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Aromatase and breast cancer

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https://www.readbyqxmd.com/read/27908454/fulvestrant-500-mg-versus-anastrozole-1-mg-for-hormone-receptor-positive-advanced-breast-cancer-falcon-an-international-randomised-double-blind-phase-3-trial
#1
John F R Robertson, Igor M Bondarenko, Ekaterina Trishkina, Mikhail Dvorkin, Lawrence Panasci, Alexey Manikhas, Yaroslav Shparyk, Servando Cardona-Huerta, Kwok-Leung Cheung, Manuel Jesus Philco-Salas, Manuel Ruiz-Borrego, Zhimin Shao, Shinzaburo Noguchi, Jacqui Rowbottom, Mary Stuart, Lynda M Grinsted, Mehdi Fazal, Matthew J Ellis
BACKGROUND: Aromatase inhibitors are a standard of care for hormone receptor-positive locally advanced or metastatic breast cancer. We investigated whether the selective oestrogen receptor degrader fulvestrant could improve progression-free survival compared with anastrozole in postmenopausal patients who had not received previous endocrine therapy. METHODS: In this phase 3, randomised, double-blind trial, we recruited eligible patients with histologically confirmed oestrogen receptor-positive or progesterone receptor-positive, or both, locally advanced or metastatic breast cancer from 113 academic hospitals and community centres in 20 countries...
November 28, 2016: Lancet
https://www.readbyqxmd.com/read/27900579/aryl-hydrocarbon-receptor-induced-intratumoral-aromatase-in-breast-cancer
#2
Ryoko Saito, Yasuhiro Miki, Shuko Hata, Takanori Ishida, Takashi Suzuki, Noriaki Ohuchi, Hironobu Sasano
PURPOSE: Aryl hydrocarbon receptor (AhR) inhibits estrogen receptor (ER) pathway, which may suppress estrogen-dependent cell proliferation. However, the correlation between AhR stimulation and intratumoral estrogen synthesis, especially through aromatase, has not been reported to date. In the present study, we examined this correlation in breast cancer cells. METHODS: We examined AhR and aromatase immunoreactivity in 29 patients with invasive ductal carcinoma. We performed in vitro studies using three breast carcinoma cell lines, MCF-7, T47D, and MDA-MB-231...
November 30, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27894075/mammographic-density-a-potential-monitoring-biomarker-for-adjuvant-and-preventative-breast-cancer-endocrine-therapies
#3
REVIEW
Michael S Shawky, Hilary Martin, Honor J Hugo, Thomas Lloyd, Kara L Britt, Andrew Redfern, Erik W Thompson
Increased mammographic density (MD) has been shown beyond doubt to be a marker for increased breast cancer risk, though the underpinning pathobiology is yet to be fully elucidated. Estrogenic activity exerts a strong influence over MD, which consequently has been observed to change predictably in response to tamoxifen anti-estrogen therapy, although results for other selective estrogen receptor modulators and aromatase inhibitors are less consistent. In both primary and secondary prevention settings, tamoxifen-associated MD changes correlate with successful modulation of risk or outcome, particularly among pre-menopausal women; an observation that supports the potential use of MD change as a surrogate marker where short-term MD changes reflect longer-term anti-estrogen efficacy...
November 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27889687/role-of-inflammation-in-obesity-related-breast-cancer
#4
REVIEW
Elisa Crespi, Giulia Bottai, Libero Santarpia
Chronic inflammation associated with obesity is now recognized to be an important condition in promoting carcinogenesis and progression in breast cancer patients, mostly in postmenopausal women with tumors expressing estrogen and progesterone receptors. In obese patients, altered levels of several inflammatory mediators regulating aromatase and estrogen expression are one of the mechanisms responsible of increase breast cancer risk. Growing attention has also been paid to the local adipose inflammation and the role played by macrophages as determinants of breast cancer risk recurrence and prognosis...
November 24, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27875786/inflammation-dysregulated-metabolism-and-aromatase-in-obesity-and-breast-cancer
#5
REVIEW
Heba Zahid, Evan R Simpson, Kristy A Brown
Obesity is associated with an increased risk of estrogen-dependent breast cancer after menopause. Adipose tissue undergoes important changes in obesity due to excess storage of lipids, leading to adipocyte cell death and the recruitment of macrophages. The resultant state of chronic low-grade inflammation is associated with the activation of NFkB signaling and elevated levels of aromatase, the rate-limiting enzyme in estrogen biosynthesis. This occurs not only in the visceral and subcutaneous fat, but also in the breast fat...
