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Aya Matsuoka, Akira Hirano, Akinori Hattori, Kaoru Ogura, Hiroaki Inoue, Hiroko Yukawa, Shiho Sakaguchi, Natsuko Tanaka, Asaka Kodera, Mari Kamimura, Yoshihiko Naritaka, Tadao Shimizu
A 71-year-old woman diagnosed with left breast cancer underwent mastectomy and axillary dissection in 1987. Pathological findings showed invasive ductal carcinoma that was ER and PgR positive and HER2 negative.5 -FU and tamoxifen were administered for 2 years as adjuvant therapy.Bone metastasis was found in 2002, and endocrine therapy was started, using anastrozole, exemestane, letrozole, medroxyprogesterone acetate, and fulvestrant.However, liver, lung, pleural, penetiral, and lymph-node metastases were observed, and the following chemotherapy regimen was administered: CAF, capecitabine, paclitaxel, vinorelbine, gemcitabine, methotrexate plus mitomycin C, and eribulin...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
James N Ingle, Fang Xie, Matthew J Ellis, Paul E Goss, Lois E Shepherd, Judith-Anne W Chapman, Bingshu E Chen, Michiaki Kubo, Yoichi Furukawa, Yukihide Momozawa, Vered Stearns, Kathleen I Pritchard, Poulami Barman, Erin E Carlson, Matthew P Goetz, Richard M Weinshilboum, Krishna R Kalari, Liewei Wang
Genetic risks in breast cancer remain only partly understood. Here we report the results of a genome-wide association study of germline DNA from 4,658 women, including 252 women experiencing a breast cancer recurrence, who were entered on the MA.27 adjuvant trial comparing the aromatase inhibitors (AI) anastrozole and exemestane. Single nucleotide polymorphisms (SNP) of top significance were identified in the gene encoding MIR2052HG, a long noncoding RNA of unknown function. Heterozygous or homozygous individuals for variant alleles exhibited a ~40% or ~63% decrease, respectively, in the hazard of breast cancer recurrence relative to homozygous wild-type individuals...
October 10, 2016: Cancer Research
Anna Kemp-Casey, Elizabeth E Roughead, Christobel Saunders, Frances Boyle, Max Bulsara, David B Preen
AIMS: To determine the frequency, timing and patterns of endocrine therapy switching in Australian practice for postmenopausal women with primary breast cancer. METHODS: We identified postmenopausal women in a population-based cohort commencing endocrine therapy for invasive primary breast cancer between December 2005 and December 2008 (n = 645). Individual-level administrative health records and self-report data were used to determine women's demographic and clinical characteristics, including preexisting and newly-treated comorbidities, and switches in endocrine therapy...
October 14, 2016: Asia-Pacific Journal of Clinical Oncology
Armando Orlandi, Carmela Di Dio, Maria Alessandra Calegari, Carlo Barone
Everolimus and exemestane represent a standard treatment for metastatic hormone receptor-positive/HER2-negative advanced breast cancer resistant to aromatase inhibitors. CA 15-3 serum levels detect soluble forms of MUC-1, a transmembrane oncoprotein aberrantly overexpressed in breast cancers. In clinical practice, CA 15-3 may be used to indicate treatment failure in the absence of readily measurable disease during cytotoxic therapy. In the targeted therapy era, it is important to note that the C-terminal subunit of MUC-1 interacts with PI3K/AKT pathway, inducting cell growth...
October 13, 2016: Biomarkers in Medicine
Sanja Mandic, Juergen Kratzsch, Dario Mandic, Zeljko Debeljak, Iva Lukic, Vesna Horvat, Alexander Gaudl, Vatroslav Seric
In this study we present a case of falsely elevated oestradiol (E2) concentration, determined by two immunoassays, in a breast cancer patient receiving exemestane therapy. The positive bias of immunochemical measurements was revealed using liquid chromatography tandem mass spectrometry (LC-MS/MS) which showed undetectable E2 concentration. The discrepancy is expected to be a consequence of the structural resemblance of E2 and exemestane sharing the same steroidal backbone. Inaccurate laboratory findings in therapy monitoring, as in this case, may lead to unnecessary changes of therapy...
September 28, 2016: Annals of Clinical Biochemistry
Swati Singh, Manika Awasthi, Veda P Pandey, Upendra N Dwivedi
In the present study, 300 plant derived secondary metabolites (100 each of alkaloid, flavonoid, and terpenoid), have been screened for their anti-cancerous activity through inhibition of selected key enzymatic targets, namely cyclooxygenases (COXs), topoisomerases (Topos), and aromatase by molecular docking approach. Furthermore, the stability of the complexes of top hits, from each class of secondary metabolites, with their respective enzymatic targets was analyzed using molecular dynamics (MD) simulation analyses and binding free energy calculations...
