients, respectively, were neutropenia (47.6% vs 32.3%), peripheral neuropathy (14

  15. Inflammatory Breast Cancer

    MedlinePlus

    ... red, or inflamed. Inflammatory breast cancer is rare, accounting for 1 to 5 percent of all breast ... Publications Site Map Digital Standards for NCI Websites POLICIES Accessibility Comment Policy Disclaimer FOIA Privacy & Security Reuse & ...

  16. Living as a Breast Cancer Survivor

    MedlinePlus

    ... a Breast Cancer Survivor Follow up Care After Breast Cancer Treatment Many women are relieved or excited to ... Menopausal Hormone Therapy After Breast Cancer More In Breast Cancer About Breast Cancer Risk and Prevention Early Detection ...

  17. Treating Male Breast Cancer by Stage

    MedlinePlus

    ... Men Treating Breast Cancer in Men Treatment of Breast Cancer in Men, by Stage Because there have been ... Doctor About Breast Cancer in Men? More In Breast Cancer In Men About Breast Cancer in Men Causes, ...

  18. Breast Cancer Risk in American Women

    MedlinePlus

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Risk in American Women On This Page What ... risk of developing the disease. Personal history of breast cancer : Women who have had breast cancer are more ...

  19. Do We Know What Causes Breast Cancer?

    MedlinePlus

    ... Research? Breast Cancer About Breast Cancer How Does Breast Cancer Form? Changes or mutations in DNA can cause ... please see our Content Usage Policy . More In Breast Cancer About Breast Cancer Risk and Prevention Early Detection ...

  20. Surgery for Breast Cancer in Men

    MedlinePlus

    ... Men Treating Breast Cancer in Men Surgery for Breast Cancer in Men The thought of surgery can be ... Doctor About Breast Cancer in Men? More In Breast Cancer In Men About Breast Cancer in Men Causes, ...

  1. Breast Cancer and Bone Loss

    MedlinePlus

    ... Menopause Map Featured Resource Find an Endocrinologist Search Breast Cancer and Bone Loss July 2010 Download PDFs English ... G. Komen Foundation What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  2. Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2–Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study

    PubMed Central

    Barrios, Carlos; Eiermann, Wolfgang; Toi, Masakazu; Im, Young-Hyuck; Conte, Pierfranco; Martin, Miguel; Pienkowski, Tadeusz; Pivot, Xavier; Burris, Howard; Petersen, Jennifer A.; Stanzel, Sven; Strasak, Alexander; Patre, Monika; Ellis, Paul

    2017-01-01

    Purpose Trastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) –targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody–drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study. Methods In the MARIANNE study, 1,095 patients with centrally assessed, HER2-positive, advanced breast cancer and no prior therapy for advanced disease were randomly assigned 1:1:1 to control (trastuzumab plus taxane), T-DM1 plus placebo, hereafter T-DM1, or T-DM1 plus pertuzumab at standard doses. Primary end point was progression-free survival (PFS), as assessed by independent review. Results T-DM1 and T-DM1 plus pertuzumab showed noninferior PFS compared with trastuzumab plus taxane (median PFS: 13.7 months with trastuzumab plus taxane, 14.1 months with T-DM1, and 15.2 months with T-DM1 plus pertuzumab). Neither experimental arm showed PFS superiority to trastuzumab plus taxane. Response rate was 67.9% in patients who were treated with trastuzumab plus taxane, 59.7% with T-DM1, and 64.2% with T-DM1 plus pertuzumab; median response duration was 12.5 months, 20.7 months, and 21.2 months, respectively. The incidence of grade ≥ 3 adverse events was numerically higher in the control arm (54.1%) versus the T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%). Numerically fewer patients discontinued treatment because of adverse events in the T-DM1 arms, and health-related quality of life was maintained for longer in the T-DM1 arms. Conclusion T-DM1 showed noninferior, but not superior, efficacy and better tolerability than did taxane plus trastuzumab for first-line treatment of HER2-positive, advanced breast

  3. Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2-Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study.

    PubMed

    Perez, Edith A; Barrios, Carlos; Eiermann, Wolfgang; Toi, Masakazu; Im, Young-Hyuck; Conte, Pierfranco; Martin, Miguel; Pienkowski, Tadeusz; Pivot, Xavier; Burris, Howard; Petersen, Jennifer A; Stanzel, Sven; Strasak, Alexander; Patre, Monika; Ellis, Paul

    2017-01-10

    Purpose Trastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) -targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study. Methods In the MARIANNE study, 1,095 patients with centrally assessed, HER2-positive, advanced breast cancer and no prior therapy for advanced disease were randomly assigned 1:1:1 to control (trastuzumab plus taxane), T-DM1 plus placebo, hereafter T-DM1, or T-DM1 plus pertuzumab at standard doses. Primary end point was progression-free survival (PFS), as assessed by independent review. Results T-DM1 and T-DM1 plus pertuzumab showed noninferior PFS compared with trastuzumab plus taxane (median PFS: 13.7 months with trastuzumab plus taxane, 14.1 months with T-DM1, and 15.2 months with T-DM1 plus pertuzumab). Neither experimental arm showed PFS superiority to trastuzumab plus taxane. Response rate was 67.9% in patients who were treated with trastuzumab plus taxane, 59.7% with T-DM1, and 64.2% with T-DM1 plus pertuzumab; median response duration was 12.5 months, 20.7 months, and 21.2 months, respectively. The incidence of grade ≥ 3 adverse events was numerically higher in the control arm (54.1%) versus the T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%). Numerically fewer patients discontinued treatment because of adverse events in the T-DM1 arms, and health-related quality of life was maintained for longer in the T-DM1 arms. Conclusion T-DM1 showed noninferior, but not superior, efficacy and better tolerability than did taxane plus trastuzumab for first-line treatment of HER2-positive, advanced breast

  4. Development of a human epidermal growth factor derivative with EGFR-blocking and depleted biological activities: A comparative in vitro study using EGFR-positive breast cancer cells.

    PubMed

    Mehrabi, Masomeh; Mansouri, Kamran; Soleymani, Bijan; Hoseinkhani, Zohreh; Shahlaie, Mohsen; Khodarahmi, Reza

    2017-10-01

    Epidermal growth factor (EGF) is a local growth factor that stimulates cell growth, proliferation, and differentiation by binding to its receptor EGFR. EGF and EGFR are involved in many aspects of the development of carcinomas. Because EGFR has been found to be over-expressed in many tumors of epithelial origin, it is a potential target for antitumor therapy. In this study we designed a mutated form of hEGF (mEGF) with a deletion of four amino acids residues (Gln(43), Tyr(44), Arg(45) and Asp(46)) in order to show importance of Leu spatial location for EGFR binding/activation. Expression vector pET32a(+) and E. Coli, strain Rosetta-gami B (DE3) were used to enhance solubility of the recombinant protein with yielding approximately 10mg/l of cell culture. The purified cleaved hEGF as well as non-cleaved fusion protein were biologically active, which was confirmed by their equal ability to stimulate proliferation of MCF7 cells. The mEGF showed specificity and high affinity for EGFR binding, however binding affinity of mEGF for EGFR was reduced about 11.5 fold compared with that of hEGF. The mEGF effect on the MCF7 cell proliferation had a relatively different outcome; mEGF simulated differential cell growth in a dose dependent manner. On the other hand, in MDA-MB468 cells, hEGF and mEGF induced growth inhibition, which was much more severe for hEGF than that of mEGF. Also, hEGF strongly induced the phosphorylation of EGF receptor in MDA-MB468 cells while mEGF induced poor EGFR phosphorylation. The same observations were also made for migration of cancer cells, especially induction of MDA-MB468 migration by mEGF was significantly lower than that of hEGF, suggesting a connection between tyrosine phosphorylation of EGFR and cell migration. Docking analysis revealed that the binding affinity and the buried surface area of mEGF to EGFR complex are lower than those of hEGF/EGFR. Although theoretical studies confirmed reduction in mEGF-EGFR binding affinity, the data of the

  5. Economic evaluation of the 70-gene prognosis-signature (MammaPrint®) in hormone receptor-positive, lymph node-negative, human epidermal growth factor receptor type 2-negative early stage breast cancer in Japan.

    PubMed

    Kondo, Masahide; Hoshi, Shu-Ling; Ishiguro, Hiroshi; Toi, Masakazu

    2012-06-01

    The 70-gene prognosis-signature is validated as a good predictor of recurrence for hormone receptor-positive (ER+), lymph node-negative (LN-), human epidermal growth factor receptor type 2-negative (HER2-) early stage breast cancer (ESBC) in Japanese patient population. Its high cost and potential in avoiding unnecessary adjuvant chemotherapy arouse interest in its economic impact. This study evaluates the cost-effectiveness of including the assay into Japan's social health insurance benefit package. An economic decision tree and Markov model under Japan's health system from the societal perspective is constructed with clinical evidence from the pool analysis of validation studies. One-way sensitivity analyses are also performed. Incremental cost-effectiveness ratio is estimated as ¥3,873,922/quality adjusted life year (QALY) (US$43,044/QALY), which is not more than the suggested social willingness-to-pay for one QALY gain from an innovative medical intervention in Japan, ¥5,000,000/QALY (US$55,556/QALY). However, sensitivity analyses show the instability of this estimation. The introduction of the assay into Japanese practice of ER+, LN-, HER2- ESBC treatment by including it to Japan's social health insurance benefit package has a reasonable chance to be judged as cost-effective and may be justified as an efficient deployment of finite health care resources.

  6. Defining the cellular precursors to human breast cancer

    PubMed Central

    Keller, Patricia J.; Arendt, Lisa M.; Skibinski, Adam; Logvinenko, Tanya; Klebba, Ina; Dong, Shumin; Smith, Avi E.; Prat, Aleix; Perou, Charles M.; Gilmore, Hannah; Schnitt, Stuart; Naber, Stephen P.; Garlick, Jonathan A.; Kuperwasser, Charlotte

    2012-01-01

    Human breast cancers are broadly classified based on their gene-expression profiles into luminal- and basal-type tumors. These two major tumor subtypes express markers corresponding to the major differentiation states of epithelial cells in the breast: luminal (EpCAM+) and basal/myoepithelial (CD10+). However, there are also rare types of breast cancers, such as metaplastic carcinomas, where tumor cells exhibit features of alternate cell types that no longer resemble breast epithelium. Until now, it has been difficult to identify the cell type(s) in the human breast that gives rise to these various forms of breast cancer. Here we report that transformation of EpCAM+ epithelial cells results in the formation of common forms of human breast cancer, including estrogen receptor-positive and estrogen receptor-negative tumors with luminal and basal-like characteristics, respectively, whereas transformation of CD10+ cells results in the development of rare metaplastic tumors reminiscent of the claudin-low subtype. We also demonstrate the existence of CD10+ breast cells with metaplastic traits that can give rise to skin and epidermal tissues. Furthermore, we show that the development of metaplastic breast cancer is attributable, in part, to the transformation of these metaplastic breast epithelial cells. These findings identify normal cellular precursors to human breast cancers and reveal the existence of a population of cells with epidermal progenitor activity within adult human breast tissues. PMID:21940501

  7. Targeted anti-HER2 cancer therapy in elderly women diagnosed with breast cancer.

    PubMed

    Molina-Garrido, M J; Guillen-Ponce, C; Mora-Rufete, A

    2014-06-01

    Trastuzumab or lapatinib treatment with chemotherapy or hormonotherapy are the gold standard treatments for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (early breast cancer or metastatic breast cancer). Older patients have been largely underrepresented in clinical trials, and few data on trastuzumab or lapatinib efficacy and toxicity have been reported for this subgroup. This article has reviewed the main articles that have analyzed these items.

  8. TBCRC 008: Early Change in 18F-FDG Uptake on PET Predicts Response to Preoperative Systemic Therapy in Human Epidermal Growth Factor Receptor 2–Negative Primary Operable Breast Cancer

    PubMed Central

    Connolly, Roisin M.; Leal, Jeffrey P.; Goetz, Matthew P.; Zhang, Zhe; Zhou, Xian C.; Jacobs, Lisa K.; Mhlanga, Joyce; Joo, H O; Carpenter, John; Storniolo, Anna Maria; Watkins, Stanley; Fetting, John H.; Miller, Robert S.; Sideras, Kostandinos; Jeter, Stacie C.; Walsh, Bridget; Powers, Penny; Zorzi, Jane; Boughey, Judy C.; Davidson, Nancy E.; Carey, Lisa A.; Wolff, Antonio C.; Khouri, Nagi; Gabrielson, Edward; Wahl, Richard L.; Stearns, Vered

    2015-01-01

    Epigenetic modifiers, including the histone deacetylase inhibitor vorinostat, may sensitize tumors to chemotherapy and enhance outcomes. We conducted a multicenter randomized phase II neo-adjuvant trial of carboplatin and nanoparticle albumin-bound paclitaxel (CP) with vorinostat or placebo in women with stage II/III, human epidermal growth factor receptor 2 (HER2)–negative breast cancer, in which we also examined whether change in maximum standardized uptake values corrected for lean body mass (SULmax) on 18F-FDG PET predicted pathologic complete response (pCR) in breast and axillary lymph nodes. Methods Participants were randomly assigned to 12 wk of preoperative carboplatin (area under the curve of 2, weekly) and nab-paclitaxel (100 mg/m2 weekly) with vorinostat (400 mg orally daily, days 1–3 of every 7-d period) or placebo. All patients underwent 18F-FDG PET and research biopsy at baseline and on cycle 1 day 15. The primary endpoint was the pCR rate. Secondary objectives included correlation of change in tumor SULmax on 18F-FDG PET by cycle 1 day 15 with pCR and correlation of baseline and change in Ki-67 with pCR. Results In an intent-to-treat analysis (n = 62), overall pCR was 27.4% (vorinostat, 25.8%; placebo, 29.0%). In a pooled analysis (n = 59), we observed a significant difference in median change in SULmax 15 d after initiating preoperative therapy between those achieving pCR versus not (percentage reduction, 63.0% vs. 32.9%; P = 0.003). Patients with 50% or greater reduction in SULmax were more likely to achieve pCR, which remained statistically significant in multivariable analysis including estrogen receptor status (odds ratio, 5.1; 95% confidence interval, 1.3–22.7; P = 0.023). Differences in baseline and change in Ki-67 were not significantly different between those achieving pCR versus not. Conclusion Preoperative CP with vorinostat or placebo is associated with similar pCR rates. Early change in SULmax on 18F-FDG PET 15 d after the

  9. Carboplatin and Eribulin Mesylate in Triple Negative Breast Cancer Patients

    ClinicalTrials.gov

    2016-06-30

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast 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; Triple-negative Breast Cancer

  10. Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes.

    PubMed

    Dai, Xiaofeng; Xiang, Liangjian; Li, Ting; Bai, Zhonghu

    2016-01-01

    Breast cancer is a complex disease encompassing multiple tumor entities, each characterized by distinct morphology, behavior and clinical implications. Besides estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, novel biomarkers have shown their prognostic and predictive values, complicating our understanding towards to the heterogeneity of such cancers. Ten cancer hallmarks have been proposed by Weinberg to characterize cancer and its carcinogenesis. By reviewing biomarkers and breast cancer molecular subtypes, we propose that the divergent outcome observed from patients stratified by hormone status are driven by different cancer hallmarks. 'Sustaining proliferative signaling' further differentiates cancers with positive hormone receptors. 'Activating invasion and metastasis' and 'evading immune destruction' drive the differentiation of triple negative breast cancers. 'Resisting cell death', 'genome instability and mutation' and 'deregulating cellular energetics' refine breast cancer classification with their predictive values. 'Evading growth suppressors', 'enabling replicative immortality', 'inducing angiogenesis' and 'tumor-promoting inflammation' have not been involved in breast cancer classification which need more focus in the future biomarker-related research. This review novels in its global view on breast cancer heterogeneity, which clarifies many confusions in this field and contributes to precision medicine.

  11. Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes

    PubMed Central

    Dai, Xiaofeng; Xiang, Liangjian; Li, Ting; Bai, Zhonghu

    2016-01-01

    Breast cancer is a complex disease encompassing multiple tumor entities, each characterized by distinct morphology, behavior and clinical implications. Besides estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, novel biomarkers have shown their prognostic and predictive values, complicating our understanding towards to the heterogeneity of such cancers. Ten cancer hallmarks have been proposed by Weinberg to characterize cancer and its carcinogenesis. By reviewing biomarkers and breast cancer molecular subtypes, we propose that the divergent outcome observed from patients stratified by hormone status are driven by different cancer hallmarks. 'Sustaining proliferative signaling' further differentiates cancers with positive hormone receptors. 'Activating invasion and metastasis' and 'evading immune destruction' drive the differentiation of triple negative breast cancers. 'Resisting cell death', 'genome instability and mutation' and 'deregulating cellular energetics' refine breast cancer classification with their predictive values. 'Evading growth suppressors', 'enabling replicative immortality', 'inducing angiogenesis' and 'tumor-promoting inflammation' have not been involved in breast cancer classification which need more focus in the future biomarker-related research. This review novels in its global view on breast cancer heterogeneity, which clarifies many confusions in this field and contributes to precision medicine. PMID:27390604

  12. Breast cancer statistics, 2011.

    PubMed

    DeSantis, Carol; Siegel, Rebecca; Bandi, Priti; Jemal, Ahmedin

    2011-01-01

    In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including trends in incidence, mortality, survival, and screening. Approximately 230,480 new cases of invasive breast cancer and 39,520 breast cancer deaths are expected to occur among US women in 2011. Breast cancer incidence rates were stable among all racial/ethnic groups from 2004 to 2008. Breast cancer death rates have been declining since the early 1990s for all women except American Indians/Alaska Natives, among whom rates have remained stable. Disparities in breast cancer death rates are evident by state, socioeconomic status, and race/ethnicity. While significant declines in mortality rates were observed for 36 states and the District of Columbia over the past 10 years, rates for 14 states remained level. Analyses by county-level poverty rates showed that the decrease in mortality rates began later and was slower among women residing in poor areas. As a result, the highest breast cancer death rates shifted from the affluent areas to the poor areas in the early 1990s. Screening rates continue to be lower in poor women compared with non-poor women, despite much progress in increasing mammography utilization. In 2008, 51.4% of poor women had undergone a screening mammogram in the past 2 years compared with 72.8% of non-poor women. Encouraging patients aged 40 years and older to have annual mammography and a clinical breast examination is the single most important step that clinicians can take to reduce suffering and death from breast cancer. Clinicians should also ensure that patients at high risk of breast cancer are identified and offered appropriate screening and follow-up. Continued progress in the control of breast cancer will require sustained and increased efforts to provide high-quality screening, diagnosis, and treatment to all segments of the population.

  13. Lapatinib-associated mucocutaneous toxicities are clinical predictors of improved progression-free survival in patients with human epidermal growth factor receptor (HER2)-positive advanced breast cancer.

    PubMed

    Araki, Kazuhiro; Fukada, Ippei; Horii, Rie; Takahashi, Shunji; Akiyama, Futoshi; Iwase, Takuji; Ito, Yoshinori

    2014-11-01

    This study is aimed to identify clinical predictors, other than HER2 overexpression, for the response to lapatinib plus capecitabine (LAPCAP) in patients with HER2-positive advanced breast cancer (HER2ABC). Data from our medical records of 76 patients from June 2009 to March 2013 were analyzed. Evaluations of these patients with HER2ABC treated with LAPCAP included baseline characteristics, dose modifications, efficacy, and incidence of adverse events (AEs). With a median follow-up of 20 months, the median number of prior therapies for ABC before LAPCAP was 2 (range 0-13), and 66 patients had previously received trastuzumab. For LAPCAP, the overall response rate was 21 %, and the clinical benefit rate was 60 %. During the initial 12-month observation period, 93 % of patients had AEs. The most common AE was hand-foot syndrome (HFS) in 55 patients. Progression-free survival (PFS) was better in patients who had HFS than in those who did not (p = 0.0002). Since HFS is a well-known AE associated with CAP, whether CAP dose affected PFS or not was investigated, but no positive relationship was found. Since several studies with EGFR-targeted agents have suggested a positive correlation between cutaneous toxicities and outcomes, whether the incidence of any AEs affected PFS or not was explored among 76 patients. HFS, diarrhea, and rash were significant favorable factors (p = 0.0002, 0.0088, and 0.0011). The median PFS of patients who had all three AEs was 13.2 months, compared with 2.6 months for those who did not (p = 0.00000174). Mucocutaneous toxicities may be predictors of the response to LAP in patients with HER2ABC.

  14. Metastatic Breast Cancer, Version 1.2012

    PubMed Central

    Carlson, Robert W.; Allred, D. Craig; Anderson, Benjamin O.; Burstein, Harold J.; Edge, Stephen B.; Farrar, William B.; Forero, Andres; Giordano, Sharon Hermes; Goldstein, Lori J.; Gradishar, William J.; Hayes, Daniel F.; Hudis, Clifford A.; Isakoff, Steven Jay; Ljung, Britt-Marie E.; Mankoff, David A.; Marcom, P. Kelly; Mayer, Ingrid A.; McCormick, Beryl; Pierce, Lori J.; Reed, Elizabeth C.; Smith, Mary Lou; Soliman, Hatem; Somlo, George; Theriault, Richard L.; Ward, John H.; Wolff, Antonio C.; Zellars, Richard; Kumar, Rashmi; Shead, Dorothy A.

    2013-01-01

    These NCCN Guidelines Insights highlight the important updates/changes specific to the management of metastatic breast cancer in the 2012 version of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer. These changes/updates include the issue of retesting of biomarkers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2) on recurrent disease, new information regarding first-line combination endocrine therapy for metastatic disease, a new section on monitoring of patients with metastatic disease, and new information on endocrine therapy combined with an mTOR inhibitor as a subsequent therapeutic option. PMID:22773798

  15. BREAST CANCER AND EXERCISE

    ClinicalTrials.gov

    2008-03-19

    Prevent Osteoporosis and Osteoporotic Fractures; Improve Quality of Life; Improve Weight Control, and Muscular and Cardiovascular Fitness; Help the Patients to Return to Working Life; Reduce the Risk of Breast Cancer Recurrence; Prevent Other Diseases and Reduce All-Cause Mortality in Patients With Primary Breast Cancer.

  16. Global breast cancer seasonality.

    PubMed

    Oh, Eun-Young; Ansell, Christine; Nawaz, Hamayun; Yang, Chul-Ho; Wood, Patricia A; Hrushesky, William J M

    2010-08-01

    Human breast cancer incidence has seasonal patterns that seem to vary among global populations. The aggregate monthly frequency of breast cancer diagnosis was collected and examined for 2,921,714 breast cancer cases diagnosed across 64 global regions over spans from 2 to 53 years. Breast cancer is consistently diagnosed more often in spring and fall, both in the Northern and Southern Hemispheres, regardless of presumable menopausal status (50). This seasonality is increasingly more prominent as population distance from the equator increases and this latitude dependence is most pronounced among women living in rural areas. Moreover, the overall annual incidence (2005-2006), per 100,000 population, of breast cancer increased as the latitude of population residence increased. These data make it clear that human breast cancer discovery occurs non-randomly throughout each year with peaks near both equinoxes and valleys near both solstices. This stable global breast cancer seasonality has implications for better prevention, more accurate screening, earlier diagnosis, and more effective treatment. This complex latitude-dependent breast cancer seasonality is clearly related to predictable local day/night length changes which occur seasonally. Its mechanism may depend upon seasonal sunlight mediation of vitamin D and seasonal mediation of nocturnal melatonin peak level and duration.

  17. Synchronous bilateral breast cancer in a male

    PubMed Central

    Rubio Hernández, María Caridad; Díaz Prado, Yenia Ivet; Pérez, Suanly Rodríguez; Díaz, Ronald Rodríguez; Aleaga, Zaili Gutiérrez

    2013-01-01

    Male breast cancer, which represents only 1% of all breast cancers, is occasionally associated with a family history of breast cancer. Sporadic male breast cancers presenting with another primary breast cancer are extremely rare. In this article, we report on a 70-year-old male patient with bilateral multifocal and synchronous breast cancer and without a family history of breast cancer. PMID:24319497

  18. CDC Vital Signs: Breast Cancer

    MedlinePlus

    ... 2.65 MB] Read the MMWR Science Clips Breast Cancer Black Women Have Higher Death Rates from Breast ... of Page U.S. State Info Number of Additional Breast Cancer Deaths Among Black Women, By State SOURCE: National ...

  19. Stages of Male Breast Cancer

    MedlinePlus

    ... spread outside the breast . In stage IB , small clusters of breast cancer cells (larger than 0.2 ... centimeters but not larger than 5 centimeters. Small clusters of breast cancer cells (larger than 0.2 ...

  20. FOXC1 identifies basal-like breast cancer in a hereditary breast cancer cohort

    PubMed Central

    Johnson, Jeff; Choi, Michael; Dadmanesh, Farnaz; Han, Bingchen; Qu, Ying; Yu-Rice, Yi; Zhang, Xiao; Bagaria, Sanjay; Taylor, Clive; Giuliano, Armando E.; Amersi, Farin; Cui, Xiaojiang

    2016-01-01

    Breast cancers arising in the setting of the hereditary breast cancer genes BRCA1 and BRCA2 are most commonly classified as basal-like breast cancer (BLBC) or luminal breast cancer, respectively. BLBC is an aggressive subtype of breast cancer associated with liver and lung metastases and poorer prognosis than other subtypes and for which chemotherapy is the only systemic therapy. Multiple immunohistochemical markers are used to identify the basal-like subtype, including the absence of estrogen receptor alpha, progesterone receptor, and human epidermal growth factor receptor 2. Forkhead box C1 (FOXC1) has been identified as a specific marker expressed in BLBC in general breast cancer cohorts. We examined an institutional cohort of breast cancer patients with germline BRCA1 (n=46) and BRCA2 (n=35) mutations and found that FOXC1 expression on immunohistochemical staining is associated with BRCA1 vs BRCA2 mutations [30/46 vs. 6/35]. In BRCA1 mutant tumors, FOXC1 was expressed in 28/31 BLBC tumors and 2/13 non-BLBC tumors, In BRCA2 mutant tumors, FOXC1 was expressed in 5/5 BLBC tumors and 1/30 non-BLBC tumors. In cell culture models of BRCA1-mutant breast cancer, FOXC1 is associated with increased proliferation and may serve as a marker for sensitivity to PARP-inhibitor therapy with olaparib. PMID:27708239

  1. Increasing Breast Cancer Surveillance Among African American Breast Cancer Survivors

    DTIC Science & Technology

    2006-07-01

    the Witness model will be tailored for breast cancer survivors and the peer interventionists (breast cancer survivors and lay health advisors) will be...by a lay health advisor; 4) discussion of concerns and myths about breast cancer and screening /surveillance that are prevalent among AAW; 5) review...Breast cancer screening surveillance Breast cancer screening Treatment/Time of Treatment intention /adherence & physician recommendation

  2. Breast Cancer and Bone Loss

    MedlinePlus

    ... Balance › Breast Cancer and Bone Loss Fact Sheet Breast Cancer and Bone Loss July, 2010 Download PDFs English ... JoAnn Pinkerton, MD What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  3. Abortion, Miscarriage, and Breast Cancer Risk

    MedlinePlus

    ... Cancers Breast Cancer Screening Research Abortion, Miscarriage, and Breast Cancer Risk: 2003 Workshop In February 2003, the National ... the development of breast cancer. Important Information about Breast Cancer Risk Factors At present, the factors known to ...

  4. Breast cancer and depression.

    PubMed

    Somerset, Wendy; Stout, Steven C; Miller, Andrew H; Musselman, Dominique

    2004-07-01

    Major depression and depressive symptoms, although commonly encountered in patients with medical illnesses, are frequently underdiagnosed and undertreated in women with breast cancer. Depression and its associated symptoms diminish quality of life, adversely affect compliance with medical therapies, and reduce survival. Treatment of depression in women with breast cancer improves their dysphoria and other depressive symptoms, enhances quality of life, and may increase longevity. In this review, studies that investigate pathophysiologic alterations in patients with cancer and comorbid depression are discussed, and the few studies on treatment of depression and related symptoms in women with breast cancer are examined.

  5. Epidemiology of basal-like breast cancer.

    PubMed

    Millikan, Robert C; Newman, Beth; Tse, Chiu-Kit; Moorman, Patricia G; Conway, Kathleen; Dressler, Lynn G; Smith, Lisa V; Labbok, Miriam H; Geradts, Joseph; Bensen, Jeannette T; Jackson, Susan; Nyante, Sarah; Livasy, Chad; Carey, Lisa; Earp, H Shelton; Perou, Charles M

    2008-05-01

    Risk factors for the newly identified "intrinsic" breast cancer subtypes (luminal A, luminal B, basal-like and human epidermal growth factor receptor 2-positive/estrogen receptor-negative) were determined in the Carolina Breast Cancer Study, a population-based, case-control study of African-American and white women. Immunohistochemical markers were used to subtype 1,424 cases of invasive and in situ breast cancer, and case subtypes were compared to 2,022 controls. Luminal A, the most common subtype, exhibited risk factors typically reported for breast cancer in previous studies, including inverse associations for increased parity and younger age at first full-term pregnancy. Basal-like cases exhibited several associations that were opposite to those observed for luminal A, including increased risk for parity and younger age at first term full-term pregnancy. Longer duration breastfeeding, increasing number of children breastfed, and increasing number of months breastfeeding per child were each associated with reduced risk of basal-like breast cancer, but not luminal A. Women with multiple live births who did not breastfeed and women who used medications to suppress lactation were at increased risk of basal-like, but not luminal A, breast cancer. Elevated waist-hip ratio was associated with increased risk of luminal A in postmenopausal women, and increased risk of basal-like breast cancer in pre- and postmenopausal women. The prevalence of basal-like breast cancer was highest among premenopausal African-American women, who also showed the highest prevalence of basal-like risk factors. Among younger African-American women, we estimate that up to 68% of basal-like breast cancer could be prevented by promoting breastfeeding and reducing abdominal adiposity.

  6. Women with Disabilities and Breast Cancer Screening

    MedlinePlus

    ... and Reasonable Accommodations (RA) Women with Disabilities and Breast Cancer Screening Recommend on Facebook Tweet Share Compartir Finding Breast Cancer Early Can Save Lives Disabilities & Breast Cancer Screening ...

  7. Human epidermal growth factor receptor 2-positive breast cancer: heat shock protein 90 overexpression, Ki67 proliferative index, and topoisomerase II-α co-amplification as predictors of pathologic complete response to neoadjuvant chemotherapy with trastuzumab and docetaxel.

    PubMed

    Bria, Emilio; Furlanetto, Jenny; Carbognin, Luisa; Brunelli, Matteo; Caliolo, Chiara; Nortilli, Rolando; Massari, Francesco; Pedron, Serena; Manfrin, Erminia; Pellini, Francesca; Bonetti, Franco; Sperduti, Isabella; Pollini, Giovanni Paolo; Scarpa, Aldo; Tortora, Giampaolo

    2015-02-01

    The combination of trastuzumab and chemotherapy is currently considered the standard of care for patients with locally advanced/operable human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The potential correlation between the pathologic complete response (pCR) and the overexpression of heat shock protein 90 (Hsp90), Ki67, and the amplification of topoisomerase II-α (TOPO2A) was investigated in a series of patients who received neoadjuvant treatment. HER2-amplified patients who received neoadjuvant trastuzumab-docetaxel were gathered. Baseline and postsurgical Hsp90 immunoscore, Ki67 proliferation index, and TOPO2A amplification were determined together with classic clinical-pathologic predictors and correlated with pCR and imaging data. A total of 24 patients were evaluated for response; pCR, clinical, and radiologic response were found in 4 patients (16.7%; 95% confidence interval [CI], 1.7-31.5), 9 patients (37.5%; 95% CI, 18.1-56.8), and 6 patients (25.0%; 95% CI, 7.6-42.3) patients, respectively. pCR was significantly higher in premenopausal (60.0% vs. 5.3%, P = .02) and negative hormonal receptor patients (50.0% vs. 5.6%, P = .03). A trend for patients with high Ki67 and TOPO2A/HER2 co-amplification was found (21.1% vs. none, P = .54; 50.0% vs. 12%, P = .16). pCR was significantly higher in patients with Hsp90 score 3+, in comparison with score 2+ and score 1+ (50.0% vs. 14.3% vs. none, P = .05). After treatment, a statistically significant lower Ki67 staining (30.0% vs. 17.5%, P = .005) and a trend for the decreased expression of high (score 3+) and moderate (score 2+) Hsp90 immunostaining (McNemar P = .25, Wilcoxon-Mann-Whitney P = .08) were found. Although underpowered, our data suggest that patients with HER2-positive breast cancer overexpressing Hsp90 should be investigated as a "newer" molecular subtype with a significantly higher chance of pCR when receiving anti-Her2 agents. Copyright © 2015 Elsevier Inc. All rights

  8. Safety Profile of Pertuzumab With Trastuzumab and Docetaxel in Patients From Asia With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: Results From the Phase III Trial CLEOPATRA

    PubMed Central

    Im, Young-Hyuck; Im, Seock-Ah; Chan, Valorie; Miles, David; Knott, Adam; Clark, Emma; Ross, Graham; Baselga, José

    2014-01-01

    Introduction. We report detailed safety analyses by geographic region from the phase III study CLEOPATRA with pertuzumab, trastuzumab, and docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive first-line metastatic breast cancer. Patients and Methods. Patients received pertuzumab/placebo at 840 mg in cycle 1 and 420 mg in subsequent cycles, and trastuzumab at 8 mg/kg in cycle 1 and 6 mg/kg in subsequent cycles; docetaxel was initiated at 75 mg/m2. All study drugs were given intravenously, 3 times weekly. Results. Docetaxel dose reductions below 75 mg/m2 were more common in patients from Asia (47.0%) than other regions (13.4%); docetaxel dose escalations to 100 mg/m2 were less frequent in Asia (2.4%) than other regions (18.7%). Rates of edema (26.1% and 5.4% for Asia and other regions, respectively), myalgia (42.3%, 14.7%), nail disorder (39.9%, 15.1%), febrile neutropenia (18.6%, 7.1%), upper respiratory tract infection (25.7%, 10.2%), decreased appetite (47.0%, 19.1%), and rash (44.3%, 22.0%) were at least twice as high in Asia as in other regions. Adverse events did not result in a reduction in the median number of study treatment cycles administered in patients from Asia. Efficacy analyses per region showed hazard ratios similar to those of the whole intention-to-treat (ITT) population for progression-free survival (ITT: 0.63; Asia: 0.68; other regions: 0.61) and overall survival (ITT: 0.66; Asia: 0.64; other regions: 0.66). Conclusion. Despite a higher proportion of docetaxel dose reductions in patients from Asia, survival benefits were comparable between regions. The benefit-risk profile of pertuzumab, trastuzumab, and docetaxel supports this regimen as the first-line therapy for patients with HER2-positive metastatic breast cancer from all geographic regions. PMID:24869931

  9. Milestones in breast cancer treatment.

    PubMed

    Zurrida, Stefano; Veronesi, Umberto

    2015-01-01

    Modern treatment started in the 1880s with Halsted's mastectomy. The next milestone-a century later-was breast-conserving surgery, with equivalent survival but better esthetic outcomes than mastectomy. Sentinel node biopsy, introduced in the 1990s, was a milestone that permitted avoidance of axillary dissection if the sentinel node was disease-free. Chemotherapy was established for early breast cancer in the 1980s and its efficacy continues to improve; however side effects remain a concern, particularly since chemotherapy does not benefit most patients. External whole breast irradiation was introduced with conservative surgery, as it reduces recurrences. By the 2000s, 3-week regimens had been shown equivalent to standard 6-week regimens-easing pressure on patients and radiation centers. Intraoperative partial breast irradiation is potentially more beneficial as it permits complete local treatment in a single session; however, trials show that patients must be very carefully selected. From the 1990s irradiation technology was combined with imaging and computer technologies to produce equipment that directs radiation to more precisely defined target volumes, allowing increased dose to the target and markedly reduced dose to nearby tissues. Irradiation systems are evolving rapidly but are being implemented without data on long-term morbidity or efficacy, while costs rise steeply. The first targeted treatment was tamoxifen, a selective estrogen receptor inhibitor. Since its widespread use starting in the 1980s, tamoxifen has saved the lives or prolonged the survival of millions with estrogen-positive disease; it is cheap and has limited (but not negligible) side effects. The same cannot be said of newer targeted treatments like trastuzumab and pertuzumab, which, although effective against human epidermal growth factor receptor 2-positive cancer, come with important side effects and huge costs. Breast cancer mortality is declining in rich countries, but treatments have

  10. Breast reconstruction after breast cancer.

    PubMed

    Serletti, Joseph M; Fosnot, Joshua; Nelson, Jonas A; Disa, Joseph J; Bucky, Louis P

    2011-06-01

    After reading this article, the participant should be able to: 1. Describe the mental, emotional, and physical benefits of reconstruction in breast cancer patients. 2. Compare the most common techniques of reconstruction in patients and detail benefits and risks associated with each. 3. Outline different methods of reconstruction and identify the method considered best for the patient based on timing of the procedures, body type, adjuvant therapies, and other coexisting conditions. 4. Distinguish between some of the different flaps that can be considered for autologous reconstruction. Breast cancer is unfortunately a common disease affecting millions of women, often at a relatively young age. Reconstruction following mastectomy offers women an opportunity to mollify some of the emotional and aesthetic effects of this devastating disease. Although varying techniques of alloplastic and autologous techniques are available, all strive to achieve the same goal: the satisfactory reformation of a breast mound that appears as natural as possible without clothing and at the very least is normal in appearance under clothing. This article summarizes the various approaches to breast reconstruction and offers a balanced view of the risks and benefits of each, all of which in the end offer the opportunity for excellent and predictable results with a high degree of patient satisfaction.