November 19, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27873127/radiotherapy-induced-global-and-regional-differences-in-early-stage-left-sided-versus-right-sided-breast-cancer-patients-speckle-tracking-echocardiography-study
#6
Suvi Sirkku Tuohinen, Tanja Skyttä, Tuija Poutanen, Heini Huhtala, Vesa Virtanen, Pirkko-Liisa Kellokumpu-Lehtinen, Pekka Raatikainen
Radiotherapy (RT) to the thoracic region increases late cardiovascular morbidity and mortality. The impact of breast cancer laterality on cardiac function is largely unknown. The aim of this prospective study was to compare RT-induced changes in left-sided and right-sided breast cancer patients using speckle tracking echocardiography (STE). Sixty eligible patients with left-sided breast cancer and 20 with right-sided breast cancer without chemotherapy were evaluated prospectively before and early after RT. A comprehensive echocardiographic examination included three dimensional measurements and STE of the left ventricle (LV)...
November 21, 2016: International Journal of Cardiovascular Imaging
https://www.readbyqxmd.com/read/27871904/steroidogenic-effect-of-erxian-decoction-for-relieving-menopause-via-the-p-akt-pkb-pathway-in-vitro-and-in-vivo
#7
Shi Wei Wang, Ho Pan Cheung, Yao Tong, Jia Lu, Tzi Bun Ng, Yan Bo Zhang, Zhang Jin Zhang, Kai Fai Lee, Jenny Ka Wing Lam, Stephen Cho Wing Sze
ETHNOPHARMACOLOGICAL RELEVANCE: Erxian decoction (EXD), an empirical Chinese medicine formula, is effectively used in the clinical treatment of menopause-related symptoms in China. Previous data from our group show that EXD has steroidogenic effect in natural menopausal Sprague-Dawley-rats (SD-rats) as an animal model of menopause. However, the mechanistic studies on steroidogenic effects of EXD are still inadequate. Hence, the mechanisms of steroidogenic effects of EXD were studied in vitro and in vivo in this study...
November 18, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27869171/epigenetic-activation-of-the-prostaglandin-receptor-ep4-promotes-resistance-to-endocrine-therapy-for-breast-cancer
#8
J F Hiken, J I McDonald, K F Decker, C Sanchez, J Hoog, N D VanderKraats, K L Jung, M Akinhanmi, L E Rois, M J Ellis, J R Edwards
Approximately 75% of breast cancers express estrogen receptor α (ERα) and depend on estrogen signals for continued growth. Aromatase inhibitors (AIs) prevent estrogen production and inhibit ER signaling, resulting in decreased cancer recurrence and mortality. Advanced tumors treated with AIs almost always develop resistance to these drugs via the upregulation of alternative growth signals. The mechanisms that drive this resistance-especially epigenetic events that alter gene expression-are, however, not well understood...
November 21, 2016: Oncogene
https://www.readbyqxmd.com/read/27865465/dysregulation-of-aromatase-in-breast-endometrial-and-ovarian-cancers-an-overview-of-therapeutic-strategies
#9
P R Manna, D Molehin, A U Ahmed
Aromatase is the rate-limiting enzyme in the biosynthesis of estrogens, which play crucial roles on a spectrum of developmental and physiological processes. The biological actions of estrogens are classically mediated by binding to two estrogen receptors (ERs), ERα and ERβ. Encoded by the cytochrome P450, family 19, subfamily A, polypeptide 1 (CYP19A1) gene, aromatase is expressed in a wide variety of tissues, as well as benign and malignant tumors, and is regulated in a pathway- and tissue-specific manner...
2016: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/27864342/systemic-levels-of-estrogens-and-pge2-synthesis-in-relation-to-postmenopausal-breast-cancer-risk
#10
Sangmi Kim, Jeff Campbell, Wonsuk Yoo, Jack A Taylor, Dale P Sandler
BACKGROUND: Prostaglandin E2 (PGE2) induces aromatase expression in adipose tissue leading to increased estrogen production that may promote the development and progression of breast cancer. However, few studies have simultaneously investigated systemic levels of PGE2 and estrogen in relation to postmenopausal breast cancer risk. METHODS: Here we determined urinary estrogen metabolites (EMs) using mass spectrometry in a case-cohort study (295 incident breast cancer cases and 294 subcohort members), and using linear regression estimated the effect of urinary levels of a major PGE2 metabolite (PGE-M) on EMs...
