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Stephen J Luen, Rebecca Asher, Chee Khoon Lee, Peter Savas, Roswitha Kammler, Patrizia Dell'Orto, Olivia Maria Biasi, David Demanse, Lellean JeBailey, Sinead Dolan, Wolfgang Hackl, Beat Thuerlimann, Giuseppe Viale, Marco Colleoni, Meredith M Regan, Sherene Loi
Importance: A range of somatic driver alterations has been described in estrogen receptor-positive, HER2-negative (ER+/HER2-) early breast cancer (BC); however, the clinical relevance is unknown. Objective: To investigate associations of driver alterations with prognosis and the role of PIK3CA mutations in prediction of benefit associated with endocrine therapy in postmenopausal patients with ER+/HER2- early BC treated with tamoxifen or letrozole. Design, Setting, and Participants: The Breast International Group (BIG) 1-98 trial randomized 8010 postmenopausal patients with hormone receptor-positive, operable, invasive BC to monotherapy with letrozole, tamoxifen, or a sequential strategy for 5 years...
June 14, 2018: JAMA Oncology
Aude Thouvenot, Yasmine Bizet, Laurent S Baccar, Michele Lamuraglia
Metastasis of non-gynaecological tumours to the cervix is a rare event, and metastasis from breast cancer is even rarer, with only a limited number of such cases reported in the literature to date. We herein report the case of an 86-year-old female patient who had undergone mastectomy and axillary lymphadenectomy for invasive ductal cell breast carcinoma 2 years prior, followed by adjuvant hormonal therapy with letrozole. During hospitalization for anemia associated with an inflammatory syndrome and abdominal pain with menorrhagia, an abdominal ultrasound examination revealed a suspicious uterine mass with irregular contours and abnormal vascularization with associated increase of the blood level of cancer antigen 15-3 to 34 kU/l...
July 2018: Molecular and Clinical Oncology
Tom Tanbo, Jan Mellembakken, Sverre Bjercke, Eva Ring, Thomas Åbyholm, Peter Fedorcsak
The objective of this narrative review is to suggest a rational order of treatment choices in anovulatory women with polycystic ovary syndrome (PCOS), for whom a multitude of treatment options exist. In obese/overweight PCOS patients the importance of weight reduction should be stressed. Inositol, a dietary supplement with a documented effect on ovulation and without side effects in the doses recommended, may be suggested. Additional first line medical alternatives include insulin sensitizers, selective estrogen receptor modulators and aromatase inhibitors...
June 11, 2018: Acta Obstetricia et Gynecologica Scandinavica
Tahmeena Khan, Rumana Ahmad, Iqbal Azad, Saman Raza, Seema Joshi, Abdul Rahman Khan
The present paper deals with in silico evaluation of 32 virtually designed transition metal complexes of 2-butanone thiosemicarbazone and N,S,O containing donor hetero-ligands namely py, bpy, furan, thiophene, 2-picoline, 1,10-phenanthroline, piperazine and liquid ammonia. The complexes were designed with a view to assess their potential anticancer, antioxidant and antibacterial activity. The absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of the chosen ligands were calculated by admetSAR software...
May 8, 2018: Computational Biology and Chemistry
Ali Nazaripour, Yadollah Yamini, Hasan Bagheri, Mohammad Tajik
An automated three-phase hollow fiber liquid-phase microextraction based on two immiscible organic solvents followed by high performance liquid chromatography with UV-vis detection was applied for the extraction and determination of exemestane, letrozole, and paclitaxel in water and urine samples. n-Dodecane was selected as the supported liquid membrane and its polarity was justified by trioctylphosphine oxide. Acetonitrile was used as an organic acceptor phase with desirable immiscibility with n-dodecane. All the effective parameters of the microextraction procedure such as type of the organic acceptor phase, the supported liquid membrane composition, extraction time, pH of the donor phase, hollow fiber length, stirring rate, and ionic strength were evaluated and optimized separately by a one variable at-a-time method...
June 4, 2018: Journal of Separation Science
Frauke von Versen-Höynck, Nairi K Strauch, Jing Liu, Yueh-Yun Chi, Maureen Keller-Woods, Kirk P Conrad, Valerie L Baker
OBJECTIVE: To investigate how the mode of conception affects maternal relaxin, creatinine, and electrolyte concentrations. BACKGROUND: Pregnancies achieved by fertility treatment often begin in a nonphysiologic endocrine milieu with no corpus luteum (CL) or with many corpora lutea. The CL produces not only estradiol and progesterone but is also the sole source of relaxin in early pregnancy, a hormone that may contribute to maternal systemic and renal vasodilation...