  11. Identifying Breast Cancer Oncogenes

    DTIC Science & Technology

    2011-10-01

    which is a study of 3131 human tumor samples and cancer cell lines including 243 breast samples. Tumorscape showed that PAK1 is located in an...chromosome 11q of human tumor samples and cancer cell lines that exhibit highest level of PAK1 amplification divided according to cancer type...breast, non-small cell (NSC) lung, ovarian (Ov), small cell lung (SCL), melanoma (Mel) and esophageal squamous (Esq). PAK1 and CCND1 1oci are marked . B

  12. Oxalate induces breast cancer.

    PubMed

    Castellaro, Andrés M; Tonda, Alfredo; Cejas, Hugo H; Ferreyra, Héctor; Caputto, Beatriz L; Pucci, Oscar A; Gil, German A

    2015-10-22

    Microcalcifications can be the early and only presenting sign of breast cancer. One shared characteristic of breast cancer is the appearance of mammographic mammary microcalcifications that can routinely be used to detect breast cancer in its initial stages, which is of key importance due to the possibility that early detection allows the application of more conservative therapies for a better patient outcome. The mechanism by which mammary microcalcifications are formed is still largely unknown but breast cancers presenting microcalcifications are more often associated with a poorer prognosis. We combined Capillary Electrochromatography, histology, and gene expression (qRT-PCR) to analyze patient-matched normal breast tissue vs. breast tumor. Potential carcinogenicity of oxalate was tested by its inoculation into mice. All data were subjected to statistical analysis. To study the biological significance of oxalates within the breast tumor microenvironment, we measured oxalate concentration in both human breast tumor tissues and adjoining non-pathological breast tissues. We found that all tested breast tumor tissues contain a higher concentration of oxalates than their counterpart non-pathological breast tissue. Moreover, it was established that oxalate induces proliferation of breast cells and stimulates the expression of a pro-tumorigenic gene c-fos. Furthermore, oxalate generates highly malignant and undifferentiated tumors when it was injected into the mammary fatpad in female mice, but not when injected into their back, indicating that oxalate does not induce cancer formation in all types of tissues. Moreover, neither human kidney-epithelial cells nor mouse fibroblast cells proliferate when are treated with oxalate. We found that the chronic exposure of breast epithelial cells to oxalate promotes the transformation of breast cells from normal to tumor cells, inducing the expression of a proto-oncogen as c-fos and proliferation in breast cancer cells

  13. "Targeting" triple-negative breast cancer: the lessons learned from BRCA1-associated breast cancers.

    PubMed

    Nanda, Rita

    2011-04-01

    Breast cancer has long been recognized as a heterogeneous entity, with distinct subsets characterized by differences in tumor biology and response to therapy. With the advent of molecular profiling, we have gained a further appreciation of the heterogeneity of this complex disease. While the last decade has seen advances in the treatment of hormone receptor (HR) and human epidermal growth factor receptor 2/erb-B2 (HER2)-positive breast cancers, outcomes for women with estrogen receptor (ER)-, progesterone receptor (PR)-, and HER2-negative-or "triple-negative"-breast cancer (TNBC) remain poor. A better understanding of the shared biology of BRCA1-associated breast cancer and sporadic TNBC holds much promise for changing the outlook for women with this aggressive disease. This review focuses on our current understanding of the clinicopathological features of TNBC, therapeutic options and ongoing research efforts.

  14. Dynamic thermal effects of epidermal melanin and plasmonic nanoparticles during photoacoustic breast imaging

    NASA Astrophysics Data System (ADS)

    Ghassemi, Pejhman; Wang, Quanzeng; Pfefer, T. Joshua

    2016-03-01

    Photoacoustic Tomography (PAT) employs high-power near-infrared (near-IR) laser pulses to generate structural and functional information on tissue chromophores up to several centimeters below the surface. Such insights may facilitate detection of breast cancer - the most common cancer in women. PAT mammography has been the subject of extensive research, including techniques based on exogenous agents for PAT contrast enhancement and molecular specificity. However, photothermal safety risks of PAT due to strong chromophores such as epidermal melanin and plasmonic nanoparticles have not been rigorously studied. We have used computational and experimental approaches to elucidate highly dynamic optical-thermal processes during PAT. A Monte Carlo model was used to simulate light propagation at 800 and 1064 nm in a multi-layer breast tissue geometry with different epidermal pigmentation levels and a tumorsimulating inclusion incorporating nanoparticles. Energy deposition results were then used in a bioheat transfer model to simulate temperature transients. Experimental measurements involved multi-layer hydrogel phantoms with inclusions incorporating gold nanoparticles. Phantom optical properties were measured using the inverse adding-doubling technique. Thermal imaging was performed as phantoms were irradiated with 5 ns near-IR pulses. Scenarios using 10 Hz laser irradiation of breast tissue containing various nanoparticle concentrations were implemented experimentally and computationally. Laser exposure levels were based on ANSI/IEC limits. Surface temperature measurements were compared to corresponding simulation data. In general, the effect of highly pigmented skin on temperature rise was significant, whereas unexpectedly small levels of temperature rise during nanoparticle irradiation were attributed to rapid photodegradation. Results provide key initial insights into light-tissue interactions impacting the safety and effectiveness of PAT.

  15. Distant invasive breast cancer recurrence risk in human epidermal growth factor receptor 2-positive T1a and T1b node-negative localized breast cancer diagnosed from 2000 to 2006: a cohort from an integrated health care delivery system.

    PubMed

    Fehrenbacher, Louis; Capra, Angela M; Quesenberry, Charles P; Fulton, Regan; Shiraz, Parveen; Habel, Laurel A

    2014-07-10

    To determine the invasive recurrence (IR) risk among patients with small, node-negative human epidermal growth factor receptor 2 (HER2) -positive breast cancer. Among 16,975 consecutive patients with invasive breast cancer diagnosed from January 1, 2000, to December 31, 2006, in a large, integrated health care system, we identified a cohort of 234 patients with HER2-positive T1aN0M0 or T1bN0M0 (T1abN0M0) disease with a median follow-up of 5.8 years. Kaplan-Meier methods were used to estimate the percentage of patients who were free of invasive recurrence (recurrence-free interval [RFI]) at 5 years for both distant (DRFI) and local (LRFI) recurrences. Of 15 IRs, 47% were locoregional only. Among T1ab patients not treated with adjuvant trastuzumab or chemotherapy (n = 171), the 5-year invasive DRFI was 98.2% (95% CI, 94.5% to 99.4%); it was 99.0% (95% CI, 93.0% to 99.9%) for T1a patients, and 97.0% (95% CI, 88.6% to 99.2%) for T1b patients. Locoregional plus distant 5-year invasive RFI was 97.0% (95% CI, 90.9% to 99.0%) for T1a and 91.9% (95% CI, 81.5% to 96.6%) for T1b patients; it was 89.4% (95% CI, 70.6% to 96.5%) for T1b tumors reported at 1.0 cm. T1b tumors reported at 1.0 cm accounted for 24% of the T1ab cohort, 61% of the cohort total tumor volume, and 75% of distant recurrences. Invasive RFI for T1b 1.0 cm tumors was lower than that for T1a tumors: 84.5% versus 97.4% (P = .009). The distant IR risk of T1a HER2-positive breast cancer appears quite low. The distant IR risk in T1b patients, particularly those with 1.0-cm tumors, is higher. Potential risk differences for T1a and T1b, including the 1.0-cm tumors, should be considered when making treatment decisions. © 2014 by American Society of Clinical Oncology.

  16. Role of epidermal growth factor receptor (EGFR)-signaling versus cellular acidosis via Na+/H+ exchanger1(NHE1)-inhibition in troglitazone-induced growth arrest of breast cancer-derived cells MCF-7.

    PubMed

    Friday, Ellen; Oliver, Robert; Welbourne, Tomas; Turturro, Francesco

    2007-01-01

    We previously showed that troglitazone (TRO) induces a profound cellular acidosis in MCF-7 cells as a result of inhibiting Na(+)/H(+) exchanger (NHE)1-mediated acid extrusion and this was associated with a marked reduction in cellular proliferation. The present study focuses on TRO-activated signaling pathways versus TRO-mediated NHE1-inhibition in reducing DNA synthesis. TRO activation of the signaling pathway involving epidermal growth factor receptor (EGFR)/MAPK/ERK kinase (MEK) 1/2/extracellular signal-regulated kinase (ERK) 1/2 was studied by Western blotting and phospho-specific antibodies. TRO induction of cellular acidosis and inhibition of NHE1 activity were measured using (2, 7)-biscarboxyethyl-5 (6)-carboxyfluorescein (BCECF) assay and NH4(+)/NH(3) pulsing. Cellular proliferation was assessed as DNA synthesis by (3)H-thymidine incorporation. TRO simultaneously reduces pH(i) and elevates phosphorylated-extracellular signal-regulated kinase (p-ERK). These responses reflected inhibition of acid extrusion and EGFR activation respectively and were sustained over 18h associated with a large decrease in DNA synthesis. Preventing TRO-induced ERK activation did not restore DNA synthesis or cellular pH. TRO activates two parallel pathways: I] EGFR/MEK1/2/ERK1/2 and II] NHE1 inhibition/cellular acidosis. Elimination of I] did not prevent the inhibition of DNA synthesis consistent with TRO-induced growth arrest dependent upon II] in tumorigenic non-metastatic breast cancer derived MCF-7 cells.

  17. Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients.

    PubMed

    Gligorov, J; Ataseven, B; Verrill, M; De Laurentiis, M; Jung, K H; Azim, H A; Al-Sakaff, N; Lauer, S; Shing, M; Pivot, X

    2017-09-01

    To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin(®) SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine.

    PubMed

    Krop, Ian E; LoRusso, Patricia; Miller, Kathy D; Modi, Shanu; Yardley, Denise; Rodriguez, Gladys; Guardino, Ellie; Lu, Michael; Zheng, Maoxia; Girish, Sandhya; Amler, Lukas; Winer, Eric P; Rugo, Hope S

    2012-09-10

    To determine whether the antibody-drug conjugate trastuzumab emtansine (T-DM1), which combines human epidermal growth factor receptor 2 (HER2) -targeted delivery of the potent antimicrotubule agent DM1 with the antitumor activity of trastuzumab, is effective in patients with HER2-positive metastatic breast cancer (MBC) who have previously received all standard HER2-directed therapies. In this single-arm phase II study, T-DM1 3.6 mg/kg was administered intravenously every 3 weeks to patients with HER2-positive MBC who had prior treatment with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. The primary objectives were overall response rate (ORR) by independent review and safety. Among 110 pretreated patients (median, seven prior agents for MBC; median follow-up, 17.4 months), the ORR was 34.5% (95% CI, 26.1% to 43.9%), clinical benefit rate was 48.2% (95% CI, 38.8% to 57.9%), median progression-free survival (PFS) was 6.9 months (95% CI, 4.2 to 8.4 months), and median duration of response was 7.2 months (95% CI, 4.6 months to not estimable). In patients with confirmed HER2-positive tumors (n = 80 by retrospective central testing), the response rate was 41.3% (95% CI, 30.4% to 52.8%), and median PFS was 7.3 months (95% CI, 4.6 to 12.3 months). Most adverse events were grades 1 to 2; the most frequent grade ≥ 3 events were thrombocytopenia (9.1%), fatigue (4.5%), and cellulitis (3.6%). T-DM1 is well tolerated and has single-agent activity in patients with HER2-positive MBC who have previously received both approved HER2-directed therapies and multiple chemotherapy agents. T-DM1 may be an effective new treatment for this patient population.

  19. Docosahexaenoic Acid in Preventing Recurrence in Breast Cancer Survivors

    ClinicalTrials.gov

    2016-06-20

    Benign Breast Neoplasm; Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Lobular Breast Carcinoma In Situ; Paget Disease of the Breast; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  20. Targeting Breast Cancer Metastasis

    PubMed Central

    Jin, Xin; Mu, Ping

    2015-01-01

    Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30–40% of patients may eventually suffer from distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various metastatic traits that contribute to the metastasis cascade of breast cancer, which may provide novel avenues for therapeutic targeting. PMID:26380552

  1. Breast Cancer in Young Women

    MedlinePlus

    ... NPCR 2017 CDC National Cancer Conference Stay Informed Breast Cancer in Young Women Recommend on Facebook Tweet Share Compartir Syndicate this page Marleah's family history of breast cancer was her motivation for pursuing a career where ...

  2. Broccoli Sprout Extract in Treating Patients With Breast Cancer

    ClinicalTrials.gov

    2017-02-14

    Ductal Breast Carcinoma; Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Postmenopausal; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  3. Breast size, handedness and breast cancer risk.

    PubMed

    Hsieh, C C; Trichopoulos, D

    1991-01-01

    Bra cup size and handedness were studied as possible risk factors for breast cancer. Data for 3918 cases and 11,712 controls from 7 centres were used to examine the association of handedness with laterality of breast cancer; data for 2325 cases and 7008 controls from 4 centres were used to assess the relation of bra cup size to breast cancer risk. There was a suggestive (P about 0.10) association of handedness with breast cancer laterality: odds ratio of a left-handed (or ambidextrous) woman having a left-sided cancer 1.22 (95% CI 0.96-1.56). Handedness may affect the lateral occurrence of breast cancer, although this tumour is in general more common in the left breast, possibly because this breast is usually slightly larger. Premenopausal women who do not wear bras had half the risk of breast cancer compared with bra users (P about 0.09), possibly because they are thinner and likely to have smaller breasts. Among bra users, larger cup size was associated with an increased risk of breast cancer (P about 0.026), although the association was found only among postmenopausal women and was accounted for, in part, by obesity. These data suggest that bra cup size (and conceivably mammary gland size) may be a risk factor for breast cancer.

  4. Quiz: How much do you know about breast cancer? | NIH MedlinePlus the Magazine

    MedlinePlus

    ... breast cancer late stage breast cancer locally advanced breast cancer Stage III breast cancer is early stage breast cancer late stage breast cancer locally advanced breast cancer Stage IV breast cancer is early stage breast cancer ...

  5. Cutaneous manifestations of breast cancer.

    PubMed

    Tan, Antoinette R

    2016-06-01

    Breast cancer may present with cutaneous symptoms. The skin manifestations of breast cancer are varied. Some of the more common clinical presentations of metastatic cutaneous lesions from breast cancer will be described. Paraneoplastic cutaneous dermatoses have been reported as markers of breast malignancy and include erythema gyratum repens, acquired ichthyosis, dermatomyositis, multicentric reticulohistiocytosis, and hypertrichosis lanuginosa acquisita. Mammary Paget's disease, often associated with an underlying breast cancer, and Cowden syndrome, which has an increased risk of breast malignancy, each have specific dermatologic findings. Recognition of these distinct cutaneous signs is important in the investigation of either newly diagnosed or recurrent breast cancer.

  6. Stages of Breast Cancer

    MedlinePlus

    ... in lymph and help fight infection and disease. Clusters of lymph nodes are found near the breast ... the tumor is 2 centimeters or smaller. Small clusters of cancer cells (larger than 0.2 millimeter ...

  7. Breast Cancer Treatment

    MedlinePlus

    ... in lymph and help fight infection and disease. Clusters of lymph nodes are found near the breast ... the tumor is 2 centimeters or smaller. Small clusters of cancer cells (larger than 0.2 millimeter ...

  8. Breast Cancer in Men

    MedlinePlus

    ... men may have radiation after surgery. Since most breast cancers in men are hormone receptor-positive, hormone therapy (with tamoxifen) is often used depending on the stage. Chemotherapy may be given before tamoxifen. For men ...

  9. Obesity and Breast Cancer.

    PubMed

    Fortner, Renée T; Katzke, Verena; Kühn, Tilman; Kaaks, Rudolf

    The relationship between adiposity and breast cancer risk and prognosis is complex, with associations that differ depending on when body size is assessed (e.g., pre- vs. postmenopausal obesity) and when breast cancer is diagnosed (i.e., pre- vs. postmenopausal disease). Further, the impact of obesity on risk differs by tumor hormone receptor status (e.g., estrogen (ER) and progesterone (PR) receptor) and, among postmenopausal women, use of exogenous hormones (i.e., hormone replacement therapy (HRT)). In the context of these complexities, this review focuses on associations between childhood and adolescent adiposity, general adiposity, weight changes (i.e., loss and gain), abdominal adiposity, and breast cancer risk and survival. Finally, we discuss potential mechanisms linking adiposity to breast cancer.

  10. The breast cancer conundrum.

    PubMed

    Adams, Patrick

    2013-09-01

    For decades, rates of breast cancer have been going up faster in rich countries than in poor ones. Scientists are beginning to understand more about its causes but unanswered questions remain. Patrick Adams reports.

  11. Breast Cancer - Multiple Languages

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Breast Cancer URL of this page: https://medlineplus.gov/languages/breastcancer.html Other topics A-Z Expand Section ...

  12. Rare breast cancer subtypes: histological, molecular, and clinical peculiarities.

    PubMed

    Dieci, Maria Vittoria; Orvieto, Enrico; Dominici, Massimo; Conte, PierFranco; Guarneri, Valentina

    2014-08-01

    Breast cancer encompasses a collection of different diseases characterized by different biological and pathological features, clinical presentation, response to treatments, clinical behavior, and outcome. On the basis of cell morphology, growth, and architecture patterns, breast cancer can be classified in up to 21 distinct histological types. Breast cancer special types, including the classic lobular invasive carcinoma, represent 25% of all breast cancers. The histological diversity of breast carcinomas has relevant prognostic implications. Indeed, the rare breast cancer group includes subtypes with very different prognoses, ranging from the tubular carcinoma, associated with an indolent clinical course, to metaplastic cancer, whose outcome is generally unfavorable. New approaches based on gene expression profiling allow the identification of molecularly defined breast cancer classes, with distinct biological features and clinical behavior. In clinical practice, immunohistochemical classification based on the expression of human epidermal growth factor receptor 2 and Ki67 is applied as a surrogate of the intrinsic molecular subtypes. However, the identification of intrinsic molecular subtypes were almost completely limited to the study of ductal invasive breast cancer. Moreover, some good-prognosis triple-negative histotypes, on the basis of gene expression profiling, can be classified among the poor-prognosis group. Therefore, histopathological classification remains a crucial component of breast cancer diagnosis. Special histologies can be very rare, and the majority of information on outcome and treatments derives from small series and case reports. As a consequence, clear recommendations about clinical management are still lacking. In this review, we summarize current knowledge about rare breast cancer histologies.

  13. Epidermal Growth Factor Receptor Expression in Triple Negative and Nontriple Negative Breast Carcinomas

    PubMed Central

    Changavi, Arathi A; Shashikala, Arundhathi; Ramji, Ashwini S

    2015-01-01

    Introduction: The panel of markers used for molecular classification include estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor (HER)-2/neu, p53, Bcl-2 and basal markers like cytokeratin 5/6 or epidermal growth factor receptor (EGFR). Among these, EGFR plays an important role and is associated with bad prognosis. Aims and Objectives: To study EGFR expression in triple negative breast carcinoma (TNBC) and non-TNBCs (NTNBCs). Materials and Methods: Fifty cases of breast carcinomas were classified and graded according to World Health Organization and Nottingham modification of Scarff-Bloom-Richardson (SBR) system, respectively. The age of the patients ranged from 28 to 69 years. Histological features such as necrosis, pushing borders, lymphocytic infiltrate and periductal elastosis were noted. The panel of markers used in our study included ER, PR, HER-2/neu and EGFR. EGFR expression was assessed based on membrane staining. Chi-square test was applied for statistical analysis to compare EGFR expression with hormonal status and prognostic factors. P < 0.05 was considered significant. Results: The mean age was 49.8 ± 7.2 years. There were 44 (88%) infiltrating ductal carcinoma, 3 (6%) medullary carcinoma and 3 (6%) mucinous carcinoma. EGFR expression was common in young patients and was predominant in TNBC (89.47%), was also expressed in few cases of NTNBC. There was a positive correlation of EGFR expression (P = 0.03491) with a high grade. Medullary carcinomas were triple negative and strongly expressed EGFR. EGFR expression was inversely associated with ER status and showed strong association with necrosis and lymphocytic infiltrate, but not with pushing border and periductal elastosis. Conclusion: EGFR is an important marker to stratify patients with breast cancer according to molecular classification. Its expression correlated positively with young age, higher SBR grade, necrosis, lymphocytic infiltrate and inversely with

  14. Epidermal Growth Factor Receptor Expression in Triple Negative and Nontriple Negative Breast Carcinomas.

    PubMed

    Changavi, Arathi A; Shashikala, Arundhathi; Ramji, Ashwini S

    2015-01-01

    The panel of markers used for molecular classification include estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor (HER)-2/neu, p53, Bcl-2 and basal markers like cytokeratin 5/6 or epidermal growth factor receptor (EGFR). Among these, EGFR plays an important role and is associated with bad prognosis. To study EGFR expression in triple negative breast carcinoma (TNBC) and non-TNBCs (NTNBCs). Fifty cases of breast carcinomas were classified and graded according to World Health Organization and Nottingham modification of Scarff-Bloom-Richardson (SBR) system, respectively. The age of the patients ranged from 28 to 69 years. Histological features such as necrosis, pushing borders, lymphocytic infiltrate and periductal elastosis were noted. The panel of markers used in our study included ER, PR, HER-2/neu and EGFR. EGFR expression was assessed based on membrane staining. Chi-square test was applied for statistical analysis to compare EGFR expression with hormonal status and prognostic factors. P < 0.05 was considered significant. The mean age was 49.8 ± 7.2 years. There were 44 (88%) infiltrating ductal carcinoma, 3 (6%) medullary carcinoma and 3 (6%) mucinous carcinoma. EGFR expression was common in young patients and was predominant in TNBC (89.47%), was also expressed in few cases of NTNBC. There was a positive correlation of EGFR expression (P = 0.03491) with a high grade. Medullary carcinomas were triple negative and strongly expressed EGFR. EGFR expression was inversely associated with ER status and showed strong association with necrosis and lymphocytic infiltrate, but not with pushing border and periductal elastosis. EGFR is an important marker to stratify patients with breast cancer according to molecular classification. Its expression correlated positively with young age, higher SBR grade, necrosis, lymphocytic infiltrate and inversely with hormonal receptor expression.

  15. Androgen Receptor: A Complex Therapeutic Target for Breast Cancer.

    PubMed

    Narayanan, Ramesh; Dalton, James T

    2016-12-02

    Molecular and histopathological profiling have classified breast cancer into multiple sub-types empowering precision treatment. Although estrogen receptor (ER) and human epidermal growth factor receptor (HER2) are the mainstay therapeutic targets in breast cancer, the androgen receptor (AR) is evolving as a molecular target for cancers that have developed resistance to conventional treatments. The high expression of AR in breast cancer and recent discovery and development of new nonsteroidal drugs targeting the AR provide a strong rationale for exploring it again as a therapeutic target in this disease. Ironically, both nonsteroidal agonists and antagonists for the AR are undergoing clinical trials, making AR a complicated target to understand in breast cancer. This review provides a detailed account of AR's therapeutic role in breast cancer.

  16. Androgen Receptor: A Complex Therapeutic Target for Breast Cancer

    PubMed Central

    Narayanan, Ramesh; Dalton, James T.

    2016-01-01

    Molecular and histopathological profiling have classified breast cancer into multiple sub-types empowering precision treatment. Although estrogen receptor (ER) and human epidermal growth factor receptor (HER2) are the mainstay therapeutic targets in breast cancer, the androgen receptor (AR) is evolving as a molecular target for cancers that have developed resistance to conventional treatments. The high expression of AR in breast cancer and recent discovery and development of new nonsteroidal drugs targeting the AR provide a strong rationale for exploring it again as a therapeutic target in this disease. Ironically, both nonsteroidal agonists and antagonists for the AR are undergoing clinical trials, making AR a complicated target to understand in breast cancer. This review provides a detailed account of AR’s therapeutic role in breast cancer. PMID:27918430

  17. Targeting metabolism in breast cancer: How far we can go?

    PubMed Central

    Long, Jing-Pei; Li, Xiao-Na; Zhang, Feng

    2016-01-01

    Adjuvant therapies for breast cancer have achieved great success in recent years and early breast cancer is now a curable or chronic disease. Targeted therapies, including endocrine therapy and human epidermal growth factor receptor-2 targeted therapy, marked a new era of breast cancer treatment. However, except for chemotherapy, an efficient drug treatment to improve the overall survival of breast cancer patients is still lacking for triple negative breast cancer. Furthermore, a certain proportion of breast cancer patients present with resistance to drug therapy, making it much more difficult to control the deterioration of the disease. Recently, altered energy metabolism has become one of the hallmarks of cancer, including breast cancer, and it may be linked to drug resistance. Targeting cellular metabolism is becoming a promising strategy to overcome drug resistance in cancer therapy. This review discusses metabolic reprogramming in breast cancer and the possible complex mechanism of modulation. We also summarize the recent advances in metabolic therapy targeted glycolysis, glutaminolysis and fatty acids synthesis in breast cancer. PMID:26862496

  18. Human Breast Cancer Histoid

    PubMed Central

    Kaur, Pavinder; Ward, Brenda; Saha, Baisakhi; Young, Lillian; Groshen, Susan; Techy, Geza; Lu, Yani; Atkinson, Roscoe; Taylor, Clive R.; Ingram, Marylou

    2011-01-01

    Progress in our understanding of heterotypic cellular interaction in the tumor microenvironment, which is recognized to play major roles in cancer progression, has been hampered due to unavailability of an appropriate in vitro co-culture model. The aim of this study was to generate an in vitro 3-dimensional human breast cancer model, which consists of cancer cells and fibroblasts. Breast cancer cells (UACC-893) and fibroblasts at various densities were co-cultured in a rotating suspension culture system to establish co-culture parameters. Subsequently, UACC-893, BT.20, or MDA.MB.453 were co-cultured with fibroblasts for 9 days. Co-cultures resulted in the generation of breast cancer histoid (BCH) with cancer cells showing the invasion of fibroblast spheroids, which were visualized by immunohistochemical (IHC) staining of sections (4 µm thick) of BCH. A reproducible quantitative expression of C-erbB.2 was detected in UACC-893 cancer cells in BCH sections by IHC staining and the Automated Cellular Imaging System. BCH sections also consistently exhibited qualitative expression of pancytokeratins, p53, Ki-67, or E-cadherin in cancer cells and that of vimentin or GSTPi in fibroblasts, fibronectin in the basement membrane and collagen IV in the extracellular matrix. The expression of the protein analytes and cellular architecture of BCH were markedly similar to those of breast cancer tissue. PMID:22034518

  19. Stereotactic Image-Guided Navigation During Breast Reconstruction in Patients With Breast Cancer

    ClinicalTrials.gov

    2017-04-12

    Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Recurrent Breast 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

  20. Preinvasive Breast Cancer

    PubMed Central

    Sgroi, Dennis C.

    2014-01-01

    Preinvasive breast cancer accounts for approximately one-third of all newly diagnosed breast cancer cases in the United States and constitutes a spectrum of neoplastic lesions with varying degrees of differentiation and clinical behavior. High-throughput genetic, epigenetic, and gene-expression analyses have enhanced our understanding of the relationship of these early neoplastic lesions to normal breast tissue, and they strongly suggest that preinvasive breast cancer develops and evolves along two distinct molecular genetic and biological pathways that correlate with tumor grade. Although unique epigenetic and gene-expression changes are not observed in the tumor epithelial compartment during the transition from preinvasive to invasive disease, distinct molecular alterations are observed in the tumor-stromal and myoepithelial cells. This suggests that the stromal and myoepithelial microenvironment of preinvasive breast cancer actively participates in the transition from preinvasive to invasive disease. An improved understanding of the transition from preinvasive to invasive breast cancer will pave the way for novel preventative and therapeutic strategies. PMID:19824828

  1. 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

  2. Viruses and Breast Cancer

    PubMed Central

    Lawson, James S.; Heng, Benjamin

    2010-01-01

    Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix. PMID:24281093

  3. Understanding EGFR Signaling in Breast Cancer and Breast Cancer Stem Cells: Overexpression and Therapeutic Implications.

    PubMed

    Alanazi, Ibrahim O; Khan, Zahid

    2016-01-01

    Epidermal growth factor receptors (EGFRs/HERs) and downstream signaling pathways have been implicated in the pathogenesis of several malignancies including breast cancer and its resistance to treatment with chemotherapeutic drugs. Consequently, several monoclonal antibodies as well as small molecule inhibitors targeting these pathways have emerged as therapeutic tools in the recent past. However, studies have shown that utilizing these molecules in combination with chemotherapy has yielded only limited success. This review describes the current understanding of EGFRs/HERs and associated signaling pathways in relation to development of breast cancer and responses to various cancer treatments in the hope of pointing to improved prevention, diagnosis and treatment. Also, we review the role of breast cancer stem cells (BCSCs) in disease and the potential to target these cells.

  4. CD147, CD44, and the epidermal growth factor receptor (EGFR) signaling pathway cooperate to regulate breast epithelial cell invasiveness.

    PubMed

    Grass, G Daniel; Tolliver, Lauren B; Bratoeva, Momka; Toole, Bryan P

    2013-09-06

    The immunoglobulin superfamily glycoprotein CD147 (emmprin; basigin) is associated with an invasive phenotype in various types of cancers, including malignant breast cancer. We showed recently that up-regulation of CD147 in non-transformed, non-invasive breast epithelial cells is sufficient to induce an invasive phenotype characterized by membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invadopodia activity (Grass, G. D., Bratoeva, M., and Toole, B. P. (2012) Regulation of invadopodia formation and activity by CD147. J. Cell Sci. 125, 777-788). Here we found that CD147 induces breast epithelial cell invasiveness by promoting epidermal growth factor receptor (EGFR)-Ras-ERK signaling in a manner dependent on hyaluronan-CD44 interaction. Furthermore, CD147 promotes assembly of signaling complexes containing CD147, CD44, and EGFR in lipid raftlike domains. We also found that oncogenic Ras regulates CD147 expression, hyaluronan synthesis, and formation of CD147-CD44-EGFR complexes, thus forming a positive feedback loop that may amplify invasiveness. Last, we showed that malignant breast cancer cells are heterogeneous in their expression of surface-associated CD147 and that high levels of membrane CD147 correlate with cell surface EGFR and CD44 levels, activated EGFR and ERK1, and activated invadopodia. Future studies should evaluate CD147 as a potential therapeutic target and disease stratification marker in breast cancer.

  5. Stand Up to Cancer Phase Ib Study of Pan-Phosphoinositide-3-Kinase Inhibitor Buparlisib With Letrozole in Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer

    PubMed Central

    Mayer, Ingrid A.; Abramson, Vandana G.; Isakoff, Steven J.; Forero, Andres; Balko, Justin M.; Kuba, María Gabriela; Sanders, Melinda E.; Yap, Jeffrey T.; Van den Abbeele, Annick D.; Li, Yisheng; Cantley, Lewis C.; Winer, Eric; Arteaga, Carlos L.

    2014-01-01

    Purpose Buparlisib, an oral reversible inhibitor of all class I phosphoinositide-3-kinases, has shown antitumoral activity against estrogen receptor (ER)-positive breast cancer cell lines and xenografts, alone and with endocrine therapy. This phase Ib study evaluated buparlisib plus letrozole's safety, tolerability, and preliminary activity in patients with metastatic ER-positive breast cancer refractory to endocrine therapy. Patients and Methods Patients received letrozole and buparlisib in two different administration schedules. Outcomes were assessed by standard solid-tumor phase I methods. [18F]fluorodeoxyglucose–positron emission tomography/computed tomography ([18F]FDG-PET/CT) scans were done at baseline and 2 weeks after treatment initiation. Tumor blocks were collected for phosphoinositide-3-kinase pathway mutation analysis. Results Fifty-one patients were allocated sequentially to continuous or intermittent (five on/two off days) buparlisib administration on an every-4-week schedule. Buparlisib's maximum-tolerated dose (MTD) was 100 mg/d. Common drug-related adverse events included ≤ grade 2 hyperglycemia, nausea, fatigue, transaminitis, and mood disorders. The clinical benefit rate (lack of progression ≥ 6 months) among all patients treated at the MTD was 31%, including two objective responses in the continuous dose arm. Of seven patients remaining on treatment ≥ 12 months, three had tumors with PIK3CA hot-spot mutation. Patients exhibiting metabolic disease progression by [18F]FDG-PET/CT scan at 2 weeks progressed rapidly on therapy. Conclusion The letrozole and buparlisib combination was safe, with reversible toxicities regardless of schedule administration. Clinical activity was observed independent of PIK3CA mutation status. No metabolic response by [18F]FDG-PET/CT scan at 2 weeks was associated with rapid disease progression. Phase III trials of buparlisib and endocrine therapy in patients with ER-positive breast cancer are ongoing. PMID

  6. Stand up to cancer phase Ib study of pan-phosphoinositide-3-kinase inhibitor buparlisib with letrozole in estrogen receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer.

    PubMed

    Mayer, Ingrid A; Abramson, Vandana G; Isakoff, Steven J; Forero, Andres; Balko, Justin M; Kuba, María Gabriela; Sanders, Melinda E; Yap, Jeffrey T; Van den Abbeele, Annick D; Li, Yisheng; Cantley, Lewis C; Winer, Eric; Arteaga, Carlos L

    2014-04-20

    Buparlisib, an oral reversible inhibitor of all class I phosphoinositide-3-kinases, has shown antitumoral activity against estrogen receptor (ER)-positive breast cancer cell lines and xenografts, alone and with endocrine therapy. This phase Ib study evaluated buparlisib plus letrozole's safety, tolerability, and preliminary activity in patients with metastatic ER-positive breast cancer refractory to endocrine therapy. Patients received letrozole and buparlisib in two different administration schedules. Outcomes were assessed by standard solid-tumor phase I methods. [(18)F]fluorodeoxyglucose-positron emission tomography/computed tomography ([(18)F]FDG-PET/CT) scans were done at baseline and 2 weeks after treatment initiation. Tumor blocks were collected for phosphoinositide-3-kinase pathway mutation analysis. Fifty-one patients were allocated sequentially to continuous or intermittent (five on/two off days) buparlisib administration on an every-4-week schedule. Buparlisib's maximum-tolerated dose (MTD) was 100 mg/d. Common drug-related adverse events included ≤ grade 2 hyperglycemia, nausea, fatigue, transaminitis, and mood disorders. The clinical benefit rate (lack of progression ≥ 6 months) among all patients treated at the MTD was 31%, including two objective responses in the continuous dose arm. Of seven patients remaining on treatment ≥ 12 months, three had tumors with PIK3CA hot-spot mutation. Patients exhibiting metabolic disease progression by [(18)F]FDG-PET/CT scan at 2 weeks progressed rapidly on therapy. The letrozole and buparlisib combination was safe, with reversible toxicities regardless of schedule administration. Clinical activity was observed independent of PIK3CA mutation status. No metabolic response by [(18)F]FDG-PET/CT scan at 2 weeks was associated with rapid disease progression. Phase III trials of buparlisib and endocrine therapy in patients with ER-positive breast cancer are ongoing.

