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Aromatase and breast cancer

Mostafa M Ghorab, Mansour S Alsaid, Ghada H Al-Ansary, Ghada A Abdel-Latif, Dalal A Abou El Ella
Twenty novel chromene derivatives carrying different sulfonamide moieties (3-22) were designed and synthesized. All the newly prepared compounds were evaluated for their in vitro anticancer activity against breast cancer cell line (T47D). Most of the synthesized compounds showed good to moderate activity (IC50 = 8.8-108.9 μM), where compound 16 (IC50 = 8.8 μM) exhibited higher activity compared to doxorubicin (IC50 = 9.8 μM). In order to determine the mechanism of the anticancer activity in T47D cells, the effect of the most potent compounds (5-8, 11-14, and 16-18) on the aromatase activity was tested...
October 13, 2016: European Journal of Medicinal Chemistry
Elizabeth Hammond, Emma Shu, Karagin Sawchuk, Yvonne Myal, Afshin Raouf, Thomas Klonisch, Sabine Hombach-Klonisch, Etienne Leygue, Sam Kung, Janice Safneck, Michael Mowat, Wayne Xu, Leigh Murphy, Marshall Pitz
BACKGROUND: Few descriptive epidemiological studies on the incidence, treatment and survival can accurately reflect a whole population. Manitoba, Canada has an accurate cancer registry, a drug information program network and a breast screening program since 1995. This combined with a stable population provides true population data that can accurately describe the region. METHODS: Using a retrospective cohort design all Breast Cancer cases were obtained from 2004-2010 (N=5399) and grouped by Intrinsic sub-type...
October 19, 2016: Cancer Epidemiology
Pat Whitworth, Peter Beitsch, Angela Mislowsky, James V Pellicane, Charles Nash, Mary Murray, Laura A Lee, Carrie L Dul, Michael Rotkis, Paul Baron, Lisette Stork-Sloots, Femke A de Snoo, Jennifer Beatty
PURPOSE: Hormone receptor-positive (HR+) tumors have heterogeneous biology and present a challenge for determining optimal treatment. In the Neoadjuvant Breast Registry Symphony Trial (NBRST) patients were classified according to MammaPrint/BluePrint subtyping to provide insight into the response to neoadjuvant endocrine therapy (NET) or neoadjuvant chemotherapy (NCT). OBJECTIVE: The purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional 'clinical' immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in 'clinical luminal' [HR+/human epidermal growth factor receptor 2-negative (HER2-)] breast cancer patients to predict treatment sensitivity...
October 21, 2016: Annals of Surgical Oncology
Wenchen Pu, Yun Yuan, Danfeng Lu, Xin Wang, Hanwei Liu, Chun Wang, Fei Wang, Guolin Zhang
Estrogen biosynthesis is pivotal to many physiological processes of human. Aberrant estrogen level is closely related to a variety of diseases, including breast cancer and osteoporosis. Previously we found that 2-phenylbenzo[b]furan glycosides could promote estrogen biosynthesis. To find high active 2-phenylbenzo[b]furans, fifty-four 2-phenylbenzo[b]furans were prepared via four strategies according to corresponding substrate scopes. Biological evaluation in HEK293A cells showed that some compounds exhibited promotive activity on estrogen biosynthesis...
October 8, 2016: Bioorganic & Medicinal Chemistry Letters
Marc A Becker, Xiaonan Hou, Piyawan Tienchaianada, Brian B Haines, Sean C Harrington, S John Weroha, Sriram Sathyanarayanan, Paul Haluska
BACKGROUND: Mammalian target of rapamycin (mTOR) represents a key downstream intermediate for a myriad of oncogenic receptor tyrosine kinases. In the case of the insulin-like growth factor (IGF) pathway, the mTOR complex (mTORC1) mediates IGF-1 receptor (IGF-1R)-induced estrogen receptor alpha (ERα) phosphorylation/activation and leads to increased proliferation and growth in breast cancer cells. As a result, the prevalence of mTOR inhibitors combined with hormonal therapy has increased in recent years...
October 20, 2016: BMC Cancer
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
Guillermo Gervasini, Carlos Jara, Clara Olier, Nuria Romero, Ruth Martínez, Juan Antonio Carrillo
AIMS: Anastrozole, an aromatase inhibitor widely used in breast cancer, has recently been pointed out as a P-glycoprotein (ABCB1) substrate. We have aimed to determine whether ABCB1 single-nucleotide polymorphisms (SNPs) can affect anastrozole plasma concentrations in these patients. In addition, we assessed the impact of SNPs in CYP19A1 and TCL1A on the development of arthralgia and cancer recurrence in our series. METHODS: One-hundred-and-ten postmenopausal women with hormone receptor-positive breast cancer were included...
