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Aromatase and breast cancer

Xueyu Wang, Guo-Cai Wang, Jianhui Rong, Shi Wei Wang, Tzi Bun Ng, Yan Bo Zhang, Kai Fai Lee, Lin Zheng, Hei-Kiu Wong, Ken Kin Lam Yung, Stephen Cho Wing Sze
Estrogen-stimulating principles have been demonstrated to relieve postmenopausal syndrome effectively. Gardenia jasminoides Ellis (GJE) is an herbal medicine possessing multiple pharmacological effects on human health with low toxicity. However, the therapeutic effects of GJE on the management of postmenopausal syndrome and its mechanism of action have not been fully elucidated. In this study, network pharmacology-based approaches were employed to examine steroidogenesis under the influence of GJE. In addition, the possibility of toxicity of GJE was ruled out and four probable active compounds were predicted...
2018: Frontiers in Pharmacology
Erin D Giles, Sonali Jindal, Elizabeth A Wellberg, Troy Schedin, Steven M Anderson, Ann D Thor, Dean P Edwards, Paul S MacLean, Pepper Schedin
BACKGROUND: Obesity and type II diabetes are linked to increased breast cancer risk in postmenopausal women. Patients treated with the antidiabetic drug metformin for diabetes or metabolic syndrome have reduced breast cancer risk, a greater pathologic complete response to neoadjuvant therapy, and improved breast cancer survival. We hypothesized that metformin may be especially effective when targeted to the menopausal transition, as this is a lifecycle window when weight gain and metabolic syndrome increase, and is also when the risk for obesity-related breast cancer increases...
June 14, 2018: Breast Cancer Research: BCR
Inmaculada Conejo, Bella Pajares, Emilio Alba, Antonio Ignacio Cuesta-Vargas
BACKGROUND: Aromatase inhibitors reduce breast cancer recurrence rates in postmenopausal women by about 30% compared with tamoxifen while treatments differ. Unfortunately, nearly half of women taking AIs report AI-associated arthralgia (AIA), leading to therapy abandon in on third of patients, which could lead to cancer recurrence. The purpose of the current study was to evaluate the effectiveness of Neuromuscular Taping (NMT) in the treatment of AIA in women who have been treated of BC...
June 11, 2018: BMC Complementary and Alternative Medicine
Stefania Gori, Fabio Puglisi, Michela Cinquini, Giovanni Pappagallo, Antonio Frassoldati, Laura Biganzoli, Laura Cortesi, Alba Fiorentino, Catia Angiolini, Corrado Tinterri, Andrea De Censi, Alessia Levaggi, Lucia Del Mastro
Premenopausal women with hormone receptor-positive early breast cancer are candidates for adjuvant endocrine therapy, as recommended by the major international guidelines. To date, adjuvant endocrine options for premenopausal women include tamoxifen with or without ovarian function suppression (OFS) or an aromatase inhibitor with OFS. Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed, and the results of randomised clinical trials have been reported over the last years...
June 7, 2018: European Journal of Cancer
Ricardo Ribas, Sunil Pancholi, Aradhana Rani, Eugene Schuster, Stephanie K Guest, Joanna Nikitorowicz-Buniak, Nikiana Simigdala, Allan Thornhill, Francesca Avogadri-Connors, Richard E Cutler, Alshad S Lalani, Mitch Dowsett, Stephen R Johnston, Lesley-Ann Martin
BACKGROUND: Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER+ ) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed...
June 8, 2018: Breast Cancer Research: BCR
Ava A John-Baptiste, Taryn Becker, Kinwah Fung, Lorraine L Lipscombe, Peter C Austin, Geoffrey M Anderson
OBJECTIVE: To conduct a Bayesian evidence synthesis using commonly available statistical procedures in order to estimate fracture risk for postmenopausal women undergoing hormonal therapy for breast cancer. STUDY DESIGN AND SETTING: Using linked administrative data, we conducted a retrospective cohort study of women age 66 or older diagnosed with stage I to III breast cancer in Ontario, Canada, between April 1, 2003 and February 28, 2010. We used data augmentation to perform Bayesian Cox regression of the hazard of a hip, spine or wrist/forearm fracture, adjusting for age, history of fragility fracture, corticosteroid use, osteoporosis, rheumatoid arthritis, dementia or diabetes diagnoses...