  7. Breast Cancer Detection

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The BioScan System was developed by OmniCorder Technologies, Inc. at the Jet Propulsion Laboratory. The system is able to locate cancerous lesions by detecting the cancer's ability to recruit a new blood supply. A digital sensor detects infrared energy emitted from the body and identifies the minute differences accompanying the blood flow changes associated with cancerous cells. It also has potential use as a monitoring device during cancer treatment. This technology will reduce the time taken to detect cancerous cells and allow for earlier intervention, therefore increasing the overall survival rates of breast cancer patients.

  8. Oral contraceptives and breast cancer.

    PubMed

    Johnson, K H; Millard, P S

    1996-10-01

    The Collaborative Group on Hormonal Factors in Breast Cancer conducted a meta-analysis of data from 10 cohort and 44 case-control studies of the association between combined oral contraceptive (OC) use and breast cancer. 53,297 women with breast cancer and 100,239 women with no breast cancer from 25 countries worldwide were studied. Current OC users faced a 24% increased risk of developing breast cancer (confidence interval = 1.15-1.33). This risk fell steadily after cessation and reached 0 at 10 years and thereafter. Use of OCs with higher doses were associated with a greater risk of breast cancer than medium or low-dose OCs. The number of excess cancers in women while using OCs and up to 10 years after OC cessation stood at 0.5/10,000 women 16-19 years old, 1.5/10,000 women 20-24 years old, and 4.7/10,000 women 25-29 years old. The elevated risk of developing breast cancer did not differ by country of origin, ethnic background, reproductive history, or family history of breast cancer. OC users had less clinically advanced breast cancer than never-users who had breast cancer. This finding plus the moderate reduced risk of breast cancer more than 10 years after OC cessation suggest that OCs may effect earlier diagnosis of existing breast cancer instead of causing new breast cancers. The findings of this meta-analysis along with a plausible biologic mechanism (estrogen stimulates breast cancer cells) suggest a causal relationship between OC use and breast cancer. They also indicate that the risk is small, decreases with time, and is lower among low-dose OC users. It is reassuring that the breast cancers found among OC users is less clinically advanced than those found in never-users.

  9. Preventing Breast Cancer: Making Progress

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues Preventing Breast Cancer: Making Progress Past Issues / Fall 2006 Table of ... 000 women will have been diagnosed with invasive breast cancer, and nearly 41,000 women will die from ...

  10. Understanding your breast cancer risk

    MedlinePlus

    ... ency/patientinstructions/000830.htm Understanding your breast cancer risk To use the sharing features on this page, ... you can do to help prevent breast cancer. Risk Factors You Cannot Control Risk factors you cannot ...

  11. Computerized Cognitive Retraining in Improving Cognitive Function in Breast Cancer Survivors

    ClinicalTrials.gov

    2017-03-02

    Cancer Survivor; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  12. Cardiac Rehabilitation Program in Improving Cardiorespiratory Fitness in Stage 0-III Breast Cancer Survivors

    ClinicalTrials.gov

    2017-08-17

    Cancer Survivor; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  13. Targeting Androgen Receptor in Breast Cancer: Enzalutamide as a Novel Breast Cancer Therapeutic

    DTIC Science & Technology

    2014-09-01

    Detroit, MI RESULTS BACKGROUND Androgen Receptor Signaling in ER/PgR+ Breast Cancer  Estrogen receptor (ER)/ progesterone receptor (PgR...phenotypes. – Distinct subtypes are classified by the presence of estrogen (ER), progesterone (PgR), and human epidermal growth factor 2 (HER2) receptors...Exclusion Criteria Stage 1 • Severe concurrent disease, infection, or comorbidity • Pregnancy or lactation • Known/suspected brain metastases or

  14. CEREBEL (EGF111438): A Phase III, Randomized, Open-Label Study of Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer.

    PubMed

    Pivot, Xavier; Manikhas, Alexey; Żurawski, Bogdan; Chmielowska, Ewa; Karaszewska, Boguslawa; Allerton, Rozenn; Chan, Stephen; Fabi, Alessandra; Bidoli, Paolo; Gori, Stefania; Ciruelos, Eva; Dank, Magdolna; Hornyak, Lajos; Margolin, Sara; Nusch, Arnd; Parikh, Roma; Nagi, Fareha; DeSilvio, Michelle; Santillana, Sergio; Swaby, Ramona F; Semiglazov, Vladimir

    2015-05-10

    CEREBEL compared the incidence of CNS metastases as first site of relapse in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer receiving lapatinib-capecitabine or trastuzumab-capecitabine. Patients without baseline CNS metastases were randomly assigned (1:1) to receive lapatinib-capecitabine (lapatinib 1,250 mg per day; capecitabine 2,000 mg/m(2) per day on days 1 to 14 every 21 days) or trastuzumab-capecitabine (trastuzumab loading dose of 8 mg/kg followed by an infusion of 6 mg/kg every 3 weeks; capecitabine 2,500 mg/m(2) per day on days 1 to 14 every 21 days). The primary end point was incidence of CNS metastases as first site of relapse. Secondary end points included progression-free survival (PFS) and overall survival (OS). The study was terminated early with 540 enrolled patients (271 received lapatinib-capecitabine, and 269 received trastuzumab-capecitabine). Incidence of CNS metastases as first site of relapse was 3% (eight of 251 patients) for lapatinib-capecitabine and 5% (12 of 250 patients) for trastuzumab-capecitabine (treatment differences, -1.6%; 95% CI, -2% to 5%; P = .360). PFS and OS were longer with trastuzumab-capecitabine versus lapatinib-capecitabine (hazard ratio [HR] for PFS, 1.30; 95% CI, 1.04 to 1.64; HR for OS, 1.34; 95% CI, 0.95 to 1.64). Serious adverse events were reported in 13% (34 of 269 patients) and 17% (45 of 267 patients) of patients in the lapatinib-capecitabine and trastuzumab-capecitabine arms, respectively. CEREBEL is inconclusive for the primary end point, and no difference was detected between lapatinb-capecitabine and trastuzumab-capecitabine for the incidence of CNS metastases. A better outcome was observed with trastuzumab-capecitabine in the overall population. However, lapatinib-capecitabine efficacy may have been affected by previous exposure to a trastuzumab regimen and/or when treatment was given as first- or second-line therapy in the metastatic setting. © 2015 by American

  15. Targeting HER2 Positive Breast Cancer with Chemopreventive Agents

    PubMed Central

    Wahler, Joseph; Suh, Nanjoo

    2015-01-01

    Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is a subtype of breast cancer that is exhibited in approximately 20-30% of breast cancer cases. The overexpression of HER2 is typically associated with a more aggressive disease and poor prognosis. Currently, the therapeutic drugs trastuzumab and lapatinib are the most commonly used to combat HER2+ breast cancer. However, tumors can develop resistance to these drugs. A better understanding of the mechanism of how HER2+ breast cancer works will help aid the development for new therapeutic approaches which more closely target the source of the signaling dysfunction. This review summarizes four major points in the context of HER2 over-expressing breast cancer (i) HER2 as a molecular target in breast cancer therapy, (ii) current treatment options as well as ongoing clinical studies, (iii) animal and cellular models for the study of HER2 over-expressing breast cancer, and (iv) future therapies and chemopreventive agents used to target HER2+ breast cancer. PMID:26442201

  16. Omega-3 Fatty Acid in Treating Patients With Stage I-III Breast Cancer

    ClinicalTrials.gov

    2017-03-13

    Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Male Breast 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

  17. Hormones and Breast Cancer.

    DTIC Science & Technology

    1997-10-01

    OHE 1 hypothesis are cancer patients and lacto- vegetarians . The evidence is rather clear that certain sparse. Schneider and co-workers used a Both of... Cancer PRINCIPAL INVESTIGATOR: Giske Ursin, M.D., Ph.D. CONTRACTING ORGANIZATION: University of Southern California School of Medicine Los Angeles...TYPE AND DATES COVERED I October 1997 Final (30 Sep 94 - 29 Sep 97) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Hormones and Breast Cancer DAMD17-94-J

  18. Vasopressin and Breast Cancer

    DTIC Science & Technology

    1996-09-01

    receptors7:on-breast cancer cells represents a way in which these peptides might influence cancer cell pathophysiology. However, the expression of...National Institutes of Health . In the conduct of research utilIzing recombinant DNA, the nvestigator(s) adhered to the NIH G.idelines for Research...possible autocrine/paracrine role for this peptide in cancer cells. In support of this hypothesis vasopressin was shown to have a growth-promoting influence

  19. Targeting the androgen receptor in triple-negative breast cancer.

    PubMed

    Gucalp, Ayca; Traina, Tiffany A

    Triple-negative breast cancer represents approximately 15%-20% of all newly diagnosed breast cancers, but it accounts for a disproportionate number of breast cancer-related deaths each year. Owing to the lack of estrogen, progesterone, and human epidermal growth factor receptor 2 expression, patients with triple-negative breast cancer do not benefit from generally well-tolerated and effective therapies targeting the estrogen and human epidermal growth factor receptor 2 signaling pathways and are faced with an increased risk of disease progression and poorer overall survival. The heterogeneity of triple-negative breast cancer has been increasingly recognized and this may lead to therapeutic opportunities because of newly defined oncogenic drivers and targets. A subset of triple-negative breast tumors expresses the androgen receptor (AR) and this may benefit from treatments that inhibit the AR-signaling pathway. The first proof-of-concept trial established activity of the AR antagonist, bicalutamide, in patients with advanced AR+ triple-negative breast cancer. Since that time, evidence further supports the activity of other next-generation AR-targeted agents such as enzalutamide. Not unlike in estrogen receptor-positive breast cancer, mechanisms of resistance are being investigated and rationale exists for thoughtful, well-designed combination regimens such as AR antagonism with CDK4/6 pathway inhibitors or PI3K inhibitors. Furthermore, novel agents developed for the treatment of prostate cancer, which reduce androgen production such as abiraterone acetate and seviteronel, are being tested as well. This review summarizes the underlying biology of AR signaling in breast cancer development and the available clinical trial data for the use of anti-androgen therapy in the treatment of AR+ triple-negative breast cancer.

  20. Pregnancy associated breast cancer and pregnancy after breast cancer treatment.

    PubMed

    Doğer, Emek; Calışkan, Eray; Mallmann, Peter

    2011-01-01

    Breast cancer is one of the most common cancers diagnosed during pregnancy and its frequency is increasing as more women postpone their pregnancies to their thirties and forties. Breast cancer diagnosis during pregnancy and lactation is difficult and complex both for the patient and doctors. Delay in diagnosis is frequent and treatment modalities are difficult to accept for the pregnant women. The common treatment approach is surgery after diagnosis, chemotherapy after the first trimester and radiotherapy after delivery. Even though early stage breast cancers have similar prognosis, advanced stage breast cancers diagnosed during pregnancy and lactation have poorer prognosis than similar stage breast cancers diagnosed in non-pregnant women. Women who desire to become pregnant after treatment of breast cancer will have many conflicts. Although the most common concern is recurrence of breast cancer due to pregnancy, the studies conducted showed that pregnancy has no negative effect on breast cancer prognosis. In this review we search for the frequency of breast cancer during pregnancy, the histopathological findings, risk factor, diagnostic and treatment modalities. We reviewed the literature for evidence based findings to help consult the patients on the outcome of breast cancer diagnosed during pregnancy and lactation, and also inform the patients who desire to become pregnant after breast cancer according to current evidences.

  1. Pregnancy associated breast cancer and pregnancy after breast cancer treatment

    PubMed Central

    Doğer, Emek; Çalışkan, Eray; Mallmann, Peter

    2011-01-01

    Breast cancer is one of the most common cancers diagnosed during pregnancy and its frequency is increasing as more women postpone their pregnancies to their thirties and forties. Breast cancer diagnosis during pregnancy and lactation is difficult and complex both for the patient and doctors. Delay in diagnosis is frequent and treatment modalities are difficult to accept for the pregnant women. The common treatment approach is surgery after diagnosis, chemotherapy after the first trimester and radiotherapy after delivery. Even though early stage breast cancers have similar prognosis, advanced stage breast cancers diagnosed during pregnancy and lactation have poorer prognosis than similar stage breast cancers diagnosed in non-pregnant women. Women who desire to become pregnant after treatment of breast cancer will have many conflicts. Although the most common concern is recurrence of breast cancer due to pregnancy, the studies conducted showed that pregnancy has no negative effect on breast cancer prognosis. In this review we search for the frequency of breast cancer during pregnancy, the histopathological findings, risk factor, diagnostic and treatment modalities. We reviewed the literature for evidence based findings to help consult the patients on the outcome of breast cancer diagnosed during pregnancy and lactation, and also inform the patients who desire to become pregnant after breast cancer according to current evidences. PMID:24592003

  2. Functional cyclic AMP response element in the breast cancer resistance protein (BCRP/ABCG2) promoter modulates epidermal growth factor receptor pathway- or androgen withdrawal-mediated BCRP/ABCG2 transcription in human cancer cells.

    PubMed

    Xie, Yi; Nakanishi, Takeo; Natarajan, Karthika; Safren, Lowell; Hamburger, Anne W; Hussain, Arif; Ross, Douglas D

    2015-03-01

    Phosphorylated cyclic-AMP (cAMP) response element binding protein (p-CREB) is a downstream effector of a variety of important signaling pathways. We investigated whether the human BCRP promoter contains a functional cAMP response element (CRE). 8Br-cAMP, a cAMP analogue, increased the activity of a BCRP promoter reporter construct and BCRP mRNA in human carcinoma cells. Epidermal growth factor receptor (EGFR) pathway activation also led to an increase in p-CREB and in BCRP promoter reporter activity via two major downstream EGFR signaling pathways: the phosphotidylinositol-3-kinase (PI3K)/AKT pathway and the mitogen-activated protein kinase (MAPK) pathway. EGF treatment increased the phosphorylation of EGFR, AKT, ERK and CREB, while simultaneously enhancing BCRP mRNA and functional protein expression. EGF-stimulated CREB phosphorylation and BCRP induction were diminished by inhibition of EGFR, PI3K/AKT or RAS/MAPK signaling. CREB silencing using RNA interference reduced basal levels of BCRP mRNA and diminished the induction of BCRP by EGF. Chromatin immunoprecipitation assays confirmed that a putative CRE site on the BCRP promoter bound p-CREB by a point mutation of the CRE site abolished EGF-induced stimulation of BCRP promoter reporter activity. Furthermore, the CREB co-activator, cAMP-regulated transcriptional co-activator (CRTC2), is involved in CREB-mediated BCRP transcription: androgen depletion of LNCaP human prostate cancer cells increased both CREB phosphorylation and CRTC2 nuclear translocation, and enhanced BCRP expression. Silencing CREB or CRTC2 reduced basal BCRP expression and BCRP induction under androgen-depletion conditions. This novel CRE site plays a central role in mediating BCRP gene expression in several human cancer cell lines following activation of multiple cancer-relevant signaling pathways.

  3. Functional cyclic AMP response element in the breast cancer resistance protein (BCRP/ABCG2) promoter modulates epidermal growth factor receptor pathway- or androgen withdrawal-mediated BCRP/ABCG2 transcription in human cancer cells

    PubMed Central

    Xie, Yi; Nakanishi, Takeo; Natarajan, Karthika; Safren, Lowell; Hamburger, Anne W.; Hussain, Arif; Ross, Douglas D.

    2015-01-01

    We report a novel cyclic-AMP (cAMP) response element (CRE) in the human BCRP promoter that is functional in human cancer cell lines of multiple lineages. 8Br-cAMP increased the activity of a BCRP promoter reporter construct and BCRP mRNA in human carcinoma cells. Activation of the epidermal growth factor receptor (EGFR) pathway also led to an increase in BCRP promoter reporter activity and to phosphorylation of the c-AMP response element binding protein (CREB) via two major downstream EGFR signaling pathways: the phosphotidylinositol-3-kinase (PI3K)/AKT pathway and the mitogen-activated protein kinase (MAPK) pathway. EGF treatment increased the phosphorylation of EGFR, AKT, ERK and CREB, while simultaneously enhancing BCRP mRNA and functional protein expression. EGF-stimulated CREB phosphorylation and BCRP induction were diminished by inhibition of EGFR, PI3K/AKT or RAS/MAPK signaling. CREB silencing using RNA interference reduced basal levels of BCRP mRNA and diminished the induction of BCRP by EGF. Chromatin immunoprecipitation assays confirmed that a putative CRE site on the BCRP promoter bound phospho-CREB; point mutation of the CRE site abolished EGF-induced stimulation of BCRP promoter reporter activity. Furthermore, the CREB co-activator, cAMP-regulated transcriptional co-activator (CRTC2), is also involved in CREB-mediated BCRP transcription: androgen depletion of LNCaP human prostate cancer cells increased both CREB phosphorylation and CRTC2 nuclear translocation, and enhanced BCRP expression. Silencing CREB or CRTC2 reduced basal BCRP expression and BCRP induction under androgen-depletion conditions. This novel CRE site plays a central role in mediating BCRP gene expression in multiple human cancer cell lines following activation of a variety of signaling pathways. PMID:25615818

  4. Affluence and Breast Cancer.

    PubMed

    Lehrer, Steven; Green, Sheryl; Rosenzweig, Kenneth E

    2016-09-01

    High income, high socioeconomic status, and affluence increase breast cancer incidence. Socioeconomic status in USA breast cancer studies has been assessed by block-group socioeconomic measures. A block group is a portion of a census tract with boundaries that segregate, as far as possible, socioeconomic groups. In this study, we used US Census income data instead of block groups to gauge socioeconomic status of breast cancer patients in relationship with incidence, prognostic markers, and survival. US state breast cancer incidence and mortality data are from the U.S. Cancer Statistics Working Group, United States Cancer Statistics: 1999-2011. Three-Year-Average Median Household Income by State, 2010 to 2012, is from the U.S. Census Bureau, Current Population Survey, 2011 to 2013 Annual Social and Economic Supplements. County incomes are from the 2005-2009 American Community Survey of the U.S. Census Bureau. The American Community Survey is an ongoing statistical survey that samples a small percentage of the population yearly. Its purpose is to provide communities the information they need to plan investments and services. Breast cancer county incidence and survival data are from the National Cancer Institute's Surveillance, Epidemiology and End Results Program (SEER) data base. We analyzed SEER data from 198 counties in California, Connecticut, Georgia, Hawaii, Iowa, New Mexico, Utah, and Washington. SEER uses the Collaborative Stage (CS) Data Collection System. We have retained the SEER CS variables. There was a significant relationship of income with breast cancer incidence in 50 USA states and the District of Columbia in White women (r = 0.623, p < 0.001). There was a significant relationship between node involvement and income in Whites in 198 USA counties. Income was significantly correlated with 5-year relative survival in Whites with localized breast cancer. Income was not correlated with 5-year survival of Black race (p = 0.364) or other races (p = 0

  5. Breast Cancer: Current Molecular Therapeutic Targets and New Players.

    PubMed

    Nagini, Siddavaram

    2017-01-01

    Breast cancer is the most common cancer and the most frequent cause of cancer death among women worldwide. Breast cancer is a complex, heterogeneous disease classified into hormone-receptor-positive, human epidermal growth factor receptor-2 overexpressing (HER2+) and triple-negative breast cancer (TNBC) based on histological features. Endocrine therapy, the mainstay of treatment for hormone-responsive breast cancer involves use of selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs) and aromatase inhibitors (AIs). Agents that target estrogen receptor (ER) and HER2 such as tamoxifen and trastuzumab have been the most extensively used therapeutics for breast cancer. Crosstalk between ER and other signalling networks as well as epigenetic mechanisms have been envisaged to contribute to endocrine therapy resistance. TNBC, a complex, heterogeneous, aggressive form of breast cancer in which the cells do not express ER, progesterone receptor or HER2 is refractory to therapy. Several molecular targets are being explored to target TNBC including androgen receptor, epidermal growth factor receptor (EGFR), poly(ADP-ribose) polymerase (PARP), and vascular endothelial growth factor (VEGF). Receptors, protein tyrosine kinases, phosphatases, proteases, PI3K/Akt signalling pathway, microRNAs (miRs) and long noncoding RNAs (lncRNAs) are potential therapeutic targets. miR-based therapeutic approaches include inhibition of oncomiRs by antisense oligonucleotides, restoration of tumour suppressors using miR mimics, and chemical modification of miRs. The lnRNAs HOTAIR, SPRY4-IT1, GAS5, and PANDAR, new players in tumour development and prognosis may have theranostic applications in breast cancer. Several novel classes of mechanism-based drugs have been designed and synthesised for treatment of breast cancer. Integration of nucleic acid sequencing studies with mass spectrometry-based peptide sequencing and posttranslational modifications as

  6. Portraying breast cancers with long noncoding RNAs

    PubMed Central

    Van Grembergen, Olivier; Bizet, Martin; de Bony, Eric J.; Calonne, Emilie; Putmans, Pascale; Brohée, Sylvain; Olsen, Catharina; Guo, Mingzhou; Bontempi, Gianluca; Sotiriou, Christos; Defrance, Matthieu; Fuks, François

    2016-01-01

    Evidence is emerging that long noncoding RNAs (lncRNAs) may play a role in cancer development, but this role is not yet clear. We performed a genome-wide transcriptional survey to explore the lncRNA landscape across 995 breast tissue samples. We identified 215 lncRNAs whose genes are aberrantly expressed in breast tumors, as compared to normal samples. Unsupervised hierarchical clustering of breast tumors on the basis of their lncRNAs revealed four breast cancer subgroups that correlate tightly with PAM50-defined mRNA-based subtypes. Using multivariate analysis, we identified no less than 210 lncRNAs prognostic of clinical outcome. By analyzing the coexpression of lncRNA genes and protein-coding genes, we inferred potential functions of the 215 dysregulated lncRNAs. We then associated subtype-specific lncRNAs with key molecular processes involved in cancer. A correlation was observed, on the one hand, between luminal A–specific lncRNAs and the activation of phosphatidylinositol 3-kinase, fibroblast growth factor, and transforming growth factor–β pathways and, on the other hand, between basal-like–specific lncRNAs and the activation of epidermal growth factor receptor (EGFR)–dependent pathways and of the epithelial-to-mesenchymal transition. Finally, we showed that a specific lncRNA, which we called CYTOR, plays a role in breast cancer. We confirmed its predicted functions, showing that it regulates genes involved in the EGFR/mammalian target of rapamycin pathway and is required for cell proliferation, cell migration, and cytoskeleton organization. Overall, our work provides the most comprehensive analyses for lncRNA in breast cancers. Our findings suggest a wide range of biological functions associated with lncRNAs in breast cancer and provide a foundation for functional investigations that could lead to new therapeutic approaches. PMID:27617288

  7. Diet and breast cancer.

    PubMed

    Bradlow, H Leon; Sepkovic, Daniel W

    2002-06-01

    The preponderance of evidence suggests a role for fat and alcohol as risk factors for breast cancer. The role of milk is more controversial with some studies suggesting that milk is a risk factor and others that consumption of milk is protective against breast cancer. No other major nutrient appears to play a significant role in increasing breast cancer risk. On the other hand, there is increasing evidence that a variety of micronutrients and hormones appear to have significant anticancer activity. These range from steroids such as dehydroepiandrosterone (DHEA) and its analysis to indoles, isothiocyanates, and isoflavone derivatives. These compounds act directly by interfering with cyclins and promoting apoptosis as well as indirectly by altering estrogen metabolism in a favorable direction. These effects are not merely theoretical actions in cell culture and tissue explants; they have been demonstrated in human patients as a range of studies have demonstrated.

  8. Virtual Weight Loss Program in Maintaining Weight in African American Breast Cancer Survivors

    ClinicalTrials.gov

    2017-01-19

    Cancer Survivor; Invasive Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  9. Inflammatory Breast Cancer from Metastatic Ovarian Cancer

    PubMed Central

    Achariyapota, Vuthinun; Chuangsuwanich, Tuenjai

    2016-01-01

    Metastases to the breast from tumors other than breast carcinomas are extremely rare and represent only 0.2–1.3% of all diagnosed malignant breast tumors. Furthermore, while the most common sites for advanced ovarian cancer metastases are the liver, lung, and pleura, metastasis to the breast from a primary ovarian cancer is uncommon and has only been reported in 0.03–0.6% of all breast cancers. Here we describe a case report of a 50-year-old female patient with a rare case of breast metastases from an advanced ovarian cancer, presenting as inflammatory breast cancer. Our observations emphasize the clinical importance of distinguishing between primary and metastatic breast cancer during diagnosis for the purpose of appropriate prognosis and treatment. PMID:27047697

  10. Accelerated Radiation Therapy After Surgery in Treating Patients With Breast Cancer

    ClinicalTrials.gov

    2017-09-21

    Inflammatory Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Tubular Ductal Breast Carcinoma

  11. Early detection of breast cancer.

    PubMed

    Nettles-Carlson, B

    1989-01-01

    Timely, comprehensive screening for breast cancer is a major, though often overlooked, component of primary health care for women. This article reviews the scientific rationale for screening and outlines the current recommendations of the American Cancer Society and the U.S. Preventive Services Task Force regarding the use of mammography, clinical breast examination (CBE), and breast self-examination (BSE). Nursing interventions to decrease barriers to effective screening are discussed, and an expanded role of nurses in breast cancer screening is proposed.

  12. Breast cancer epidemiology.

    PubMed

    Kelsey, J L; Berkowitz, G S

    1988-10-15

    The various risk factors for breast cancer have been recognized for many years. A table lists these established breast cancer risk factors together with the approximate magnitude of the increase in risk associated with them. Breast cancer incidence rates increase with age throughout the life span in Western countries, although the rate of increase is greater up to age 50 years than after 50 years. Breast cancer is more common among women in upper rather than lower social classes, among women who never have been married, among women living in urban areas, among women living in the northern US than in the southern US, and among whites than blacks, at least among those over age 50. Women in North American and Northern European countries have the highest risk for breast cancer, women in Southern European and Latin American countries are at intermediate risk, and women in Africa and Asian countries have the lowest risk. Yet, rapid rates of increase in incident rates have been noted in recent years in many Asian, Central European, and some South American countries. The later the age at which a woman has her 1st full-term pregnancy, the higher her risk for breast cancer; the earlier the age at menarche and the later the age at menopause the higher the risk; and among women who have a premenopausal oophorectomy, the earlier the age at which this occurs the lower the risk. Among postmenopausal women, obesity is associated with an increase in risk. Lactation is negatively associated with subsequent breast cancer risk. Some current research is considering potential risk factors that have not been well studied in the past, including alcohol consumption, cigarette smoking, caffeine consumption, exposure to diethylstilbestrol (DES), emotional stress, exposure to electric power, and lack of physical activity. Other areas of current research reviewed here include radiation, mammographic parenchymal patterns, a high-fat diet, use of oral contraceptives (OCs), use of estrogen

  13. Pertuzumab, Trastuzumab, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With HER2-Positive Advanced Breast Cancer

    ClinicalTrials.gov

    2016-12-23

    HER2-positive Breast Cancer; Recurrent Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Breast Adenocarcinoma; Inflammatory Breast Carcinoma

  14. Breast cancer screening with digital breast tomosynthesis.

    PubMed

    Skaane, Per

    2017-01-01

    To give an overview of studies comparing full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) in breast cancer screening. The implementation of tomosynthesis in breast imaging is rapidly increasing world-wide. Experimental clinical studies of relevance for DBT screening have shown that tomosynthesis might have a great potential in breast cancer screening, although most of these retrospective reading studies are based on small populations, so that final conclusions are difficult to draw from individual reports. Several retrospective studies and three prospective trials on tomosynthesis in breast cancer screening have been published so far, confirming the great potential of DBT in mammography screening. The main results of these screening studies are presented. The retrospective screening studies from USA have all shown a significant decrease in the recall rate using DBT as adjunct to mammography. Most of these studies have also shown an increase in the cancer detection rate, and the non-significant results in some studies might be explained by a lack of statistical power. All the three prospective European trials have shown a significant increase in the cancer detection rate. The retrospective and the prospective screening studies comparing FFDM and DBT have all demonstrated that tomosynthesis has a great potential for improving breast cancer screening. DBT should be regarded as a better mammogram that could improve or overcome limitations of the conventional mammography, and tomosynthesis might be considered as the new technique in the next future of breast cancer screening.

  15. Surveying Breast Cancer's Genomic Landscape.

    PubMed

    2016-07-01

    An in-depth analysis has produced the most comprehensive portrait to date of the myriad genomic alterations involved in breast cancer. In sequencing the whole genomes of 560 breast cancers and combining this information with published data from another 772 breast tumors, the research team uncovered several new genes and mutational signatures that potentially influence this disease.

  16. Ultrasound in Detecting Taxane-Induced Neuropathy in Patients With Breast Cancer

    ClinicalTrials.gov

    2017-05-15

    Peripheral Neuropathy; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  17. Breast cancer in systemic lupus.

    PubMed

    Bernatsky, S; Ramsey-Goldman, R; Petri, M; Urowitz, M B; Gladman, D D; Fortin, P F; Ginzler, E; Romero-Diaz, J; Peschken, C; Jacobsen, S; Hanly, J G; Gordon, C; Nived, O; Yelin, E H; Isenberg, D; Rahman, A; Bae, S-C; Joseph, L; Witte, T; Ruiz-Irastorza, G; Aranow, C; Kamen, D; Sturfeldt, G; Foulkes, W D; Hansen, J E; St Pierre, Y; Raymer, P Chrétien; Tessier-Cloutier, B; Clarke, A E

    2017-03-01

    Objective There is a decreased breast cancer risk in systemic lupus erythematosus (SLE) versus the general population. We assessed a large sample of SLE patients, evaluating demographic and clinical characteristics and breast cancer risk. Methods We performed case-cohort analyses within a multi-center international SLE sample. We calculated the breast cancer hazard ratio (HR) in female SLE patients, relative to demographics, reproductive history, family history of breast cancer, and time-dependent measures of anti-dsDNA positivity, cumulative disease activity, and drugs, adjusted for SLE duration. Results There were 86 SLE breast cancers and 4498 female SLE cancer-free controls. Patients were followed on average for 7.6 years. Versus controls, SLE breast cancer cases tended to be white and older. Breast cancer cases were similar to controls regarding anti-dsDNA positivity, disease activity, and most drug exposures over time. In univariate and multivariate models, the principal factor associated with breast cancers was older age at cohort entry. Conclusions There was little evidence that breast cancer risk in this SLE sample was strongly driven by any of the clinical factors that we studied. Further search for factors that determine the lower risk of breast cancer in SLE may be warranted.

  18. [Adjuvant therapy of breast cancer with trastuzumab].

    PubMed

    Beneder, Christine; Marth, Christian

    2008-01-01

    With the approval of trastuzumab (Herceptin) in 1998, a new era of breast cancer treatment has been heralded. This antibody is directed at the intracellular domain of a member of the epidermal growth factor receptor family, the so-called HER2 receptor. About 25-30% of all breast cancers overexpress this factor, which is associated with a more unfavorable prognosis. Trastuzumab is indicated for patients whose tumor overexpresses HER2. All previous studies on the adjuvant therapy with trastuzumab show very consistent results and provide evidence that the risk of recurrence can be reduced by half by the antibody. Nevertheless, there are still numerous open and controversially discussed questions concerning the use of trastuzumab in adjuvant therapy.

  19. Breast cancer screening and biomarkers.

    PubMed

    Brooks, Mai

    2009-01-01

    Annual screening mammograms have been shown to be cost-effective and are credited for the decline in mortality of breast cancer. New technologies including breast magnetic resonance imaging (MRI) may further improve early breast cancer detection in asymptomatic women. Serum tumor markers such as CA 15-3, carcinoembyonic antigen (CEA), and CA 27-29 are ordered in the clinic mainly for disease surveillance, and not useful for detection of localized cancer. This review will discuss blood-based markers and breast-based markers, such as nipple/ductal fluid, with an emphasis on biomarkers for early detection of breast cancer. In the future, it is likely that a combination approach to simultaneously measure multiple markers would be most successful in detecting early breast cancer. Ideally, such a biomarker panel should be able to detect breast cancer in asymptomatic patients, even in the setting of normal mammogram and physical examination results.

  20. DNA methylation epigenotypes in breast cancer molecular subtypes

    PubMed Central

    2010-01-01

    Introduction Identification of gene expression-based breast cancer subtypes is considered a critical means of prognostication. Genetic mutations along with epigenetic alterations contribute to gene-expression changes occurring in breast cancer. So far, these epigenetic contributions to sporadic breast cancer subtypes have not been well characterized, and only a limited understanding exists of the epigenetic mechanisms affected in those particular breast cancer subtypes. The present study was undertaken to dissect the breast cancer methylome and to deliver specific epigenotypes associated with particular breast cancer subtypes. Methods By using a microarray approach, we analyzed DNA methylation in regulatory regions of 806 cancer-related genes in 28 breast cancer paired samples. We subsequently performed substantial technical and biologic validation by pyrosequencing, investigating the top qualifying 19 CpG regions in independent cohorts encompassing 47 basal-like, 44 ERBB2+ overexpressing, 48 luminal A, and 48 luminal B paired breast cancer/adjacent tissues. With the all-subset selection method, we identified the most subtype-predictive methylation profiles in multivariable logistic regression analysis. Results The approach efficiently recognized 15 individual CpG loci differentially methylated in breast cancer tumor subtypes. We further identified novel subtype-specific epigenotypes that clearly demonstrate the differences in the methylation profiles of basal-like and human epidermal growth factor 2 (HER2)-overexpressing tumors. Conclusions Our results provide evidence that well-defined DNA methylation profiles enable breast cancer subtype prediction and support the utilization of this biomarker for prognostication and therapeutic stratification of patients with breast cancer. PMID:20920229

  1. Obesity and Breast Cancer Prognosis: Evidence, Challenges, and Opportunities.

    PubMed

    Jiralerspong, Sao; Goodwin, Pamela J

    2016-12-10

    Purpose To summarize the evidence of an association between obesity and breast cancer prognosis. Methods We reviewed the literature regarding overweight and obesity and breast cancer survival outcomes, overall and with regard to breast cancer subtypes, breast cancer therapies, biologic mechanisms, and possible interventions. We summarize our findings and provide clinical management recommendations. Results Obesity is associated with a 35% to 40% increased risk of breast cancer recurrence and death and therefore poorer survival outcomes. This is most clearly established for estrogen receptor-positive breast cancer, with the relationship in triple-negative and human epidermal growth factor receptor 2-positive subtypes less well established. A range of biologic mechanisms that may underlie this association has been identified. Weight loss and lifestyle interventions, as well as metformin and other obesity-targeted therapies, are promising avenues that require further study. Conclusion Obesity is associated with inferior survival in breast cancer. Understanding the nature and mechanisms of this effect provides an important opportunity for interventions to improve the diagnosis, treatment, and outcomes of obese patients with breast cancer.

  2. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Dr. Harry Mahtani analyzes the gas content of nutrient media from Bioreactor used in research on human breast cancer. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  3. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Dr. Harry Mahtani analyzes the gas content of nutrient media from Bioreactor used in research on human breast cancer. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  4. [Changes in epidermal growth factor concentrations in neonates with late-onset breast milk jaundice after stopping breast feeding].