October 17, 2016: British Journal of Clinical Pharmacology
Martine Extermann, Christiaan Leeuwenburgh, Laila Samiian, Marina Sehovic, Jinze Xu, Christopher Cubitt, Paul B Jacobsen, Marco Pahor, Stephen R Grobmyer, Todd M Manini
OBJECTIVE: Chemotherapy is less often prescribed in older individuals due to concerns about post-treatment morbidity and quality of life. We evaluated the physical performance of breast cancer survivors treated with and without adjuvant chemotherapy. MATERIALS AND METHODS: We conducted a case-control study in 56 estrogen receptor positive breast cancer survivors (BCS) on adjuvant aromatase inhibitors 1-2years after definitive surgery. Cases had received adjuvant chemotherapy (n=27; age 70...
October 13, 2016: Journal of Geriatric 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
Kaori Tane, Chiyomi Egawa, Shintaro Takao, Kazuhiko Yamagami, Masaru Miyashita, Masashi Baba, Shigetoshi Ichii, Muneharu Konishi, Yuichiro Kikawa, Junya Minohata, Toshitaka Okuno, Keisuke Miyauchi, Kazuyuki Wakita, Hirofumi Suwa, Takashi Hashimoto, Masayuki Nishino, Takashi Matsumoto, Toshiharu Hidaka, Yutaka Konishi, Yoko Sakoda, Akihiro Miya, Masahiro Kishimoto, Hidefumi Nishikawa, Seishi Kono, Ikuo Kokufu, Isao Sakita, Koushiro Kitatsuji, Koushi Oh, Kouhei Akazawa, Yasuo Miyoshi
BACKGROUND: Adverse events related to endocrine therapies have a major impact not only on patients' quality of life but also on treatment discontinuation. Although vasomotor symptoms induced by aromatase inhibitors are frequently recognized, risk factors, especially for Japanese women, are not well reported. To identify risk factors for vasomotor symptoms of Japanese breast cancer patients treated with adjuvant anastrozole, we conducted a prospective cohort study based on patient-reported outcomes (PROs)...
October 12, 2016: Breast Cancer: the Journal of the Japanese Breast Cancer Society
Ute Berndt, Bernd Leplow, Robby Schoenfeld, Tilmann Lantzsch, Regina Grosse, Christoph Thomssen
INTRODUCTION: It is generally accepted that estrogens play a protective role in cognitive function. Therefore, it can be expected that subtotal estrogen deprivation following aromatase inhibition will alter cognitive performance. METHODS: In a cross-sectional study we investigated 80 postmenopausal women with breast cancer. Memory and spatial cognition were compared across 4 treatment groups: tamoxifen only (TAM, n = 22), aromatase inhibitor only (AI, n = 22), TAM followed by AI ('SWITCH group', n = 15), and patients with local therapy (LT) only (surgery and radiation, n = 21)...
August 2016: Breast Care
Gretchen L Gierach, Rochelle E Curtis, Ruth M Pfeiffer, Maeve Mullooly, Estelle A Ntowe, Robert N Hoover, Sarah J Nyante, Heather Spencer Feigelson, Andrew G Glass, Amy Berrington de Gonzalez
Importance: Within 10 years after breast cancer diagnosis, roughly 5% of patients develop contralateral breast cancer (CBC). Randomized trials have found that therapy including tamoxifen citrate and aromatase inhibitors (AIs) reduces CBC risk. But little is known about the magnitude and duration of protective associations within the context of real-world clinical management settings, where varying durations of and gaps in treatment are common. Objective: To determine the association between adjuvant tamoxifen and AI therapy and CBC risk within a general community setting...
October 6, 2016: JAMA Oncology
Cláudia de Brito, Margareth Crisóstomo Portela, Mauricio Teixeira Leite de Vasconcellos
Objectives To better understand the role that health care plays in breast cancer survival by investigating the effects that hormone therapy adherence and other select health care variables, adjusted for clinical and sociodemographic factors, had among a population of women in Rio de Janeiro, Brazil. Methods This was a longitudinal study based on secondary data of 5 861 women treated with hormone therapy (tamoxifen or aromatase inhibitors) at the National Cancer Institute of Brazil (INCA), from 1 January 2004 - 29 October 2010...
June 2016: Revista Panamericana de Salud Pública, Pan American Journal of Public Health
Roberta Baravalle, Giovanna Di Nardo, Andrea Bandino, Ines Barone, Stefania Catalano, Sebastiano Andò, Gianfranco Gilardi
The cytochrome P450 aromatase is involved in the last step of sex hormones biosynthesis by converting androgens into estrogens. The human enzyme is highly polymorphic and literature data correlate aromatase single nucleotide polymorphisms to the onset of pathologies such as breast cancer and neurodegenerative diseases. The aims of this study were i) to study the influence of the mutations R264C and R264H on the structure-function of the enzyme also upon phosphorylation by selected kinases and ii) to compare the activity of the variants to that of aromatase wild type in two different cell lines...