September 25, 2016: Journal of Biomolecular Structure & Dynamics
D L Hertz, K M Kidwell, N J Seewald, C L Gersch, Z Desta, D A Flockhart, A-M Storniolo, V Stearns, T C Skaar, D F Hayes, N L Henry, J M Rae
Discovery of clinical and genetic predictors of exemestane pharmacokinetics was attempted in 246 postmenopausal patients with breast cancer enrolled on a prospective clinical study. A sample was collected 2 h after exemestane dosing at a 1- or 3-month study visit to measure drug concentration. The primary hypothesis was that patients carrying the low-activity CYP3A4*22 (rs35599367) single-nucleotide polymorphism (SNP) would have greater exemestane concentration. Additional SNPs in genes relevant to exemestane metabolism (CYP1A1/2, CYP1B1, CYP3A4, CYP4A11, AKR1C3/4, AKR7A2) were screened in secondary analyses and adjusted for clinical covariates...
August 23, 2016: Pharmacogenomics Journal
Sarat Chandarlapaty, David Chen, Wei He, Patricia Sung, Aliaksandra Samoila, Daoqi You, Trusha Bhatt, Parul Patel, Maurizio Voi, Michael Gnant, Gabriel Hortobagyi, José Baselga, Mary Ellen Moynahan
Importance: Estrogen receptor α (ESR1) mutations found in metastatic breast cancer (MBC) promote ligand-independent receptor activation and resistance to estrogen-deprivation therapy in laboratory models. The prevalence of these mutations and their potential impact on clinical outcomes has not been established. Objective: To determine the prevalence of ESR1 mutations (Y537S and D538G) in estrogen receptor (ER)-positive MBC and determine whether mutation is associated with inferior outcomes...
October 1, 2016: JAMA Oncology
Serine Baydoun, Atia-Tul Wahab, Saira Bano, Rehan Imad, M Iqbal Choudhary
Structural transformation of anticancer drug exemestane (1) with fungi Cunninghamella blakesleeana (ATCC 8688A), Curvularia lunata (ATCC 12017), Aspergillus niger (ATCC 10549), and Gibberella fujikuroi (ATCC 10704) yielded eleven metabolites 2-12, in which 2 and 8 were identified as new. Their structures were characterized as 6-methylene-5α-androstane-3β,16β,17β-triol (2), 17β-hydroxy-6-methyleneandrosta-4-ene-3-one (3), 6α-spiroxirandrost-4-ene-3,17-dione (4), 6-methyleneandrosta-4-ene-3,17-dione (5), 6β,17β-dihydroxyandrost-4-en-3-one (6), 17β-hydroxy-6α-spiroxirandrost-1,4-diene-3-one (7), 17β-hydroxy-6α-hydroxymethylandrosta-1,4-dien-3-one (8), 6α-hydroxymethylandrosta-1,4-diene-3,17-dione (9), 17β-hydroxy-6-methyleneandrosta-1,4-diene-3,16-dione (10), 6α-hydroxy-4-androstene-3,17-dione (11), and 6α-hydroxymethylandrost-4-ene-3,17-dione (12)...
November 2016: Steroids
Risa B Burns, Mara A Schonberg, Nadine M Tung, Howard Libman
In November 2013, the U.S. Preventive Services Task Force issued a guideline on medications for risk reduction of primary breast cancer in women. Although mammography can detect early cases, it cannot prevent development of breast cancer. Tamoxifen and raloxifene are selective estrogen receptor modulators that have been shown to reduce the risk for estrogen receptor-positive breast cancer and are approved by the U.S. Food and Drug Administration (FDA) for this indication. However, neither medication reduces the risk for estrogen receptor-negative breast cancer or all-cause mortality...
August 2, 2016: Annals of Internal Medicine
L Moscetti, P Vici, T Gamucci, C Natoli, E Cortesi, P Marchetti, D Santini, R Giuliani, I Sperduti, M Mauri, L Pizzuti, M L Mancini, M A Fabbri, V Magri, L Iezzi, V Sini, L D'Onofrio, L Mentuccia, A Vaccaro, S Ramponi, C L Roma, E M Ruggeri
PURPOSE: The everolimus and exemestane combination represents a treatment option for the endocrine sensitive metastatic breast cancer (MBC) patients. The toxicity profile reported in the Bolero 2 trial showed the feasibility in the selected patients. Few data are available for the unselected population. METHODS: In order to evaluate the safety in the unselected population of the clinical practice and to evaluate a possible association of toxicities with previous treatments, clinical data from 181 consecutive patients were retrospectively collected...
October 2016: Breast: Official Journal of the European Society of Mastology
Marloes G M Derks, Nienke A de Glas, Esther Bastiaannet, Anton J M de Craen, Johanneke E A Portielje, Cornelis J H van de Velde, Floor E van Leeuwen, Gerrit-Jan Liefers
BACKGROUND: Previous retrospective studies have shown that physical functioning in older cancer survivors is affected after treatment, yet prospective data are lacking. The aim of this study was to assess change in physical functioning in different age groups of patients with hormone receptor-positive breast cancer who were enrolled in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) phase III trial. METHODS: Two physical parameters were assessed. Physical functioning was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire 1 year (T1) and 2 years (T2) after diagnosis...