    PubMed

    Xiao, Ling-Ling; Zhang, Xue-Feng; Wang, Xin-Yu

    2013-12-01

    To investigate the changes in epidermal growth factor (EGF) concentrations in infants' serum and breast milk in neonates with late-onset breast milk jaundice after stopping breast feeding. Thirty full-term infants with late-onset breast milk jaundice were included in the study. Infants' serum and breast milk were collected before and 72 hours after stopping breast feeding, and the total bilirubin and EGF concentrations in infants' serum and EGF concentration in breast milk were measured respectively. At 72 hours after stopping breast feeding, the total bilirubin and EGF concentrations in infants' serum were significantly decreased (P<0.05), but the EGF concentration in breast milk did not show significant change (P>0.05). After stopping breast feeding, the neonates with late-onset breast milk jaundice show significant decreases in serum EGF concentration, but the EGF concentration in breast milk shows no significant change. The role and action mechanism of EGF in late-onset breast milk jaundice need further study.

  5. Genetic epidemiology of breast cancer.

    PubMed

    Thompson, W D

    1994-07-01

    It has been recognized for some time that a family history of breast cancer is associated rather strongly with a woman's own risk of developing the disease. Recent segregation analyses of population-based data on familial patterns provide evidence for a rare autosomal dominant allele that increases a carrier's susceptibility to breast cancer. The estimated proportion of breast cancer patients who carry this allele declines sharply with age at diagnosis. Empirical estimates of the risk associated with particular patterns of family history of breast cancer indicate the following: (1) having any first-degree relative with breast cancer increases a woman's risk of breast cancer 1.5-3-fold, depending on age, (2) having multiple first degree relatives affected is associated with particularly elevated risks, (3) having a second-degree relative affected increases the risk by approximately 50%, (4) affected family members on the maternal side and the paternal side contribute similarly to the risk, (5) a family history of breast cancer is associated with bilateral disease, and (6) breast cancer in males is associated with breast cancer in female relatives in much the same way as is breast cancer in women. Ovarian cancer clearly has been shown to be associated with breast cancer in families, and genetic linkage has provided strong evidence for a breast-ovarian cancer gene located somewhere on chromosome 17q. At the population level, having a first degree relative with ovarian cancer may be at least as predictive of a woman's risk for developing breast cancer as is having a second-degree relative with breast cancer. Considerably weaker evidence points to a possible familial relationship between breast and endometrial cancer and between breast cancer in women and prostatic cancer in males. The clinical applications of the genetic epidemiology of breast cancer are complicated by uncertainty as to the efficacy of mammographic screening in women under the age of 50. For the vast

  6. Azacitidine in Treating Patients With Triple Negative Stage I-IV Invasive Breast Cancer That Can Be Removed By Surgery

    ClinicalTrials.gov

    2014-02-05

    Recurrent Breast 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; Triple-negative Breast Cancer

  7. Mindfulness Meditation or Survivorship Education in Improving Behavioral Symptoms in Younger Stage 0-III Breast Cancer Survivors (Pathways to Wellness)

    ClinicalTrials.gov

    2017-03-21

    Cancer Survivor; Early-Stage Breast Carcinoma; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  8. Selection of Optimal Adjuvant Chemotherapy Regimens for Human Epidermal Growth Factor Receptor 2 (HER2) -Negative and Adjuvant Targeted Therapy for HER2-Positive Breast Cancers: An American Society of Clinical Oncology Guideline Adaptation of the Cancer Care Ontario Clinical Practice Guideline.

    PubMed

    Denduluri, Neelima; Somerfield, Mark R; Eisen, Andrea; Holloway, Jamie N; Hurria, Arti; King, Tari A; Lyman, Gary H; Partridge, Ann H; Telli, Melinda L; Trudeau, Maureen E; Wolff, Antonio C

    2016-07-10

    A Cancer Care Ontario (CCO) guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer including adjuvant targeted therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancers was identified for adaptation. The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for adapting clinical practice guidelines developed by other organizations. The CCO guideline was reviewed for developmental rigor and content applicability. On the basis of the content review of the CCO guideline, the ASCO Panel agreed that, in general, the recommendations were clear and thorough and were based on the most relevant scientific evidence, and they presented options that will be acceptable to patients. However, for some topics addressed in the CCO guideline, the ASCO Panel formulated a set of adapted recommendations on the basis of local context and practice beliefs of the Panel members. Decisions regarding adjuvant chemotherapy regimens should take into account baseline recurrence risk, toxicities, likelihood of benefit, and host factors such as comorbidities. In high-risk HER2-negative populations with excellent performance status, anthracycline- and taxane-containing regimens are the standard of care. Docetaxel and cyclophosphamide for four cycles is an acceptable non-anthracycline regimen. In high-risk HER2-positive disease, sequential anthracycline and taxanes administered concurrently with trastuzumab or docetaxel, carboplatin, and trastuzumab for six cycles are recommended. An alternative regimen in a lower-risk, node-negative, HER2-positive population is paclitaxel and trastuzumab once per week for 12 cycles. Trastuzumab should be given for 1 year. Platinum salts should not be routinely administered in the adjuvant triple-negative population until survival efficacy data become available. © 2016 by American Society of Clinical Oncology.

  9. Evaluation of Human Epidermal Growth Factor Receptor 2 (HER2) Gene Status in Human Breast Cancer Formalin-Fixed Paraffin-Embedded (FFPE) Tissue Specimens by Fluorescence In Situ Hybridization (FISH).

    PubMed

    Hwang, Harry C; Gown, Allen M

    2016-01-01

    Current standard of care requires that HER2 gene testing be performed on all newly diagnosed invasive breast cancers in order to determine eligibility for anti-HER2 antibody therapy and should be performed in accordance with current ASCO-CAP guidelines (Hammond et al., J Clin Oncol 29(15):e458, 2011; Wolff et al., J Clin Oncol 31(31):3997-4013, 2013). Here we describe a HER2 FISH methodology to evaluate HER2 gene status in FFPE breast tumor specimens.

  10. Heterogeneity in breast cancer.

    PubMed

    Polyak, Kornelia

    2011-10-01

    Breast cancer is a heterogeneous disease. There is a high degree of diversity between and within tumors as well as among cancer-bearing individuals, and all of these factors together determine the risk of disease progression and therapeutic resistance. Advances in technologies such as whole-genome sequencing and functional viability screens now allow us to analyze tumors at unprecedented depths. However, translating this increasing knowledge into clinical practice remains a challenge in part due to tumor evolution driven by the diversity of cancer cell populations and their microenvironment. The articles in this Review series discuss recent advances in our understanding of breast tumor heterogeneity, therapies tailored based on this knowledge, and future ways of assessing and treating heterogeneous tumors.

  11. Hormones, Women and Breast Cancer

    MedlinePlus

    ... diagnosed? The most common way to find breast cancer is through a breast exam or mammogram (x-ray). Some women at high risk may need a screening MRI (magnetic resonance imaging) scan, which is more sensitive than a mammogram. ...

  12. HER-2 Positive Breast Cancer - a Mini-Review.

    PubMed

    Asif, Hafiz Muhammad; Sultana, Sabira; Ahmed, Saeed; Akhtar, Naheed; Tariq, Muhammad

    2016-01-01

    Breast cancer is one of among all cancers with increased incidence, high mortality rate, and high economic and social costs. The the most common type of cancer among females worldwide, breast cancer is actually the uncontrolled proliferation of cells which attain malignancy. Recently it has shown that breast cancer contributes 11% among all types of cancer diagnosed globally on an annual basis and it is one of the leading causes of death among women. The human epidermal growth factor receptor 2 (HER-2) is a receptor tyrosine-protein kinase erbB-2 normally involved in the proliferation and division of breast cells. In some abnormal cases the HER2 gene does not work correctly and makes too many copies of itself. HER2-positive (HER2+) breast cancers constitute an aggressive type of breast cancer and tend to grow faster and are more likely to spread. However, therapies that specifically target HER2, such as Herceptin® (traztuzumab), are very effective. HER2 targeted therapies, has significantly improved the therapeutic outcome for patients with HER2 positive breast cancer.

  13. Male breast cancer.

    PubMed

    Reis, Leonardo Oliveira; Dias, Fernando Gf; Castro, Marcos As; Ferreira, Ubirajara

    2011-06-01

    Male breast cancer (MBC) is a rare disease. However, as global populace ages, there is a trend to MBC increasing. Although aetiology is still unclear, constitutional, environmental, hormonal (abnormalities in estrogen/androgen balance) and genetic (positive family history, Klinefelter syndrome, mutations in BRCA1 and specially BRCA2) risk factors are already known. Clinic manifestation is painless hard and fixed nodule in the subareolar region in 75% of cases, with nipple commitment earlier than in women. Breast cancer has similar prognostic factors in males and females, among which axillary adenopathy (present in 40-55% cases) is the most important one. Although mammography, ultrasonography and scintigraphy can be useful tools in diagnosis; clinical assessment, along with a confirmatory biopsy, remains the main step in the evaluation of men with breast lesions. Infiltrating ductal carcinoma is the most frequent histological type. The established standard of care is modified radical mastectomy followed by tamoxifen for endocrine-responsive positive disease, although other options are being explored. While similarities between breast cancer in males and females exist, it is not appropriate to extrapolate data from female disease to the treatment of male. There is a need for specific multi-institutional trials to better understanding of clinicopathologic features and establishment of optimal therapy for this disease.

  14. 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

  15. [Occult multicentric breast cancer].

    PubMed

    Vtorushin, S V; Zab'ialova, M V; Glushchenko, S A; Perel'muter, V M; Slonimskaia, E M

    2009-01-01

    The study included 92 patients with invasive ductal breast cancer (T2-4N0-2M0-1). In 38 cases, tumor growth was unicentric while histologically identifiable ones as multicentric in 44. Multicentricity mostly occurred in cases of macroscopically-identifiable nodes located in the central segments of the breast. Clinically-identifiable nodes of multicentric tumor growth measured more than 3 cm. Multicentric tumors were mostly grade III, featured lower expression of sex hormone receptors and positive Her2 status.

  16. What Happens After Treatment for Breast Cancer in Men?

    MedlinePlus

    ... Men After Treatment What Happens After Treatment for Breast Cancer in Men? For many men with breast cancer, ... Breast Cancer in Men Stops Working More In Breast Cancer In Men About Breast Cancer in Men Causes, ...

  17. Increasing Breast Cancer Surveillance among African American Breast Cancer Survivors

    DTIC Science & Technology

    2007-07-01

    predictors of surveillance and follow-up care is Baldwin’s Afrocentric model for describing AA women’s participation in breast and cervical cancer screening...African American women’s participation in breast and cervical cancer early detection and screening. Adv Nurs Sci. 1996;19(2):27Y42. 28. Marin G. Subjective...AD_________________ Award Number: DAMD17-03-1-0454 TITLE: Increasing Breast Cancer Surveillance

  18. Effect of Fu-Zheng-Xiao-Liu Granules on Expression of Human Epidermal Growth Factor Receptor 2 (HER-2) and Proliferation and Apoptosis of Breast Cancer Cell Line SKBR-3.

    PubMed

    Mo, Ting; Yue, Shuangbing; Tian, Huan; Lin, Hong; Zhang, Guanglu; Zhang, Zili

    2016-12-23

    BACKGROUND Previous research showed that granulized Fu-Zheng-Xiao-Liu has a significant effect on breast cancer. However, it remains unclear whether HER-2 plays a role in this anti-cancer effect. MATERIAL AND METHODS Serum of male SD rats administered Fu-Zheng-Xiao-Liu granules (SF) was prepared and used to treat HER-2 positive breast cancer cell line SKBR-3. PBS and herceptin were used as negative and positive controls, respectively. MTT was used to detect the proliferation of SKBR-3 cells. Flow cytometry was used to measure the apoptosis of SKBR-3 cells. Western blot and immunofluorescence were used to measure the expression change of HER-2. RESULTS Serum of male SD rats administered Fu-Zheng-Xiao-Liu granules had significantly reduced HER-2 expression at both mRNA level and protein level, significantly inhibited proliferation of SKBR-3 cells, and significantly increased apoptosis of SKBR-3 cells, compared to that of the blank control group or serum control group. CONCLUSIONS Fu-Zheng-Xiao-Liu granules affect proliferation and apoptosis through inhibition of HER-2 transcription and translation, providing an experimental basis for further study of the mechanism by which Fu-Zheng-Xiao-Liu granules affect breast cancer.

  19. Educating Normal Breast Mucosa to Prevent Breast Cancer

    DTIC Science & Technology

    2015-05-01

    1 Award Number: W81XWH-12-1-0059 TITLE: Educating normal breast mucosa to prevent breast cancer PRINCIPAL INVESTIGATOR: Keith L Knutson...SUBTITLE Educating Normal Breast Mucosa to Prevent Breast Cancer 5a. CONTRACT NUMBER W81XWH-12-1-0059 5b. GRANT NUMBER W81XWH-12-1-0059 5c...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Breast cancer develops from breast mucosa and breast mucosa has intact immune system to

  20. Breast-Conserving Surgery Followed by Radiation Therapy With MRI-Detected Stage I or Stage II Breast Cancer

    ClinicalTrials.gov

    2011-12-07

    Ductal Breast Carcinoma in Situ; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Male Breast Cancer; Medullary Ductal Breast Carcinoma With Lymphocytic Infiltrate; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Tubular Ductal Breast Carcinoma

  1. Promising molecular targeted therapies in breast cancer

    PubMed Central

    Munagala, Radha; Aqil, Farrukh; Gupta, Ramesh C.

    2011-01-01

    In recent years, there has been a significant improvement in the understanding of molecular events and critical pathways involved in breast cancer. This has led to the identification of novel targets and development of anticancer therapies referred to as targeted therapy. Targeted therapy has high specificity for the molecules involved in key molecular events that are responsible for cancer phenotype such as cell growth, survival, migration, invasion, metastasis, apoptosis, cell-cycle progression, and angiogenesis. Targeted agents that have been approved for breast cancer include trastuzumab and lapatinib, directed against human epidermal growth factor receptor 2 (HER2) and bevacizumab, directed against vascular endothelial growth factor (VEGF). Several other targeted agents currently under evaluation in preclinical and clinical trials include inhibitors of epidermal growth factor receptor (EGFR), dual EGFR and HER2 inhibitors, VEGF/VEGFR inhibitors, and agents that interfere with crucial signaling pathways such as PI3K/AKT/mTOR and RAS/MEK/ERK; agents against other tyrosine kinases such as Src, insulin-like growth factor (IGF)/IGF-receptor (IGFR); agents that promote apoptosis such as Poly ADP ribose polymerase inhibitors; agents that target invasion and metastasis such as matrix metalloproteinases inhibitors and others. In this review, we highlight the most promising targeted agents and their combination with mainstream chemotherapeutic drugs in clinical trials. PMID:21713084

  2. Promising molecular targeted therapies in breast cancer.

    PubMed

    Munagala, Radha; Aqil, Farrukh; Gupta, Ramesh C

    2011-05-01

    In recent years, there has been a significant improvement in the understanding of molecular events and critical pathways involved in breast cancer. This has led to the identification of novel targets and development of anticancer therapies referred to as targeted therapy. Targeted therapy has high specificity for the molecules involved in key molecular events that are responsible for cancer phenotype such as cell growth, survival, migration, invasion, metastasis, apoptosis, cell-cycle progression, and angiogenesis. Targeted agents that have been approved for breast cancer include trastuzumab and lapatinib, directed against human epidermal growth factor receptor 2 (HER2) and bevacizumab, directed against vascular endothelial growth factor (VEGF). Several other targeted agents currently under evaluation in preclinical and clinical trials include inhibitors of epidermal growth factor receptor (EGFR), dual EGFR and HER2 inhibitors, VEGF/VEGFR inhibitors, and agents that interfere with crucial signaling pathways such as PI3K/AKT/mTOR and RAS/MEK/ERK; agents against other tyrosine kinases such as Src, insulin-like growth factor (IGF)/IGF-receptor (IGFR); agents that promote apoptosis such as Poly ADP ribose polymerase inhibitors; agents that target invasion and metastasis such as matrix metalloproteinases inhibitors and others. In this review, we highlight the most promising targeted agents and their combination with mainstream chemotherapeutic drugs in clinical trials.

  3. You, Your Teenage Daughter and Breast Cancer.

    ERIC Educational Resources Information Center

    Brateman, Libby

    1991-01-01

    Discusses breast cancer and teenagers, focusing on how parents can introduce the subject and encourage breast self-examination. The article provides information on breast cancer statistics, mammography, and American Cancer Society services. (SM)

  4. How Is Breast Cancer in Men Diagnosed?

    MedlinePlus

    ... Men Early Detection, Diagnosis, and Staging How Is Breast Cancer in Men Diagnosed? Medical history and physical exam ... in Men Survival Rates, by Stage More In Breast Cancer In Men About Breast Cancer in Men Causes, ...

  5. You, Your Teenage Daughter and Breast Cancer.

    ERIC Educational Resources Information Center

    Brateman, Libby

    1991-01-01

    Discusses breast cancer and teenagers, focusing on how parents can introduce the subject and encourage breast self-examination. The article provides information on breast cancer statistics, mammography, and American Cancer Society services. (SM)

  6. Axillary Lymph Nodes and Breast Cancer

    MedlinePlus

    ... nodes . The axillary nodes are the first place breast cancer is likely to spread. During breast surgery, some ... if cancer cells are present. This helps determine breast cancer stage and guide treatment. So, it is more ...

  7. Breast cancer fear in African American breast cancer survivors.

    PubMed

    Gibson, Lynette M; Thomas, Sheila; Parker, Veronica; Mayo, Rachel; Wetsel, Margaret Ann

    2014-01-01

    The purpose of this study was to describe breast cancer fear according to phase of survivorship, determine whether breast cancer fear levels differed among survivorship phases, and determine the relationship between fear and age in African-American breast cancer survivors. The study utilized secondary data analysis from the study, Inner Resources as Predictors of Psychological Well-Being in AABCS. A new subscale entitled, "Breast Cancer Fear" was adapted from the Psychological Well Being Subscale by Ferrell and Grant. There was no significant difference between fear and phase of survivorship. There was a significant positive relationship between age and fear.

  8. Reproduction and Breast Cancer Risk

    PubMed Central

    Hanf, Volker; Hanf, Dorothea

    2014-01-01

    Summary Reproduction is doubtlessly one of the main biological meanings of life. It is therefore not surprising that various aspects of reproduction impact on breast cancer risk. Various developmental levels may become targets of breast tumorigenesis. This review follows the chronologic sequence of events in the life of a female at risk, starting with the intrauterine development. Furthermore, the influence of both contraceptive measures and fertility treatment on breast cancer development is dealt with, as well as various pregnancy-associated factors, events, and perinatal outcomes. Finally, the contribution of breast feeding to a reduced breast cancer risk is discussed. PMID:25759622

  9. Breast Cancer Metastasis

    PubMed Central

    Marino, Natascia; Woditschka, Stephan; Reed, L. Tiffany; Nakayama, Joji; Mayer, Musa; Wetzel, Maria; Steeg, Patricia S.

    2014-01-01

    Despite important progress in adjuvant and neoadjuvant therapies, metastatic disease often develops in breast cancer patients and remains the leading cause of their deaths. For patients with established metastatic disease, therapy is palliative, with few breaks and with mounting adverse effects. Many have hypothesized that a personalized or precision approach (the terms are used interchangeably) to cancer therapy, in which treatment is based on the individual characteristics of each patient, will provide better outcomes. Here, we discuss the molecular basis of breast cancer metastasis and the challenges in personalization of treatment. The instability of metastatic tumors remains a leading obstacle to personalization, because information from a patient’s primary tumor may not accurately reflect the metastasis, and one metastasis may vary from another. Furthermore, the variable presence of tumor subpopulations, such as stem cells and dormant cells, may increase the complexity of the targeted treatments needed. Although molecular signatures and circulating biomarkers have been identified in breast cancer, there is lack of validated predictive molecular markers to optimize treatment choices for either prevention or treatment of metastatic disease. Finally, to maximize the information that can be obtained, increased attention to clinical trial design in the metastasis preventive setting is needed. PMID:23895915

  10. [Immediate breast reconstruction for breast cancer].

    PubMed

    Yamamoto, Daigo; Tanaka, Yoshihito; Tsubota, Yu; Sueoka, Noriko; Endo, Kayoko; Ogura, Tsunetaka; Nagumo, Yoshinori; Kwon, A-Hon

    2014-11-01

    We performed immediate breast reconstruction after nipple-sparing mastectomy or skin-sparing mastectomy and evaluated the reconstruction procedure, cosmesis, and complications. Among the 30 patients included in the study, 6 received latissimus dorsi flaps, 1 received a transverse rectus abdominis myocutaneous flap, 7 received deep inferior epigastric perforator flaps, 1 received an implant, and 15 received tissue expanders. In addition, the results were excellent in 25 patients, good in 3 patients, and poor in 2 patients. As the number of patients with breast cancer is increasing, the demand for breast reconstruction will increase. Therefore, it is essential to choose an appropriate method of breast reconstruction for each case.

  11. Eccrine spiradenoma arising in the breast misdiagnosed as an epidermal inclusion cyst.

    PubMed

    Lee, Hyun Ho; Park, Sung Hee; Choi, Hye Young; Park, Heung Kyu

    2011-01-01

    Eccrine spiradenomas are rare, benign, cutaneous tumors that originate in the sweat glands. Eccrine spiradenomas in the breast are very rare and only a few cases have been reported. We report here on the case of a 47-year-old woman with superficial masses in the breast and these masses had gradually increased in size during follow-up. They were confirmed to be an eccrine spiradenoma on pathologic examination. There have been a few reports about the radiologic findings of eccrine spiradenomas of the breast. This is the first case of an eccrine spiradenoma in the breast that was characterized by multiple imaging modalities, including mammography, ultrasonography and MRI. The lesion in our patient was first diagnosed as an epidermal inclusion cyst based on the imaging findings and the mass's superficial location. Although the mammographic and ultrasonographic imaging findings of eccrine spiradenomas and epidermal inclusion cysts are similar, the MRI findings are different between epidermal inclusion cysts and eccrine spiradenomas. Eccrine spiradenomas should be considered in the differential diagnosis of cutaneous and subcutaneous lesions of the breast.

  12. Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer

    SciTech Connect

    Spellman, Paul T.; Heiser, Laura; Gray, Joe W.

    2009-06-18

    Breast cancer is predominantly a disease of the genome with cancers arising and progressing through accumulation of aberrations that alter the genome - by changing DNA sequence, copy number, and structure in ways that that contribute to diverse aspects of cancer pathophysiology. Classic examples of genomic events that contribute to breast cancer pathophysiology include inherited mutations in BRCA1, BRCA2, TP53, and CHK2 that contribute to the initiation of breast cancer, amplification of ERBB2 (formerly HER2) and mutations of elements of the PI3-kinase pathway that activate aspects of epidermal growth factor receptor (EGFR) signaling and deletion of CDKN2A/B that contributes to cell cycle deregulation and genome instability. It is now apparent that accumulation of these aberrations is a time-dependent process that accelerates with age. Although American women living to an age of 85 have a 1 in 8 chance of developing breast cancer, the incidence of cancer in women younger than 30 years is uncommon. This is consistent with a multistep cancer progression model whereby mutation and selection drive the tumor's development, analogous to traditional Darwinian evolution. In the case of cancer, the driving events are changes in sequence, copy number, and structure of DNA and alterations in chromatin structure or other epigenetic marks. Our understanding of the genetic, genomic, and epigenomic events that influence the development and progression of breast cancer is increasing at a remarkable rate through application of powerful analysis tools that enable genome-wide analysis of DNA sequence and structure, copy number, allelic loss, and epigenomic modification. Application of these techniques to elucidation of the nature and timing of these events is enriching our understanding of mechanisms that increase breast cancer susceptibility, enable tumor initiation and progression to metastatic disease, and determine therapeutic response or resistance. These studies also reveal the

  13. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Dr. Robert Richmond extracts breast cell tissue from one of two liquid nitrogen dewars. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  14. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Breast tissue specimens in traditional sample dishes. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  15. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Breast tissue specimens in traditional sample dishes. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  16. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Dr. Robert Richmond extracts breast cell tissue from one of two liquid nitrogen dewars. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  17. [Organized breast cancer screening].

    PubMed

    Rouëssé, Jacques; Sancho-Garnier, Hélèn

    2014-02-01

    Breast screening programs are increasingly controversial, especially regarding two points: the number of breast cancer deaths they avoid, and the problem of over-diagnosis and over-treatment. The French national breast cancer screening program was extended to cover the whole country in 2004. Ten years later it is time to examine the risk/benefit ratio of this program and to discuss the need for change. Like all forms of cancer management, screening must be regularly updated, taking into account the state of the art, new evidence, and uncertainties. All screening providers should keep themselves informed of the latest findings. In the French program, women aged 50-74 with no major individual or familial risk factors for breast cancer are offered screening mammography and clinical breast examination every two years. Images considered non suspicious of malignancy by a first reader are re-examined by a second reader. The devices and procedures are subjected to quality controls. Participating radiologists (both public and private) are required to read at least 500 mammographies per year. The program's national participation rate was 52.7 % in 2012. When individual screening outside of the national program is taken into account (nearly 15 % of women), coverage appears close to the European recommendation of 65 %. Breast cancer mortality has been falling in France by 0.6 % per year for over 30 years, starting before mass screening was implemented, and by 1.5 % since 2005. This decline can be attributed in part to earlier diagnosis and better treatment, so that the specific impact of screening cannot easily be measured. Over-treatment, defined as the detection and treatment of low-malignancy tumors that would otherwise not have been detected in a person's lifetime, is a major negative effect of screening, but its frequency is not precisely known (reported to range from 1 % to 30 %). In view of these uncertainties, it would be advisable to modify the program in order to

  18. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    High magnification view of human primary breast tumor cells after 56 days of culture in a NASA Bioreactor. The arrow points to bead surface indicating breast cancer cells (as noted by the staining of tumor cell intermediate filaments). NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida

  19. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    High magnification view of human primary breast tumor cells after 56 days of culture in a NASA Bioreactor. The arrow points to bead surface indicating breast cancer cells (as noted by the staining of tumor cell intermediate filaments). NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida

  20. Genistein Programming Against Breast Cancer

    DTIC Science & Technology

    2003-09-01

    DEOXYRIBONUCLEIC ACIDS, *GENES, *DIET, *ESTROGENS, *SOY PROTEIN, *BREAST CANCER, RATS , CHEMICALS, MOLECULES, ENZYMES, PROTEINS, SENSITIVITY, WOMEN, SENSE ORGANS, ASIA, MAMMARY GLANDS, METHYLATION, ANDROGENS, TRANSFERASES.

  1. Unemployment among breast cancer survivors.

    PubMed

    Carlsen, Kathrine; Ewertz, Marianne; Dalton, Susanne Oksbjerg; Badsberg, Jens Henrik; Osler, Merete

    2014-05-01

    Though about 20% of working age breast cancer survivors do not return to work after treatment, few studies have addressed risk factors for unemployment. The majority of studies on occupational consequences of breast cancer focus on non-employment, which is a mixture of sickness absence, unemployment, retirement pensions and other reasons for not working. Unemployment in combination with breast cancer may represent a particular challenge for these women. The aim of the present study is therefore to analyze the risk for unemployment in the years following diagnosis and treatment for breast cancer. This study included 14,750 women diagnosed with breast cancer in Denmark 2001-2009 identified through a population-based clinical database and linked with information from Danish administrative population based registers for information on labour market affiliation, socio-demography and co-morbid conditions. Multivariable analyses were performed by Cox's proportional hazard models. Two years after treatment, 81% of patients were still part of the work force, 10% of which were unemployed. Increasing duration of unemployment before breast cancer was associated with an adjusted HR = 4.37 (95% CI: 3.90-4.90) for unemployment after breast cancer. Other risk factors for unemployment included low socioeconomic status and demography, while adjuvant therapy did not increase the risk of unemployment. Duration of unemployment before breast cancer was the most important determinant of unemployment after breast cancer treatment. This allows identification of a particularly vulnerable group of patients in need of rehabilitation.

  2. Amphiphysin and Breast Cancer

    DTIC Science & Technology

    1998-10-01

    condition appears to represent a novel entity within the emerging family of neurological autoimmune paraneoplastic syndromes , conditions in which...We have recently identified a new human syndrome characterized by breast cancer, autoimmunity directed against the neuronal protein in amphiphysin...and Stiff-Man syndrome (SMS). SMS is a rare disease of the central nervous system characterized by progressive rigidity of the body musculature. This

  3. Erythropoietin and Breast Cancer

    DTIC Science & Technology

    2008-03-01

    and/or findings contained in this report are those of the author( s ) and should not be construed as an official Department of the Army position...CONTRACT NUMBER Erythropoietin and Breast Cancer 5b. GRANT NUMBER W81XWH-06-1-0737 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT...NUMBER Arthur J. Sytkowski, MD 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) 8. PERFORMING

  4. Breast cancer risk factors

    PubMed Central

    Ciszewski, Tomasz; Łopacka-Szatan, Karolina; Miotła, Paweł; Starosławska, Elżbieta

    2015-01-01

    Breast cancer is the most frequently diagnosed neoplastic disease in women around menopause often leading to a significant reduction of these women's ability to function normally in everyday life. The increased breast cancer incidence observed in epidemiological studies in a group of women actively participating in social and professional life implicates the necessity of conducting multidirectional studies in order to identify risk factors associated with the occurrence of this type of neoplasm. Taking the possibility of influencing the neoplastic transformation process in individuals as a criterion, all the risk factors initiating the process can be divided into two groups. The first group would include inherent factors such as age, sex, race, genetic makeup promoting familial occurrence of the neoplastic disease or the occurrence of benign proliferative lesions of the mammary gland. They all constitute independent parameters and do not undergo simple modification in the course of an individual's life. The second group would include extrinsic factors conditioned by lifestyle, diet or long-term medical intervention such as using oral hormonal contraceptives or hormonal replacement therapy and their influence on the neoplastic process may be modified to a certain degree. Identification of modifiable factors may contribute to development of prevention strategies decreasing breast cancer incidence. PMID:26528110

  5. Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway.

    PubMed

    Zhang, Mingdi; Cai, Shizhong; Zuo, Bin; Gong, Wei; Tang, Zhaohui; Zhou, Di; Weng, Mingzhe; Qin, Yiyu; Wang, Shouhua; Liu, Jun; Ma, Fei; Quan, Zhiwei

    2017-05-01

    Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA-epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.

  6. 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

  7. Breast-feeding after breast cancer in childbearing women.

    PubMed

    Camune, Barbara; Gabzdyl, Elizabeth

    2007-01-01

    According to the American Cancer Society in 2007, about 178,000 women are diagnosed with breast cancer each year in the United States. Of these, 25% have tumors in their childbearing years and may desire future opportunities for pregnancy and lactation. Although there is a multitude of options related to preserving fertility, little is known about the residual effects of breast cancer treatment and the ability to breast-feed afterward. This article describes the epidemiological relationship between breast cancer and pregnancy and lactation. Basic types of treatment for breast cancer including surgery, chemotherapy, and radiation are reviewed. Practical information on how to support breast-feeding after breast cancer is included.

  8. 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.

  9. Rosuvastatin in Treating Women With Cardiovascular Complications Who Are Undergoing Chemotherapy For Breast Cancer

    ClinicalTrials.gov

    2017-05-25

    Cardiovascular Complications; Recurrent Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  10. Vascular and Cognitive Assessments in Patients With Breast Cancer Undergoing Chemotherapy After Surgery

    ClinicalTrials.gov

    2017-02-20

    Cognitive/Functional Effects; Recurrent Breast 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

  11. African American patients with breast cancer have worse prognosis than white patients in certain subtypes and stages.

    PubMed

    Arciero, Cletus A; Yang, Jing; Peng, Limin; Ward, Kevin C; O'Regan, Ruth; Sahin, Aysegul A; Li, Xiaoxian

    2017-08-30

    Racial disparity of breast cancer in each subtype and substage is not clear. We reviewed 156,938 patients with breast cancer from 2010 to 2012 from the National Cancer Institute Surveillance, Epidemiology, and End Results database. Breast cancer was subtyped by hormone receptor (HR) and human epidermal growth factor 2 (HER2) status as HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. African American (AA) patients had worse overall survival (OS) and breast cancer cause-specific survival (BCSS) in HR+/HER2- stages III and IV breast cancer and HR-/HER2+ stage IV cancer; they had worse OS but not BCSS in HR+ /HER2- stage II cancer and HR-/HER2- stage II cancer. AA patients with breast cancer had worse survival in certain subtype and stage, especially in ER+ breast cancer.

  12. Pathways to Breast Cancer Recurrence

    PubMed Central

    2013-01-01

    Breast cancer remains a deadly disease, even with all the recent technological advancements. Early intervention has made an impact, but an overwhelmingly large number of breast cancer patients still live under the fear of “recurrent” disease. Breast cancer recurrence is clinically a huge problem and one that is largely not well understood. Over the years, a number of factors have been studied with an overarching aim of being able to prognose recurrent disease. This paper attempts to provide an overview of our current knowledge of breast cancer recurrence and its associated challenges. Through a survey of the literature on cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), various signaling pathways such as Notch/Wnt/hedgehog, and microRNAs (miRNAs), we also examine the hypotheses that are currently under investigation for the prevention of breast cancer recurrence. PMID:23533807

  13. Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Older Patients With Locally Advanced or Metastatic Breast Cancer

    ClinicalTrials.gov

    2016-10-14

    Male Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  14. Drugs Approved for Breast Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for breast cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  15. Hormone Therapy for Breast Cancer

    MedlinePlus

    ... outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P–2 trial. JAMA 2006; 295(23):2727– ... and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing breast cancer. Cancer Prevention ...

  16. Present and future evolution of advanced breast cancer therapy

    PubMed Central

    2010-01-01

    Although the introduction of novel therapies and drug combinations has improved the prognosis of metastatic breast cancer, the disease remains incurable. Increased knowledge of the biology and the molecular alterations in breast cancer has facilitated the design of targeted therapies. These agents include receptor and nonreceptor tyrosine kinase inhibitors (epidermal growth factor receptor family), intracellular signaling pathways (phosphatidylinositol-3-kinase, AKT, mammalian target of rapamycin) angiogenesis inhibitors and agents that interfere with DNA repair (poly(ADP-ribose) polymerase inhibitors). In the present review, we present the most promising studies of these new targeted therapies and novel combinations of targeted therapies with cytotoxic agents. PMID:21050422

  17. Pregnancy associated breast cancer: an institutional experience.

    PubMed

    Gogia, A; Deo, S V S; Shukla, N K; Mohanti, B K; Raina, V

    2014-01-01

    Pregnancy-associated breast cancer (PABC) has been defined as breast cancer diagnosed during pregnancy or within 1 year of delivery. There is a paucity of data on PABC from India. The aim of our study was to assess the clinical-pathological parameters and outcome of PABC at Institute Rotary Cancer Hospital, All India Institute of Medical Sciences. We screened approximately 3,750 cases registered from January 2001 to December 2012 and found 26 cases of PABC. Patients' records were obtained from the computer database using International Classification of Diseases code (C-50). The median age was 26 years (range 20-35). The median duration of symptoms was 11.5 months. The American Joint Committee on Cancer stage distribution was Stage I - 1, Stage II - 3, Stage III - 14 and in Stage IV - 8 patients. Median clinical tumor size is 5.5 cm. Four patients were presented with the inflammatory breast cancer. Positive family history was elicited in three patients. Twenty-one patients were diagnosed after delivery, two patients in the first trimester, two patients in the second trimester and three patients in the third trimester. Estrogen receptor (ER), progesterone receptor (PR) negativity and human epidermal growth factor receptor 2 (HER2/neu) positivity was 56% and 38%, respectively. Nearly, 40% of patients had a high-grade tumor and 70% had pathological node positivity. With a median follow-up of 33 months, 3 years relapse free survival and overall survival was 40% and 50% respectively. Bone was the most common site for systemic relapse. PABC constituted 0.7% of all breast cancer patients. It is associated with advanced stage at presentation. Half of them were ER/PR negative and one-third was HER2/neu positive.

