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Aromatase and breast cancer

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https://www.readbyqxmd.com/read/29676087/-anti-breast-cancer-mechanism-of-flavonoids
#1
REVIEW
Bai-Bing Pang, Yuan-Kui Chu, Hua Yang
Flavonoids are a kind of ubiquitous natural products in plants and essential active ingredients of many medicinal plants. They have the characteristics of broad biological activity, high efficiency and low toxicity, with good prevention and cure effects on various types of tumors. Breast cancer is the commonest cancer disease and the main cause of cancer death in women worldwide. In China, the morbidity and mortality are still on the rise. Flavonoids can inhibit the occurrence and development of breast cancer in various aspects...
March 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29670855/current-therapies-for-human-epidermal-growth-factor-receptor-2-positive-metastatic-breast-cancer-patients
#2
REVIEW
Alexey A Larionov
The median survival of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) has more than doubled, since the discovery of HER2-targeted treatments: it rose from less than 2 years in 2001 (prior introduction of trastuzumab) to more than 4 years in 2017. The initial generation of HER2-targeted therapies included trastuzumab with taxanes in the first line, followed by the addition of lapatinib and by a switch to another cytotoxic agent after progression. Results of CLEOPATRA, EMILIA, and TH3RESA trials have changed this clinical practice...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29666928/implications-of-esr1-mutations-in-hormone-receptor-positive-breast-cancer
#3
REVIEW
Tomás Reinert, Rodrigo Gonçalves, José Bines
Endocrine treatment resistance eventually develops during adjuvant and even more often during hormonal treatment for advanced breast cancer (ABC). An ESR1 gene mutation, which encodes for the estrogen receptor (ER) protein, is one of the potential mechanisms of therapy resistance. The ESR1 mutations result in conformational changes in the ER leading to subsequent estrogen-independent transcriptional activity. These mutations are found at a lower level in early stage when compared to metastatic BC, more often through selective pressure after aromatase inhibitor (AI) treatment...
April 17, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29664714/randomized-phase-ii-trial-of-fulvestrant-plus-everolimus-or-placebo-in-postmenopausal-women-with-hormone-receptor-positive-human-epidermal-growth-factor-receptor-2-negative-metastatic-breast-cancer-resistant-to-aromatase-inhibitor-therapy-results-of-pre0102
#4
Noah Kornblum, Fengmin Zhao, Judith Manola, Paula Klein, Bhuvaneswari Ramaswamy, Adam Brufsky, Phillip J Stella, Brian Burnette, Melinda Telli, Della F Makower, Puneet Cheema, Cristina I Truica, Antonio C Wolff, Gamini S Soori, Barbara Haley, Timothy R Wassenaar, Lori J Goldstein, Kathy D Miller, Joseph A Sparano
Purpose The mammalian target of rapamycin inhibitor everolimus targets aberrant signaling through the PI3K/AKT/mammalian target of rapamycin pathway, a mechanism of resistance to anti-estrogen therapy in estrogen receptor (ER)-positive breast cancer. We hypothesized that everolimus plus the selective ER downregulator fulvestrant would be more efficacious than fulvestrant alone in ER-positive metastatic breast cancer resistant to aromatase inhibitor (AI) therapy. Patients and Methods This randomized, double-blind, placebo-controlled, phase II study included 131 postmenopausal women with ER-positive, human epidermal growth factor receptor 2-negative, AI-resistant metastatic breast cancer randomly assigned to fulvestrant (500 mg days 1 and 15 of cycle 1, then day 1 of cycles 2 and beyond) plus everolimus or placebo...
April 17, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29662534/obesity-and-outcome-of-post-menopausal-women-receiving-adjuvant-letrozole-for-breast-cancer
#5
Jamal Zekri, Kamel Farag, Ahmed Allithy
Introduction: Aromatase enzyme activity is predominant in adipose tissue. This has led to speculation that aromatase activity is elevated in obese women and subsequently decreased the clinical activity of adjuvant aromatase inhibitors (AIs) in women with estrogen receptor positive (ER+) breast cancer (BC). We investigated the effect of obesity on the outcome of this population. Patients and methods: Records of 320 consecutive post-menopausal (PM) women with ER+ BC starting single agent adjuvant letrozole between years 2005 and 2014 were retrospectively reviewed...
