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https://www.readbyqxmd.com/read/29651367/-lazarus-response-to-olaparib-in-a-virtually-chemonaive-breast-cancer-patient-carrying-gross-brca2-gene-deletion
#1
Vladimir M Moiseyenko, Vyacheslav A Chubenko, Fedor V Moiseyenko, Lyudmila A Zagorskaya, Yuliya A Zaytseva, Nataliya E Gesha, Evgeny N Zykov, Valeriya I Ni, Elena V Preobrazhenskaya, Anna P Sokolenko, Evgeny N Imyanitov
This report describes an estrogen receptor-positive breast cancer patient, who relapsed at two and a half years after the completion of adjuvant chemotherapy while being on the aromatase inhibition. Based on the clinical evidence for potential sensitivity of the tumor to hormone ablation, everolimus was added to continuing exemestane treatment. Oral chemotherapy was administered at further disease progression, however, it lasted only for 10 days due to rapidly deteriorating condition of the patient. BRCA test was performed just before the failure of endocrine therapy and revealed a gross deletion within BRCA2 gene...
February 4, 2018: Curēus
https://www.readbyqxmd.com/read/29610032/personalized-prevention-in-high-risk-individuals-managing-hormones-and-beyond
#2
D Gareth Evans, Sacha J Howell, Anthony Howell
Increasing numbers of women are being identified at 'high-risk' of breast cancer, defined by The National Institute of Health and Care Excellence (NICE) as a 10-year risk of ≥8%. Classically women have been so identified through family history based risk algorithms or genetic testing of high-risk genes. Recent research has shown that assessment of mammographic density and single nucleotide polymorphisms (SNPs), when combined with established risk factors, trebles the number of women reaching the high risk threshold...
March 30, 2018: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29566104/everolimus-plus-endocrine-therapy-for-postmenopausal-women-with-estrogen-receptor-positive-human-epidermal-growth-factor-receptor-2-negative-advanced-breast-cancer-a-clinical-trial
#3
Melanie Royce, Thomas Bachelot, Cristian Villanueva, Mustafa Özgüroglu, Sergio J Azevedo, Felipe Melo Cruz, Marc Debled, Roberto Hegg, Tatsuya Toyama, Carla Falkson, Joon Jeong, Vichien Srimuninnimit, William J Gradishar, Christina Arce, Antonia Ridolfi, Chinjune Lin, Fatima Cardoso
Importance: Cotargeting the mammalian target of rapamycin pathway and estrogen receptor may prevent or delay endocrine resistance in patients receiving first-line treatment for advanced breast cancer. Objective: To investigate the combination of everolimus plus endocrine therapy in first-line and second-line treatment settings for postmenopausal women with estrogen receptor-positive, human epidermal growth receptor 2-negative advanced breast cancer. Design, Setting, and Participants: In the multicenter, open-label, single-arm, phase 2 BOLERO-4 (Breast Cancer Trials of Oral Everolimus) clinical trial, 245 patients were screened for eligibility; 202 were enrolled between March 7, 2013, and December 17, 2014...
March 22, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29554282/effects-of-celecoxib-and-low-dose-aspirin-on-outcomes-in-adjuvant-aromatase-inhibitor-treated-patients-cctg-ma-27
#4
Kathrin Strasser-Weippl, Michaela J Higgins, Judith-Anne W Chapman, James N Ingle, George W Sledge, George T Budd, Matthew J Ellis, Kathleen I Pritchard, Mark J Clemons, Tanja Badovinac-Crnjevic, Lei Han, Karen A Gelmon, Manuela Rabaglio, Catherine Elliott, Lois E Shepherd, Paul E Goss
Background: Celecoxib and low-dose aspirin might decrease risk of breast cancer recurrence. Methods: In the Canadian Cancer Trials Group MA.27, postmenopausal hormone receptor-positive breast cancer patients were randomly assigned (2 × 2) to adjuvant exemestane or anastrozole, and celecoxib or placebo. Low-dose aspirin of 81 mg or less was a stratification factor. Due to concerns about cardiac toxicity, celecoxib use was stopped in December 2004, while stratification by aspirin use was removed through protocol amendment...