November 18, 2016: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27863287/bone-health-in-the-elderly-cancer-patient-a-siog-position-paper
#11
REVIEW
J J Body, E Terpos, B Tombal, P Hadji, A Arif, A Young, M Aapro, R Coleman
More than a third of cancers are diagnosed in people over the age of 75. Androgen deprivation for prostate cancer and aromatase inhibitors in breast cancer accelerate age-related bone loss and increase fracture rates. BMD should be checked by dual energy X-ray absorptiometry at baseline and, dependent on risk, every 12-24months. Sufficient calcium, vitamin D and exercise are part of primary fracture prevention. Resistance exercise in particular may improve functional activity and bone density. In men at increased fracture risk and women with postmenopausal early breast cancer, antiresorptive treatment is warranted to reduce fracture rate and to increase overall survival in breast cancer...
December 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27852186/supportive-care-of-women-with-breast-cancer-key-concerns-and-practical-solutions
#12
Nicholas Zdenkowski, Stephanie Tesson, Janine Lombard, Melanie Lovell, Sandra Hayes, Prudence A Francis, Haryana M Dhillon, Frances M Boyle
Patients diagnosed with breast cancer may have supportive care needs for many years after diagnosis. High quality multidisciplinary care can help address these needs and reduce the physical and psychological effects of breast cancer and its treatment. Ovarian suppression and extended endocrine therapy benefits are associated with vasomotor, musculoskeletal, sexual and bone density-related side effects. Aromatase inhibitor musculoskeletal syndrome is a common reason for treatment discontinuation. Treatment strategies include education, exercise, simple analgesia and a change to tamoxifen or another aromatase inhibitor...
November 21, 2016: Medical Journal of Australia
https://www.readbyqxmd.com/read/27848887/metabolism-and-toxicological-implications-of-commonly-used-chemopreventive-drugs-against-breast-cancer-carcinogenesis
#13
Aliyu Muhammad, Mohammed Auwal Ibrahim, Ochuko Lucky Erukainure, Ibrahim Malami, Hadiza Sani, Hafsat Abdullahi Mohammed
BACKGROUND: Breast cancer has been reported to be among the frequently diagnosed cancer in women worldwide despite advances in early detection and treatment. Several drugs are currently used for chemoprevention as a result of a number of drawbacks associated with breast cancer therapy. AIM: This review focuses on the metabolism and toxicological implications of these drugs against breast cancer/carcinogenesis. METHODOLOGY: Relevant articles on the commonly used anti-breast cancer drugs (raloxifene, tamoxifen, anastrozole, letrozole and exemestane) used in chemoprevention were searched using the major scientific databases including Scopus, Embase, PubMed/ Medline, Sciencedirect and Google Scholar...
November 16, 2016: Current Drug Metabolism
https://www.readbyqxmd.com/read/27848152/the-presence-and-impact-of-estrogen-metabolism-on-the-biology-of-triple-negative-breast-cancer
#14
Keely May McNamara, Saki Oguro, Fumiya Omata, Kyoko Kikuchi, Fouzia Guestini, Koyu Suzuki, Yang Yang, Eriko Abe, Hisashi Hirakawa, Kristy A Brown, Ishida Takanori, Noriaki Ohuchi, Hironobu Sasano
PURPOSE: While triple-negative breast cancer (TNBC) is negative for estrogen receptor alpha, a substantial proportion of carcinomas express estrogen receptor beta (ERβ); consequently, estrogen actions and metabolism may be relevant in this cancer subtype. METHODS: A cohort of 81 TNBC patients from Tohoku University Hospital, Japan were characterised with regard to the expression of estrogen receptor beta and enzymes known to modulate levels of estrogens in breast and other tissues (Aromatase, 17-beta- Hydroxysteroid dehydrogenases 1, 2 and 6)...
November 15, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27843622/review-of-hormone-based-treatments-in-postmenopausal-patients-with-advanced-breast-cancer-focusing-on-aromatase-inhibitors-and-fulvestrant
#15
REVIEW
Iben Kümler, Ann S Knoop, Christina A R Jessing, Bent Ejlertsen, Dorte L Nielsen
BACKGROUND: Endocrine therapy constitutes a central modality in the treatment of oestrogen receptor (ER)-positive advanced breast cancer. PURPOSE: To evaluate the evidence for endocrine treatment in postmenopausal patients with advanced breast cancer focusing on the aromatase inhibitors, letrozole, anastrozole, exemestane and fulvestrant. METHODS: A review was carried out using PubMed. Randomised phase II and III trials reporting on ≥100 patients were included...