2018: Ecancermedicalscience
https://www.readbyqxmd.com/read/29651409/incidence-of-comorbidities-in-women-with-breast-cancer-treated-with-tamoxifen-or-an-aromatase-inhibitor-an-australian-population-based-cohort-study
#6
Huah Shin Ng, Bogda Koczwara, David Roder, Theo Niyonsenga, Agnes Vitry
Background: The development of comorbidities has become increasingly relevant with longer-term cancer survival. Objective: To assess the pattern of comorbidities among Australian women with breast cancer treated with tamoxifen or an aromatase inhibitor. Design: Retrospective cohort study using Pharmaceutical Benefits Scheme (PBS) data (10% sample) from January 2003 to December 2014. Dispensing claims data were used to identify comorbidities and classified with the Rx-Risk-V model...
2018: Journal of Comorbidity
https://www.readbyqxmd.com/read/29651367/-lazarus-response-to-olaparib-in-a-virtually-chemonaive-breast-cancer-patient-carrying-gross-brca2-gene-deletion
#7
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/29644889/comparing-exercise-responses-to-aerobic-plus-resistance-training-between-postmenopausal-breast-cancer-survivors-undergoing-aromatase-inhibitor-therapy-and-healthy-women
#8
Thais R S de Paulo, Kerri M Winters-Stone, Juliana Viezel, Fabricio E Rossi, Bruna L Aro, Ana Carolina A C Trindade, Jamile S Codogno, Ismael F Freitas Junior
BACKGROUND: The aim of this study was to explore whether postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy differ from healthy postmenopausal women in their response to the same aerobic + resistance training. METHODS: The participants were separated into two groups: postmenopausal breast cancer survivors undergoing aromatase inhibitor therapy for an average of 20 months (18 women) and healthy postmenopausal women (24 women). We assessed aerobic capacity (predicted maximum oxygen uptake (VO2 max) and maximum running velocity test (Vmax)) through a walking test, upper and lower body muscle strength using an estimated one-repetition maximum test, and body composition by dual-energy X-ray absorptiometry at baseline and at three, six, and nine months, respectively...
April 12, 2018: Disability and Rehabilitation
https://www.readbyqxmd.com/read/29644007/impact-of-adjuvant-hormonotherapy-on-radiation-induced-breast-fibrosis-according-to-the-individual-radiosensitivity-results-of-a-multicenter-prospective-french-trial
#9
Céline Bourgier, Florence Castan, Olivier Riou, Tan-Dat Nguyen, Karine Peignaux, Claire Lemanski, Jean-Léon Lagrange, Youlia Kirova, Eric Lartigau, Yazid Belkacemi, Sofia Rivera, Georges Noël, Sébastien Clippe, Françoise Mornex, Christophe Hennequin, Sophie Gourgou, Muriel Brengues, Pascal Fenoglietto, Esat Mahmut Ozsahin, David Azria
Background: To evaluate risk of severe breast fibrosis occurrence in patients treated by breast-conserving surgery, adjuvant radiotherapy and hormonotherapy (HT) according to individual radiosensitivity (RILA assay). Results: HT- and RILAhigh were the two independent factors associated with improved breast-fibrosis free survival (BFFS). BFFS rate at 36 months was lower in patients with RILAlow and HT+ than in patients with RILAhigh and HT- (75.8% and 100%, respectively; p = 0...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29627127/the-action-of-estrogens-and-progestogens-in-the-young-female-breast
#10
Irene Zolfaroli, Juan J Tarín, Antonio Cano
Evidence from different sources sustains a pro-oncogenic role of hormones, estrogens and progestogens, on the breast. The issue is of interest for young women, who are exposed to the hormonal changes imposed by the ovarian cycle and, often, take hormones with contraceptive purposes. Experimental and clinical studies show that both estrogens and progesterone are involved in mammary development during puberty and lactation, the changes being observed across mammalian species, including humans. Estrogen receptors, and more particularly the alpha isoform, participate in molecular processes of stem cells differentiation and epithelial proliferation through paracrine actions implicating growth factors...