March 15, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29531841/impact-of-clinical-response-to-neoadjuvant-endocrine-therapy-on-patient-outcomes-a-follow-up-study-of-jfmc34-0601-multicentre-prospective-neoadjuvant-endocrine-trial
#5
Takayuki Ueno, Shigehira Saji, Norikazu Masuda, Katsumasa Kuroi, Nobuaki Sato, Hiroyuki Takei, Yutaka Yamamoto, Shinji Ohno, Hiroko Yamashita, Kazufumi Hisamatsu, Kenjiro Aogi, Hiroji Iwata, Takeharu Yamanaka, Hironobu Sasano, Masakazu Toi
Background: Neoadjuvant endocrine therapy (NET) has been demonstrated to improve breast-conserving rate and is a widely accepted treatment option for postmenopausal patients with hormone receptor-positive breast cancer. There are few reports on the association of NET response and long-term outcomes. Objectives: To investigate the prognostic value of clinical response to NET. Methods: Long-term outcomes of NET were examined in 107 patients who participated in the multicentre prospective neoadjuvant exemestane study, JFMC34-0601...
2018: ESMO Open
https://www.readbyqxmd.com/read/29520681/predictive-markers-for-efficacy-of-everolimus-plus-exemestane-in-patients-with-luminal-her2-negative-metastatic-breast-cancer
#6
Misato Okazaki, Yoshiya Horimoto, Masahiko Tanabe, Yuko Ichikawa, Emi Tokuda, Atsushi Arakawa, Toshiyuki Kobayashi, Mitsue Saito
Metastatic breast cancer (MBC) is essentially incurable despite recent improvements in systemic therapies. We often encounter difficulties in choosing the most appropriate treatments, with optimal timing, for individual patients. Everolimus, one of the mTOR inhibitors, is usually used with endocrine therapy for MBC. Identification of predictive markers for everolimus-based treatment remains a major issue, but to date, no predictive markers have been established. We retrospectively investigated predictive markers for treatments with everolimus plus exemestane in patients with ER-positive and HER2-negative breast cancer...
March 8, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29507656/estrogen-receptor-alpha-drives-mtorc1-inhibitor-induced-feedback-activation-of-pi3k-akt-in-er-breast-cancer
#7
Wei Yang, Gary N Schwartz, Jonathan D Marotti, Vivian Chen, Nicole A Traphagen, Jiang Gui, Todd W Miller
The mTORC1 inhibitor RAD001 (everolimus) is approved for treatment of recurrent/metastatic estrogen receptor (ER)-positive breast cancer in combination with the aromatase inhibitor (AI) exemestane. The benefits of A) continued anti-estrogen therapy for anti-estrogen-resistant disease in the context of mTORC1 inhibition, and B) adjuvant everolimus in combination with anti-estrogen therapy for early-stage disease are being tested clinically, but molecular rationale remains unclear. We hypothesized that mTORC1 inhibition activates the IGF-1R/InsR/IRS-1/2 axis in an ER-dependent manner to drive PI3K/AKT and promote cancer cell survival, implicating ER in survival signaling induced by mTORC1 inhibition...
February 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29490302/endocrine-treatment-with-2-years-of-tamoxifen-versus-2-years-of-exemestane-in-postmenopausal-patients-with-high-risk-early-breast-cancer-and-persisting-circulating-tumor-cells-first-results-of-the-success-c-endocrine-treatment-sub-study
#8
Fabienne Schochter, Brigitte Rack, Marie Tzschaschel, Arkadius Polasik, Ulrich Andergassen, Elisabeth Trapp, Marianna Alunni-Fabbroni, Andreas Schneeweiss, Volkmar Müller, Klaus Pantel, Jörg Gade, Ralf Lorenz, Mahdi Rezai, Hans Tesch, Ulrike Soeling, Tanja Fehm, Sven Mahner, Christian Schindlbeck, Werner Lichtenegger, Matthias W Beckmann, Peter A Fasching, Wolfgang Janni, Thomas W P Friedl
BACKGROUND: Optimal choice and sequence of endocrine treatment following adjuvant chemotherapy in postmenopausal early breast cancer patients are still under discussion and treatment stratification factors are missing. PATIENTS AND METHODS: Postmenopausal women with HER2-negative, hormone receptor-positive tumors and persisting circulating tumor cells (CTCs; assessed using the FDA-approved CellSearch® System, Janssen Diagnostics, LLC) after chemotherapy were randomized to 2 years of tamoxifen followed by 3 years of exemestane (tamoxifen-exemestane group, n = 54) or 5 years of exemestane (exemestane-only group, n = 54)...
