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https://www.readbyqxmd.com/read/28326839/entinostat-a-promising-treatment-option-for-patients-with-advanced-breast-cancer
#1
Roisin M Connolly, Michelle A Rudek, Richard Piekarz
Entinostat is a synthetic benzamide derivative histone deacetylase (HDAC) inhibitor, which potently and selectively inhibits class I and IV HDAC enzymes. This action promotes histone hyperacetylation and transcriptional activation of specific genes, with subsequent inhibition of cell proliferation, terminal differentiation and apoptosis. This oral HDAC inhibitor has been evaluated in Phase I and II trials in patients with advanced malignancies, and is in general well tolerated. Entinostat does not currently have regulatory approval for clinical use; however promising preclinical and clinical data exist in hormone-resistant breast cancer...
March 9, 2017: Future Oncology
https://www.readbyqxmd.com/read/28324268/a-phase-ii-study-of-combined-ridaforolimus-and-dalotuzumab-compared-with-exemestane-in-patients-with-estrogen-receptor-positive-breast-cancer
#2
José Baselga, Serafin M Morales, Ahmad Awada, Joanne L Blum, Antoinette R Tan, Marianne Ewertz, Javier Cortes, Beverly Moy, Kathryn J Ruddy, Tufia Haddad, Eva M Ciruelos, Peter Vuylsteke, Scot Ebbinghaus, Ellie Im, Lamar Eaton, Kumudu Pathiraja, Christine Gause, David Mauro, Mary Beth Jones, Hope S Rugo
PURPOSE: Combining the mTOR inhibitor ridaforolimus and the anti-IGFR antibody dalotuzumab demonstrated antitumor activity, including partial responses, in estrogen receptor (ER)-positive advanced breast cancer, especially in high proliferation tumors (Ki67 > 15%). METHODS: This randomized, multicenter, international, phase II study enrolled postmenopausal women with advanced ER-positive breast cancer previously treated with a nonsteroidal aromatase inhibitor (NCT01234857)...
March 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28314691/prevention-of-everolimus-related-stomatitis-in-women-with-hormone-receptor-positive-her2-negative-metastatic-breast-cancer-using-dexamethasone-mouthwash-swish-a-single-arm-phase-2-trial
#3
Hope S Rugo, Lasika Seneviratne, J Thaddeus Beck, John A Glaspy, Julio A Peguero, Timothy J Pluard, Navneet Dhillon, Leon Christopher Hwang, Chaitali Nangia, Ingrid A Mayer, Timothy F Meiller, Mark S Chambers, Robert W Sweetman, J Randy Sabo, Jennifer K Litton
BACKGROUND: Stomatitis is a class effect associated with the inhibition of mTOR and is associated with everolimus therapy for breast cancer. Topical steroids might reduce stomatitis incidence and severity, and the need for dose reductions and interruptions of everolimus. Anecdotal use of topical steroid oral prophylaxis has been reported in patients with breast cancer. We aimed to assess dexamethasone-based mouthwash for prevention of stomatitis in patients with breast cancer. METHODS: This US-based, multicentre, single-arm, phase 2 prevention study enrolled women aged 18 years and older with postmenopausal status who had histologically or cytologically confirmed metastatic hormone receptor-positive, HER2-negative breast cancer...
March 14, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28288389/ovarian-ablation-for-premenopausal-breast-cancer-a-review-of-treatment-considerations-and-the-impact-of-premature-menopause
#4
REVIEW
Melica Nourmoussavi, Gary Pansegrau, Jason Popesku, Geoffrey L Hammond, Janice S Kwon, Mark S Carey
Historically, ovarian ablation (OA) was used as therapy for women with recurrent hormone-receptor-positive (HRP) premenopausal breast cancer. With the publication of the SOFT (Suppression of Ovarian Function Trial) and TEXT (Tamoxifen and Exemestane Trial) randomized trials, there is considerable interest in OA as an adjuvant treatment, either in combination with tamoxifen or an aromatase inhibitor (AI). Thus, we have reviewed current guidelines and key studies on this important topic and have highlighted the relevant biological and pharmacological aspects of the various endocrine therapies...
February 22, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28287854/polypharmacy-and-adherence-to-adjuvant-endocrine-therapy-for-breast-cancer
#5
Gregory S Calip, Shan Xing, Da-Hae Jun, Wan-Ju Lee, Kent F Hoskins, Naomi Y Ko
PURPOSE: Many patients with breast cancer are treated for other conditions and experience polypharmacy with multiple concurrent medications. Our aim was to evaluate polypharmacy in relation to adherence to adjuvant endocrine therapy (AET) in breast cancer. METHODS: We conducted a retrospective cohort study of women with incident, invasive breast cancer initiating AET (tamoxifen, letrozole, anastrozole, exemestane) between 2009 and 2013 in the Truven Health MarketScan Database...