  18. Epidermal growth factor receptor-targeted therapy for pancreatic cancer.

    PubMed

    Xiong, Henry Q; Abbruzzese, James L

    2002-10-01

    Epidermal growth factor receptor (EGFR) plays an important role in tumor development and maintenance. It is a cell surface molecule that mediates signal transduction from the cell surface to cytoplasm. Elevated expression of EGFR or its ligand correlates with worse prognosis in a variety of human cancers. Therefore, blockade of EGFR activity would provide a novel strategy for the treatment of cancer. Two classes of EGFR inhibitors, monoclonal antibodies and tyrosine kinase inhibitors, have been described. The preclinical activity of these EGFR inhibitors and phase I clinical data are summarized in this article. A phase II trial of the EGFR inhibitor IMC-C225 in combination with gemcitabine for patients with advanced pancreatic cancer is discussed. Copyright 2002, Elsevier Science (USA). All rights reserved.

  19. Breast Cancer Stem Cells

    PubMed Central

    Velasco-Velázquez, Marco A.; Homsi, Nora; De La Fuente, Marisol; Pestell, Richard G.

    2012-01-01

    Breast cancer stem cells (BCSCs) constitute a subpopulation of tumor cells that express stem cell-associated markers and have a high capacity for tumor generation in vivo. Identification of BCSCs from tumor samples or breast cancer cell lines has been based mainly on CD44+/CD24−/low or ALDH+ phenotypes. BCSCs isolation has allowed the analysis of the molecular mechanisms involved in their origin, self-renewal, differentiation into tumor cells, resistance to radiation therapy and chemotherapy, and invasiveness and metastatic ability. Molecular genetic analysis using knockout animals and inducible transgenics have identified NF-κB, c-Jun, p21CIP1, and Forkhead-like-protein Dach1 in BCSC expansion and fate. Clinical analyses of BCSCs in breast tumors have found a correlation between the proportion of BCSCs and poor prognosis. Therefore, new therapies that specifically target BCSCs are an urgent need. We summarize recent evidence that partially explain the biological characteristics of BCSCs. PMID:22249027

  20. Fulvestrant and/or Anastrozole in Treating Postmenopausal Patients With Stage II-III Breast Cancer Undergoing Surgery

    ClinicalTrials.gov

    2017-09-29

    Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Recurrent Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  1. Breast and Colon Cancer Family Registries

    Cancer.gov

    The Breast Cancer Family Registry and the Colon Cancer Family Registry were established by the National Cancer Institute as a resource for investigators to use in conducting studies on the genetics and molecular epidemiology of breast and colon cancer.

  2. 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

  3. Benign Breast Disease: Toward Molecular Prediction of Breast Cancer Risk

    DTIC Science & Technology

    2007-06-01

    cancer risk in women with radial scars in benign breast biopsies. Breast cancer Research and Treatment . Published online May 22, 2007... scars and involution. We explored the link between centrosome amplification, COX-2 expression and breast cancer outcomes and are currently exploring...5. Radial Scars The significance of radial scars to subsequent risk of breast cancer has been debated. Radial scars (RS) are benign breast

  4. Breast cancer patient stories project.

    PubMed

    Tanna, Nuttan; Buijs, Helene; Pitkin, Joan; Reichert, Robert

    2012-12-01

    It is estimated that there are almost half a million women living with or beyond a breast cancer diagnosis in the UK, often referred to as the breast cancer survivor population. We report on the setting up of a dedicated breast cancer and menopause symptoms service (BCMS), and present results from research undertaken with breast cancer survivors with the aim of obtaining their perspectives on the BCMS service. An action-oriented approach incorporating improvement science methodology has been used to help develop and drive changes to support a high standard of NHS patient care delivery for women with breast cancer within the BCMS setting. Evaluation was undertaken of this innovative service using qualitative methodology, and included discussion within a focus group setting, patient consent to record discussion, followed by thematic analysis of transcription. Women who have survived breast cancer identified a need for specialist support to help improve their quality of life, which is also affected by menopause type symptomology. This support can be provided within the BCMS service setting. Our recommendations are that the BCMS service model is incorporated into any regional or national breast cancer patient pathway and service redesign work in place. Breast cancer survivors would support the setting up of a BCMS service, and would actively help raise awareness and market this service.

  5. PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy-Safety and Efficacy in Asian Patients.

    PubMed

    Iwata, Hiroji; Im, Seock-Ah; Masuda, Norikazu; Im, Young-Hyuck; Inoue, Kenichi; Rai, Yoshiaki; Nakamura, Rikiya; Kim, Jee Hyun; Hoffman, Justin T; Zhang, Ke; Giorgetti, Carla; Iyer, Shrividya; Schnell, Patrick T; Bartlett, Cynthia Huang; Ro, Jungsil

    2017-08-01

    To assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy-resistant metastatic breast cancer. The Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3) trial, a double-blind phase III study, included 521 patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs) were assessed on study treatment and at the end of treatment. This preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71) or placebo plus fulvestrant (n = 31). Palbociclib plus fulvestrant improved progression-free survival (PFS) compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached) but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065). The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92%) and leukopenia (29%); febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant. This is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study.

  6. The Nuclear Epidermal Growth Factor Receptor Signaling Network and its Role in Cancer

    PubMed Central

    Brand, Toni M.; Iida, Mari; Li, Chunrong; Wheeler, Deric L.

    2012-01-01

    The epidermal growth factor receptor (EGFR) is a member of the EGFR family of receptor tyrosine kinases (RTKs). EGFR activation via ligand binding results in signaling through various pathways ultimately resulting in cellular proliferation, survival, angiogenesis, invasion, and metastasis. Aberrant expression or activity of EGFR has been strongly linked to the etiology of several human epithelial cancers including but not limited to head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), breast cancer, pancreatic cancer and brain cancer. Thus intense efforts have been made to inhibit the activity of EGFR by designing antibodies against the ligand binding domains (cetuximab and panitumumab) or small molecules against the tyrosine kinase domains (erlotinib, gefitinib, and lapatinib). Although targeting membrane bound EGFR has shown benefit a new and emerging role for the EGFR is now being elucidated. In this review we will summarize the current knowledge of the nuclear EGFR signaling network, including how it is trafficked to the nucleus, the functions it serves in the nucleus, and how these functions impact cancer progression, survival and response to chemotherapeutics. PMID:22127113

  7. Hereditary breast cancer in Jews.

    PubMed

    Rubinstein, Wendy S

    2004-01-01

    A family history of breast cancer poses higher risks for Jewish versus non-Jewish women, particularly for early-onset breast cancer. This appears to be due in large part to the high prevalence (2.5%) of three BRCA1 and BRCA2 founder mutations in Ashkenazi Jews. About 4 to 8% of non-Jewish male breast cancer cases versus 19% of Jewish male breast cancer cases carry germline BRCA mutations. Jewish women are disproportionately impacted by BRCA mutations throughout life, with a 10% carrier rate for breast cancer diagnosed at any age and a 21 to 30% carrier rate for breast cancer diagnosed by age 40. Comparable rates in non-Jewish populations are 6.1% for breast cancer diagnosed before age 50. Lifetime penetrance estimates based on genotyping of probands have ranged widely in Jewish and non-Jewish populations. However, a study of 1008 Jewish women with breast cancer which extended genotyping to relatives found high penetrance rates with considerably smaller standard errors. This study and studies of early-onset incident breast cancer in non-Jews have found that at least half of high-risk cases would be missed by family history screening alone. While the carrier rate in non-Jewish populations is too low to consider genetic screening, the carrier rate in Ashkenazi Jews is high and genetic screening poses fewer technical barriers. The high genetic attributable cancer risks of Ashkenazi BRCA founder mutations, the sobering lethality of ovarian and early onset breast cancers, and the increasing clarity about effectiveness of medical interventions make imperative further dialogue and research to keep guidelines for genetic screening up to date.

  8. Inflammatory breast cancer: A decade of experience.

    PubMed

    Do Nascimento, Vinicius C; Rajan, Ruben; Redfern, Andrew; Saunders, Christobel

    2016-09-01

    Inflammatory breast cancer (IBC) is an aggressive and rare form of breast cancer. At present, there are no established diagnostic, radiological, pathological or molecular diagnostic criteria for this entity. The aim of this study was to examine the patterns of presentation, treatment and outcomes of IBC in this institution over the course of a decade. This is a retrospective observational study using data from the Royal Perth Hospital from January 2001 to December 2010. Our results identified 57 women with IBC, representing 1.9% of all new breast cancer presentations. Human Epidermal Growth Factor Receptor 2 (HER2)-positive and triple negative tumors were overrepresented (41% and 18%, respectively). Forty-four (77%) patients had early disease at diagnosis, of whom 35 underwent surgery and 16 are relapse-free. All six patients achieving complete pathological response were relapse-free in contrast to 11 (38%) with lesser responses at a median follow-up of 59 months. Median survival in 13 patients with metastatic disease at diagnosis was 21.7 months, with two patients still in remission. Clearly, this small but important group continues to offer management challenges and warrants ongoing study, including better molecular and pathological profiling of tumors to allow improved diagnostic clarity and more effective targeted therapy.

  9. Management of patients with metastatic breast cancer.

    PubMed

    Cruz Jurado, J; Richart Aznar, P; García Mata, J; Fernández Martínez, R; Peláez Fernández, I; Sampedro Gimeno, T; Galve Calvo, E; Murillo Jaso, L; Polo Marqués, E; García Palomo, A

    2011-09-01

    Hormone treatment is one of the key strategies in the management of metastatic breast cancer. Hormone treatment is one of the key strategies in the management of metastatic breast cancer. Aromatase inhibitors (AI) have been extensively studied in this setting. This section summarizes the key data regarding the use of AI in advanced breast cancer. In postmenopausal women, AI are the first line of treatment for untreated patients, or those who had prior AI treatment and progress after 12 months of adjuvant therapy. A longer disease-free interval and absence of visceral disease is associated with a better response. If tumors recur in less than 12 months, it is recommended that tamoxifen (TAM) or the estrogen-receptor antagonist fulvestrant (FUL) treatment be initiated. In the second-line setting, the best option after progression is the administration of either FUL or TAM. In the third-line setting, reintroduction of AI is considered an acceptable option. In premenopausal women who have not received prior treatment or who have progressed after 12 months following adjuvant treatment, it is recommended to initiate therapy with a combination of TAM and a luteinizing hormone-releasing hormone (LHRH) analog. If there is treatment failure with the use of this combination, megestrol acetate or an LHRH agonist plus an AI may be reasonable alternatives. Intensive research is ongoing to understand the mechanisms of resistance to hormone therapy. In human epidermal growth factor receptor 2 positive-patients, combinations with HER2 antagonists are associated with significant clinical activity.

  10. Can Smog Raise Breast Cancer Risk?

    MedlinePlus

    ... gov/news/fullstory_164495.html Can Smog Raise Breast Cancer Risk? Exposure to fine-particle air pollution linked ... have dense breasts, a known risk factor for breast cancer, new research suggests. "It appears that women who ...

  11. Treatment Option Overview (Male Breast Cancer)

    MedlinePlus

    ... spread outside the breast . In stage IB , small clusters of breast cancer cells (larger than 0.2 ... centimeters but not larger than 5 centimeters. Small clusters of breast cancer cells (larger than 0.2 ...

  12. Treatment Options for Male Breast Cancer

    MedlinePlus

    ... spread outside the breast . In stage IB , small clusters of breast cancer cells (larger than 0.2 ... centimeters but not larger than 5 centimeters. Small clusters of breast cancer cells (larger than 0.2 ...

  13. General Information about Male Breast Cancer

    MedlinePlus

    ... spread outside the breast . In stage IB , small clusters of breast cancer cells (larger than 0.2 ... centimeters but not larger than 5 centimeters. Small clusters of breast cancer cells (larger than 0.2 ...

  14. Green Tea and Breast Cancer

    PubMed Central

    Wu, Anna H; Butler, Lesley M

    2014-01-01

    The identification of modifiable lifestyle factors that could reduce the risk of breast cancer is a research priority. Despite the enormous chemo preventive potential of green tea and compelling evidence from animal studies, its role in breast cancer development in humans is still unclear. Part of the uncertainty is related to the relatively small number of epidemiological studies on green tea and breast cancer and that the overall results from case-control studies and prospective cohort studies are discordant. In addition, the mechanisms by which green tea intake may influence risk of breast cancer in humans remains not well studied. We review the human studies that have evaluated the relationship between green tea intake and four biomarkers (sex steroid hormones, mammographic density, insulin-like growth factor, adiponectin) that are believed to be important in breast cancer development. Results from these biomarker studies are also inconclusive. Limitations of human studies and areas of further investigations are discussed. PMID:21538855

  15. Radiation-induced breast cancer

    SciTech Connect

    Finnerty, N.A.; Buzdar, A.U.; Blumenschein, G.R.

    1984-06-01

    Between 1975 and 1983, sixteen patients with a history of irradiation at an early age to the head, neck, or chest areas for a variety of conditions in whom breast cancer subsequently developed were seen at out institute. The median latent period between the irradiation and the development of breast cancer was 420 months. The distribution of patients by stage of the disease and the median age at diagnosis of this subgroup was similar to the breast cancer observed in the general population. The subsequent course of this disease was also similar to the breast cancer observed in the general population. A substantial number of women have been exposed to irradiation at a young age, and these women are at a higher risk of having breast cancer develop. These women should be closely observed to discover the disease in an early curable stage.

  16. [Can breast cancer be prevented?].

    PubMed

    Vatten, L J

    1991-05-30

    More than six-fold variation in incidence between countries, an increasing incidence among immigrants to high incidence areas, and a general increase in the incidence of breast cancer within countries, are factors which suggest a potential for prevention. Reproductive factors such as early menarche, late age at first full term birth, nulliparity, and late age at menopause increase risk of breast cancer, but manipulation of any one of these factors does not seem to be a realistic preventive tool. Nevertheless, the future possibility of using tamoxifen as a chemopreventive agent against breast cancer is discussed, particularly in relation to women at increased risk due to familial clustering. Alcohol consumption by young women, and overweight among postmenopausal women may also increase the incidence of breast cancer. Consequently, reduced alcohol intake by young women, and weight reduction among overweight women after menopause may reduce the risk of breast cancer.

  17. [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.

  18. Triple-negative breast cancer: new perspectives for targeted therapies

    PubMed Central

    Tomao, Federica; Papa, Anselmo; Zaccarelli, Eleonora; Rossi, Luigi; Caruso, Davide; Minozzi, Marina; Vici, Patrizia; Frati, Luigi; Tomao, Silverio

    2015-01-01

    Breast cancer is a heterogeneous disease, encompassing a large number of entities showing different morphological features and having clinical behaviors. It has became apparent that this diversity may be justified by distinct patterns of genetic, epigenetic, and transcriptomic aberrations. The identification of gene-expression microarray-based characteristics has led to the identification of at least five breast cancer subgroups: luminal A, luminal B, normal breast-like, human epidermal growth factor receptor 2, and basal-like. Triple-negative breast cancer is a complex disease diagnosed by immunohistochemistry, and it is characterized by malignant cells not expressing estrogen receptors or progesterone receptors at all, and human epidermal growth factor receptor 2. Along with this knowledge, recent data show that triple-negative breast cancer has specific molecular features that could be possible targets for new biological targeted drugs. The aim of this article is to explore the use of new drugs in this particular setting, which is still associated with poor prognosis and high risk of distant recurrence and death. PMID:25653541

  19. Immunophenotyping invasive breast cancer: paving the road for molecular imaging.

    PubMed

    Vermeulen, Jeroen F; van Brussel, Aram S A; van der Groep, Petra; Morsink, Folkert H M; Bult, Peter; van der Wall, Elsken; van Diest, Paul J

    2012-06-13

    Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. The combination of highly tumor-specific markers glucose transporter 1 (GLUT1), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF1-R), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor receptor (MET), and carbonic anhydrase 9 (CAIX) 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6) resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R) that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate.

  20. What Are the Key Statistics about Breast Cancer in Men?

    MedlinePlus

    ... in Men What Are the Key Statistics About Breast Cancer in Men? The American Cancer Society estimates for ... Treatment in Breast Cancer in Men? More In Breast Cancer In Men About Breast Cancer in Men Causes, ...

  1. Addition of Carboplatin to Neoadjuvant Therapy for Triple-negative and HER2-positive Early Breast Cancer

    ClinicalTrials.gov

    2016-02-12

    Tubular Breast Cancer Stage II; Mucinous Breast Cancer Stage II; Breast Cancer Female NOS; Invasive Ductal Breast Cancer; Tubular Breast Cancer Stage III; HER-2 Positive Breast Cancer; Inflammatory Breast Cancer Stage IV; Inflammatory Breast Cancer

  2. Carboplatin and Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IIB-IIIC Breast Cancer

    ClinicalTrials.gov

    2017-05-10

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  3. Functional Magnetic Resonance Imaging in Assessing Affect Reactivity and Regulation in Patients With Stage 0-III Breast Cancer

    ClinicalTrials.gov

    2017-02-27

    Healthy Subject; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  4. Optimal breast cancer pathology manifesto.

    PubMed

    Tot, T; Viale, G; Rutgers, E; Bergsten-Nordström, E; Costa, A

    2015-11-01

    This manifesto was prepared by a European Breast Cancer (EBC) Council working group and launched at the European Breast Cancer Conference in Glasgow on 20 March 2014. It sets out optimal technical and organisational requirements for a breast cancer pathology service, in the light of concerns about variability and lack of patient-centred focus. It is not a guideline about how pathology services should be performed. It is a call for all in the cancer community--pathologists, oncologists, patient advocates, health administrators and policymakers--to check that services are available that serve the needs of patients in a high quality, timely way.

  5. Breast Tissue Composition and Susceptibility to Breast Cancer

    PubMed Central

    Martin, Lisa J.; Bronskill, Michael; Yaffe, Martin J.; Duric, Neb; Minkin, Salomon

    2010-01-01

    Breast density, as assessed by mammography, reflects breast tissue composition. Breast epithelium and stroma attenuate x-rays more than fat and thus appear light on mammograms while fat appears dark. In this review, we provide an overview of selected areas of current knowledge about the relationship between breast density and susceptibility to breast cancer. We review the evidence that breast density is a risk factor for breast cancer, the histological and other risk factors that are associated with variations in breast density, and the biological plausibility of the associations with risk of breast cancer. We also discuss the potential for improved risk prediction that might be achieved by using alternative breast imaging methods, such as magnetic resonance or ultrasound. After adjustment for other risk factors, breast density is consistently associated with breast cancer risk, more strongly than most other risk factors for this disease, and extensive breast density may account for a substantial fraction of breast cancer. Breast density is associated with risk of all of the proliferative lesions that are thought to be precursors of breast cancer. Studies of twins have shown that breast density is a highly heritable quantitative trait. Associations between breast density and variations in breast histology, risk of proliferative breast lesions, and risk of breast cancer may be the result of exposures of breast tissue to both mitogens and mutagens. Characterization of breast density by mammography has several limitations, and the uses of breast density in risk prediction and breast cancer prevention may be improved by other methods of imaging, such as magnetic resonance or ultrasound tomography. PMID:20616353

  6. Exercise in Targeting Metabolic Dysregulation in Stage I-III Breast or Prostate Cancer Survivors

    ClinicalTrials.gov

    2017-09-12

    Cancer Survivor; No Evidence of Disease; Obesity; Overweight; Prostate Carcinoma; Sedentary Lifestyle; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  7. Exercise Intervention in Targeting Adiposity and Inflammation With Movement to Improve Prognosis in Breast Cancer

    ClinicalTrials.gov

    2017-08-19

    Cancer Survivor; Central Obesity; Estrogen Receptor Positive; Postmenopausal; Progesterone Receptor Positive; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  8. Curing Metastatic Breast Cancer.

    PubMed

    Sledge, George W

    2016-01-01

    Metastatic breast cancer is generally considered incurable, and this colors doctor-patient interactions for patients with metastatic disease. Although true for most patients, there appear to be important exceptions, instances where long-term disease-free survival occurs. Although these instances are few in number, they suggest the possibility of cure. How will we move toward cure for a much larger population of patients with metastatic disease? This article outlines a potential research agenda that might move us toward that distant goal. Copyright © 2016 by American Society of Clinical Oncology.

  9. [Breast cancer in elderly].

    PubMed

    Diab, Sami G

    2007-10-01

    The question of the breast cancer in elderly is enlightened by two constituted epidemiological data bases in the United-States: the data basis of San Antonio and the SEER (Surveillance Epidemology and End Results) which represent a follow-up of 26% of the American population. The listed data allow an approach of the clinical and biological constituents according to the age of the disease as well as the factors of comorbidity. The informations relative to the therapeutic choices are more fragmentary and must be developed first and foremost during the programs. double dagger.

  10. Breast Cancer: Epidemiology and Etiology.

    PubMed

    Tao, ZiQi; Shi, Aimin; Lu, Cuntao; Song, Tao; Zhang, Zhengguo; Zhao, Jing

    2015-06-01

    Breast cancer, the most frequently occurring cancer in women, is a major public health problem, with 1,384,155 estimated new cases worldwide with nearly 459,000 related deaths. Breast cancer is highly heterogeneous in its pathological characteristics, some cases showing slow growth with excellent prognosis, while others being aggressive tumors. Current predictions and statistics suggest that both worldwide incidence of breast cancer and related mortality are on the rise. According to 2012 GLOBOCAN statistics, nearly 1.7 million women were diagnosed with breast cancer with 522,000 related deaths-an increase in breast cancer incidence and related mortality by nearly 18 % from 2008. According to American Cancer Society, one in eight women in the United States will develop breast cancer in her lifetime. It has been predicted that the worldwide incidence of female breast cancer will reach approximately 3.2 million new cases per year by 2050. These numbers reflect the magnitude of breast cancer incidence, its effect on society worldwide and the need for urgency for preventive and treatment measures. While technological advances in medical sciences and health care have made it possible to detect the disease early and to start the treatment early on to prevent the progress of the disease into a metastatic state, there are several unanswered questions with regard to the molecular mechanisms that underlie the aggressiveness of certain forms of this disease. Epidemiological studies suggest that addressing socio economical issues is utmost important, so that all women have equal access to medical care from screening to advanced treatment, and only such decisive action can help reduce the worldwide burden of breast cancer.

  11. Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid

    ClinicalTrials.gov

    2017-06-07

    Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  12. Inhibiting the Epidermal Growth Factor Receptor | Center for Cancer Research

    Cancer.gov

    The Epidermal Growth Factor Receptor (EGFR) is a widely distributed cell surface receptor that responds to several extracellular signaling molecules through an intracellular tyrosine kinase, which phosphorylates target enzymes to trigger a downstream molecular cascade. Since the discovery that EGFR mutations and amplifications are critical in a number of cancers, efforts have been under way to develop and use targeted EGFR inhibitors. These efforts have met with some spectacular successes, but many patients have not responded as expected, have subsequently developed drug-resistant tumors, or have suffered serious side effects from the therapies to date. CCR Investigators are studying EGFR from multiple vantage points with the goal of developing even better strategies to defeat EGFR-related cancers.

  13. Features of aggressive breast cancer.

    PubMed

    Arpino, Grazia; Milano, Monica; De Placido, Sabino

    2015-10-01

    Aggressive breast cancer is a term commonly used in literature to describe breast cancer with a poor prognosis. Identifying and understanding the factors associated with aggressiveness could be helpful to the management of patients with breast cancer. Breast cancer is a heterogeneous disease, both clinically and biologically, which may be responsible for the wide range of survival durations for patients with metastatic disease. The goal of this study was to identify the factors most often described in association with aggressive metastatic breast cancer (MBC). A systematic review was performed by querying PubMed from January 1, 2012 to June 1, 2014 for "metastatic breast cancer" ("aggressive" or "poor prognosis" or "high risk"). The level of evidence to support each potential prognostic factor of aggressive MBC was also reviewed. The identified factors were grouped into 3 principle categories: clinical, biological, and patient related. Because patient-related factors may not be indicative of inherent cancer aggressiveness, this review focused only on clinical and biological factors. The factors with the highest levels of evidence to support associations with survival in metastatic breast cancer were visceral metastases, number of metastatic sites, disease-free interval, presence of CTCs, triple-negative disease, and tumour grade. Identification of these factors and understanding their contribution to the aggressiveness of MBC and disease progression may lead to more personalized treatment in this patient population. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Oncolytic virotherapy of breast cancer.

    PubMed

    Hartkopf, Andreas D; Fehm, Tanja; Wallwiener, Diethelm; Lauer, Ulrich M

    2011-10-01

    The use of replication competent viruses that selectively target and destroy cancer cells has rapidly evolved over the past decade and numerous innovative oncolytic viruses have been created. Many of these promising anti-cancer agents have recently entered into clinical trials (including those on breast cancer) and demonstrated encouraging safety and efficacy. Virotherapeutic strategies are thus of considerable interest to combat breast cancer in both (i) the primary disease situation in which relapse should be avoided as good as possible and (ii) in the metastatic situation which remains incurable to date. Here, we summarize data from preclinical and clinical trials using oncolytic virotherapy to treat breast cancer. This includes strategies to specifically target breast cancer cells, to arm oncolytic viruses with additional therapeutic transgenes and an outlining of future challenges when translating these promising therapeutics "from bench to bedside".

  15. Molecular basis of breast cancer.

    PubMed

    Al-Mansouri, Layla J; Alokail, Majed S

    2006-01-01

    Breast cancer is the most frequent cancer in women and represents the second leading cause of cancer death among women after lung cancer. A common phenotypic abnormality of breast cancer cells is dysregulation of cell cycle control. The transformation of normal cell to a cancer cell appears to depend on mutation in genes that normally control cell cycle progression, thus leading to loss of the regulatory cell growth. We summarize here the molecular regulation of mammary carcinoma with regards to the most prominent oncogenes and tumor suppressor genes and their outcome in terms of cellular prognosis, and tumor development.

  16. Aluminium, antiperspirants and breast cancer.

    PubMed

    Darbre, P D

    2005-09-01

    Aluminium salts are used as the active antiperspirant agent in underarm cosmetics, but the effects of widespread, long term and increasing use remain unknown, especially in relation to the breast, which is a local area of application. Clinical studies showing a disproportionately high incidence of breast cancer in the upper outer quadrant of the breast together with reports of genomic instability in outer quadrants of the breast provide supporting evidence for a role for locally applied cosmetic chemicals in the development of breast cancer. Aluminium is known to have a genotoxic profile, capable of causing both DNA alterations and epigenetic effects, and this would be consistent with a potential role in breast cancer if such effects occurred in breast cells. Oestrogen is a well established influence in breast cancer and its action, dependent on intracellular receptors which function as ligand-activated zinc finger transcription factors, suggests one possible point of interference from aluminium. Results reported here demonstrate that aluminium in the form of aluminium chloride or aluminium chlorhydrate can interfere with the function of oestrogen receptors of MCF7 human breast cancer cells both in terms of ligand binding and in terms of oestrogen-regulated reporter gene expression. This adds aluminium to the increasing list of metals capable of interfering with oestrogen action and termed metalloestrogens. Further studies are now needed to identify the molecular basis of this action, the longer term effects of aluminium exposure and whether aluminium can cause aberrations to other signalling pathways in breast cells. Given the wide exposure of the human population to antiperspirants, it will be important to establish dermal absorption in the local area of the breast and whether long term low level absorption could play a role in the increasing incidence of breast cancer.

  17. Immunology and breast cancer: toward a new way of understanding breast cancer and developing novel therapeutic strategies.

    PubMed

    Gingras, Isabelle; Azim, Hatem A; Ignatiadis, Michail; Sotiriou, Christos

    2015-06-01

    Every cancer triggers an immune response that constitutes an important first-line protection against cancer progression. In breast cancer, there is an increasing awareness of the relationship between the immune system and tumor evolution. The tumor microenvironment is composed of a variety of immune cells that can control or arrest malignant progression. Chemotherapy and targeted therapy have been shown to modulate this immune microenvironment. Recently, tumor-infiltrating lymphocytes have emerged as a predictive and prognostic biomarker in early breast cancer. In addition, immune gene expression signatures have been shown to be associated with prognosis in triple-negative and human epidermal growth factor receptor 2-positive breast cancer. Such findings have increased interest in the development of immunotherapeutic agents for breast cancer, and multiple clinical trials of anticancer vaccines and immune checkpoint inhibitors are ongoing. In this review, we summarize what is known about the relationship between immunity and breast carcinoma, explore the relevance of this information to the clinical and research settings, and give a portrait of new therapeutic strategies using immunotherapy in breast cancer.

  18. The functional role of Notch signaling in triple-negative breast cancer.

    PubMed

    Speiser, Jodi J; Erşahin, Cağatay; Osipo, Clodia

    2013-01-01

    The term "triple-negative breast cancer" (TNBC) is a heterogeneous subtype of breast cancer. Unfortunately, due to the lack of expression of hormone receptors and human epidermal growth factor receptor-2, therefore the lack of US Food and Drug Administration-approved targeted therapies, TNBC has the worst prognosis of all subtypes of breast cancer. Notch signaling has emerged as a pro-oncogene in several human malignancies and has particularly been associated with the triple-negative subtype of breast cancer. This chapter explores the role of Notch signaling in triple negative and other subtypes of breast cancer, the relationship of Notch with other breast cancer biomarkers, prognostic indicators associated with Notch, and potential therapeutic strategies targeting Notch inhibition. Hopefully, better understanding of this signaling pathway in the future will lead to optimal molecular therapeutic treatments for TNBC patients, improving their quality of life and outcome.

  19. Approach to inflammatory breast cancer

    PubMed Central

    Molckovsky, Andrea; Fitzgerald, Barbara; Freedman, Orit; Heisey, Ruth; Clemons, Mark

    2009-01-01

    Abstract OBJECTIVE To review the definition, clinical presentation, and management of inflammatory breast cancer in primary care. SOURCES OF INFORMATION Relevant research and review articles, as well as personal experience of the authors practising in a specialized locally advanced breast cancer program at a comprehensive cancer centre. Evidence is levels II and III. MAIN MESSAGE Inflammatory breast cancer is a rare disease that typically presents with a rapidly enlarging erythematous breast, often with no discernable breast mass. Identification of warning signs and recognition of clinical symptoms are crucial to prompt diagnosis and appropriate referral. Management in the primary care setting includes treatment of symptoms, psychosocial support, regular surveillance and follow-up, as well as palliative care. CONCLUSION Family physicians are usually the entry point to the health care system and are well positioned to assess inflammation of the breast and recognize the warning signs of an underlying inflammatory breast cancer. They are also important members of the team that provides support for breast cancer patients and their families during treatment, follow-up, and end-of-life care. PMID:19155362

  20. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Time-lapse exposure depicts Bioreactor rotation. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  1. Breast Cancer Center Support Grant

    DTIC Science & Technology

    1999-09-01

    may make potential referral candidates more receptive when medical professionals approach them about being tested. Currently, there are barriers to...1985;253:1908-13. (39) Parazzini F, La Vecchia C, Negri E, Franceschi S, Tozzi L. Family history of breast, ovarian and endometrial cancer and risk of...Raloxifene reduces the risk of breast cancer and may decrease the risk of endometrial cancer in post- menopausal women. Two year findings from the

  2. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Time-lapse exposure depicts Bioreactor rotation. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues.

  3. The Biology of Breast Cancer Metastasis

    DTIC Science & Technology

    2002-10-01

    Breast cancer is the second most common cause of brain metastases, diagnosed in 10 to 15% of breast cancer patients and found at autopsy in 20 to 30...Relatively little is known about how breast cancer cells metastasize to the brain , and what phenotypes characterize these cells. This is due in...breast cancer brain metastases, using intra-carotid artery injection of breast cancer cells into nude mice.

  4. Copanlisib, Letrozole, and Palbociclib in Treating Patients With Hormone Receptor Positive HER2 Negative Stage I-IV Breast Cancer

    ClinicalTrials.gov

    2017-08-17

    Estrogen Receptor Positive; HER2/Neu Negative; Invasive Breast Carcinoma; Multifocal Breast Carcinoma; Postmenopausal; Progesterone Receptor Positive; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  5. Brain metastases from breast cancer during pregnancy

    PubMed Central

    Sharma, Ashish; Nguyen, Ha Son; Lozen, Andrew; Sharma, Abhishiek; Mueller, Wade

    2016-01-01

    Background: Brain metastasis during pregnancy is a rare occurrence. In particular, there have only been three prior cases regarding breast cancer metastasis. We report a patient with breast cancer metastasis to the brain during pregnancy and review the literature. Case Description: The patient was a 35-year-old female with a history of breast cancer (estrogen receptor/progesterone receptor negative, human epidermal growth factor receptor 2/neu positive, status post-neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab therapy, status post-bilateral mastectomies), and prior right frontal brain metastases (status post-resection, capecitabine/lapatinib/temozolomide therapy, and cyberknife treatment). Patient was found to be pregnant at 9 weeks’ gestation while on chemotherapy; the patient elected to continue with the pregnancy and chemotherapy was discontinued. At 14 weeks’ gestation, she returned with recurrent right frontal disease. She was taken for a craniotomy at 16 weeks’ gestation, which confirmed metastases. Six weeks later, patient returned with worsening headaches and fatigue, with more recurrent right frontal disease. She was started on decadron and chemotherapy (5-fluorouracil, adriamycin, and cyclophosphamide). Serial magnetic resonance imaging (MRI) demonstrated enlarging right frontal lesions. She underwent a craniotomy at 27 weeks’ gestation, and chemotherapy was discontinued promptly. Starting at 30 weeks’ gestation, she received whole brain radiation for 2 weeks. Subsequently, she delivered a baby girl via cesarean section at 32 weeks’ gestation. At 6 weeks follow-up, an MRI brain demonstrated no new intracranial disease, with stable postoperative findings. Conclusion: There is a lack of guidelines and clinical consensus on medical and surgical treatment for breast cancer metastases in pregnant patients. Treatment usually varies based upon underlying tumor burden, location, gestational age of the fetus, and patient's preference and

  6. Triple-negative breast cancer: epidemiological considerations and recommendations.

    PubMed

    Boyle, P

    2012-08-01

    Breast cancer is a major problem for global public health. Breast Cancer is the most common incident form of cancer in women around the world. The incidence is increasing while mortality is declining in many high-income countries. The last decade has seen a revolution in the understanding of breast cancer, with new classifications proposed that have significant prognostic value and provide guides to treatment options. Breast cancers that demonstrate the absence of oestrogen receptor and progesterone receptor and no overexpression of human epidermal growth factor receptor 2 (HER2) are referred to as triple-negative breast cancer (TNBC). There is now evidence emerging from epidemiological studies regarding important characteristics of this group of tumours that carry a relatively poorer prognosis than the major breast cancer sub-types. From this review of available data and information, there are some consistent findings that emerge. Women with TNBC experience the peak risk of recurrence within 3 years of diagnosis, and the mortality rates appear to be increased for 5 years after diagnosis. TNBC represents 10%-20% of invasive breast cancers and has been associated with African-American race, deprivation status, younger age at diagnosis, more advanced disease stage, higher grade, high mitotic indices, family history of breast cancer and BRCA1 mutations. TNBC is regularly reported to be three times more common in women of African descent and in pre-menopausal women, and carries a poorer prognosis than other forms of breast cancer. Although prospects for prevention of non-hormone-dependent breast cancer are currently poor, it is still important to understand the aetiology of such tumours. There remains a great deal of work to be done to arrive at a comprehensive picture of the aetiology of breast cancer. Key recommendations are that there is a clear and urgent need to have more epidemiological studies of the breast cancer sub-types to integrate aetiological and

  7. Family History of Breast Cancer, Breast Density, and Breast Cancer Risk in a U.S. Breast Cancer Screening Population.

    PubMed

    Ahern, Thomas P; Sprague, Brian L; Bissell, Michael C S; Miglioretti, Diana L; Buist, Diana S M; Braithwaite, Dejana; Kerlikowske, Karla

    2017-06-01

    Background: The utility of incorporating detailed family history into breast cancer risk prediction hinges on its independent contribution to breast cancer risk. We evaluated associations between detailed family history and breast cancer risk while accounting for breast density.Methods: We followed 222,019 participants ages 35 to 74 in the Breast Cancer Surveillance Consortium, of whom 2,456 developed invasive breast cancer. We calculated standardized breast cancer risks within joint strata of breast density and simple (1(st)-degree female relative) or detailed (first-degree, second-degree, or first- and second-degree female relative) breast cancer family history. We fit log-binomial models to estimate age-specific breast cancer associations for simple and detailed family history, accounting for breast density.Results: Simple first-degree family history was associated with increased breast cancer risk compared with no first-degree history [Risk ratio (RR), 1.5; 95% confidence interval (CI), 1.0-2.1 at age 40; RR, 1.5; 95% CI, 1.3-1.7 at age 50; RR, 1.4; 95% CI, 1.2-1.6 at age 60; RR, 1.3; 95% CI, 1.1-1.5 at age 70). Breast cancer associations with detailed family history were strongest for women with first- and second-degree family history compared with no history (RR, 1.9; 95% CI, 1.1-3.2 at age 40); this association weakened in higher age groups (RR, 1.2; 95% CI, 0.88-1.5 at age 70). Associations did not change substantially when adjusted for breast density.Conclusions: Even with adjustment for breast density, a history of breast cancer in both first- and second-degree relatives is more strongly associated with breast cancer than simple first-degree family history.Impact: Future efforts to improve breast cancer risk prediction models should evaluate detailed family history as a risk factor. Cancer Epidemiol Biomarkers Prev; 26(6); 938-44. ©2017 AACR. ©2017 American Association for Cancer Research.