January 1, 2018: Reproductive Sciences
Stefanie L Groenland, Merel van Nuland, Remy B Verheijen, Jan H M Schellens, Jos H Beijnen, Alwin D R Huitema, Neeltje Steeghs
Oral anti-hormonal drugs are essential in the treatment of breast and prostate cancer. It is well known that the interpatient variability in pharmacokinetic exposure is high for these agents and exposure-response relationships exist for many oral anti-hormonal drugs. Yet, they are still administered at fixed doses. This could lead to underdosing and thus suboptimal efficacy in some patients, while other patients could be overdosed resulting in unnecessary side effects. Therapeutic drug monitoring (TDM), individualized dosing based on measured blood concentrations of the drug, could therefore be a valid option to further optimize treatment...
June 4, 2018: Clinical Pharmacokinetics
Gabriel Tremblay, David Chandiwana, Mike Dolph, Jaclyn Hearnden, Anna Forsythe, Mauricio Monaco
Background: Ribociclib (RIBO) and palbociclib (PALBO), combined with letrozole (LET), have been evaluated as treatments for hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in separate Phase III randomized controlled trials (RCTs), but not head-to-head. Population differences can lead to biased results by classical indirect treatment comparison (ITC). Matching-adjusted indirect comparison (MAIC) aims to correct these differences. We compared RIBO and PALBO in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer using MAIC...
2018: Cancer Management and Research
Jigal Haas, Rawad Bassil, Noa Gonen, Jim Meriano, Andrea Jurisicova, Robert F Casper
BACKGROUND: Previous studies have shown that androgens, in addition to serving as precursors for ovarian estrogen synthesis, also have a fundamental role in primate ovarian follicular development by augmentation of FSH receptor expression on granulosa cells. Recent studies have shown that aromatase inhibitor, letrozole, improves ovarian response to FSH in normal and poor responder patients, possibly by increasing intraovarian androgen levels. Studies in mice also showed an effect of letrozole to increase pigment epithelium-derived factor (PEDF) and to lower vascular epithelial growth factor (VEGF), which might be expected to reduce the risk of ovarian hyperstimulation syndrome (OHSS) with stimulation...
May 29, 2018: Reproductive Biology and Endocrinology: RB&E
Alejandra Hernández, Alonso Fernández-Guasti
Sex preference in male rats is partly determined by the organizational action of estradiol. Thus, several paradigms have used aromatase inhibitors to manipulate sex preference. We recently showed that a subpopulation of male rats prenatally treated with letrozole (0.56 μg/kg, G10-G22), a non-steroidal third generation aromatase inhibitor, had same sex preference, female sexual behavior (including lordosis and proceptivity) and penile erections when exposed to other males. These males, in addition, displayed high levels of experimental anxiety in the plus maze test and were insensitive to the anxiogenic-like acute effect of FLX (10 mg/kg)...
May 25, 2018: Pharmacology, Biochemistry, and Behavior
Shunde Wang, Shuhong Wang, Hang Li, Xiaoxia Li, Menglin Xie, Jiayu Wen, Meicai Li, Tengbo Long
The molecular mechanism of the aromatase inhibitor letrozole was investigated. It promotes the proliferation of spermatogonia by regulating the mitogen-activated protein kinase (MAPK) pathway. Six different concentrations were selected for letrozole in order to incubate mouse spermatogonia [GC-1 spermatogonia (spg)] for 24, 48 and 72 h, respectively. Cell Counting Kit-8 (CCK-8) was used to observe the effect of letrozole on the proliferation of GC-1 spg cells, and the effect was further verified by cell plate clone formation assay...
June 2018: Experimental and Therapeutic Medicine
Debu Tripathy, Seock-Ah Im, Marco Colleoni, Fabio Franke, Aditya Bardia, Nadia Harbeck, Sara A Hurvitz, Louis Chow, Joohyuk Sohn, Keun Seok Lee, Saul Campos-Gomez, Rafael Villanueva Vazquez, Kyung Hae Jung, K Govind Babu, Paul Wheatley-Price, Michelino De Laurentiis, Young-Hyuck Im, Sherko Kuemmel, Nagi El-Saghir, Mei-Ching Liu, Gary Carlson, Gareth Hughes, Ivan Diaz-Padilla, Caroline Germa, Samit Hirawat, Yen-Shen Lu
BACKGROUND: In MONALEESA-2, ribociclib plus letrozole showed improved progression-free survival compared with letrozole alone as first-line treatment for postmenopausal patients with hormone receptor (HR)-positive, HER2-negative, advanced breast cancer. MONALEESA-7 aimed to assess the efficacy and safety of ribociclib plus endocrine therapy in premenopausal women with advanced, HR-positive breast cancer. METHODS: This phase 3, randomised, double-blind, placebo-controlled trial was done at 188 centres in 30 countries...
May 24, 2018: Lancet Oncology
Rohit Mistry, Jessica R May, Gaurav Suri, Kate Young, Diana Brixner, Gary Oderda, Joseph Biskupiak, Derek Tang, Subrata Bhattacharyya, Dinesh Mishra, Devarshi Bhattacharyya, Anand A Dalal
BACKGROUND: U.S. regulatory approvals of the cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors ribociclib and palbociclib as add-ons to letrozole greatly enhance the prospects for treating postmenopausal women with hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2-) advanced or metastatic breast cancer. Clinical trials have established that the combination of a CDK 4/6 inhibitor with letrozole can significantly improve progression-free survival (PFS) versus letrozole monotherapy and is safe and well tolerated...