March 13, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28280092/a-phase-i-ib-study-of-enzalutamide-alone-and-in-combination-with-endocrine-therapies-in-women-with-advanced-breast-cancer
#6
Lee S Schwartzberg, Denise Yardley, Anthony Elias, Manish Patel, Patricia M LoRusso, Howard A Burris, Ayca Gucalp, Amy Peterson, Martha Blaney, Joyce Steinberg, Jacqueline Gibbons, Tiffany A Traina
PURPOSE: Several lines of evidence support targeting the androgen signaling pathway in breast cancer. Enzalutamide is a potent inhibitor of androgen receptor signaling. Preclinical data in estrogen-expressing breast cancer models demonstrated activity of enzalutamide monotherapy and enhanced activity when combined with various endocrine therapies (ETs). Enzalutamide is a strong cytochrome P450 3A4 (CYP3A4) inducer, and ETs are commonly metabolized by CYP3A4. The pharmacokinetic (PK) interactions, safety, and tolerability of enzalutamide monotherapy and in combination with ETs were assessed in this phase I/Ib study...
March 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28252426/adjuvant-hormonal-therapy-as-a-cause-of-bone-loss-in-patients-with-breast-cancer-review-of-literature
#7
N Khachidze, E Giorgadze, M Tsagareli
Adjuvant (hormonal) therapy is the main method of treatment after surgery in hormone (estrogen and/or progesterone) positive breast cancer patients. The goal of above mentioned treatment is to reduce or block the level of estrogen and progesterone. ultiple clinical trials have revealed that hormonal therapy in breast cancer patients affect bone mineral density (BMD). Authors have analyzed data obtained from several clinical trials conducted in several countries (including Georgia). The final conclusion is that selective estrogen receptor modulators (SERMs) have negative effect on BMD in pre-menopausal women and aromatase inhibitors (anastrozole, letrozole, exemestane) are associated with significant bone loss in post-menopausal women...
January 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28223674/-a-case-of-recurrent-breast-cancer-with-bone-metastasis-successfully-treated-with-everolimus-and-exemestane-therapy
#8
Hidefumi Kubo, Yuta Kimura, Toru Kawaoka, Makoto Miyahara, Ryouichi Shimizu, Yukiko Nagashima, Shigeru Yamamoto, Hiroaki Nagano
We report a case of a patient treated with everolimus and exemestane combination therapy for bone metastasis after breast surgery.The patient, a 58-year-old woman, consulted our department for back pain in October 2014.S he was diagnosed with left breast cancer when she was 41 years old.She had received Bt+Ax for left breast cancer and administered tamoxifen for 5 years.We decided on everolimus and exemestane combination therapy after observing an abnormal uptake in the 7th to 8th thoracic vertebrae on a PET-CT scan...
February 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28167101/quinone-related-hexacyclic-by-products-in-the-production-process-of-exemestane
#9
Giovanni Battista Giovenzana, Norberto Masciocchi, Roberto Negri, Giovanni Palmisano, Andrea Penoni, Lucio Toma
Exemestane, a 3rd-generation aromatase inhibitor, is clinically used in the treatment of breast cancer in postmenopausal women. The key step of the industrial synthetic process, i.e., a dehydrogenation to introduce the Δ(1)-unsaturation, is normally performed with quinones such as p-chloranil or DDQ. We observed the formation of two different hexacyclic by-products, depending on the quinone used in the oxidation step. These compounds arise from an initial [4+2] cycloaddition between the precursor 6-methylenandrost-4-ene-3,17-dione and the quinone reagent, followed by a twofold dehydrohalogenation (with p-chloranil) or dehydrogenation (with DDQ)...