  8. Constitutional variants are not associated with HER2-positive breast cancer: results from the SIGNAL/PHARE clinical cohort.

    PubMed

    Pivot, Xavier; Romieu, Gilles; Fumoleau, Pierre; Rios, Maria; Bonnefoi, Hervé; Bachelot, Thomas; Soulié, Patrick; Jouannaud, Christelle; Bourgeois, Hugues; Petit, Thierry; Tennevet, Isabelle; Assouline, David; Mathieu, Marie-Christine; Jacquin, Jean-Philippe; Lavau-Denes, Sandrine; Darut-Jouve, Ariane; Ferrero, Jean-Marc; Tarpin, Carole; Lévy, Christelle; Delecroix, Valérie; Trillet-Lenoir, Véronique; Cojocarasu, Oana; Meunier, Jérôme; Pierga, Jean-Yves; Agostini, Cécile; Kerbrat, Pierre; Faure-Mercier, Céline; Blanché, Hélène; Sahbatou, Mourad; Boland, Anne; Bacq, Delphine; Besse, Céline; Calvo, Fabien; Renaud, Alexia; Deleuze, Jean-François; Pauporté, Iris; Thomas, Gilles; Cox, David G

    2017-01-01

    Human epidermal growth factor receptor 2-positive breast cancer is a subtype of interest regarding its outcome and the impressive impact of human epidermal growth factor receptor 2 targeted therapy. Constitutional variants may be involved in the aetiology of human epidermal growth factor receptor 2-positive breast cancer, and we propose a case-case study to test the hypothesis that single nucleotide polymorphisms may be associated with human epidermal growth factor receptor 2 status. A Genome-Wide Association Study was used in a cohort of 9836 patients from the SIGNAL/PHARE study (NCT00381901-RECF1098). The main goal was to identify variants specifically related to human epidermal growth factor receptor 2-positive breast cancer. A two-staged genotyping strategy was carried out to cover as large a proportion of the genome as possible. All subjects were genotyped using the Illumina HumanCore Exome chip set. Principal Components Analysis and k-means were then used to characterize the ancestry of the participants. A random sample of subjects from the main "European" cluster was genotyped with the Omni5 chip set. These data were then used to impute missing genotypes from the remaining subjects genotyped only using the HumanCore Exome array. From the 9836 patients, a total of 8703 cases including 3230 patients with human epidermal growth factor receptor 2-positive breast cancer were analyzed. Despite having 80% power to detect an odds ratio of 1.23 in this population, no variant achieved genome-wide significance for association with the occurrence of human epidermal growth factor receptor 2-positive breast cancer vs. any other subtype of breast tumour. Our study was unable to identify constitutional polymorphisms that are strongly associated with human epidermal growth factor receptor 2-positive status among breast cancer patients.

  9. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Human primary breast tumor cells after 56 days of culture in a NASA Bioreactor. A cross-section of a construct, grown from surgical specimens of brease cancer, stained for microscopic examination, reveals areas of tumor cells dispersed throughout the non-epithelial cell background. The arrow denotes the foci of breast cancer cells. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida

  10. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Human primary breast tumor cells after 56 days of culture in a NASA Bioreactor. A cross-section of a construct, grown from surgical specimens of brease cancer, stained for microscopic examination, reveals areas of tumor cells dispersed throughout the non-epithelial cell background. The arrow denotes the foci of breast cancer cells. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida

  11. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Human primary breast tumor cells after 49 days of growth in a NASA Bioreactor. Tumor cells aggregate on microcarrier beads (indicated by arrow). NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida

  12. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    High magnification of view of tumor cells aggregate on microcarrier beads, illustrting breast cells with intercellular boundaires on bead surface and aggregates of cells achieving 3-deminstional growth outward from bead after 56 days of culture in a NASA Bioreactor. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida.

  13. Adjuvant therapy of breast cancer.

    PubMed

    Davidson, N E; Abeloff, M D

    1994-01-01

    About 180,000 American women will be diagnosed with early stage breast cancer during 1993. In many of these patients breast cancer is a systemic disease at diagnosis and thus not curable by local treatment alone. The development of optimal forms of systemic adjuvant therapy has been a major area of research for more than 30 years. The two most widely employed types of adjuvant therapy, cytotoxic chemotherapy and tamoxifen, have been shown to improve relapse-free and overall survival in certain patient subsets. This review highlights recent advances in adjuvant therapy of early stage breast cancer and discusses current treatment guidelines.

  14. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    High magnification of view of tumor cells aggregate on microcarrier beads, illustrting breast cells with intercellular boundaires on bead surface and aggregates of cells achieving 3-deminstional growth outward from bead after 56 days of culture in a NASA Bioreactor. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida.

  15. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Human primary breast tumor cells after 49 days of growth in a NASA Bioreactor. Tumor cells aggregate on microcarrier beads (indicated by arrow). NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Jearne Becker, University of South Florida

  16. Progress in breast cancer: overview.

    PubMed

    Arteaga, Carlos L

    2013-12-01

    This edition of CCR Focus titled Research in Breast Cancer: Frontiers in Genomics, Biology, and Clinical Investigation reviews six topics that cover areas of translational research of high impact in breast cancer. These topics represent areas of breast cancer research where significant progress has occurred but also where very important challenges remain. The papers in this CCR Focus section are contributed by experts in the respective areas of investigation. Herein, key aspects of these contributions and the research directions they propose are reviewed. ©2013 AACR.

  17. Antiperspirants/Deodorants and Breast Cancer

    MedlinePlus

    ... Directory Cancer Prevention Overview Research Antiperspirants/Deodorants and Breast Cancer On This Page Is there a link between antiperspirants or deodorants and breast cancer? What is known about the ingredients in antiperspirants ...

  18. Breast Cancer Chemotherapy and Your Heart

    MedlinePlus

    ... of the American Heart Association Cardiology Patient Page Breast Cancer Chemotherapy and Your Heart Christine Unitt , Kamaneh Montazeri , ... Disclosures Footnotes Figures & Tables Info & Metrics eLetters Introduction Breast cancer is the most commonly diagnosed cancer in women. ...

  19. Triple Negative Breast Cancer: Nanosolutions for a Big Challenge

    PubMed Central

    Mendes, Tânia Filipa S.; Kluskens, Leon D.

    2015-01-01

    Triple negative breast cancer (TNBC) is a particular immunopathological subtype of breast cancer that lacks expression of estrogen and progesterone receptors (ER/PR) and amplification of the human epidermal growth factor receptor 2 (HER2) gene. Characterized by aggressive and metastatic phenotypes and high rates of relapse, TNBC is the only breast cancer subgroup still lacking effective therapeutic options, thus presenting the worst prognosis. The development of targeted therapies, as well as early diagnosis methods, is vital to ensure an adequate and timely therapeutic intervention in patients with TNBC. This review intends to discuss potentially emerging approaches for the diagnosis and treatment of TNBC patients, with a special focus on nano‐based solutions that actively target these particular tumors. PMID:27980912

  20. An overview of triple negative breast cancer for surgical oncologists.

    PubMed

    Sharma, Shiva; Barry, Mitchel; Gallagher, David J; Kell, Malcolm; Sacchini, Virgilio

    2015-09-01

    Triple negative breast cancers (TNBCs) represent a distinct subgroup of breast cancers with an immunohistochemical phenotype that is negative for oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). The aim of this article is to provide a broad overview of recent developments in the diagnosis and management of TNBC for surgical oncologists. This overview discusses the subtypes of TNBC and the relationship between this type of breast cancer and the BRCA1 gene. In addition, the article explores recent advances in the treatment of TNBC from a surgical, radiation, and medical oncology point of view. Lastly, evolving therapeutic strategies that have potential to enhance outcomes for patients with TNBC are also discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Targeted Therapies for Brain Metastases from Breast Cancer

    PubMed Central

    Venur, Vyshak Alva; Leone, José Pablo

    2016-01-01

    The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor, mechanistic target of rapamycin (mTOR) pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6) pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%–30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways. PMID:27649142

  2. Targeted Therapies for Brain Metastases from Breast Cancer.

    PubMed

    Venur, Vyshak Alva; Leone, José Pablo

    2016-09-13

    The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor, mechanistic target of rapamycin (mTOR) pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6) pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%-30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways.

  3. Targeting Breast Cancer Stem Cells In Triple Negative Breast Cancer

    DTIC Science & Technology

    2014-10-01

    breast cancer (TNBC) and drug resistance. We hypothesize that obesity effects on TNBC occur via leptin -signaling stimulation of breast cancer stem...human TNBC cell lines treated with leptin , and novel leptin receptor inhibitor bound to nanoparticles (IONPs-LPrA) alone, and combined with cisplatin...a chemotherapeutic) and Sunitinib (an inhibitor of VEGFR-2 kinase). Our data show that leptin increased cell proliferation and expression of BCSC

  4. Doxorubicin Hydrochloride, Cyclophosphamide, and Filgrastim Followed By Paclitaxel Albumin-Stabilized Nanoparticle Formulation With or Without Trastuzumab in Treating Patients With Breast Cancer Previously Treated With Surgery

    ClinicalTrials.gov

    2013-05-07

    Estrogen Receptor-positive Breast Cancer; HER2-positive Breast 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

  5. Vitamin D and Breast Cancer

    DTIC Science & Technology

    1995-07-15

    Sadler M, Vollmer RT, Lobaugh B, Drezner MK, Vogelman JH, Orentreich N. Vitamin D and prostate cancer: a prediagnostic study with stored sera. Cancer ... Epidemiology , Biomarkers & Prevention 2:467-472,1993. 6. Blot WJ, Fraumeni JF, Stone BJ. Geographic patterns of breast cancer in the United States. J

  6. Treatment of triple negative breast cancer (TNBC): current options and future perspectives.

    PubMed

    De Laurentiis, M; Cianniello, D; Caputo, R; Stanzione, B; Arpino, G; Cinieri, S; Lorusso, V; De Placido, S

    2010-11-01

    Breast cancer is not considered anymore a unique disease. Microarray gene expression analysis led to the identification of 4 major breast cancer "intrinsic" subtypes, including hormone receptor (HR)-positive luminal A and B, human epidermal growth receptor 2 (HER2)-positive and basal-like breast cancer (BLBC). These subtypes have distinct phenotypes, molecular profiles, clinical behaviour and response to therapy, with the BLBC carrying the worst outcome. Microarray analysis is not feasible in routine practice and therefore oncologists rely on a simpler immunohistochemical (IHC) classification to identify relevant breast cancer subtypes. Triple negative breast cancer (TNBC) is defined by the absence of oestrogen receptor, progesterone receptor and HER2 expression at IHC analysis. TNBC is strictly related to BLBC and, given the lack of common therapeutic targets, represent a major challenge for breast oncologist. In this review we will summarize the updated knowledge on TNBC, with emphasis on its current treatment and on the new therapeutic options under development.

  7. Aromatase and breast cancer.

    PubMed

    Brodie, A; Sabnis, G; Jelovac, D

    2006-12-01

    Several aromatase inhibitors and also new antiestrogens are now available for treating breast cancer. We have developed a model to compare the antitumor efficacy of these agents and to explore strategies for their optimal use. Results from the model have been predictive of clinical outcome. In this model, tumors are grown in ovariectomized, immunodeficient mice from MCF-7 human breast cancer cells transfected with the aromatase gene (MCF-7Ca). The possibility that blockade of estrogen action and estrogen synthesis may be synergistic was explored by treating mice with the aromatase inhibitor letrozole and the antiestrogen tamoxifen alone and in combination. The results indicated that letrozole alone was better than all other treatments. In addition, when tamoxifen treatment was no longer effective, tumor growth was significantly reduced in mice switched to letrozole treatment. However, tumors ultimately began to grow during continued treatment. To investigate the mechanisms by which tumors eventually adapt and grow during letrozole treatment, we determined the expression of signaling proteins in tumors during the course of letrozole treatment compared to the tumors of control mice. Tumors initially up-regulated the ER while responding to treatment, but subsequently receptor levels decreased in tumors unresponsive to letrozole. Also, Her-2 and adapter proteins (p-Shc and Grb-2) as well as all of the signaling proteins in the MAPK cascade (p-Raf, p-Mekl/2, and p-MAPK), but not in the Pl3/Akt pathway, were increased in tumors no longer responsive to letrozole. To investigate whether sensitivity to letrozole could be regained, cells were isolated from the letrozole resistant tumors (LTLT) and treated with inhibitors of the MAPKinase pathway (PD98059 and UO126). These compounds reduced MAPK activity and increased ER expression. EGFR/Her-2 inhibitors, gefitinib and AEE78S although not effective in the parental MCF-70a cells, restored the sensitivity of LTLT cells to

  8. Organochlorine pesticides accumulation and breast cancer: A hospital-based case-control study.

    PubMed

    He, Ting-Ting; Zuo, An-Jun; Wang, Ji-Gang; Zhao, Peng

    2017-05-01

    The aim of this study is to detect the accumulation status of organochlorine pesticides in breast cancer patients and to explore the relationship between organochlorine pesticides contamination and breast cancer development. We conducted a hospital-based case-control study in 56 patients with breast cancer and 46 patients with benign breast disease. We detected the accumulation level of several organochlorine pesticides products (β-hexachlorocyclohexane, γ-hexachlorocyclohexane, polychlorinated biphenyls-28, polychlorinated biphenyls-52, pentachlorothioanisole, and pp'-dichlorodiphenyldichloroethane) in breast adipose tissues of all 102 patients using gas chromatography. Thereafter, we examined the expression status of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER2), and Ki-67 in 56 breast cancer cases by immunohistochemistry. In addition, we analyzed the risk of breast cancer in those patients with organochlorine pesticides contamination using a logistic regression model. Our data showed that breast cancer patients suffered high accumulation levels of pp'-dichlorodiphenyldichloroethane and polychlorinated biphenyls-52. However, the concentrations of pp'-dichlorodiphenyldichloroethane and polychlorinated biphenyls-52 were not related to clinicopathologic parameters of breast cancer. Further logistic regression analysis showed polychlorinated biphenyls-52 and pp'-dichlorodiphenyldichloroethane were risk factors for breast cancer. Our results provide new evidence on etiology of breast cancer.

  9. Do We Know What Causes Breast Cancer in Men?

    MedlinePlus

    ... Factors, and Prevention Do We Know What Causes Breast Cancer in Men? Although certain risk factors may increase ... Breast Cancer in Men Be Prevented? More In Breast Cancer In Men About Breast Cancer in Men Causes, ...

  10. Soy Isoflavones Supplementation in Treating Women at High Risk For or With Breast Cancer

    ClinicalTrials.gov

    2017-04-08

    BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer

  11. Onalespib and Paclitaxel in Treating Patients With Advanced Triple Negative Breast Cancer

    ClinicalTrials.gov

    2017-02-02

    Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  12. Pembrolizumab and Binimetinib in Treating Patients With Locally Advanced or Metastatic Triple Negative Breast Cancer

    ClinicalTrials.gov

    2017-09-27

    Breast Adenocarcinoma; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  13. Could HER2 Heterogeneity Open New Therapeutic Options in Patients with HER2-Primary Breast Cancer

    DTIC Science & Technology

    2016-10-01

    Zr-trastuzumab PET / CT . Two of nine patients with suspicious foci had biopsy-proven HER2-positive metastases. Thus, 89 Zr-trastuzumab PET / CT may...into clinical use, and a more specific radiotracer will be needed. 15. SUBJECT TERMS Breast cancer, HER2, tumor heterogeneity, PET / CT , 89Zr...KEYWORDS: Breast cancer Human epidermal growth factor receptor 2 (HER2) Tumor heterogeneity PET / CT Targeted imaging 89Zr-trastuzumab 3

  14. Erythema multiforme after radiotherapy with aromatase inhibitor administration in breast-conservation treatment for breast cancer.

    PubMed

    Nakatani, Kimiko; Matsumoto, Masaaki; Ue, Hironobu; Nishioka, Akihito; Tanaka, Yousuke; Kodama, Hajime; Sasaguri, Shiro; Ogawa, Yasuhiro

    2008-01-01

    Generalized eruptions associated with radiotherapy such as erythema multiforme (EM), Steven-Johnson syndrome and toxic epidermal necrolysis are uncommon reactions. A few cases of generalized eruptions during and after radiotherapy have been reported with the use of anticonvulsants and anticancer drugs. However, no reports have described mucocutaneous reactions associated with radiotherapy and concurrent use of anastrozole, an aromatase inhibitor. This report describes EM occurring after radiotherapy performed during breast-conserving treatment for breast cancer in a patient who was taking oral anastrozole.

  15. Consumer Health Education. Breast Cancer.

    ERIC Educational Resources Information Center

    Arkansas Univ., Fayetteville, Cooperative Extension Service.

    This short booklet is designed to be used by health educators when teaching women about breast cancer and its early detection and the procedure for breast self-examination. It includes the following: (1) A one-page teaching plan consisting of objectives, subject matter, methods (including titles of films and printed materials), target audience,…

  16. Triiodothyronine and breast cancer

    PubMed Central

    De Sibio, Maria Teresa; de Oliveira, Miriane; Moretto, Fernanda Cristina Fontes; Olimpio, Regiane Marques Castro; Conde, Sandro José; Luvizon, Aline Carbonera; Nogueira, Célia Regina

    2014-01-01

    The thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), are essential for survival; they are involved in the processes of development, growth, and metabolism. In addition to hyperthyroidism or hypothyroidism, THs are involved in other diseases. The role of THs in the development and differentiation of mammary epithelium is well established; however, their specific role in the pathogenesis of breast cancer (BC) is controversial. Steroid hormones affect many human cancers and the abnormal responsiveness of the mammary epithelial cells to estradiol (E2) in particular is known to be an important cause for the development and progression of BC. The proliferative effect of T3 has been demonstrated in various types of cancer. In BC cell lines, T3 may foster the conditions for tumor proliferation and increase the effect of cell proliferation by E2; thus, T3 may play a role in the development and progression of BC. Studies show that T3 has effects similar to E2 in BC cell lines. Despite controversy regarding the relationship between thyroid disturbances and the incidence of BC, studies show that thyroid status may influence the development of tumor, proliferation and metastasis. PMID:25114863

  17. Triiodothyronine and breast cancer.

    PubMed

    De Sibio, Maria Teresa; de Oliveira, Miriane; Moretto, Fernanda Cristina Fontes; Olimpio, Regiane Marques Castro; Conde, Sandro José; Luvizon, Aline Carbonera; Nogueira, Célia Regina

    2014-08-10

    The thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), are essential for survival; they are involved in the processes of development, growth, and metabolism. In addition to hyperthyroidism or hypothyroidism, THs are involved in other diseases. The role of THs in the development and differentiation of mammary epithelium is well established; however, their specific role in the pathogenesis of breast cancer (BC) is controversial. Steroid hormones affect many human cancers and the abnormal responsiveness of the mammary epithelial cells to estradiol (E2) in particular is known to be an important cause for the development and progression of BC. The proliferative effect of T3 has been demonstrated in various types of cancer. In BC cell lines, T3 may foster the conditions for tumor proliferation and increase the effect of cell proliferation by E2; thus, T3 may play a role in the development and progression of BC. Studies show that T3 has effects similar to E2 in BC cell lines. Despite controversy regarding the relationship between thyroid disturbances and the incidence of BC, studies show that thyroid status may influence the development of tumor, proliferation and metastasis.

  18. Survivorship Care Plan in Promoting Physical Activity in Breast or Colorectal Cancer Survivors in Wisconsin

    ClinicalTrials.gov

    2017-05-01

    Cancer Survivor; Healthy Subject; Stage I Colorectal Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer; Stage IIC Colorectal Cancer; Stage IIIA Breast Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Breast Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer

  19. Association of Breast Cancer Risk loci with Breast Cancer Survival

    PubMed Central

    Barrdahl, Myrto; Canzian, Federico; Lindström, Sara; Shui, Irene; Black, Amanda; Hoover, Robert N.; Ziegler, Regina G.; Buring, Julie E.; Chanock, Stephen J.; Diver, W. Ryan; Gapstur, Susan M.; Gaudet, Mia M.; Giles, Graham G.; Haiman, Christopher; Henderson, Brian E.; Hankinson, Susan; Hunter, David J.; Joshi, Amit D.; Kraft, Peter; Lee, I-Min; Le Marchand, Loic; Milne, Roger L.; Southey, Melissa C.; Willett, Walter; Gunter, Marc; Panico, Salvatore; Sund, Malin; Weiderpass, Elisabete; Sánchez, María-José; Overvad, Kim; Dossus, Laure; Peeters, Petra H; Khaw, Kay-Tee; Trichopoulos, Dimitrios; Kaaks, Rudolf; Campa, Daniele

    2015-01-01

    The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele=0.70; 95% CI: 0.58–0.85; Ptrend=2.84×10−4; HRheterozygotes=0.71; 95% CI: 0.55–0.92; HRhomozygotes=0.48; 95% CI: 0.31–0.76; P2DF=1.45×10−3). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04–1.15; Ptrend=6.6×10−4; HRheterozygotes=0.96 95% CI: 0.90–1.03; HRhomozygotes= 1.21; 95% CI: 1.09–1.35; P2DF=1.25×10−4). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662. PMID:25611573

  20. Treatment Option Overview (Breast Cancer)

    MedlinePlus

    ... in lymph and help fight infection and disease. Clusters of lymph nodes are found near the breast ... the tumor is 2 centimeters or smaller. Small clusters of cancer cells (larger than 0.2 millimeter ...

  1. General Information about Breast Cancer

    MedlinePlus

    ... in lymph and help fight infection and disease. Clusters of lymph nodes are found near the breast ... the tumor is 2 centimeters or smaller. Small clusters of cancer cells (larger than 0.2 millimeter ...

  2. 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.

  3. Fostering early breast cancer detection.

    PubMed

    Shackelford, Judy A; Weyhenmeyer, Diana P; Mabus, Linda K

    2014-12-01

    This article examines how faith community nurses (FCNs) fostered early breast cancer detection for those at risk in rural and African American populations throughout nine counties in midwestern Illinois to decrease breast cancer disparities. Flexible methods for breast cancer awareness education through FCNs, effective strategies for maximizing participation, and implications for practice were identified. In addition, networking within faith communities, connecting with complementary activities scheduled in those communities, and offering refreshments and gift items that support educational efforts were identified as effective ways of maximizing outcomes and reinforcing learning. Flexible educational programming that could be adapted to situational and learning needs was important to alleviate barriers in the project. As a result, the number of participants in the breast cancer awareness education program exceeded the grant goal, and the large number of African American participants and an unexpected number of Hispanic and Latino participants exceeded the target.

  4. Tumour markers in breast cancer.

    PubMed Central

    Cove, D. H.; Woods, K. L.; Smith, S. C.; Burnett, D.; Leonard, J.; Grieve, R. J.; Howell, A.

    1979-01-01

    The clinical usefulness of 8 potential tumour markers has been evaluated in 69 patients with Stage I and II breast cancer and 57 patients with Stage III and IV. Serum CEA concentrations were raised in 13% of patients with local and 65% of those with advanced breast cancer. In patients with clinical evidence of progression or regression of tumour, serum CEA levels changed appropriately in 83% of cases. Taking 4 of the markers (carcinoembryonic antigen (CEA), lactalbumin, alpha subunit and haptoglobin) serum concentrations of one or more were raised in 33% of patients with local disease and 81% of those with advanced breast cancer. However, marker concentrations were often only marginally raised, and are unlikely to provide sensitive guide to tumour burden. CEA, lactalbumin and alpha subunit were detectable in 68%, 43% and 40% respectively of extracts of primary breast cancers. PMID:92331

  5. Incremental cancer detection using breast ultrasonography versus breast magnetic resonance imaging in the evaluation of newly diagnosed breast cancer patients

    PubMed Central

    Plaxco, Jeri S; Wei, Wei; Huo, Lei; Candelaria, Rosalind P; Kuerer, Henry M; Yang, Wei T

    2016-01-01

    Objective: To compare the incremental cancer detection rate (ICDR) using bilateral whole-breast ultrasonography (BWBUS) vs dynamic contrast-enhanced MRI in patients with primary breast cancer. Methods: A retrospective database search in a single institution identified 259 patients with breast cancer diagnosed from January 2011 to August 2014 who underwent mammography, BWBUS and MRI before surgery. Patient characteristics, tumour characteristics and lesions seen on each imaging modality were recorded. The sensitivity, specificity and accuracy for each modality were calculated. ICDRs according to index tumour histology and receptor status were also evaluated. The effect of additional cancer detection on surgical planning was obtained from the medical records. Results: A total of 266 additional lesions beyond 273 index malignancies were seen on at least 1 modality, of which 121 (45%) lesions were malignant and 145 (55%) lesions were benign. MRI was significantly more sensitive than BWBUS (p = 0.01), while BWBUS was significantly more accurate and specific than MRI (p < 0.0001). Compared with mammography, the ICDRs using BWBUS and MRI were significantly higher for oestrogen receptor-positive and triple-negative cancers, but not for human epidermal growth factor receptor 2-positive cancers. 22 additional malignant lesions in 18 patients were seen on MRI only. Surgical planning remained unchanged in 8 (44%) of those 18 patients. Conclusion: MRI was more sensitive than BWBUS, while BWBUS was more accurate and specific than MRI. MRI-detected additional malignant lesions did not change surgical planning in almost half of these patients. Advances in knowledge: BWBUS may be a cost-effective and practical tool in breast cancer staging. PMID:27384241

  6. Incremental cancer detection using breast ultrasonography versus breast magnetic resonance imaging in the evaluation of newly diagnosed breast cancer patients.

    PubMed

    He, Hongying; Plaxco, Jeri S; Wei, Wei; Huo, Lei; Candelaria, Rosalind P; Kuerer, Henry M; Yang, Wei T

    2016-09-01

    To compare the incremental cancer detection rate (ICDR) using bilateral whole-breast ultrasonography (BWBUS) vs dynamic contrast-enhanced MRI in patients with primary breast cancer. A retrospective database search in a single institution identified 259 patients with breast cancer diagnosed from January 2011 to August 2014 who underwent mammography, BWBUS and MRI before surgery. Patient characteristics, tumour characteristics and lesions seen on each imaging modality were recorded. The sensitivity, specificity and accuracy for each modality were calculated. ICDRs according to index tumour histology and receptor status were also evaluated. The effect of additional cancer detection on surgical planning was obtained from the medical records. A total of 266 additional lesions beyond 273 index malignancies were seen on at least 1 modality, of which 121 (45%) lesions were malignant and 145 (55%) lesions were benign. MRI was significantly more sensitive than BWBUS (p = 0.01), while BWBUS was significantly more accurate and specific than MRI (p < 0.0001). Compared with mammography, the ICDRs using BWBUS and MRI were significantly higher for oestrogen receptor-positive and triple-negative cancers, but not for human epidermal growth factor receptor 2-positive cancers. 22 additional malignant lesions in 18 patients were seen on MRI only. Surgical planning remained unchanged in 8 (44%) of those 18 patients. MRI was more sensitive than BWBUS, while BWBUS was more accurate and specific than MRI. MRI-detected additional malignant lesions did not change surgical planning in almost half of these patients. BWBUS may be a cost-effective and practical tool in breast cancer staging.

  7. 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.

  8. Metals and Breast Cancer

    PubMed Central

    Byrne, Celia; Divekar, Shailaja D.; Storchan, Geoffrey B.; Parodi, Daniela A.; Martin, Mary Beth

    2014-01-01

    Metalloestrogens are metals that activate the estrogen receptor in the absence of estradiol. The metalloestrogens fall into two subclasses: metal/metalloid anions and bivalent cationic metals. The metal/metalloid anions include compounds such as arsenite, nitrite, selenite, and vanadate while the bivalent cations include metals such as cadmium, calcium, cobalt, copper, nickel, chromium, lead, mercury, and tin. The best studied metalloestrogen is cadmium. It is a heavy metal and a prevalent environmental contaminant with no known physiological function. This review addresses our current understanding of the mechanism by which cadmium and the bivalent cationic metals activate estrogen receptor-α. The review also summarizes the in vitro and in vivo evidence that cadmium functions as an estrogen and the potential role of cadmium in breast cancer. PMID:23338949

  9. Tea phytochemicals for breast cancer prevention and intervention: From bench to bedside and beyond.

    PubMed

    Sinha, Dona; Biswas, Jaydip; Nabavi, Seyed Mohammad; Bishayee, Anupam

    2017-04-07

    The National Cancer Institute of the United States had projected breast cancer as one of the topmost prevalent malignancies of 2016. It was estimated that in 2016, 246,660 new cases of invasive breast cancer were expected to be diagnosed in women in the US, along with 61,000 new cases of non-invasive (in situ) breast cancer. The heterogeneity of breast cancer accounts for its differential molecular subtyping. Recent incorporation of high throughput approaches helps early prognosis of breast cancer, but recurrence of the disease stands to be one of the most daunting fact behind non-availability of third line treatment. At this point of crisis, application of chemopreventive measures could possibly resolve the enigma of breast cancer. The world class beverage tea has proven its efficacy in ameliorating various genetic and epigenetic anomalies in breast cancer. Tea phytoconstituents are known to modulate myriad molecular events which include prominent regulators of intracellular signaling, such as phosphatidylinositide 3-kinase/protein kinase B/nuclear factor-κB, epidermal growth factor receptor, vascular endothelial growth factor, B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein in the development and progression of breast carcinoma. This review aims to encompass the detailed modulatory roles of tea phytochemicals, their analogs and nanoformulations against mammary carcinoma and the probability of using tea in therapeutic management of breast cancer. Finally, current limitations, challenges and future directions of tea and breast cancer research are also critically discussed.

  10. Endocrine Therapy of Breast Cancer

    DTIC Science & Technology

    2009-06-01

    obtained breast specimens from breast cancer patients treated with endocrine therapy (or not, i.e., surgery and radiation only in selected...motility in vitro (Hiscox et al., 2006). In models of lung cancer and CML, Dasatinib can reduce AKT activity and expression of the prosurvival protein...measured by terminal deoxynucleotidyl transferse-mediated dUTP nick-end labeling (TUNEL) staining (Wedam et al., 2006). In an in vitro model of lung

  11. Endocrine Therapy of Breast Cancer

    DTIC Science & Technology

    2005-06-01

    breast cancers is whether an aromatase inhibitor, e.g., letrozole (LET) or TAM should be given as first line endocrine therapy . Unfortunately...response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies , e.g., -40% of tumors...effective treatment for hormone receptor positive invasive breast cancer. Such therapy includes antiestrogens (tamoxifen, fulvestrant ) and aromatase

  12. BILATERAL BREAST CANCER: DIAGNOSIS AND PROGNOSIS.

    PubMed

    Ursaru, Manuela; Jari, Irma; Gheorghe, Liliana; Naum, A G; Scripcariu, V; Negru, D

    2016-01-01

    To assess bilateral breast cancer patients, initially diagnosed with stage II unilateral breast cancer. 113 patients with stage 0-II breast cancer diagnosed between 1983 and 2011 were assessed. Of these, 8 patients had bilateral breast cancer: 7 patients with metachronous bilateral breast cancer and 1 patient with synchronous breast cancer. Breast ultrasound, mammography, computed tomography and magnetic resonance imaging were used to diagnose recurrence, loco regional and distant metastasis. Age at diagnosis ranged from 37 to 59 years, with a maximum age incidence in the 4th decade (age between: 31-40 years). The average time interval between the two breast cancers was 8.125 years. The most common histological type was invasive ductal carcinoma. All eight patients with bilateral breast cancer had at least one type of recurrence/metastasis, mostly in the liver, and statistically the pleuropulmonary and liver metastases were the most frequent causes of death. Patients in the 4th decade diagnosed with unilateral breast cancer are at risk of developing bilateral breast cancer. In metachronous breast cancer, the time interval between the detection of the second breast cancer and death is directly proportional to the time interval between the two breast cancers. TASTASES, DEATH.

  13. [Radiotherapy of breast cancer].

    PubMed

    Hennequin, C; Barillot, I; Azria, D; Belkacémi, Y; Bollet, M; Chauvet, B; Cowen, D; Cutuli, B; Fourquet, A; Hannoun-Lévi, J M; Leblanc, M; Mahé, M A

    2016-09-01

    In breast cancer, radiotherapy is an essential component of the treatment. After conservative surgery for an infiltrating carcinoma, radiotherapy must be systematically performed, regardless of the characteristics of the disease, because it decreases the rate of local recurrence and by this way, specific mortality. Partial breast irradiation could not be proposed routinely but only in very selected and informed patients. For ductal carcinoma in situ, adjuvant radiotherapy must be also systematically performed after lumpectomy. After mastectomy, chest wall irradiation is required for pT3-T4 tumours and if there is an axillary nodal involvement, whatever the number of involved lymph nodes. After neo-adjuvant chemotherapy and mastectomy, in case of pN0 disease, chest wall irradiation is recommended if there is a clinically or radiologically T3-T4 or node positive disease before chemotherapy. Axillary irradiation is recommended only if there is no axillary surgical dissection and a positive sentinel lymph node. Supra and infra-clavicular irradiation is advised in case of positive axillary nodes. Internal mammary irradiation must be discussed case by case, according to the benefit/risk ratio (cardiac toxicity). Dose to the chest wall or the breast must be between 45-50Gy with a conventional fractionation. A boost dose over the tumour bed is required if the patient is younger than 60 years old. Hypofractionation (42.5 Gy in 16 fractions, or 41.6 Gy en 13 or 40 Gy en 15) is possible after tumorectomy and if a nodal irradiation is not mandatory. Delineation of the breast, the chest wall and the nodal areas are based on clinical and radiological evaluations. 3D-conformal irradiation is the recommended technique, intensity-modulated radiotherapy must be proposed only in case of specific clinical situations. Respiratory gating could be useful to decrease the cardiac dose. Concomitant administration of chemotherapy in unadvised, but hormonal treatment could be start with

  14. Breast cancer: origins and evolution.

    PubMed

    Polyak, Kornelia

    2007-11-01

    Breast cancer is not a single disease, but rather is composed of distinct subtypes associated with different clinical outcomes. Understanding this heterogeneity is key for the development of targeted cancer-preventative and -therapeutic interventions. Current models explaining inter- and intratumoral diversity are the cancer stem cell and the clonal evolution hypotheses. Although tumor initiation and progression are predominantly driven by acquired genetic alterations, recent data implicate a role for microenvironmental and epigenetic changes as well. Comprehensive unbiased studies of tumors and patient populations have significantly advanced our molecular understanding of breast cancer, but translating these findings into clinical practice remains a challenge.