2016: ESMO Open
https://www.readbyqxmd.com/read/27832985/effects-of-raloxifene-against-letrozole-induced-bone-loss-in-chemically-induced-model-of-menopause-in-mice
#16
Abul Kalam, Sushama Talegaonkar, Divya Vohora
INTRODUCTION: The deleterious effects of letrozole, an aromatase inhibitor, used in the adjuvant treatment of breast cancer in postmenopausal women, on bone are well-documented and represent a major drawback to its clinical use. Raloxifene, a selective estrogen receptor modulator and a clinically approved anti-osteoporotic drug, has been recently demonstrated to be efficacious in women with breast cancer. The present study evaluated the effects of preventive and curative treatment with raloxifene on letrozole-induced alterations of bone microarchitecture and turnover markers in a chemically-induced menopause model in mice...
November 8, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27832260/vaginal-testosterone-cream-vs-estradiol-vaginal-ring-for-vaginal-dryness-or-decreased-libido-in-women-receiving-aromatase-inhibitors-for-early-stage-breast-cancer-a-randomized-clinical-trial
#17
Michelle E Melisko, Mindy E Goldman, Jimmy Hwang, Amy De Luca, Sally Fang, Laura J Esserman, Amy J Chien, John W Park, Hope S Rugo
Importance: Aromatase inhibitors (AI) are associated with significant urogenital atrophy, affecting quality of life and drug compliance. Objective: To evaluate safety of intravaginal testosterone cream (IVT) or an estradiol-releasing vaginal ring (7.5 μg/d) in patients with early-stage breast cancer (BC) receiving an AI. Intervention was considered unsafe if more than 25% of patients had persistent elevation in estradiol (E2), defined as E2 greater than 10 pg/mL (to convert to pmol/L, multiply by 3...
November 10, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27827358/impact-of-mutational-profiles-on-response-of-primary-oestrogen-receptor-positive-breast-cancers-to-oestrogen-deprivation
#18
Pascal Gellert, Corrinne V Segal, Qiong Gao, Elena López-Knowles, Lesley-Ann Martin, Andrew Dodson, Tiandao Li, Christopher A Miller, Charles Lu, Elaine R Mardis, Alexa Gillman, James Morden, Manuela Graf, Kally Sidhu, Abigail Evans, Michael Shere, Christopher Holcombe, Stuart A McIntosh, Nigel Bundred, Anthony Skene, William Maxwell, John Robertson, Judith M Bliss, Ian Smith, Mitch Dowsett
Pre-surgical studies allow study of the relationship between mutations and response of oestrogen receptor-positive (ER+) breast cancer to aromatase inhibitors (AIs) but have been limited to small biopsies. Here in phase I of this study, we perform exome sequencing on baseline, surgical core-cuts and blood from 60 patients (40 AI treated, 20 controls). In poor responders (based on Ki67 change), we find significantly more somatic mutations than good responders. Subclones exclusive to baseline or surgical cores occur in ∼30% of tumours...
November 9, 2016: Nature Communications
https://www.readbyqxmd.com/read/27823654/aromatase-inhibitors-in-premenopause-great-expectations-fulfilled
#19
REVIEW
Rosalba Torrisi, Selene Rota, Agnese Losurdo, Monica Zuradelli, Giovanna Masci, Armando Santoro
Tamoxifen and GnRH analogues (GnRHa) represent the mainstay of endocrine manipulations in premenopausal women. The estrogen blockade obtained by aromatase inhibitors (AIs) plus GnRHa suppresses circulating estrogens more deeply than tamoxifen plus GnRHa. Retrospective and prospective evidence confirm a substantial activity for AIs and GnRHa in locally advanced and metastatic breast cancer. In early breast cancer inconsistent evidence emerged from 2 large randomized studies with anastrozole performing as tamoxifen in terms of DFS, but significantly worse as of OS while exemestane outperformed tamoxifen as of DFS particularly in very young and high-risk women...
November 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27810693/bone-health-and-adherence-to-vitamin-d-and-calcium-therapy-in-early-breast-cancer-patients-on-endocrine-therapy-with-aromatase-inhibitors
#20
Lidija Bošković, Maja Gašparić, Marija Petković, Damir Gugić, Ingrid Belac Lovasić, Željko Soldić, Branka Petrić Miše, Nina Dabelić, Ljubica Vazdar, Eduard Vrdoljak
OBJECTIVES: Randomized trials involving aromatase inhibitors (AIs) in the adjuvant treatment of breast cancer patients have reported increased osteoporosis risk. Bone loss can be reduced with appropriate life style, vitamin D and calcium supplements, and with bisphosphonate therapy. The aim of this analysis was to investigate adherence to vitamin D and calcium in postmenopausal breast cancer patients receiving adjuvant non-steroidal AIs, and oncologists' adherence to the bone health guidelines...
October 27, 2016: Breast: Official Journal of the European Society of Mastology
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