June 4, 2018: Journal of Clinical Epidemiology
James A Simon, Irwin Goldstein, Noel N Kim, Susan R Davis, Susan Kellogg-Spadt, Lior Lowenstein, JoAnn V Pinkerton, Cynthia A Stuenkel, Abdulmaged M Traish, David F Archer, Gloria Bachmann, Andrew T Goldstein, Rossella E Nappi, Linda Vignozzi
OBJECTIVE: The objective of this consensus document is to broaden the perspective on clinical management of genitourinary syndrome of menopause to include androgens. METHODS: A modified Delphi method was used to reach consensus among the 14 international panelists representing multiple disciplines and societies. RESULTS: Menopause-related genitourinary symptoms affect over 50% of midlife and older women. These symptoms have a marked impact on sexual functioning, daily activities, emotional well-being, body image, and interpersonal relations...
June 4, 2018: Menopause: the Journal of the North American Menopause Society
Prudence A Francis, Olivia Pagani, Gini F Fleming, Barbara A Walley, Marco Colleoni, István Láng, Henry L Gómez, Carlo Tondini, Eva Ciruelos, Harold J Burstein, Hervé R Bonnefoi, Meritxell Bellet, Silvana Martino, Charles E Geyer, Matthew P Goetz, Vered Stearns, Graziella Pinotti, Fabio Puglisi, Simon Spazzapan, Miguel A Climent, Lorenzo Pavesi, Thomas Ruhstaller, Nancy E Davidson, Robert Coleman, Marc Debled, Stefan Buchholz, James N Ingle, Eric P Winer, Rudolf Maibach, Manuela Rabaglio-Poretti, Barbara Ruepp, Angelo Di Leo, Alan S Coates, Richard D Gelber, Aron Goldhirsch, Meredith M Regan
Background In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials...
June 4, 2018: New England Journal of Medicine
François Montastruc, Farzin Khosrow-Khavar, Sibylle de Germay, Christel Renoux, Vanessa Rousseau, Geneviève Durrieu, Marion Montastruc, Olivier Rascol, Agnès Sommet, Maryse Lapeyre-Mestre, Justine Benevent, Jean-Louis Montastruc
BACKGROUND: Three studies have suggested a potential positive association between the use of tamoxifen in breast cancer and Parkinsonism, mainly after long-term exposure. OBJECTIVES: To explore this potential signal, we performed a case/non-case study using the World Health Organization Global Individual Case Safety Reports (ICSRs) database, VigiBase® between 1979 and 2018. METHODS: Among women ≥ 55 years, we measured the risk of reporting "Parkinsonism" compared with all other adverse drug reactions [as a reporting odds ratio (ROR 95% CI)] for tamoxifen compared to all other drugs or aromatase inhibitors...
June 3, 2018: European Journal of Clinical Pharmacology
Guy Jerusalem, Richard H de Boer, Sara Hurvitz, Denise A Yardley, Elena Kovalenko, Bent Ejlertsen, Sibel Blau, Mustafa Özgüroglu, László Landherr, Marianne Ewertz, Tetiana Taran, Jenna Fan, Florence Noel-Baron, Anne-Laure Louveau, Howard Burris
Importance: Everolimus plus exemestane and capecitabine are approved second-line therapies for advanced breast cancer. Objective: A postapproval commitment to health authorities to estimate the clinical benefit of everolimus plus exemestane vs everolimus or capecitabine monotherapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Design: Open-label, randomized, phase 2 trial of treatment effects in postmenopausal women with advanced breast cancer that had progressed during treatment with nonsteroidal aromatase inhibitors...
June 3, 2018: JAMA Oncology
Julia P Brockway, Charles L Shapiro
Aromatase inhibitors (AIs) are the standard treatment for postmenopausal women with hormone receptor-positive breast cancers. One of the most common side effects of AIs is joint pain; it is also the most frequently cited reason for nonadherence and discontinuation before completion of the prescribed treatment course. Nonadherence and, in particular, discontinuation, can lead to increased rates of breast cancer mortality. The prevalence of AI-induced arthralgias is about 50%, and there are several interventions, including switching to a different AI, that can increase adherence...
May 15, 2018: Oncology (Williston Park, NY)
Louis Jacob, Paulina Christiana Scholten, Karel Kostev, Matthias Kalder
PURPOSE: The goal of the present study was to analyze the impact of sleep disorders on the development of metastases in women with breast cancer followed in gynecological practices in Germany. METHODS: The study included women who were initially diagnosed with breast cancer in 262 gynecological practices in Germany between January 2000 and December 2015 (index date). Participants were followed for up to 5 years. Women diagnosed with breast cancer metastases within a period of 6 months and before the end of follow-up were matched (1:1) by age, index year, physician, type of hormonal therapy (tamoxifen or aromatase inhibitors) and follow-up time (in months) with women without metastases...