  15. Cigarette smoking and breast cancer.

    PubMed

    Baron, J A; Newcomb, P A; Longnecker, M P; Mittendorf, R; Storer, B E; Clapp, R W; Bogdan, G; Yuen, J

    1996-05-01

    A priori hypotheses suggest that cigarette smoking could either increase or decrease breast cancer incidence. To clarify these competing hypotheses, we used data from a very large population-based breast cancer case-control study to investigate the impact of smoking on breast cancer risk. Breast cancer patients less than 75 years old were identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire; controls were randomly selected from driver's license lists (age less than 65) or lists of Medicare beneficiaries (age 65-74). Information on reproductive history, medical history, and personal habits including cigarette smoking was obtained by telephone interview. A total of 6,888 cases and 9,529 controls were interviewed. There was virtually no relationship between current smoking and breast cancer risk (multivariate odds ratio, 1.00; 95% confidence interval, 0.92-1.09), and former smokers had a barely increased risk (odds ratio, 1.10; 95% confidence interval, 1.01-1.19). Similar results were observed among both premenopausal and postmenopausal women. There was no suggestion that heavy or long-term smoking increased or decreased risk, nor were there indications that women who began smoking at an early age were at increased risk, as has been hypothesized. The results of this large population-based study indicate that smoking does not influence the risk of breast cancer, even among heavy smokers who began smoking at an early age.

  16. BREAST CANCER, DERMATOFIBROMAS AND ARSENIC

    PubMed Central

    Dantzig, Paul I

    2009-01-01

    Background: Dermatofibromas are common benign tumors in women, and breast cancer is the most common malignancy in women. The aim of this study is to determine if there is any relationship between the two conditions. Materials and Methods: Five patients with dermatofibromas and 10 control patients (two groups) had their skin biopsies measured for arsenic by inductively coupled mass spectrometry. Fifty randomly selected patients with breast cancer and 50 control patients were examined for the presence of dermatofibromas. Results: The dermatofibromas were found to have an arsenic concentration of 0.171 micrograms/gram, compared with 0.06 and 0.07 micrograms/gram of the two control groups. Forty-three out of 50 patients with breast cancer had dermatofibromas and 32/50 patients with breast cancer had multiple dermatofibromas, compared to 10/50 control patients with dermatofibromas and only 1/50 with multiple dermatofibromas. Conclusions: Arsenic is important in the development of dermatofibromas and dermatofibromas represent a reservoir and important sign of chronic arsenic exposure. Dermatofibromas represent an important sign for women at risk for breast cancer, and arsenic may represent the cause of the majority of cases of breast cancer. PMID:20049264

  17. Danish Breast Cancer Cooperative Group

    PubMed Central

    Christiansen, Peer; Ejlertsen, Bent; Jensen, Maj-Britt; Mouridsen, Henning

    2016-01-01

    Aim of database Danish Breast Cancer Cooperative Group (DBCG), with an associated database, was introduced as a nationwide multidisciplinary group in 1977 with the ultimate aim to improve the prognosis in breast cancer. Since then, the database has registered women diagnosed with primary invasive nonmetastatic breast cancer. The data reported from the departments to the database included details of the characteristics of the primary tumor, of surgery, radiotherapy, and systemic therapies, and of follow-up reported on specific forms from the departments in question. Descriptive data From 1977 through 2014, ~110,000 patients are registered in the nationwide, clinical database. The completeness has gradually improved to more than 95%. DBCG has continuously prepared evidence-based guidelines on diagnosis and treatment of breast cancer and conducted quality control studies to ascertain the degree of adherence to the guidelines in the different departments. Conclusion Utilizing data from the DBCG database, a long array of high-quality DBCG studies of various designs and scope, nationwide or in international collaboration, have contributed to the current updating of the guidelines, and have been an instrumental resource in the improvement of management and prognosis of breast cancer in Denmark. Thus, since the establishment of DBCG, the prognosis in breast cancer has continuously improved with a decrease in 5-year mortality from ~37% to 15%. PMID:27822082

  18. Urinary rubidium in breast cancers.

    PubMed

    Su, Yi; Chen, Li-Juan; He, Jian-Rong; Yuan, Xue-Jiao; Cen, Yu-Ling; Su, Feng-Xi; Tang, Lu-Ying; Zhang, Ai-Hua; Chen, Wei-Qing; Lin, Ying; Wang, Shen-Ming; Ren, Ze-Fang

    2011-11-20

    Rubidium is a putative anticancer agent, but no studies have been performed on the association of rubidium levels in biospecimen with breast cancer risk and the potential as a biomarker of the risk assessment. Survey data and urine specimens were collected from 240 women with incident invasive breast cancer before their treatments and 246 age-matched female controls between October 2009 and July 2010. Urinary concentrations of rubidium were determined by inductively coupled plasma mass spectrometry. Creatinine-adjusted levels [median (25th, 75th) ug/g] of rubidium in cases [2253.01(1606.81, 3110.46)] were significantly lower than that in the controls [2921.85 (2367.94, 4142.04)]. After adjustment for potential risk factors of breast cancer, women in the second and highest tertile decreased risk of breast cancer in a dose-dependent manner as compared with those in the lowest tertile [ORs and 95% CIs were 0.45 (0.27-0.73) and 0.22 (0.13-0.38), respectively]. The area under the receive-operating-characteristic curve for urinary rubidium level was 0.697 (95% CI: 0.650-0.743). The urinary levels of rubidium were significantly and inversely associated with risk of breast cancer and had potential to be a biomarker for breast cancer risk assessment. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Iodide transport and breast cancer.

    PubMed

    Poole, Vikki L; McCabe, Christopher J

    2015-10-01

    Breast cancer is the second most common cancer worldwide and the leading cause of cancer death in women, with incidence rates that continue to rise. The heterogeneity of the disease makes breast cancer exceptionally difficult to treat, particularly for those patients with triple-negative disease. To address the therapeutic complexity of these tumours, new strategies for diagnosis and treatment are urgently required. The ability of lactating and malignant breast cells to uptake and transport iodide has led to the hypothesis that radioiodide therapy could be a potentially viable treatment for many breast cancer patients. Understanding how iodide is transported, and the factors regulating the expression and function of the proteins responsible for iodide transport, is critical for translating this hypothesis into reality. This review covers the three known iodide transporters - the sodium iodide symporter, pendrin and the sodium-coupled monocarboxylate transporter - and their role in iodide transport in breast cells, along with efforts to manipulate them to increase the potential for radioiodide therapy as a treatment for breast cancer.

  20. Genes that mediate breast cancer metastasis to the brain.

    PubMed

    Bos, Paula D; Zhang, Xiang H-F; Nadal, Cristina; Shu, Weiping; Gomis, Roger R; Nguyen, Don X; Minn, Andy J; van de Vijver, Marc J; Gerald, William L; Foekens, John A; Massagué, Joan

    2009-06-18

    The molecular basis for breast cancer metastasis to the brain is largely unknown. Brain relapse typically occurs years after the removal of a breast tumour, suggesting that disseminated cancer cells must acquire specialized functions to take over this organ. Here we show that breast cancer metastasis to the brain involves mediators of extravasation through non-fenestrated capillaries, complemented by specific enhancers of blood-brain barrier crossing and brain colonization. We isolated cells that preferentially infiltrate the brain from patients with advanced disease. Gene expression analysis of these cells and of clinical samples, coupled with functional analysis, identified the cyclooxygenase COX2 (also known as PTGS2), the epidermal growth factor receptor (EGFR) ligand HBEGF, and the alpha2,6-sialyltransferase ST6GALNAC5 as mediators of cancer cell passage through the blood-brain barrier. EGFR ligands and COX2 were previously linked to breast cancer infiltration of the lungs, but not the bones or liver, suggesting a sharing of these mediators in cerebral and pulmonary metastases. In contrast, ST6GALNAC5 specifically mediates brain metastasis. Normally restricted to the brain, the expression of ST6GALNAC5 in breast cancer cells enhances their adhesion to brain endothelial cells and their passage through the blood-brain barrier. This co-option of a brain sialyltransferase highlights the role of cell-surface glycosylation in organ-specific metastatic interactions.

  1. Detection of HER2-Positive Metastases in Patients with HER2-Negative Primary Breast Cancer Using 89Zr-Trastuzumab PET/CT.

    PubMed

    Ulaner, Gary A; Hyman, David M; Ross, Dara S; Corben, Adriana; Chandarlapaty, Sarat; Goldfarb, Shari; McArthur, Heather; Erinjeri, Joseph P; Solomon, Stephen B; Kolb, Hartmuth; Lyashchenko, Serge K; Lewis, Jason S; Carrasquillo, Jorge A

    2016-10-01

    Our objective was to determine whether imaging with a human epidermal growth factor receptor 2 (HER2)-targeted PET tracer can detect HER2-positive metastases in patients with HER2-negative primary breast cancer.

  2. Asian ethnicity and breast cancer subtypes: a study from the California Cancer Registry

    PubMed Central

    Chang, Ellen T.; Kurian, Allison W.; Keegan, Theresa H. M.; McClure, Laura A.; Lichtensztajn, Daphne; Ford, James M.; Gomez, Scarlett L.

    2015-01-01

    The distribution of breast cancer molecular subtypes has been shown to vary by race/ethnicity, highlighting the importance of host factors in breast tumor biology. We undertook the current analysis to determine population-based distributions of breast cancer subtypes among six ethnic Asian groups in California. We defined immunohistochemical (IHC) surrogates for each breast cancer subtype among Chinese, Japanese, Filipina, Korean, Vietnamese, and South Asian patients diagnosed with incident, primary, invasive breast cancer between 2002 and 2007 in the California Cancer Registry as: hormone receptor-positive (HR+)/HER2− [estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+), human epidermal growth factor receptor 2-negative (HER2−)], triple-negative (ER−, PR−, and HER2−), and HER2-positive (ER±, PR±, and HER2+). We calculated frequencies of breast cancer subtypes among Asian ethnic groups and evaluated their associations with clinical and demographic factors. Complete IHC data were available for 8,140 Asian women. Compared to non-Hispanic White women, Korean [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.5–2.2], Filipina (OR = 1.3, 95% CI = 1.2–1.5), Vietnamese (OR = 1.3, 95% CI = 1.1–1.6), and Chinese (OR =1.1, 95% CI = 1.0–1.3) women had a significantly increased risk of being diagnosed with HER2-positive breast cancer subtypes after adjusting for age, stage, grade, socioeconomic status, histology, diagnosis year, nativity, and hospital ownership status. We report a significant ethnic disparity in HER2-positive breast cancer in a large population-based cohort enriched for Asian-Americans. Given the poor prognosis and high treatment costs of HER2-positive breast cancer, our results have implications for healthcare resource utilization, cancer biology, and clinical care. PMID:20957431

  3. Natural Products for Chemoprevention of Breast Cancer

    PubMed Central

    Ko, Eun-Yi; Moon, Aree

    2015-01-01

    Breast cancer is the primary cause of cancer death in women. Although current therapies have shown some promise against breast cancer, there is still no effective cure for the majority of patients in the advanced stages of breast cancer. Development of effective agents to slow, reduce, or reverse the incidence of breast cancer in high-risk women is necessary. Chemoprevention of breast cancer by natural products is advantageous, as these compounds have few side effects and low toxicity compared to synthetic compounds. In the present review, we summarize natural products which exert chemopreventive activities against breast cancer, such as curcumin, sauchinone, lycopene, denbinobin, genipin, capsaicin, and ursolic acid. This review examines the current knowledge about natural compounds and their mechanisms that underlie breast cancer chemopreventive activity both in vitro and in vivo. The present review may provide information on the use of these compounds for the prevention of breast cancer. PMID:26734584

  4. Environmental exposures, breast development and cancer risk: Through the looking glass of breast cancer prevention.

    PubMed

    Forman, Michele R; Winn, Deborah M; Collman, Gwen W; Rizzo, Jeanne; Birnbaum, Linda S

    2015-07-01

    This review summarizes the report entitled: Breast Cancer and the Environment: Prioritizing Prevention, highlights research gaps and the importance of focusing on early life exposures for breast development and breast cancer risk. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Environmental pollutants and breast cancer.

    PubMed Central

    Brody, Julia Green; Rudel, Ruthann A

    2003-01-01

    Breast cancer is the most common cancer in women and the leading cause of cancer death among women 35-54 years of age. Rising incidence, increased risk among migrants to higher risk regions, and poor prediction of individual risk have prompted a search for additional modifiable factors. Risk factors for breast cancer include reproductive characteristics associated with estrogen and other hormones, pharmaceutical hormones, and activities such as alcohol use and lack of exercise that affect hormone levels. As a result, investigation of hormonally active compounds in commercial products and pollution is a priority. Compounds that cause mammary tumors in animals are additional priorities. Animal models provide insight into possible mechanisms for effects of environmental pollutants on breast cancer and identify chemical exposures to target in epidemiologic studies. Although few epidemiologic studies have been conducted for chemical exposures, occupational studies show associations between breast cancer and exposure to certain organic solvents and polycyclic aromatic hydrocarbons (PAHs). Population-based studies have been limited to a few organochlorine compounds and PAHs and have been mostly negative. A variety of challenges in studies of breast cancer and the environment may have contributed to negative findings. Lack of exposure assessment tools and few hypothesis-generating toxicologic studies limit the scope of epidemiologic studies. Issues of timing with respect to latency and periods of breast vulnerability, and individual differences in susceptibility pose other challenges. Substantial work is needed in exposure assessment, toxicology, and susceptibility before we can expect a pay-off from large epidemiologic studies of breast cancer and environment. PMID:12826474

  6. Expression of MAGE-A11 in breast cancer tissues and its effects on the proliferation of breast cancer cells.

    PubMed

    Xia, Li-Ping; Xu, Min; Chen, Yan; Shao, Wei-Wei

    2013-01-01

    The melanoma-associated antigen (MAGE) genes are commonly expressed in tumors, but the function of many of these genes remains unknown. Here, we investigated the expression of one family member, MAGE-A11, in breast cancer tissues and corresponding adjacent normal tissues. MAGE-A11 expression was assessed in breast cancer tissues and adjacent normal tissues from 100 women by immunohistochemistry. MAGE-A11 was significantly more highly expressed in breast tumors (56% of samples) compared to normal tissues (0%; P<0.05). Additionally, its expression in breast tumors was investigated in relation to various clinicopathological features, including patient age, tumor stage and volume, and lymph node metastasis. MAGE-A11 protein expression was correlated with expression of the human epidermal growth factor receptor-2 (HER-2) and estrogen receptor (ER)-β (P<0.05), but not with age, pathological type, histological grade, clinical stage, tumor size or lymph node metastasis, or ER-α, progesterone receptor (PR) or amplified in breast cancer 1 (AIB-1) expression. To determine how its expression affects cancer cell proliferation in vitro, MCF-7 human breast cancer cells were transfected with pCMV-AC-MAGE-A11-GFP. MTT colorimetry and colony-forming assays indicated that MAGE-A11 overexpression significantly increased breast cancer cell proliferation and the ability to form colonies (P<0.05). These findings indicate that MAGE-A11, similarly to HER-2 and ER-β, may be an important diagnostic or prognostic indicator in breast cancer and potentially promotes tumor proliferation.

  7. New Immunotherapy Strategies in Breast Cancer

    PubMed Central

    Yu, Lin-Yu; Tang, Jie; Zhang, Cong-Min; Zeng, Wen-Jing; Yan, Han; Li, Mu-Peng; Chen, Xiao-Ping

    2017-01-01

    Breast cancer is the most commonly diagnosed cancer among women. Therapeutic treatments for breast cancer generally include surgery, chemotherapy, radiotherapy, endocrinotherapy and molecular targeted therapy. With the development of molecular biology, immunology and pharmacogenomics, immunotherapy becomes a promising new field in breast cancer therapies. In this review, we discussed recent progress in breast cancer immunotherapy, including cancer vaccines, bispecific antibodies, and immune checkpoint inhibitors. Several additional immunotherapy modalities in early stages of development are also highlighted. It is believed that these new immunotherapeutic strategies will ultimately change the current status of breast cancer therapies. PMID:28085094

  8. New Immunotherapy Strategies in Breast Cancer.

    PubMed

    Yu, Lin-Yu; Tang, Jie; Zhang, Cong-Min; Zeng, Wen-Jing; Yan, Han; Li, Mu-Peng; Chen, Xiao-Ping

    2017-01-12

    Breast cancer is the most commonly diagnosed cancer among women. Therapeutic treatments for breast cancer generally include surgery, chemotherapy, radiotherapy, endocrinotherapy and molecular targeted therapy. With the development of molecular biology, immunology and pharmacogenomics, immunotherapy becomes a promising new field in breast cancer therapies. In this review, we discussed recent progress in breast cancer immunotherapy, including cancer vaccines, bispecific antibodies, and immune checkpoint inhibitors. Several additional immunotherapy modalities in early stages of development are also highlighted. It is believed that these new immunotherapeutic strategies will ultimately change the current status of breast cancer therapies.

  9. Breast Cancer Surgery

    MedlinePlus

    ... and nipple-sparing mastectomy If you are having breast reconstruction at the same time as a mastectomy, the ... a few surgeons (and if you are getting breast reconstruction, a few plastic surgeons). Choose one who does ...

  10. Phosphatidylinositol 3-Kinase and Antiestrogen Resistance in Breast Cancer

    PubMed Central

    Miller, Todd W.; Balko, Justin M.; Arteaga, Carlos L.

    2011-01-01

    Although antiestrogen therapies targeting estrogen receptor (ER) α signaling prevent disease recurrence in the majority of patients with hormone-dependent breast cancer, a significant fraction of patients exhibit de novo or acquired resistance. Currently, the only accepted mechanism linked with endocrine resistance is amplification or overexpression of the ERBB2 (human epidermal growth factor receptor 2 [HER2]) proto-oncogene. Experimental and clinical evidence suggests that hyperactivation of the phosphatidylinositol 3-kinase (PI3K) pathway, the most frequently mutated pathway in breast cancer, promotes antiestrogen resistance. PI3K is a major signaling hub downstream of HER2 and other receptor tyrosine kinases. PI3K activates several molecules involved in cell-cycle progression and survival, and in ER-positive breast cancer cells, it promotes estrogen-dependent and -independent ER transcriptional activity. Preclinical tumor models of antiestrogen-resistant breast cancer often remain sensitive to estrogens and PI3K inhibition, suggesting that simultaneous targeting of the PI3K and ER pathways may be most effective. Herein, we review alterations in the PI3K pathway associated with resistance to endocrine therapy, the state of clinical development of PI3K inhibitors, and strategies for the clinical investigation of such drugs in hormone receptor–positive breast cancer. PMID:22010023

  11. Breast Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing breast cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  12. Screening for Breast Cancer: Detection and Diagnosis

    MedlinePlus

    ... page please turn JavaScript on. Feature: Screening For Breast Cancer Detection and Diagnosis Past Issues / Summer 2014 Table ... States Preventive Services Task Force updated recommendations on breast cancer screening, suggesting that women ages 50 to 74 ...

  13. Screening for Breast Cancer: Staging and Treatment

    MedlinePlus

    ... page please turn JavaScript on. Feature: Screening For Breast Cancer Staging and Treatment Past Issues / Summer 2014 Table of Contents Staging The extent (stage) of breast cancer needs to be determined to help choose the ...

  14. Breast Cancer and Estrogen-Alone Update

    MedlinePlus

    ... Current Issue Past Issues Research News From NIH Breast Cancer and Estrogen-Alone Update Past Issues / Summer 2006 ... hormone therapy does not increase the risk of breast cancer in postmenopausal women, according to an updated analysis ...

  15. Breast Cancer and the Environment Research Program

    Cancer.gov

    The Breast Cancer and the Environment Research Program supports a multidisciplinary network of scientists, clinicians, and community partners to examine the effects of environmental exposures that may predispose a woman to breast cancer throughout her life.

  16. What Is Breast Cancer in Men?

    MedlinePlus

    ... or spread (metastasize) to distant areas of the body. Cells in nearly any part of the body can ... if any lobules. Like all cells of the body, a man's breast duct cells can undergo cancerous changes. But breast cancer is ...

  17. Loneliness May Sabotage Breast Cancer Survival: Study

    MedlinePlus

    ... gov/news/fullstory_162498.html Loneliness May Sabotage Breast Cancer Survival: Study Weak social ties linked to higher ... 2016 (HealthDay News) -- Loneliness may impede long-term breast cancer survival, a new study suggests. In the years ...

  18. Hormone Therapy for Breast Cancer in Men

    MedlinePlus

    ... this is largely based on how well they work in women with breast cancer. Tamoxifen and toremifene (Fareston ® ) These anti-estrogen drugs work by temporarily blocking estrogen receptors on breast cancer ...

  19. Treatment of HER2-positive breast cancer.

    PubMed

    Figueroa-Magalhães, Maria Cristina; Jelovac, Danijela; Connolly, Roisin M; Wolff, Antonio C

    2014-04-01

    The human epidermal growth factor receptor 2 gene (HER2) is overexpressed and/or amplified in ~15% of breast cancer patients and was identified a quarter century ago as a marker of poor prognosis. By 1998, antibody therapy targeting the HER2 pathway was shown to demonstrably improve progression-free and overall survival in metastatic disease, and in 2005 evidence of improvement in disease-free and overall survival from the first generation of trastuzumab adjuvant trials became available. However, not all patients with HER2 overexpression benefit from trastuzumab. Second-generation studies in metastatic disease led to the approval of several new HER2-targeted therapies using small molecule tyrosine kinase inhibitors such as lapatinib, new HER2/HER3 antibodies such as pertuzumab, and the new antibody chemotherapy conjugate ado-trastuzumab emtansine. These successes supported the launch of second-generation adjuvant trials testing single and dual HER2-targeted agents, administered concomitantly or sequentially with chemotherapy that will soon complete accrual. HER2-positive breast cancer in the setting of HER2-targeted therapy is no longer associated with poor prognosis, and recent guidance by the US Food and Drug Administration suggests that pathologic response to HER2-targeted therapy given preoperatively may allow an earlier assessment of their clinical benefit in the adjuvant setting. An adjuvant trial of trastuzumab in patient whose tumors express normal levels of HER2 and trials of single/dual HER2-targeting without chemotherapy are also ongoing. In this article, we review the current data on the therapeutic management of HER2-positive breast cancer.

  20. Pertuzumab in breast cancer: a systematic review.

    PubMed

    Zagouri, Flora; Sergentanis, Theodoros N; Chrysikos, Dimosthenis; Zografos, Constantine G; Filipits, Martin; Bartsch, Rupert; Dimopoulos, Meletios-Athanassios; Psaltopoulou, Theodora

    2013-10-01

    Pertuzumab is a monoclonal antibody that represents the first among a new class of agents known as human epidermal growth factor receptor (HER) dimerization inhibitors. This is the first systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to synthesize all available data of pertuzumab in breast cancer. The search strategy retrieved 11 studies that evaluated pertuzumab. One study was conducted in the neoadjuvant setting (417 patients), whereas all the others dealt with patients with recurrent, metastatic, or refractory disease (1023 patients). Six studies were conducted in HER2(+) breast cancer population (1354 patients), whereas 5 studies (86 patients) were conducted in HER2(-) (or unknown HER2 status) disease. Pertuzumab is the most recent agent approved by the US Food and Drug Administration in combination with trastuzumab and docetaxel for the treatment of patients with HER2(+) metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. This approval has been based on data from a phase III Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study. The antitumor activity with the significant reduction in the risk of progression or death, as reflected upon the increase of 6.1 months in median progression-free survival, indicates that pertuzumab may provide an avenue for achieving additional benefit for patients with HER2(+). Moreover, pertuzumab seems to have a putative role in the management of patients with HER2 who are resistant to trastuzumab. The promising role of pertuzumab in the neoadjuvant and adjuvant settings remains to be further investigated and established in the future.

  1. Contralateral Breast Cancers: Independent Cancers or Metastases?

    PubMed

    Begg, Colin B; Ostrovnaya, Irina; Geyer, Felipe C; Papanastasiou, Anastasios D; Ng, Charlotte Ky; Sakr, Rita; Bernstein, Jonine L; Burke, Kathleen A; King, Tari A; Piscuoglio, Salvatore; Mauguen, Audrey; Orlow, Irene; Weigelt, Britta; Seshan, Venkatraman E; Morrow, Monica; Reis-Filho, Jorge S

    2017-09-16

    A cancer in the contralateral breast in a woman with a previous or synchronous breast cancer is typically considered to be an independent primary tumor. Emerging evidence suggests that in a small subset of these cases the second tumor represents a metastasis. We sought to investigate the issue using massively parallel sequencing targeting 254 genes recurrently mutated in breast cancer. We examined the tumor archives at Memorial Sloan Kettering Cancer Center for the period 1995-2006 to identify cases of contralateral breast cancer where surgery for both tumors was performed at the Center. We report results from 49 patients successfully analyzed by a targeted massively parallel sequencing assay. Somatic mutations and copy number alterations were defined by state-of-the-art algorithms. Clonal relatedness was evaluated by statistical tests specifically designed for this purpose. We found evidence that the tumors in contralateral breasts were clonally related in 3 cases (6%) on the basis of matching mutations at codons where somatic mutations are rare. Clinical data and the presence of similar patterns of gene copy number alterations were consistent with metastasis for all 3 cases. In 3 additional cases there was a solitary matching mutation at a common PIK3CA locus. The results suggest that a subset of contralateral breast cancers represent metastases rather than independent primary tumors. Massively parallel sequencing analysis can provide important evidence to clarify the diagnosis. However, given the inter-tumor mutational heterogeneity in breast cancer, sufficiently large gene panels need to be employed to define clonality convincingly in all cases. This article is protected by copyright. All rights reserved. © 2017 UICC.

  2. Veliparib, Cisplatin, and Vinorelbine Ditartrate in Treating Patients With Recurrent and/or Metastatic Breast Cancer

    ClinicalTrials.gov

    2017-02-27

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Hereditary Breast/Ovarian Cancer - BRCA1; Hereditary Breast/Ovarian Cancer - BRCA2; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

  3. Alternative Dosing of Exemestane Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer

    ClinicalTrials.gov

    2017-02-17

    Estrogen Receptor Positive; Postmenopausal; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  4. Fulvestrant and Palbociclib in Treating Older Patients With Hormone Responsive Breast Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-09-21

    Estrogen Receptor and/or Progesterone Receptor Positive; HER2/Neu Negative; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  5. Heavy Metal Exposure in Predicting Peripheral Neuropathy in Patients With Stage I-III Breast Cancer Undergoing Chemotherapy

    ClinicalTrials.gov

    2017-06-14

    Male Breast Cancer; Neurotoxicity; Peripheral Neuropathy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  6. Minocycline Hydrochloride in Reducing Chemotherapy Induced Depression and Anxiety in Patients With Stage I-III Breast Cancer

    ClinicalTrials.gov

    2017-01-28

    Anxiety Disorder; Depression; Recurrent Breast 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

  7. Saracatinib in Treating Patients With Metastatic or Locally Advanced Breast Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2014-04-02

    Estrogen Receptor-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  8. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Same long-term growth human mammary epithelial cells (HMEC), but after 3 weeks in concinuous culture. Note attempts to reform duct elements, but this time in two dimensions in a dish rather that in three demensions in tissue. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Tichmond, NASA/Marshall Space Flight Center (MSFC).

  9. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Isolate of long-term growth human mammary epithelial cells (HMEC) from outgrowth of duct element; cells shown soon after isolation and early in culture in a dish. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Tichmond, NASA/Marshall Space Flight Center (MSFC).

  10. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Outgrowth of cells from duct element in upper right corner cultured in a standard dish; most cells spontaneously die during early cell divisions, but a few will establish long-term growth. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Tichmond, NASA/Marshall Space Flight Center (MSFC).

  11. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Outgrowth of cells from duct element in upper right corner cultured in a standard dish; most cells spontaneously die during early cell divisions, but a few will establish long-term growth. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Tichmond, NASA/Marshall Space Flight Center (MSFC).

  12. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Same long-term growth human mammary epithelial cells (HMEC), but after 3 weeks in concinuous culture. Note attempts to reform duct elements, but this time in two dimensions in a dish rather that in three demensions in tissue. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Tichmond, NASA/Marshall Space Flight Center (MSFC).

  13. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Isolation of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Isolate of long-term growth human mammary epithelial cells (HMEC) from outgrowth of duct element; cells shown soon after isolation and early in culture in a dish. NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cell (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunorous tissue. Credit: Dr. Robert Tichmond, NASA/Marshall Space Flight Center (MSFC).

  14. Targeted therapies with companion diagnostics in the management of breast cancer: current perspectives.

    PubMed

    Myers, Meagan B

    2016-01-01

    Breast cancer is a multifaceted disease exhibiting both intertumoral and intratumoral heterogeneity as well as variable disease course. Over 2 decades of research has advanced the understanding of the molecular substructure of breast cancer, directing the development of new therapeutic strategies against these actionable targets. In vitro diagnostics, and specifically companion diagnostics, have been integral in the successful development and implementation of these targeted therapies, such as those directed against the human epidermal growth factor receptor 2. Lately, there has been a surge in the development, commercialization, and marketing of diagnostic assays to assist in breast cancer patient care. More recently, multigene signature assays, such as Oncotype DX, MammaPrint, and Prosigna, have been integrated in the clinical setting in order to tailor decisions on adjuvant endocrine and chemotherapy treatment. This review provides an overview of the current state of breast cancer management and the use of companion diagnostics to direct personalized approaches in the treatment of breast cancer.

  15. Epidermal growth factor receptor and KRAS mutations in Brazilian lung cancer patients

    PubMed Central

    Bacchi, Carlos E.; Ciol, Heloísa; Queiroga, Eduardo M.; Benine, Lucimara C.; Silva, Luciana H.; Ojopi, Elida B.

    2012-01-01

    OBJECTIVE: Epidermal growth factor receptor is involved in the pathogenesis of non-small cell lung cancer and has recently emerged as an important target for molecular therapeutics. The KRAS oncogene also plays an important role in the development of lung cancer. The aim of this study was to evaluate the frequency of epidermal growth factor receptor and KRAS mutations in a population of Brazilian patients with non-small cell lung cancer. METHODS: A total of 207 specimens from Brazilian patients with non-small cell lung cancer were analyzed for activating epidermal growth factor receptor and KRAS somatic mutations, and their associations with clinicopathological characteristics (including age, gender, ethnicity, smoking habits, and histological subtype) were examined. RESULTS: We identified 63 cases (30.4%) with epidermal growth factor receptor mutations and 30 cases (14.6%) with KRAS mutations. The most frequent epidermal growth factor receptor mutation we detected was a deletion in exon 19 (60.3%, 38 patients), followed by an L858R amino acid substitution in exon 21 (27%, 17 patients). The most common types of KRAS mutations were found in codon 12. There were no significant differences in epidermal growth factor receptor or KRAS mutations by gender or primary versus metastatic lung cancer. There was a higher prevalence of KRAS mutations in the non-Asian patients. Epidermal growth factor receptor mutations were more prevalent in adenocarcinomas than in non-adenocarcinoma histological types. Being a non-smoker was significantly associated with the prevalence of epidermal growth factor receptor mutations, but the prevalence of KRAS mutations was significantly associated with smoking. CONCLUSIONS: This study is the first to examine the prevalence of epidermal growth factor receptor and KRAS mutations in a Brazilian population sample with non-small cell lung cancer. PMID:22666783

  16. The Epidemiology of Male Breast Cancer.

    PubMed

    Ferzoco, Raina M; Ruddy, Kathryn J

    2016-01-01

    Male breast cancer is a rare disease, accounting for only 1% of breast cancer diagnoses in the USA. The current literature suggests that genetic factors including BRCA2 mutations, family history, age, androgen/estrogen imbalance, and environmental exposures may predispose to male breast cancer. In this manuscript, we will review known and possible risk factors for male breast cancer, as well as describe the clinical patterns of the disease.

  17. Pro-Apoptotic Breast Cancer Nanotherapeutics

    DTIC Science & Technology

    2013-07-01

    basal-like breast cancer using a novel nanotechnology platform pioneered by my mentor Prof. Stupp. Our original plan was to combine nanoparticles ...Fellowship has supported my training in translational breast cancer research as part of an interdisciplinary team of scientists using nanotechnology to...basal-like breast cancer . 15. SUBJECT TERMS Nanotechnology ; Peptide Amphiphile; Drug Delivery; Breast Cancer ; Cell Death 16. SECURITY CLASSIFICATION OF

  18. Multi-epitope Folate Receptor Alpha Peptide Vaccine, Sargramostim, and Cyclophosphamide in Treating Patients With Triple Negative Breast Cancer

    ClinicalTrials.gov

    2017-01-24

    Bilateral Breast Carcinoma; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma; Unilateral Breast Carcinoma

  19. Targeting Androgen Receptor in Breast Cancer: Enzalutamide as a Novel Breast Cancer Therapeutic

    DTIC Science & Technology

    2016-09-01

    Award Number: W81XWH-13-1-0091 TITLE: Targeting Androgen Receptor in Breast Cancer : Enzalutamide as a Novel Breast Cancer Therapeutic PRINCIPAL...2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting Androgen Receptor in Breast Cancer : Enzalutamide as a Novel Breast Cancer Therapeutic 5b...activity in breast cancer as a single agent and in combination with exemestane. Activity is seen in both triple negative AR+ BC and also ER+AR+ BC

  20. Targeting of CD151 in Breast Cancer and in Breast Cancer Stem Cells

    DTIC Science & Technology

    2007-04-01

    role in the progression of breast cancer . 15. SUBJECT TERMS CD151 protein, breast cancer progression, ErbB2 amplification, breast carcinoma invasion... malignancy in breast cancer and other types of cancer . Others had found that CD151 knockout mice show normal development, but deficiencies in wound...antagonists can disrupt mammary carcinoma functions. BODY: a. Establishing a mouse model for breast cancer - We attempted to cross our CD151 null

  1. Breast cancer molecular subtypes: from TNBC to QNBC.

    PubMed

    Hon, Jane Date C; Singh, Baljit; Sahin, Aysegul; Du, Gang; Wang, Jinhua; Wang, Vincent Y; Deng, Fang-Ming; Zhang, David Y; Monaco, Marie E; Lee, Peng

    2016-01-01

    Treatment protocols for breast cancer depend predominantly on receptor status with respect to estrogen (estrogen receptor alpha), progesterone (progesterone receptor) and human epidermal growth factor [human epidermal growth factor receptor 2 (HER2)]. The presence of one or more of these receptors suggests that a treatment targeting these pathways might be effective, while the absence of, or in the case of HER2, lack of overexpression of, all of these receptors, termed triple negative breast cancer (TNBC), indicates a need for the more toxic chemotherapy. In an effort to develop targeted therapies for TNBC, it will be necessary to differentiate among specific TNBC subtypes. The subset of TNBC that expresses androgen receptor (AR) has been determined to express genes consistent with a luminal subtype and therefore may be amenable to therapies targeting either AR, itself, or other pathways typical of a luminal subtype. Recent investigations of the AR signal pathway within breast cancer lead to AR as a significant target for breast cancer therapy with several clinical trials currently in progress. The subclass of TNBC that lacks AR, which we have termed quadruple negative breast cancer (QNBC) currently lacks a defined targetable pathway. Unlike AR-positive TNBC, QNBC predominantly exhibits a basal-like molecular subtype. Several subtypes and related pathway proteins are preferentially expressed in QNBC that may serve as effective targets for treatment, such as ACSL4, SKP2 and EGFR. ACSL4 expression has been demonstrated to be inversely correlated with expression of hormone/growth factor receptors and may thus serve as a biomarker for QNBC as well as a target for therapy. In the following review we summarize some of the current efforts to develop alternatives to chemotherapy for TNBC and QNBC.