October 1, 2016: Journal of Steroid Biochemistry and Molecular Biology
Edoardo Colzani, Mark Clements, Anna L V Johansson, Annelie Liljegren, Wei He, Judith Brand, Jan Adolfsson, Tommy Fornander, Per Hall, Kamila Czene
BACKGROUND: Bone fractures may have an impact on prognosis of breast cancer. The long-term risks of bone fracture in breast cancer patients have not been thoroughly studied. METHODS: Poisson regression was used to investigate the incidence of hospitalisation due to bone fracture comparing women with and without breast cancer based on Swedish National registers. Cox regression was used to investigate the risk of being hospitalised with bone fracture, and subsequent risk of death, in a regional cohort of breast cancer patients...
October 4, 2016: British Journal of Cancer
Husam Abdel-Qadir, Eitan Amir, Hadas D Fischer, Longdi Fu, Peter C Austin, Paula J Harvey, Paula A Rochon, Douglas S Lee, Geoffrey M Anderson
BACKGROUND: Aromatase inhibitors (AIs) may increase cardiovascular risk relative to tamoxifen in post-menopausal women with breast cancer. This risk has not been well-quantified outside of clinical trials. METHODS: Observational population-based cohort study of women aged >55 years diagnosed with stage I-III breast cancer between 2005 and 2010. Women treated with AIs or tamoxifen were followed to March 2012. The primary outcome was hospitalisation for myocardial infarction (MI)...
September 29, 2016: European Journal of Cancer
Jin Song, Zehui Wu, Phumvadee Wangtrakuldee, Seok Rye Choi, Zhihao Zha, Karl Ploessl, Robert H Mach, Hank F Kung
Aromatase (CYP19) is a rate-limiting enzyme that catalyzes the biosynthesis of estrogens. Imaging agents based on aromatase inhibitors (AIs) has been developed for a PET/SPECT study. A series of compounds was synthesized based on YM511, which has previously been used for breast cancer treatment. Two examples of these derivatives, 4-(((4-iodophenyl)methyl)-4H-1,2,4-triazol-4-yl-amino)-benzonitrile (5) and 4-((1H-imidazol-1-yl)(4-iodobenzyl)amino)benzonitrile (11), displayed potent binding affinities to human aromatase (IC50 = 0...
October 2, 2016: Journal of Medicinal Chemistry
Palak Choksi, Margaret E Williams, Kelley M Kidwel, Julia Stella, Mary Soyster, David Hanauer, Catherine Van Poznak
BACKGROUND: Falling increases the risk for fracture. The impact of adjuvant aromatase inhibitors (AI) on the risk of falls is undefined. METHODS: A retrospective case control study was performed examining women with early stage breast cancer on adjuvant AI and matched controls without cancer. Fall and fracture data were abstracted from the medical record. RESULTS: Matched pairs of 332 women were identified (total N = 664). There was no statistically significant difference in the odds of a fall between cases and controls, p = 0...
2016: J Bone Rep Recomm
Suzanne N Landi, Kemi M Doll, Jeannette T Bensen, Laura Hendrix, Carey K Anders, Jennifer M Wu, Hazel B Nichols
PURPOSE: Endocrine therapy for breast cancer can exacerbate menopausal symptoms. The association between endocrine therapy and common pelvic floor disorders including urinary incontinence has rarely been evaluated. We examined urogenital and sexual side effects among women with a breast cancer diagnosis, comparing endocrine therapy users to nonusers. METHODS: Urogenital and sexual symptoms were self-reported during the enrollment interview within the University of North Carolina Cancer Survivorship Cohort...
September 28, 2016: Cancer Causes & Control: CCC
Miho Kono, Takeo Fujii, Genevieve Ray Lyons, Lei Huo, Roland Bassett, Yun Gong, Meghan Sri Karuturi, Debu Tripathy, Naoto T Ueno
PURPOSE: The purpose of this study is to evaluate survival outcome in patients with hormone receptor (HR)-positive (+) metastatic breast cancer (MBC) who received fluoxymesterone after disease progression while receiving contemporary hormonal therapy, as well as the association between estrogen receptor (ER)/androgen receptor (AR) status and survival outcome in these patients. METHODS: We retrospectively identified 103 patients treated with fluoxymesterone for HR + MBC from 2000 to 2014 and with at least one previous hormonal therapy in a metastatic setting...
November 2016: Breast Cancer Research and Treatment
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