May 29, 2018: Breast Cancer Research and Treatment
Takanori Hayashi, Masahiro Hikichi, Jun Yukitake, Toru Wakatsuki, Eiji Nishio, Toshiaki Utsumi, Nobuhiro Harada
Aromatase inhibitor (AI) resistance is a major obstacle in the treatment of estrogen receptor-positive breast cancer. Everolimus (EVE) ameliorates AI-resistant breast cancer and is therefore used in cancer treatment. However, some patients show resistance to EVE. Here, we used 30 clones of long-term estrogen-deprived (LTED) MCF-7 cells as a model of AI-resistant breast cancer. We examined changes in protein phosphatase type 2A (PP2A) and cancerous inhibitor of PP2A (CIP2A), a negative regulator of PP2A, in LTED cells treated with EVE...
May 4, 2018: Oncotarget
Rainer Girgert, Günter Emons, Carsten Gründker
Currently, conventional chemotherapy is the only treatment option for triple-negative breast cancers (TNBC) due to a lack of a unique target. In TNBC, a high expression of the membrane bound G protein-coupled estrogen receptor (GPER), correlates with a worse outcome. There is a potential for an association between growth hormone receptor (GHR) and GPER expression. To confirm this hypothesis, GHR was inhibited in TNBC cells with Somavert, and GPER expression levels, and the effect on signal transduction and proliferation induction in TNBC cells were analyzed...
June 2018: Oncology Letters
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
Senem Ozcan-Sezer, Elif Ince, Atilla Akdemir, Özlem Öztürk Ceylan, Sibel Suzen, Hande Gurer-Orhan
1. A causal association is reported between prolonged exposures to elevated levels of estrogen and breast cancer. Therefore inhibiting aromatase (CYP19A), which catalyses the conversion of androgens to estrogens, is an important approach in prevention and treatment of estrogen receptor positive (ER+) breast cancer. 2. Melatonin, a natural indolic hormone, is reported to prevent free radical induced carcinogenesis and block local estrogen synthesis in breast tissue via aromatase inhibition. However several features of melatonin limit its therapeutic use...
May 28, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Benjamin E Blass, Pravin Iyer, Magid Abou-Gharbia, Wayne E Childers, John C Gordon, Mercy Ramanjulu, George Morton, Premkumar Arumugam, Joshodeep Boruwa, John Ellingboe, Sayan Mitra, Rajashekar Reddy Nimmareddy, Shalini Paliwal, Jamallamudi Rajasekhar, Savithiri Shivakumar, Pratima Srivastava, Raghuram S Tangirala, Konda Venkataramanaiah, Ramreddy Bobbala, Mahesh Yanamandra, L Krishnakanth Reddy
The synthesis of steroid hormones is critical to human physiology and improper regulation of either the synthesis of these key molecules or activation of the associated receptors can lead to disease states. This has led to intense interest in developing compounds capable of modulating the synthesis of steroid hormones. Compounds capable of inhibiting Cyp19 (Aromatase), a key enzyme in the synthesis of estrogens, have been successfully employed as breast cancer therapies, while inhibitors of Cyp17 (17α-hydroxylase-17,20-lyase), a key enzyme in the synthesis of glucocorticoids, mineralocorticoids and steroidal sex hormones, are a key component of prostate cancer therapy...
May 22, 2018: Bioorganic & Medicinal Chemistry Letters
Laura Smy, Joely Straseski
The measurement of estrogens is important for diagnosing and monitoring the health of women, men, and children. For example, for postmenopausal women or women undergoing treatment for breast cancer with aromatase inhibitors, the measurement of extremely low concentrations of estrogens in serum, especially estradiol, is problematic but essential for proper medical care. Achieving superb analytical sensitivity and specificity has been and continues to be a challenge for the clinical laboratory, but is a challenge that is being taken seriously...
May 22, 2018: Clinical Biochemistry
Bao Ngoc N Tran, Qing Z Ruan, Justin B Cohen, Parisa Kamali, Andres F Doval, Adam M Tobias, Dhruv Singhal, Samuel J Lin, Bernard T Lee
BACKGROUND: The use of hormone therapy (tamoxifen and aromatase inhibitors) has been shown to increase venous thromboembolism. As breast cancer patients undergoing microsurgical breast reconstruction are often receiving hormone therapy, it is unclear whether this increased thrombotic risk is associated with increased flap loss. METHODS: A retrospective review was performed on patients undergoing abdominally based microsurgical breast reconstruction at an academic institution from 2004 to 2015...
June 2018: Plastic and Reconstructive Surgery
(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
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