  2. Multicenter Breast Cancer Collaborative Registry

    PubMed Central

    Sherman, Simon; Shats, Oleg; Fleissner, Elizabeth; Bascom, George; Yiee, Kevin; Copur, Mehmet; Crow, Kate; Rooney, James; Mateen, Zubeena; Ketcham, Marsha A.; Feng, Jianmin; Sherman, Alexander; Gleason, Michael; Kinarsky, Leo; Silva-Lopez, Edibaldo; Edney, James; Reed, Elizabeth; Berger, Ann; Cowan, Kenneth

    2011-01-01

    The Breast Cancer Collaborative Registry (BCCR) is a multicenter web-based system that efficiently collects and manages a variety of data on breast cancer (BC) patients and BC survivors. This registry is designed as a multi-tier web application that utilizes Java Servlet/JSP technology and has an Oracle 11g database as a back-end. The BCCR questionnaire has accommodated standards accepted in breast cancer research and healthcare. By harmonizing the controlled vocabulary with the NCI Thesaurus (NCIt) or Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT), the BCCR provides a standardized approach to data collection and reporting. The BCCR has been recently certified by the National Cancer Institute’s Center for Biomedical Informatics and Information Technology (NCI CBIIT) as a cancer Biomedical Informatics Grid (caBIG®) Bronze Compatible product. The BCCR is aimed at facilitating rapid and uniform collection of critical information and biological samples to be used in developing diagnostic, prevention, treatment, and survivorship strategies against breast cancer. Currently, seven cancer institutions are participating in the BCCR that contains data on almost 900 subjects (BC patients and survivors, as well as individuals at high risk of getting BC). PMID:21918596

  3. Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)

    ClinicalTrials.gov

    2017-03-30

    Breast Tumor; Breast Cancer; Cancer of the Breast; Estrogen Receptor- Negative Breast Cancer; HER2- Negative Breast Cancer; Progesterone Receptor- Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer; Triple-negative Metastatic Breast Cancer; Metastatic Breast Cancer

  4. Breast Cancer and Posttraumatic Growth

    PubMed Central

    İnan, Figen Şengün; Üstün, Besti

    2014-01-01

    The current methods for early diagnosis and increased treatment options have improved survival rates in breast cancer. Breast cancer diagnosis effects individuals in physical, psychological and social dimensions either positively or negatively. In the literature, usually the negative effects encountered in the period after the diagnosis of breast cancer are mostly described, with limited data on the positive effects. Nevertheless, the identification of positive changes and defining its determinants is important in supporting and strengthening posttraumatic growth in this group. The objective of this review is to explain posttraumatic growth and its determinants in breast cancer during the post-treatment period in accordance with the relevant literature. In our evaluation, it was noticed that breast cancer survivors experience posttraumatic growth in the post-treatment period, but the literature is limited in explaining the nature of posttraumatic growth and its determinants. Both qualitative and quantitative research that will provide in-depth information on the subject, explaining culture-specific posttraumatic growth and related factors, are required. PMID:28331647

  5. Internet Use and Breast Cancer Survivors

    ERIC Educational Resources Information Center

    Muhamad, Mazanah; Afshari, Mojgan; Mohamed, Nor Aini

    2011-01-01

    A survey was administered to 400 breast cancer survivors at hospitals and support group meetings in Peninsular Malaysia to explore their level of Internet use and factors related to the Internet use by breast cancer survivors. Findings of this study indicated that about 22.5% of breast cancer survivors used Internet to get information about breast…

  6. Do underarm cosmetics cause breast cancer?

    PubMed

    Gikas, Panagiotis D; Mansfield, Lucy; Mokbel, Kefah

    2004-01-01

    Although animal and laboratory studies suggest a possible link between certain chemicals used in underarm cosmetics and breast cancer development, there is no reliable evidence that underarm cosmetics use increases breast cancer risk in humans. This article reviews the evidence for and against the possible link between breast cancer and underarm cosmetics and highlights the need for further research to clarify this issue.

  7. Breast cancer in young women.

    PubMed

    Winchester, D P

    1996-04-01

    Breast cancer is an uncommon disease in women under the age of 40 years, reportedly accounting for 7.5% of reported cases. Delay in diagnosis is attributable to a clinically low index of suspicion, difficulty in examining dense and nodular breasts in younger women, and less frequently performed screening mammography. Genetic mutations should be suspected in women with breast cancer who are under the age of 30 years. In relation to older women, younger women have more adverse pathologic features and have a poorer prognosis. Younger age, per se, is not a contraindication to breast-conserving surgery. In node-negative young women, the benefits of adjuvant chemotherapy need to be considered in relation to the short- and long-term risks of treatment. A strong support system should be in place to deal with the adverse psychosocial impact of the disease.

  8. Characterization of the Role of Breast Tumor Kinase (BRK) in Breast Cancer Cells Non-responsive to EGFR-targeted Agents

    DTIC Science & Technology

    2006-07-01

    Epidermal growth factor (EGF) receptor tyrosine kinases (erbB family), EGFR (erbB1) and HER2, are highly expressed in breast cancer and are associated...utilizing microRNA ( miRNA ) instead of shRNA approach. Three different miRNA sequences targeting Brk and one scramble miRNA control were generated and...Tumor Kinase (BRK) in Breast Cancer Cells Non-responsive to EGFR-targeted Agents PRINCIPAL INVESTIGATOR: Anjaruwee Nimnual, Ph.D

  9. Intensity Modulated Accelerated Partial Breast Irradiation Before Surgery in Treating Older Patients With Hormone Responsive Stage 0-I Breast Cancer

    ClinicalTrials.gov

    2017-09-18

    Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Ductal Breast Carcinoma With Predominant Intraductal Component; Medullary Ductal Breast Carcinoma With Lymphocytic Infiltrate; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Tubular Ductal Breast Carcinoma

  10. Can We Prevent Breast Cancer?

    PubMed Central

    Saadat, Sabiha

    2008-01-01

    Breast cancer is the second most common cancer in the world and the most common cancer in females accounting to 23% of all cases. Between January 1998 and December 2004–2004, 6,882 cases were reported from all GCC states accounting to 11.8% from all cancers and 22.7% from cancers in females. An ASR/100,000 woman was 46.4 from Bahrain, 44.3 from Kuwait, 35.5 from Qatar, 19.2 from UAE, 14.2 from Oman and 12.9 from KSA. Breast cancer is the most frequent cancer in Arab women constituting 14–42% of all women cancers. Breast cancer in Arab countries presents almost 10 yrs younger than in USA and Europe. Median age at presentation is 48–52 and 50% of all cases are below the age of 50 where as only 25% of cases in industrialized nations are below the age of 50 yrs. What we need to fight this deadly disease is opening of screening centers with trained physicians equipped with ultrasound, x-ray unit, a pathology lab and most of all a system where a patient is seen urgently on referral to a secondary level care. Health education campaigns should be organized, female medical students should be encouraged to be general surgeons in a community where social customs still have value. PMID:21475500

  11. Cytokines, Neovascularization and Breast Cancer

    DTIC Science & Technology

    1995-10-01

    which support tumor growth and metastasis. In order to test our hypothesis, we are examining t ie expression of 11-8 antigen in human breast tissue using...Revised 1985). S4 For the protection of human subjects, the investigator(s) adhered to policies of applicable Federal Law 45 CFR 46. In conducting...Contents INTRODUCTION 5 BODY: EXPERIMENTAL METHODS AND RESULTS 6 Specific Aim I- To characterize IL-8 expression in human breast cancer 6 Study IA- To

  12. Partial breast irradiation for early breast cancer.

    PubMed

    Lehman, Margot; Hickey, Brigid E; Francis, Daniel P; See, Adrienne M

    2014-06-18

    Breast conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiation therapy (RT). RT is given to sterilize tumour cells that may remain after surgery to decrease the risk of local tumour recurrence. Most true recurrences occur in the same quadrant as the original tumour. Whole breast RT may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane Review, we investigated the role of delivering radiation to a limited volume of the breast around the tumour bed (partial breast irradiation: PBI) sometimes with a shortened treatment duration (accelerated partial breast irradiation: APBI). To determine whether PBI/APBI is equivalent to or better than conventional or hypofractionated WBRT after breast conservation therapy for early-stage breast cancer. We searched the Cochrane Breast Cancer Group Specialised Register (07 November 2013), CENTRAL (2014, Issue 3), MEDLINE (January 1966 to 11 April 2014), EMBASE (1980 to 11 April 2014), CINAHL (11 April 2014) and Current Contents (11 April 2014). Also we searched the International Standard Randomised Controlled Trial Number Register, the World Health Organization's International Clinical Trials Registry Platform (07 November 2013) and US clinical trials registry (www.clinicaltrials.gov) (22 April 2014). We searched for grey literature: Open Grey (23 April 2014), reference lists of articles, a number of conference proceedings and published abstracts, and did not apply any language restrictions. Randomised controlled trials (RCTs) without confounding and evaluating conservative surgery plus PBI/APBI versus conservative surgery plus whole breast RT. We included both published and unpublished trials. Three review authors (ML, DF and BH) performed data extraction and resolved any disagreements through discussion. We entered data into Review Manager for analysis. BH and ML assessed trials

  13. Epidermal Growth Factor Receptor in Prostate Cancer Derived Exosomes

    PubMed Central

    Kharmate, Geetanjali; Hosseini-Beheshti, Elham; Caradec, Josselin; Chin, Mei Yieng; Tomlinson Guns, Emma S.

    2016-01-01

    Exosomes proteins and microRNAs have gained much attention as diagnostic tools and biomarker potential in various malignancies including prostate cancer (PCa). However, the role of exosomes and membrane-associated receptors, particularly epidermal growth factor receptor (EGFR) as mediators of cell proliferation and invasion in PCa progression remains unexplored. EGFR is frequently overexpressed and has been associated with aggressive forms of PCa. While PCa cells and tissues express EGFR, it is unknown whether exosomes derived from PCa cells or PCa patient serum contains EGFR. The aim of this study was to detect and characterize EGFR in exosomes derived from PCa cells, LNCaP xenograft and PCa patient serum. Exosomes were isolated from conditioned media of different PCa cell lines; LNCaP xenograft serum as well as patient plasma/serum by differential centrifugation and ultracentrifugation on a sucrose density gradient. Exosomes were confirmed by electron microscopy, expression of exosomal markers and NanoSight™ analysis. EGFR expression was determined by western blot analysis and ELISA. This study demonstrates that exosomes may easily be derived from PCa cell lines, serum obtained from PCa xenograft bearing mice and clinical samples derived from PCa patients. Presence of exosomal EGFR in PCa patient exosomes may present a novel approach for measuring of the disease state. Our work will allow to build on this finding for future understanding of PCa exosomes and their potential role in PCa progression and as minimal invasive biomarkers for PCa. PMID:27152724

  14. Multiparametric Breast MRI of Breast Cancer

    PubMed Central

    Rahbar, Habib; Partridge, Savannah C.

    2015-01-01

    Synopsis Breast MRI has increased in popularity over the past two decades due to evidence for its high sensitivity for cancer detection. Current clinical MRI approaches rely on the use of a dynamic contrast enhanced (DCE-MRI) acquisition that facilitates morphologic and semi-quantitative kinetic assessments of breast lesions. The use of more functional and quantitative parameters, such as pharmacokinetic features from high temporal resolution DCE-MRI, apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM) on diffusion weighted MRI, and choline concentrations on MR spectroscopy, hold promise to broaden the utility of MRI and improve its specificity. However, due to wide variations in approach among centers for measuring these parameters and the considerable technical challenges, robust multicenter data supporting their routine use is not yet available, limiting current applications of many of these tools to research purposes. PMID:26613883

  15. Treatment and prognosis of breast cancer patients with brain metastases according to intrinsic subtype.

    PubMed

    Kuba, Sayaka; Ishida, Mayumi; Nakamura, Yoshiaki; Yamanouchi, Kosho; Minami, Shigeki; Taguchi, Kenichi; Eguchi, Susumu; Ohno, Shinji

    2014-11-01

    How breast cancer subtypes should affect treatment decisions for breast cancer patients with brain metastases is unclear. We analyzed local brain metastases treatments and their outcomes according to subtype in patients with breast cancer and brain metastases. We reviewed records and database information for women treated at the National Kyushu Cancer Center between 2001 and 2010. Patients were divided into three breast cancer subtype groups: Luminal (estrogen receptor positive and/or progesterone receptor positive, but human epidermal growth factor receptor 2 negative); human epidermal growth factor receptor 2 positive and triple negative (estrogen receptor negative, progesterone receptor negative and human epidermal growth factor receptor 2 negative). Of 524 advanced breast cancer patients, we reviewed 65 (12%) with brain metastases and records showing estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status, as well as outcome data; there were 26 (40%) Luminal, 26 (40%) had human epidermal growth factor receptor 2 and 13 (20%) had triple negative subtypes. There was no statistical difference in the number of brain metastases among subtypes; however, rates of stereotactic radiosurgery or surgery for brain metastases differed significantly by subtype (human epidermal growth factor receptor 2: 81%, Luminal: 42% and triple negative: 47%; P = 0.03). Patients having the human epidermal growth factor receptor 2 subtype, a performance status of ≤1 and ≤4 brain metastases, who underwent systemic therapy after brain metastases and underwent stereotactic radiosurgery or surgery, were predicted to have longer overall survival after brain metastases. Multivariate analysis demonstrated that not having systemic therapy and not having the human epidermal growth factor receptor 2 subtype were independent factors associated with an increased risk of death (hazard ratio 2.4, 95% confidence interval 1.01-5.6; P = 0.05 and hazard ratio 2.9, 95

  16. Multiple primary breast and thyroid cancer.

    PubMed Central

    Ron, E.; Curtis, R.; Hoffman, D. A.; Flannery, J. T.

    1984-01-01

    The occurrence of breast and thyroid multiple primary cancers was evaluated using data from the Connecticut Tumor Registry. The study population consisted of 1618 women with primary thyroid cancer and 39,194 women with primary breast cancer diagnosed between 1935 and 1978. Thirty-four thyroid cancer patients subsequently developed breast cancer and 24 breast cancer patients later had thyroid cancer. A significantly elevated risk of thyroid cancer following breast cancer (SIR = 1.68) and breast cancer following thyroid cancer (SIR = 1.89) was demonstrated. The finding was even more notable when compared with the risks obtained for other sites. The elevated risk was particularly evident in women under 40 years of age at time of diagnosis of the first cancer. Analysis by histologic type revealed that the highest risk of second primary breast cancer was found among patients with follicular or mixed papillary-follicular thyroid cancer. Women under age 40 with follicular carcinoma had a 10-fold risk of developing breast cancer (4 observed, 0.4 expected). An enhanced risk of second primary tumours was evident for the entire period after treatment of the first primary, although it was highest within one year after diagnosis of the first primary. This may be due to the close medical surveillance of cancer patients which would increase early diagnosis of second tumours. Our findings suggest that breast and thyroid cancer may share common aetiologic features. PMID:6691901

  17. Multiple primary breast and thyroid cancer.

    PubMed

    Ron, E; Curtis, R; Hoffman, D A; Flannery, J T

    1984-01-01

    The occurrence of breast and thyroid multiple primary cancers was evaluated using data from the Connecticut Tumor Registry. The study population consisted of 1618 women with primary thyroid cancer and 39,194 women with primary breast cancer diagnosed between 1935 and 1978. Thirty-four thyroid cancer patients subsequently developed breast cancer and 24 breast cancer patients later had thyroid cancer. A significantly elevated risk of thyroid cancer following breast cancer (SIR = 1.68) and breast cancer following thyroid cancer (SIR = 1.89) was demonstrated. The finding was even more notable when compared with the risks obtained for other sites. The elevated risk was particularly evident in women under 40 years of age at time of diagnosis of the first cancer. Analysis by histologic type revealed that the highest risk of second primary breast cancer was found among patients with follicular or mixed papillary-follicular thyroid cancer. Women under age 40 with follicular carcinoma had a 10-fold risk of developing breast cancer (4 observed, 0.4 expected). An enhanced risk of second primary tumours was evident for the entire period after treatment of the first primary, although it was highest within one year after diagnosis of the first primary. This may be due to the close medical surveillance of cancer patients which would increase early diagnosis of second tumours. Our findings suggest that breast and thyroid cancer may share common aetiologic features.

  18. DNA damage and breast cancer

    PubMed Central

    Davis, Jennifer D; Lin, Shiaw-Yih

    2011-01-01

    Cancer is intimately related to the accumulation of DNA damage, and repair failures (including mutation prone repair and hyperactive repair systems). This article relates current clinical categories for breast cancer and their common DNA damage repair defects. Information is included on the potential for accumulation of DNA damage in the breast tissue of a woman during her lifetime and the role of DNA damage in breast cancer development. We then cover endogenous and exogenous sources of DNA damage, types of DNA damage repair and basic signal transduction pathways for three gene products involved in the DNA damage response system; namely BRCA1, BRIT1 and PARP-1. These genes are often considered tumor suppressors because of their roles in DNA damage response and some are under clinical investigation as likely sources for effective new drugs to treat breast cancers. Finally we discuss some of the problems of DNA damage repair systems in cancer and the conundrum of hyper-active repair systems which can introduce mutations and confer a survival advantage to certain types of cancer cells. PMID:21909479

  19. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues. Here, two High-Aspect Ratio Vessels turn at about 12 rmp to keep breast tissue constructs suspended inside the culture media. Syringes allow scientists to pull for analysis during growth sequences. The tube in the center is a water bubbler that dehumidifies the air to prevent evaporation of the media and thus the appearance of destructive bubbles in the bioreactor.

  20. Inflammatory breast cancer: an overview.

    PubMed

    van Uden, D J P; van Laarhoven, H W M; Westenberg, A H; de Wilt, J H W; Blanken-Peeters, C F J M

    2015-02-01

    Inflammatory breast cancer (IBC) is the most aggressive entity of breast cancer. Management involves coordination of multidisciplinary management and usually includes neoadjuvant chemotherapy, ablative surgery if a tumor-free resection margin is expected and locoregional radiotherapy. This multimodal therapeutic approach has significantly improved patient survival. However, the median overall survival among women with IBC is still poor. By elucidating the biologic characteristics of IBC, new treatment options may become available. We performed a comprehensive review of the English-language literature on IBC through computerized literature searches. The objective of the current review is to present an overview of the literature related to the biology, imaging and multidisciplinary treatment of inflammatory breast cancer.

  1. Tamoxifen for breast cancer prevention

    SciTech Connect

    Jordan, V.C.

    1995-02-01

    The case for tamoxifen to be tested as a preventive for breast cancer has merit. Animal studies demonstrate that tamoxifen prevents mammary carcinogenesis and clinical studies now confirm that adjuvant tamoxifen therapy is the only systemic treatment that will prevent contralateral breast cancer. Developing clinical studies confirm the laboratory data that tamoxifen will maintain post-menopausal bone density in the lumbar spine and the neck of the femur; two important skeletal sites for the ultimate prevention of osteoporosis. However, a most important target site-specific effect of tamoxifen is the decrease in low-density lipoprotein cholesterol levels in postmenopausal women. This positive property of tamoxifen may be responsible for the recorded decreases in hospital visits for the treatment of cardiac conditions and the significant decrease in fatal myocardial infarction for women treated with 5 years of adjuvant tamoxifen. These data provide the scientific basis to undertake randomized, placebocontrolled clinical trials to test the worth of tamoxifen to prevent breast cancer.

  2. Breast Cancer Research at NASA

    NASA Technical Reports Server (NTRS)

    1998-01-01

    NASA's Marshall Space Flight Center (MSFC) is sponsoring research with Bioreactors, rotating wall vessels designed to grow tissue samples in space, to understand how breast cancer works. This ground-based work studies the growth and assembly of human mammary epithelial cells (HMEC) from breast cancer susceptible tissue. Radiation can make the cells cancerous, thus allowing better comparisons of healthy vs. tunourous tissues. Here, two High-Aspect Ratio Vessels turn at about 12 rmp to keep breast tissue constructs suspended inside the culture media. Syringes allow scientists to pull for analysis during growth sequences. The tube in the center is a water bubbler that dehumidifies the air to prevent evaporation of the media and thus the appearance of destructive bubbles in the bioreactor.

  3. Immunohistochemical characteristics of basal-like breast cancer

    PubMed Central

    Budzik, Michał P.

    2017-01-01

    Basal-like breast cancer (BLBC) occurs mainly in young patients. It is characterized by an aggressive clinical outcome, presence of distant metastases, particularly within the first five years of the disease, bad prognosis and relatively high mortality. Recently greater interest of scientists in this subtype of breast cancer has been observed. Despite such many well-known potential biomarkers of BLBC, currently there is no official international panel of antigens dedicated to diagnosis of this subtype of breast cancer. The most commonly used set in this case contains four antibodies – estrogen receptor (ER), epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) and cytokeratins (CK) 5/6 – although it cannot provide one hundred percent detectability of these lesions. Incorporation of additional biomarkers into a panel can increase specificity, at the potential cost of sensitivity. Many biomarkers have been associated with the basal-like phenotype, and those with high sensitivity and/or specificity could improve the performance of immunohistochemical surrogate panels. Work on detection of the best of them is constantly being performed. PMID:28239279

  4. Breast cancer risk assessment in primary care.

    PubMed

    Brown, Shannon Lynn; Kartoz, Connie

    2014-01-01

    Breast cancer is the most common cancer (when excluding skin cancers) in women and the second most common cause of cancer death in women, with a lifetime prevalence of 12.5% (, ; ). Breast cancer screening reduces risk of cancer death, thereby increasing rate of survival to up to 89% for women with stage 1 and 2 breast cancer (; ). Despite these data, undue harm may occur with unnecessary screening because overidentification of risk, and excessive, costly biopsies may result. Costs and benefits of screening must be weighed. Nurses at all levels can play a pivotal role in promotion of appropriate breast cancer screening and subsequently breast cancer prevention by using accurate screening tools, such as the Tyrer-Cuzick model. Although there are some limitations with this tool, screening at the primary care level has demonstrated improved clinical outcomes (). Its use can help nurses accurately assess a woman's breast cancer risk, by promoting appropriate screening at the primary care level ().

  5. Hormonal therapy followed by chemotherapy or the reverse sequence as first-line treatment of hormone-responsive, human epidermal growth factor receptor-2 negative metastatic breast cancer patients: results of an observational study.

    PubMed

    Bighin, Claudia; Dozin, Beatrice; Poggio, Francesca; Ceppi, Marcello; Bruzzi, Paolo; D'Alonzo, Alessia; Levaggi, Alessia; Giraudi, Sara; Lambertini, Matteo; Miglietta, Loredana; Vaglica, Marina; Fontana, Vincenzo; Iacono, Giuseppina; Pronzato, Paolo; Mastro, Lucia Del

    2017-01-18

    Introduction Although hormonal-therapy is the preferred first-line treatment for hormone-responsive, HER2 negative metastatic breast cancer, no data from clinical trials support the choice between hormonal-therapy and chemotherapy.Methods Patients were divided into two groups according to the treatment: chemotherapy or hormonal-therapy. Outcomes in terms of clinical benefit and median overall survival (OS) were retrospectively evaluated in the two groups. To calculate the time spent in chemotherapy with respect to OS in the two groups, the proportion of patients in chemotherapy relative to those present in either group was computed at every day from the start of therapy.Results From 1999 to 2013, 119 patients received first-line hormonal-therapy (HT-first group) and 100 first-line chemotherapy (CT-first group). Patients in the CT-first group were younger and with poorer prognostic factors as compared to those in HT-first group. Clinical benefit (77 vs 81%) and median OS (50.7 vs 51.1 months) were similar in the two groups. Time spent in chemotherapy was significantly longer during the first 3 years in CT-first group (54-34%) as compared to the HT-first group (11-18%). This difference decreased after the third year and overall was 28% in the CT-first group and 18% in the HT-first group.Conclusions The sequence first-line chemotherapy followed by hormonal-therapy, as compared with the opposite sequence, is associated with a longer time of OS spent in chemotherapy. However, despite the poorer prognostic factors, patients in the CT-first group had a superimposable OS than those in the HT-first group.

  6. Job Authority and Breast Cancer

    PubMed Central

    Pudrovska, Tetyana

    2014-01-01

    Using the 1957–2011 data from the Wisconsin Longitudinal Study, I integrate the gender relations theory, a life course perspective, and a biosocial stress perspective to explore the effect of women’s job authority in 1975 (at age 36) and 1993 (at age 54) on breast cancer incidence up to 2011. Findings indicate that women with the authority to hire, fire, and influence others’ pay had a significantly higher risk of a breast cancer diagnosis over the next 30 years compared to housewives and employed women with no job authority. Because job authority conferred the highest risk of breast cancer for women who also spent more hours dealing with people at work in 1975, I suggest that the assertion of job authority by women in the 1970s involved stressful interpersonal experiences, such as social isolation and negative social interactions, that may have increased the risk of breast cancer via prolonged dysregulation of the glucocorticoid system and exposure of breast tissue to the adverse effects of chronically elevated cortisol. This study contributes to sociology by emphasizing gendered biosocial pathways through which women’s occupational experiences become embodied and drive forward physiological repercussions. PMID:25506089

  7. Dynamic tracing for epidermal growth factor receptor mutations in urinary circulating DNA in gastric cancer patients.

    PubMed

    Shi, Xiu-Qin; Xue, Wen-Hua; Zhao, Song-Feng; Zhang, Xiao-Jian; Sun, Wukong

    2017-02-01

    The mutations of epidermal growth factor receptor are detected in gastric cancer, indicating its suitability as a target for receptor tyrosine kinase inhibitors, as well as a marker for clinical outcome of chemotherapeutic treatments. However, extraction of quality tumor tissue for molecular processes remains challenging. Here, we aimed to examine the clinical relevance of urinary cell-free DNA as an alternative tumor material source used specifically for monitoring epidermal growth factor receptor mutations. Therefore, 120 gastric cancer patients with epidermal growth factor receptor mutations and 100 healthy controls were recruited for the study. The gastric patients also received epidermal growth factor receptor inhibitor treatment for a serial monitoring study. Paired primary tumor specimens were obtained with blood and urine samples, which were taken at a 1-month interval for a duration of 12 months. We found that urinary cell-free DNA yielded a close agreement of 92% on epidermal growth factor receptor mutation status when compared to primary tissue at baseline, and of 99% epidermal growth factor receptor mutation status when compared to plasma samples at different time points. Thus, our data suggest that urinary cell-free DNA may be a reliable source for screening and monitoring epidermal growth factor receptor mutations in the primary gastric cancer.

  8. Reconstruction for breast cancer in a nutshell.

    PubMed

    Harmer, Victoria

    Breast cancer is a disease many will experience. Depending on the size of the cancer, the size of the host breast, and whether it is multi-focal, a mastectomy may be recommended as part of the treatment. If this is the case, an immediate breast reconstruction may be offered. This article will describe the three main types of breast reconstruction and discuss pertinent issues regarding this, including complications, surgery to the other (contraleteral) breast and potential psychological implications of this surgery.

  9. Occupational exposure and risk of breast cancer

    PubMed Central

    FENGA, CONCETTINA

    2016-01-01

    Breast cancer is a multifactorial disease and the most commonly diagnosed cancer in women. Traditional risk factors for breast cancer include reproductive status, genetic mutations, family history and lifestyle. However, increasing evidence has identified an association between breast cancer and occupational factors, including environmental stimuli. Epidemiological and experimental studies demonstrated that ionizing and non-ionizing radiation exposure, night-shift work, pesticides, polycyclic aromatic hydrocarbons and metals are defined environmental factors for breast cancer, particularly at young ages. However, the mechanisms by which occupational factors can promote breast cancer initiation and progression remains to be elucidated. Furthermore, the evaluation of occupational factors for breast cancer, particularly in the workplace, also remains to be explained. The present review summarizes the occupational risk factors and the associated mechanisms involved in breast cancer development, in order to highlight new environmental exposures that could be correlated to breast cancer and to provide new insights for breast cancer prevention in the occupational settings. Furthermore, this review suggests that there is a requirement to include, through multidisciplinary approaches, different occupational exposure risks among those associated with breast cancer development. Finally, the design of new epigenetic biomarkers may be useful to identify the workers that are more susceptible to develop breast cancer. PMID:26998264

  10. Occupational exposure and risk of breast cancer.

    PubMed

    Fenga, Concettina

    2016-03-01

    Breast cancer is a multifactorial disease and the most commonly diagnosed cancer in women. Traditional risk factors for breast cancer include reproductive status, genetic mutations, family history and lifestyle. However, increasing evidence has identified an association between breast cancer and occupational factors, including environmental stimuli. Epidemiological and experimental studies demonstrated that ionizing and non-ionizing radiation exposure, night-shift work, pesticides, polycyclic aromatic hydrocarbons and metals are defined environmental factors for breast cancer, particularly at young ages. However, the mechanisms by which occupational factors can promote breast cancer initiation and progression remains to be elucidated. Furthermore, the evaluation of occupational factors for breast cancer, particularly in the workplace, also remains to be explained. The present review summarizes the occupational risk factors and the associated mechanisms involved in breast cancer development, in order to highlight new environmental exposures that could be correlated to breast cancer and to provide new insights for breast cancer prevention in the occupational settings. Furthermore, this review suggests that there is a requirement to include, through multidisciplinary approaches, different occupational exposure risks among those associated with breast cancer development. Finally, the design of new epigenetic biomarkers may be useful to identify the workers that are more susceptible to develop breast cancer.

  11. Nanoparticle-based Paclitaxel vs Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Early Breast Cancer (GeparSepto)

    ClinicalTrials.gov

    2016-10-11

    Tubular Breast Cancer Stage II; Mucinous Breast Cancer Stage II; Breast Cancer Female NOS; Invasive Ductal Breast Cancer; Tubular Breast Cancer Stage III; HER-2 Positive Breast Cancer; Inflammatory Breast Cancer Stage IV; Inflammatory Breast Cancer

  12. Combination Chemotherapy and Peripheral Blood Stem Cell Transplant Followed By Aldesleukin and Sargramostim in Treating Patients With Inflammatory Stage IIIB or Metastatic Stage IV Breast Cancer

    ClinicalTrials.gov

    2017-06-16

    Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; Inflammatory Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer

  13. Radiation-Induced Vaccination to Breast Cancer

    DTIC Science & Technology

    2015-10-01

    targeting TGF-beta on the activities and numbers of breast cancer stem cells with and without irradiation. 2 Body 2.1 Immune-monitoring Twenty-two...longer than those getting the lower 1mg dose. 2.2 Effects of TGF-beta on breast cancer stem - cells Recent preclinical and clinical data...support that solid cancers including breast cancers are organized hierarchically with a small population of cancer stem cells (CSCs), capable of re

  14. [Hormonal therapy in breast cancer].

    PubMed

    Espinós, J; Reyna, C; de la Cruz, S; Oiler, C; Hernández, A; Fernández Hidalgo, O; Santisteban, M; García Foncillas, J

    2008-01-01

    Hormonal therapy has been the first systemic treatment against breast cancer. Up to now Tamoxifen and ovarian supression/ablation were the best optionts we had to treat early breast cancer as advancer disease. The advent of aromatase inhibitors, new SERMS and antistrogen Fulvestrant have supoused a great advance in the treatment of this disease and at the same time have complicated the election of the optimal drug for each patient. This article tries to review the aviable treatment options insiting on its indications.

  15. Partial breast irradiation for early breast cancer.

    PubMed

    Hickey, Brigid E; Lehman, Margot; Francis, Daniel P; See, Adrienne M

    2016-07-18

    Breast-conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiotherapy (RT). RT is given to sterilize tumour cells that may remain after surgery to decrease the risk of local tumour recurrence. Most true recurrences occur in the same quadrant as the original tumour. Whole breast radiotherapy (WBRT) may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane review, we investigated the delivery of radiation to a limited volume of the breast around the tumour bed (partial breast irradiation (PBI)) sometimes with a shortened treatment duration (accelerated partial breast irradiation (APBI)). To determine whether PBI/APBI is equivalent to or better than conventional or hypo-fractionated WBRT after breast-conserving therapy for early-stage breast cancer. We searched the Cochrane Breast Cancer Group Specialized Register (4 May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 5), MEDLINE (January 1966 to 4 May 2015), EMBASE (1980 to 4 May 2015), CINAHL (4 May 2015) and Current Contents (4 May 2015). We searched the International Standard Randomised Controlled Trial Number Register (5 May 2015), the World Health Organization's International Clinical Trials Registry Platform (4 May 2015) and ClinicalTrials.gov (17 June 2015). We searched for grey literature: OpenGrey (17 June 2015), reference lists of articles, several conference proceedings and published abstracts, and applied no language restrictions. Randomized controlled trials (RCTs) without confounding, that evaluated conservative surgery plus PBI/APBI versus conservative surgery plus WBRT. Published and unpublished trials were eligible. Two review authors (BH and ML) performed data extraction and used Cochrane's 'Risk of bias' tool, and resolved any disagreements through discussion. We entered data into Review Manager 5 for analysis. We included

  16. Skeletal manifestations of treatment of breast cancer.

    PubMed

    Choksi, Palak; Williams, Margaret; Clark, Patricia M; Van Poznak, Catherine

    2013-12-01

    Breast cancer and osteoporosis are common diagnoses in women. Breast cancer survival has improved due to earlier detection and improved treatments. As most breast cancers are estrogen receptor positive, treatment is often aimed at altering the hormonal environment. Both pre and postmenopausal women undergoing these therapies are at risk for bone loss. The patient's health care team ought to have an awareness of the potential for breast cancer treatments to accelerate bone loss. Women with early stage breast cancer are treated with curative intent and, therefore, maintaining bone health is important and is part of the survivorship care to ensure an optimal quality of life.

  17. Genetic epidemiology of breast cancer in Britain.

    PubMed

    Iselius, L; Slack, J; Littler, M; Morton, N E

    1991-05-01

    A complex segregation analysis was conducted on two British series (one consecutive series of probands with breast cancer and one series ascertained through a normal consultand). Altogether there were 1248 nuclear families with breast cancer. A dominant gene with a frequency of 0.003 giving a lifetime penetrance of 0.83 is favoured. Ovarian, endometrial and cancers associated with the SBLA syndrome, as well as benign breast disease, were significantly more common in familial breast cancer than in families of single cases. Probands in families with more than one individual with breast cancer were non-significantly younger than isolated probands.

  18. Skeletal Manifestations of Treatment of Breast Cancer

    PubMed Central

    Choksi, Palak; Williams, Margaret; Clark, Patricia M.; Van Poznak, Catherine

    2014-01-01

    Breast cancer and osteoporosis are common diagnoses in women. Breast cancer survival has improved due to earlier detection and improved treatments. As most breast cancers are estrogen receptor positive, treatment is often aimed at altering the hormonal environment. Both pre and postmenopausal women undergoing these therapies are at risk for bone loss. The patient's health care team ought to have an awareness of the potential for breast cancer treatments to accelerate bone loss. Women with early stage breast cancer are treated with curative intent and, therefore, maintaining bone health is important and is part of the survivorship care to ensure an optimal quality of life. PMID:24132726

  19. What Breast Cancer Survivors Need to Know about Osteoporosis

    MedlinePlus

    ... browser. Home Osteoporosis Osteoporosis and Other Conditions What Breast Cancer Survivors Need to Know About Osteoporosis Publication available ... Print-Friendly Page April 2016 The Impact of Breast Cancer Other than skin cancer, breast cancer is the ...

  20. What's New in Breast Cancer Research and Treatment?

    MedlinePlus

    ... Cancer Research? Breast Cancer About Breast Cancer What’s New in Breast Cancer Research? Researchers around the world ... she considers most important in choosing a treatment. New lab tests Tests for circulating tumor cells (CTCs) ...