2018: Oncology Research and Treatment
https://www.readbyqxmd.com/read/29482983/adjuvant-anastrozole-versus-exemestane-versus-letrozole-upfront-or-after-2-years-of-tamoxifen-in-endocrine-sensitive-breast-cancer-fata-gim3-a-randomised-phase-3-trial
#9
Sabino De Placido, Ciro Gallo, Michelino De Laurentiis, Giancarlo Bisagni, Grazia Arpino, Maria Giuseppa Sarobba, Ferdinando Riccardi, Antonio Russo, Lucia Del Mastro, Alessio Aligi Cogoni, Francesco Cognetti, Stefania Gori, Jennifer Foglietta, Antonio Frassoldati, Domenico Amoroso, Lucio Laudadio, Luca Moscetti, Filippo Montemurro, Claudio Verusio, Antonio Bernardo, Vito Lorusso, Adriano Gravina, Gabriella Moretti, Rossella Lauria, Antonella Lai, Carmen Mocerino, Sergio Rizzo, Francesco Nuzzo, Paolo Carlini, Francesco Perrone
BACKGROUND: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. METHODS: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer...
February 23, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29476820/testosterone-complex-and-non-steroidal-ligands-of-human-aromatase
#10
Debashis Ghosh, Chinaza Egbuta, Jessica Lo
Cytochrome P450 aromatase (AROM) catalyzes the biosynthesis of estrogen from androgen. Previously crystal structures of human AROM in complex with the substrate androstenedione, and inhibitors exemestane, as well as the newly designed steroidal compounds, have been reported. Here we report the first crystal structure of testosterone complex of human placental AROM. Testosterone binds at the androgen-specific heme distal pocket. The polar and hydrophobic interactions with the surrounding residues resemble the interactions observed for other ligands...
February 21, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29455298/patient-reported-predictors-of-early-treatment-discontinuation-treatment-related-symptoms-and-health-related-quality-of-life-among-postmenopausal-women-with-primary-breast-cancer-randomized-to-anastrozole-or-exemestane-on-ncic-clinical-trials-group-cctg-ma
#11
Lynne I Wagner, Fengmin Zhao, Paul E Goss, Judith-Anne W Chapman, Lois E Shepherd, Timothy J Whelan, Bassam I Mattar, Jose A Bufill, William C Schultz, Irving E LaFrancis, Gauri G Nagargoje, Radhakrishna Vemuri, Daniel A Nikcevich, George W Sledge, David Cella
PURPOSE: Aromatase inhibitors are the most commonly prescribed adjuvant endocrine therapy for hormone-dependent early breast cancer in postmenopausal women. Among Canadian Cancer Trials Group MA.27 participants, anastrozole and exemestane had comparable 5-year event-free survival. This companion study examined differences in patient-reported treatment-related symptoms (TRS) and health-related quality of life (HRQL) among postmenopausal women randomized to anastrozole or exemestane. METHODS: MA...
February 17, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29442014/improvement-of-treatment-outcomes-after-implementation-of-comprehensive-pharmaceutical-care-in-breast-cancer-patients-receiving-everolimus-and-exemestane
#12
M Todo, S Ueda, S Osaki, I Sugitani, T Takahashi, M Takahashi, H Makabe, T Saeki, Y Itoh
Combination therapy with everolimus and an aromatase inhibitor such as exemestane is an effective treatment option for advanced or recurrent breast cancer. However, the therapy is often limited because of the occurrence of severe adverse events (AEs), including oral mucositis, interstitial lung disease, diarrhea, and rash. Therefore, early management of AEs is extremely important to obtain maximum treatment outcome. We investigated here the effects of comprehensive pharmaceutical care for prevention of severe AEs on patient's quality-of-life (QOL) and continuation of therapy...