June 2018: Journal of Managed Care & Specialty Pharmacy
Sebastian Franik, Stephanie M Eltrop, Jan Am Kremer, Ludwig Kiesel, Cindy Farquhar
BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 4% to 8% of women worldwide and often leads to anovulatory subfertility. Aromatase inhibitors (AIs) are a class of drugs that were introduced for ovulation induction in 2001. Since about 2001 clinical trials have reached differing conclusions as to whether the AI letrozole is at least as effective as the first-line treatment clomiphene citrate (CC)...
May 24, 2018: Cochrane Database of Systematic Reviews
(no author information available yet)
Aromatase inhibitors have been used for the treatment of breast cancer, ovulation induction, endometriosis, and other estrogen-modulated conditions. For women with breast cancer, bone mineral density screening is recommended with long-term aromatase inhibitor use because of the risk of osteoporosis due to estrogen deficiency. Based on long-term adverse effects and complication safety data, when compared with tamoxifen, aromatase inhibitors are associated with a reduced incidence of thrombosis, endometrial cancer, and vaginal bleeding...
June 2018: Obstetrics and Gynecology
(no author information available yet)
Aromatase inhibitors have been used for the treatment of breast cancer, ovulation induction, endometriosis, and other estrogen-modulated conditions. For women with breast cancer, bone mineral density screening is recommended with long-term aromatase inhibitor use because of the risk of osteoporosis due to estrogen deficiency. Based on long-term adverse effects and complication safety data, when compared with tamoxifen, aromatase inhibitors are associated with a reduced incidence of thrombosis, endometrial cancer, and vaginal bleeding...
June 2018: Obstetrics and Gynecology
Daneng Li, Linda M McCall, Olwen M Hahn, Clifford A Hudis, Harvey J Cohen, Hyman B Muss, Aminah Jatoi, Jacqueline M Lafky, Karla V Ballman, Eric P Winer, Debu Tripathy, Bryan Schneider, William Barry, Maura N Dickler, Arti Hurria
BACKGROUND: In hormone receptor-positive advanced breast cancer, a progression-free survival benefit was reported with addition of bevacizumab to first-line letrozole. However, increased toxicity was observed. We hypothesized that functional age measures could be used to identify patients at risk for toxicity while receiving letrozole plus bevacizumab for hormone receptor-positive advanced breast cancer. METHODS: CALGB 40503 was a phase III trial that enrolled patients with hormone receptor-positive advanced breast cancer randomized to letrozole with or without bevacizumab...
May 22, 2018: Breast Cancer Research and Treatment
Tingting Zhang, Fubin Feng, Wenge Zhao, Jinhui Tian, Yan Yao, Chao Zhou, Shengjie Dong, Congcong Wang, Chuanxin Zang, Qingliang Lv, Changgang Sun
Background: Endocrine therapy is the cornerstone treatment for patients with hormone receptor-positive advanced breast cancer. We aimed to assess the effectiveness of various first-line endocrine monotherapies or combinations to determine the optimal sequence in a network meta-analysis. Materials and methods: We searched PubMed, EMBASE, and the Cochrane Library for randomized controlled trials (RCTs) from inception up to November 21, 2017. We included only RCTs that assessed the effectiveness of the following treatments as a monotherapy or in combination as the first-line treatment: tamoxifen, anastrozole, letrozole, exemestane, fulvestrant, palbociclib, and ribociclib...
2018: OncoTargets and Therapy
Emily A Evans-Hoeker, Esther Eisenberg, Michael P Diamond, Richard S Legro, Ruben Alvero, Christos Coutifaris, Peter R Casson, Gregory M Christman, Karl R Hansen, Heping Zhang, Nanette Santoro, Anne Z Steiner
OBJECTIVE: To determine if maternal major depression (MD), antidepressant use, or paternal MD are associated with pregnancy outcomes after non-IVF fertility treatments. DESIGN: Cohort study. SETTING: Clinics. PATIENT(S): Participants in two randomized trials: PPCOS II (clomiphene citrate versus letrozole for polycystic ovary syndrome), and AMIGOS (gonadotropins versus clomiphene citrate versus letrozole for unexplained infertility)...
May 2018: Fertility and Sterility
Shuo Huang, Rui Wang, Rong Li, Haiyan Wang, Jie Qiao, Ben Willem J Mol
OBJECTIVE: To study the effectiveness of different ovarian stimulation protocols compared with natural cycle treatment in an intrauterine insemination (IUI) program. DESIGN: Retrospective cohort study. SETTING: Large reproductive medicine center. PATIENT(S): Couples with unexplained or mild male-factor infertility. INTERVENTION(S): Couples were treated with the use of natural-cycle IUI, or IUI after ovarian stimulation with the use of clomiphene citrate (CC), letrozole, or gonadotropins...
May 2018: Fertility and Sterility
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