April 2017: Steroids
https://www.readbyqxmd.com/read/28156498/prevention-of-everolimus-exemestane-eve-exe-stomatitis-in-postmenopausal-pm-women-with-hormone-receptor-positive-hr-metastatic-breast-cancer-mbc-using-a-dexamethasone-based-mouthwash-mw-results-of-the-swish-trial
#10
J Thaddeus Beck, John A Glaspy, Julio Antonio Peguero, Timothy J Pluard, Navneet Dhillon, Leon C Hwang, Chaitali Singh Nangia, Ingrid A Mayer, Timothy F Meiller, Mark Steven Chambers, Ghulam Warsi, Robert William Sweetman, J Randy Sabo, Lasikas Seneviratne
189 Background: Stomatitis is a frequent adverse event (AE) associated with mTOR inhibition. In BOLERO-2 patients (pts) receiving EVE/EXE, all grade (Gr) stomatitis was 67%; 33% had Gr ≥ 2 and 8% Gr 3. Median time to ≥ Gr 2 onset was 15.5 days; incidence of new stomatitis (Gr ≥ 2) plateaued at 6 wks. In a meta-analysis, 89% of first stomatitis events occurred within 8 wks. Topical steroids are used to treat aphthous ulcers; anecdotal use as prophylaxis has been reported. METHODS: Eligibility included PM women with HR+ MBC prescribed EVE/EXE...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28133215/-long-term-survival-of-a-patient-with-stage-iv-breast-cancer-and-an-intrathoracic-space-occupying-metastatic-lesion
#11
Toshimori Koh, Tomohito Sakai, Shunji Kato, Shoji Hirajima, Minoru Nishio, Koji Soga, Atsushi Oguro, Noboru Nakagawa
A 50-year old woman noticed left axillary lymph node swelling and presented at our hospital. CNB showed adenocarcinoma( pap-tub, ER+, PgR+, HER2 3+). CT revealed a right lung metastatic nodule and swollen lymph nodes above the left collarbone and left axilla. However, no breast tumor was found at that time. We diagnosed occult breast cancer, TxN3bM1 (lung), Stage IV . FEC(100), paclitaxel, letrozole, anastrozole, exemestane plus trastuzumab, tegafur/uracil plus trastuzumab, and lapatinib plus capecitabine were sequentially administered...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28133213/-a-case-of-recurrent-breast-cancer-with-adrenal-metastasis-resected-using-laparoscopic-surgery
#12
Hirotomo Murakami, Yoko Ohtani, Tatsuya Kinoshita, Kiyo Tanaka, Hiroyuki Yasojima, Makiko Mizutani, Shoji Nakamori, Mitsugu Sekimoto, Kiyoshi Mori, Masayuki Mano, Norikazu Masuda
We report a case of recurrent breast cancer with involvement of the right adrenal grand, which was resected using laparoscopic surgery. The patient was a 41-year-old woman who underwent duct-lobular segmentectomy for ductal carcinoma in situ. Histopathology showed microinvasion, and tested positive for ER and PR, but negative for HER2, so we applied radiation to the remaining breast and administered tamoxifen. After 9 months, local recurrence was detected and quadrantectomy with axillary lymph node dissection was performed...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28101033/maximizing-the-benefit-cost-ratio-of-anthracyclines-in-metastatic-breast-cancer-case-report-of-a-patient-with-a-complete-response-to-high-dose-doxorubicin
#13
Kevin Shee, Alan T Kono, Susan P D'Anna, Mark A Seltzer, Xiaoying Lu, Todd W Miller, Mary D Chamberlin
Despite the clinical efficacy of anthracycline agents such as doxorubicin, dose-limiting cardiac toxicities significantly limit their long-term use. Here, we present the case of a 33-year-old female patient with extensive metastatic ER+/PR+/HER2- mucinous adenocarcinoma of the breast, who was started on doxorubicin/cyclophosphamide therapy after progressing on paclitaxel and ovarian suppressor goserelin with aromatase inhibitor exemestane. The patient was comanaged by cardiology, who carefully monitored measures of cardiac function, including EKGs, serial echocardiograms, and profiling of lipids, troponin, and pro-BNP every 2 months...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/28068170/factors-associated-with-early-discontinuation-of-study-treatment-in-the-mammary-prevention-3-breast-cancer-chemoprevention-trial
#14
Olivia Meggetto, Elizabeth Maunsell, Rowan Chlebowski, Paul Goss, Dongsheng Tu, Harriet Richardson
Purpose Aromatase inhibitors are established breast cancer chemoprevention interventions. However, nonadherence remains a significant challenge. We investigated the association between worsening menopause-specific quality of life, baseline participant characteristics, and early treatment discontinuation within the Mammary Prevention.3 (MAP.3) breast cancer prevention trial. Methods In the MAP.3 randomized, placebo-controlled trial evaluating exemestane, participants completed the Menopause-Specific Quality of Life Questionnaire (MENQOL) at entry and at 6 months...
February 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28054005/data-of-aromatase-inhibitors-alone-and-in-combination-with-raloxifene-on-microarchitecture-of-lumbar-vertebrae-and-strength-test-in-femoral-diaphysis-of-vcd-treated-ovotoxic-mice
#15
Abul Kalam, Sushama Talegaonkar, Divya Vohora
Currently, the third generation aromatase inhibitors are the drugs of choice for treatment of early and advanced breast cancer in postmenopausal women. The negative impact of these drugs on bone health is the significant limiting factor during this therapy. Here we report the effect of two aromatase inhibitors viz. letrozole and exemestane alone and in combination with raloxifene on lumbar vertebrae and femoral diaphysis after one month of treatment but no discernible effects were observed on bone when tested by micro CT and strength test except in trabecular number which was reduced in lumbar vertebrae following letrozole and exemestane...