February 1, 2018: Die Pharmazie
https://www.readbyqxmd.com/read/29441507/economic-evaluation-of-fulvestrant-500-mg-compared-to-generic-aromatase-inhibitors-in-patients-with-advanced-breast-cancer-in-sweden
#13
Ugne Sabale, Mattias Ekman, Daniel Thunström, Claire Telford, Christopher Livings
OBJECTIVES: In Sweden, breast cancer (BC) represents 30% of newly diagnosed cancers and is the most common cancer in women. For hormone-dependent BC, endocrine therapies varying in efficacy and price are available. The aim of this study is to assess the cost effectiveness of fulvestrant 500 mg as a second-line hormonal therapy for postmenopausal women with estrogen receptor-positive metastatic or locally advanced BC versus letrozole, anastrozole, and exemestane in Sweden. METHODS: A three-state (pre-progression, post-progression, and death) partitioned-survival model was used to estimate progression-free (PFS) and overall survival (OS) by extrapolating trial results beyond the trial period to capture costs and benefits over a lifetime perspective...
December 2017: PharmacoEconomics Open
https://www.readbyqxmd.com/read/29394793/-a-case-of-long-term-survival-of-breast-cancer-with-lymph-node-and-liver-metastases-treated-with-sequential-anti-her2-drugs-chemotherapy-and-endocrine-therapy
#14
Takashi Katsumori, Hisami Ohshima, Hiromitsu Hamaguchi, Shinichi Yamamoto, Yukika Tsukamoto, Tomohiro Iwanaga, Susumu Ohkawara
A 50s-year-old woman underwent left partial mastectomy with axillary lymphadenectomy for breast cancer. Histological examination indicated invasive ductal carcinoma, pT1c, pN0, Stage I , ly(+), ER(+), PgR(+). She received adjuvant therapy with tamoxifen and 50 Gy of irradiation to the residual breast. Four years after mastectomy, she was found to have left Rotter lymph node metastasis; then, anastrozole was administered instead of tamoxifen. Nine months later, she was found to have liver metastasis. Immunohistostaining revealed that the breast cancer was HER2-positive; she received AC followed by paclitaxel(PTX)with trastuzumab(T), and achieved complete response(CR)...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29394600/-efficacy-and-safety-of-everolimus-plus-exemetane-in-postmenopausal-endocrine-responsive-metastatic-breast-cancer-patients
#15
Noriko Maeda, Shigeru Yamamoto, Yoko Sato, Kazuhiko Sakamoto, Nobuaki Suzuki, Shigeru Takeda, Yukiko Nagashima, Hidefumi Kubo, Hiroaki Nagano
Everolimus and exemestane combination therapy represents a treatment option for estrogen receptor(ER)-positive metastatic breast cancer. We evaluated the efficacy and safety of everolimus and exemestane therapy, retrospectively. After a median follow-up of 10.5 months, the median progression-free survivalin patients was 4.7 months. The clinicalbenefit rate was 27%and the disease controlrate was 64%. The most common all-grade adverse events(AEs)were stomatitis(82%) and non-infectious lung disease(27%). The most commonB3 grade AEs were cellulitis(18%)and hyperglycemia(18%)...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29354686/e2112-randomized-phase-iii-trial-of-endocrine-therapy-plus-entinostat-placebo-in-patients-with-hormone-receptor-positive-advanced-breast-cancer
#16
REVIEW
Sri Lakshmi Hyndavi Yeruva, Fengmin Zhao, Kathy D Miller, Amye J Tevaarwerk, Lynne I Wagner, Robert J Gray, Joseph A Sparano, Roisin M Connolly
Endocrine therapies are effective in the treatment of hormone receptor (HR)-positive breast cancer, however, de novo or acquired treatment resistance is a significant clinical problem. A potential mechanism of resistance involves changes in gene expression secondary to epigenetic modifications, which might be reversed with the use of histone deacetylase (HDAC) inhibitors such as entinostat. The ENCORE 301 phase II randomized, placebo-controlled study demonstrated a significant improvement in progression-free survival (PFS) and overall survival (OS), with the addition of entinostat to exemestane in patients with HR-positive advanced breast cancer with disease progression after prior non-steroidal aromatase inhibitor (AI)...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29344106/overall-survival-and-progression-free-survival-with-endocrine-therapy-for-hormone-receptor-positive-her2-negative-advanced-breast-cancer-review
#17
REVIEW
Tomás Reinert, Carlos H Barrios
We reviewed randomized phase II/III trials comparing first- or second-line endocrine therapy as monotherapy or in combination with targeted therapies for treatment of postmenopausal patients with hormone receptor-positive advanced breast cancer. First-line was defined as treatment for endocrine therapy-naïve advanced breast cancer or advanced disease treated with endocrine therapy in the adjuvant/neoadjuvant setting. Second-line was defined as endocrine therapy for advanced breast cancer following disease progression on endocrine therapy for advanced disease...