August 2016: Oncologist
Naoki Niikura, Yoshihide Ota, Naoki Hayashi, Mariko Naito, Kosuke Kashiwabara, Ken-Ichi Watanabe, Toshinari Yamashita, Hirofumi Mukai, Masahiro Umeda
This is a randomized, multi-center, open-label, phase III study to evaluate the efficacy of professional oral care in preventing oral mucositis induced by everolimus in postmenopausal estrogen receptor-positive metastatic breast cancer. Patients will be randomized into professional oral care and control groups (1:1 ratio). All patients will receive everolimus with exemestane and will continue everolimus until disease progression. In the professional oral care group, patients will receive teeth surface cleaning, scaling and tongue cleaning before starting everolimus, and will continue to receive professional oral care weekly from oral surgeons throughout the 8 week treatment...
September 2016: Japanese Journal of Clinical Oncology
G Jerusalem, G Mariani, E M Ciruelos, M Martin, V C G Tjan-Heijnen, P Neven, J G Gavila, A Michelotti, F Montemurro, D Generali, E Simoncini, I Lang, J Mardiak, B Naume, M Camozzi, K Lorizzo, S Bianchetti, P Conte
BACKGROUND: This European phase IIIb, expanded-access multicenter trial evaluated the safety of EVE plus EXE in a patient population similar to BOLERO-2. PATIENTS AND METHODS: Post-menopausal women aged ≥18 years with hormone receptor-positive, human epidermal growth factor-receptor-2-negative advanced breast cancer (ABC) recurring/progressing during/after prior non-steroidal aromatase inhibitors were enrolled. The primary objective was safety of EVE plus EXE based on frequency of adverse events (AEs), and serious AEs (SAEs)...
September 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
A Y Altinok, S Yildirim, T Altug, N Sut, A Ober, E M Ozsahin, D Azria, N S Bese
PURPOSE: In experimental and clinical trials, tamoxifen (TAM) has been shown to increase radiation-induced lung fibrosis (RILF). Furthermore, aromatase inhibitors (AI) have been shown to be superior to TAM in the adjuvant setting and preclinical data suggest that letrozole (LET) sensitizes breast cancer cells to ionizing radiation in other studies. In this experimental study, we evaluated whether AI have any impact on the development of RILF in rats. MATERIALS AND METHODS: 60 female wistar- albino rats were divided into 6 groups: Control (group A), RT alone (group B), RT + TAM (group C), RT + anastrozole (ANA group D), RT + LET (group E), and RT + exemestane (EXE, group F)...
August 2016: Breast: Official Journal of the European Society of Mastology
Miguel Martin, Sara Lopez-Tarruella, Yolanda Jerez Gilarranz
A proportion of patients with hormone receptor-positive locally advanced or metastatic breast cancer will not have received prior endocrine therapy. However, there are limited clinical data specifically in these patients. We conducted a review of randomized phase II and III clinical studies of anastrozole, letrozole, exemestane, palbociclib, and fulvestrant to determine the evidence base supporting use of specific endocrine therapies in this patient population. From our findings, there is a paucity of clinical studies in patients with endocrine therapy-naïve disease; however, it appears that first-line treatment effects are consistent between patients who have and have not received prior endocrine treatment...
August 2016: Breast: Official Journal of the European Society of Mastology
Barbara Nuvoli, Andrea Sacconi, Giancarlo Cortese, Sabrina Germoni, Bruno Murer, Rossella Galati
This study aimed to investigate intratumoural estradiol and estrogen-receptors (ERα, ERβ and GPR30) in malignant pleural mesothelioma (MPM) to understand their function. Here, we report that immunohistochemistry of estradiol showed cytoplasmatic staining in 95% of fifty-seven human MPM samples with a trend toward a negative correlation between estradiol levels and the median post-diagnosis survival time. ERβ was only focally positive in 5.3% of cases, GPR30 and ERα were negative in our cases of MPM. GPR30 was detected mainly in glycosylated form in MPM cells...
June 13, 2016: Oncotarget
Kana Sakiyama, Takashi Yoshida, Yoshinari Goto, Morihiko Kimura
An 80-year-old woman was diagnosed with right breast cancer with clinical Stage IIIA 6 years previously. She underwent mastectomy and axillary lymph node dissection. The pathological diagnosis was invasive micropapillary carcinoma with lymph node involvement. Immunohistochemically, the tumor was positive for estrogen receptor and progesterone receptor, and negative for HER2. Postoperatively, the patient was treated with adjuvant chemotherapy consisting of cyclophosphamide, epirubicin, 5-fluorouracil, and paclitaxel, followed by endocrine therapy with letrozole...
June 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Robert J MacInnis, Malcolm C Pike, John L Hopper
No abstract text is available yet for this article.
June 16, 2016: New England Journal of Medicine
Amer Karam
No abstract text is available yet for this article.
June 16, 2016: New England Journal of Medicine
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