February 2017: Data in Brief
https://www.readbyqxmd.com/read/28053622/role-of-ovarian-function-suppression-in-premenopausal-women-with-early-breast-cancer
#16
REVIEW
Woo-Chan Park
Historically, endocrine therapy for breast cancer began with ovarian ablation (OA) for the treatment of premenopausal patients. After the identification of estrogen receptors and the development of many antiestrogens, tamoxifen has been approved and used as the standard endocrine therapy for hormonal receptor (HR)-positive premenopausal patients to date. With the development of luteinizing hormone-releasing hormone agonists, the paradigm of endocrine therapy for premenopausal women with HR-positive breast cancer began to change from OA to ovarian function suppression (OFS)...
December 2016: Journal of Breast Cancer
https://www.readbyqxmd.com/read/28045625/ki67-proliferation-index-as-a-tool-for-chemotherapy-decisions-during-and-after-neoadjuvant-aromatase-inhibitor-treatment-of-breast-cancer-results-from-the-american-college-of-surgeons-oncology-group-z1031-trial-alliance
#17
Matthew J Ellis, Vera J Suman, Jeremy Hoog, Rodrigo Goncalves, Souzan Sanati, Chad J Creighton, Katherine DeSchryver, Erika Crouch, Amy Brink, Mark Watson, Jingqin Luo, Yu Tao, Michael Barnes, Mitchell Dowsett, G Thomas Budd, Eric Winer, Paula Silverman, Laura Esserman, Lisa Carey, Cynthia X Ma, Gary Unzeitig, Timothy Pluard, Pat Whitworth, Gildy Babiera, J Michael Guenther, Zoneddy Dayao, David Ota, Marilyn Leitch, John A Olson, D Craig Allred, Kelly Hunt
Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) -positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) level was > 10% after 2 to 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objective was to examine risk of relapse using the Ki67-based Preoperative Endocrine Prognostic Index (PEPI). Methods The American College of Surgeons Oncology Group (ACOSOG) Z1031A trial enrolled postmenopausal women with stage II or III ER-positive (Allred score, 6 to 8) breast cancer whose treatment was randomly assigned to neoadjuvant AI therapy with anastrozole, exemestane, or letrozole...
January 3, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28017458/specific-adverse-events-are-associated-with-response-to-exemestane-therapy-in-postmenopausal-breast-cancer-patients-results-from-the-teamiia-study-boog2006-04
#18
D B Y Fontein, A Charehbili, J W R Nortier, H Putter, E Meershoek-Klein Kranenbarg, J R Kroep, S C Linn, C J H van de Velde
PURPOSE: In the adjuvant setting, specific adverse events (AEs) such as vasomotor symptoms (VMS) and musculoskeletal AEs are associated with relapse-free survival in aromatase inhibitor (AI)-treated patients. In the neoadjuvant setting, specific AEs may be associated with tumor response to AIs as well. METHODS: Between 2007 and 2012, 107 patients participated in the prospective TEAMIIA trial, a prospective, phase II trial investigating 6 months of neoadjuvant exemestane in patients with strongly ER-positive breast cancer...
December 10, 2016: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/27999738/the-interplay-of-epigenetic-therapy-and-immunity-in-locally-recurrent-or-metastatic-estrogen-receptor-positive-breast-cancer-correlative-analysis-of-encore-301-a-randomized-placebo-controlled-phase-ii-trial-of-exemestane-with-or-without-entinostat
#19
Yusuke Tomita, Min-Jung Lee, Sunmin Lee, Saori Tomita, Saranya Chumsri, Scott Cruickshank, Peter Ordentlich, Jane B Trepel
Entinostat, a class I-selective histone deacetylase inhibitor, has shown promising activity in ENCORE 301, a randomized, placebo-controlled, phase II trial of exemestane with or without entinostat in women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on a nonsteroidal aromatase inhibitor. ENCORE 301 showed an 8.3-mo improvement in median overall survival among patients who received entinostat. We investigated the impact of entinostat on immune subsets with CD40, HLA-DR, and immune checkpoint receptor expression analyses in 34 patient blood samples from ENCORE 301...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27967255/endocrine-therapy-in-epithelial-ovarian-cancer
#20
Simon P Langdon, Charlie Gourley, Hani Gabra, Barbara Stanley
The estrogen receptor (ER) is expressed at high levels in many epithelial ovarian cancers (EOC) and represents a potential target for endocrine therapy. Both anti-estrogens and aromatase inhibitors have been evaluated in phase II clinical trials. Areas covered: We present an overview of the phase II and phase III trials of anti-estrogens (tamoxifen and fulvestrant) and aromatase inhibitors (letrozole, anastrazole and exemestane) undertaken in epithelial ovarian cancer identified through a Pubmed search. We describe predictive biomarkers that are being investigated to identify responsive cancers...
February 2017: Expert Review of Anticancer Therapy
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