November 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29306943/clinically-observed-estrogen-receptor-alpha-mutations-within-the-ligand-binding-domain-confer-distinguishable-phenotypes
#18
Shanhang Jia, Mark T Miedel, Marilyn Ngo, Ryan Hessenius, Ning Chen, Peilu Wang, Amir Bahreini, Zheqi Li, Zhijie Ding, Tong Ying Shun, Daniel M Zuckerman, D Lansing Taylor, Shannon L Puhalla, Adrian V Lee, Steffi Oesterreich, Andrew M Stern
OBJECTIVE: Twenty to fifty percent of estrogen receptor-positive (ER+) metastatic breast cancers express mutations within the ER ligand-binding domain. While most studies focused on the constitutive ER signaling activity commonly engendered by these mutations selected during estrogen deprivation therapy, our study was aimed at investigating distinctive phenotypes conferred by different mutations within this class. METHODS: We examined the two most prevalent mutations, D538G and Y537S, employing corroborative genome-edited and lentiviral-transduced ER+ T47D cell models...
2018: Oncology
https://www.readbyqxmd.com/read/29287126/comparison-of-changes-in-the-lipid-profiles-of-eastern-chinese-postmenopausal-women-with-early-stage-breast-cancer-treated-with-different-aromatase-inhibitors-a-retrospective-study
#19
Wei Tian, Miaowei Wu, Yongchuan Deng
Cardiovascular morbidity is closely associated with serum lipid level. We aimed to investigate the effects of different aromatase inhibitors, including letrozole, anastrozole, and exemestane, on the lipid profile of eastern Chinese breast cancer patients. We evaluated a retrospective cohort of eastern Chinese postmenopausal women with early-stage breast cancer who received aromatase inhibitors. A total of 116 postmenopausal women with early-stage breast cancer without prior cardiovascular disease were included...
December 29, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29284708/-esr1-methylation-a-liquid-biopsy-based-epigenetic-assay-for-the-follow-up-of-patients-with-metastatic-breast-cancer-receiving-endocrine-treatment
#20
Sophia Mastoraki, Areti Strati, Eleni Tzanikou, Maria Chimonidou, Eleni Politaki, Alexandra Voutsina, Amanda Psyrri, Vassilis Georgoulias, Evi Lianidou
Purpose: Liquid biopsy provides real-time monitoring of tumor evolution and response to therapy through analysis of circulating tumor cells (CTCs) and plasma-circulating tumor DNA (ctDNA). ESR1 epigenetic silencing potentially affects response to endocrine treatment. We evaluated ESR1 methylation in CTCs and paired plasma ctDNA. We evaluated ESR1 methylation in CTCs and paired plasma ctDNA as a potential biomarker for response to everolimus/exemestane treatment. Experimental Design: A highly sensitive and specific real-time MSP assay for ESR1 methylation was developed and validated in (i) 65 primary breast tumors formalin-fixed paraffin-embedded (FFPE), (ii) EpCAM+ CTC fractions (122 patients and 30 healthy donors; HD), (iii) plasma ctDNA (108 patients and 30HD), and (iv) in CTCs (CellSearch) and in paired plasma ctDNA for 58 patients with breast cancer...
March 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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