March 28, 2018: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/29623577/use-of-dual-mtor-inhibitor-mln0128-against-everolimus-resistant-breast-cancer
#11
Karineh Petrossian, Duc Nguyen, Chiao Lo, Noriko Kanaya, George Somlo, Yvonne Xiaoyong Cui, Chiun-Sheng Huang, Shiuan Chen
PURPOSE: HR+/HER2- aromatase inhibitor-resistant metastatic breast cancer can be treated with everolimus and a second AI until the cancer recurs. Targeting these everolimus-resistant patients with the latest standard of care, CDK4/6 inhibitors, has not been clearly addressed. Understanding the signaling transduction pathways, which everolimus resistance activates, will elucidate the mechanisms and offer treatment strategies of everolimus resistance. METHODS: To mimic the clinical setting, letrozole-resistant cells were used to generate an everolimus-resistant model (RAD-R)...
April 5, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29620427/blocking-oestradiol-synthesis-pathways-with-potent-and-selective-coumarin-derivatives
#12
Sanna Niinivehmas, Pekka A Postila, Sanna Rauhamäki, Elangovan Manivannan, Sami Kortet, Mira Ahinko, Pasi Huuskonen, Niina Nyberg, Pasi Koskimies, Sakari Lätti, Elina Multamäki, Risto O Juvonen, Hannu Raunio, Markku Pasanen, Juhani Huuskonen, Olli T Pentikäinen
A comprehensive set of 3-phenylcoumarin analogues with polar substituents was synthesised for blocking oestradiol synthesis by 17-β-hydroxysteroid dehydrogenase 1 (HSD1) in the latter part of the sulphatase pathway. Five analogues produced ≥62% HSD1 inhibition at 5 µM and, furthermore, three of them produced ≥68% inhibition at 1 µM. A docking-based structure-activity relationship analysis was done to determine the molecular basis of the inhibition and the cross-reactivity of the analogues was tested against oestrogen receptor, aromatase, cytochrome P450 1A2, and monoamine oxidases...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29619093/aromatase-inhibitors-are-associated-with-a-higher-fracture-risk-than-tamoxifen-a-systematic-review-and-meta-analysis
#13
REVIEW
Olivia L Tseng, John J Spinelli, Carolyn C Gotay, Wan Y Ho, Mary L McBride, Martin G Dawes
Background: In this paper, our aim was to systematically evaluate published evidence of bone fracture risk associated with tamoxifen and aromatase inhibitors in women aged 65 and under, and diagnosed with nonmetastatic breast cancer. Methods: We comprehensively searched MEDLINE, EMBASE and CINAHL databases from January 1997 through May 2015, and reference lists of the selected articles to identify English-language randomized controlled trials and cohort studies of fracture risk...
April 2018: Therapeutic Advances in Musculoskeletal Disease
https://www.readbyqxmd.com/read/29610032/personalized-prevention-in-high-risk-individuals-managing-hormones-and-beyond
#14
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/29609880/progression-free-survival-with-first-line-endocrine-based-therapies-among-postmenopausal-women-with-hr-her2-metastatic-breast-cancer-a-network-meta-analysis
#15
REVIEW
Rajeev Ayyagari, Derek Tang, Oscar Patterson-Lomba, Zhou Zhou, Jipan Xie, David Chandiwana, Anand A Dalal, Polly Ann Niravath
PURPOSE: The comparative efficacy of endocrine-based therapies (ETs) for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) is not well characterized. This network meta-analysis (NMA) synthesized available evidence on progression-free survival (PFS) with first-line ETs for postmenopausal HR+/HER2- mBC. METHODS: A systematic literature review identified randomized controlled trials of first-line ETs...
March 30, 2018: Clinical Therapeutics
https://www.readbyqxmd.com/read/29607425/investigation-of-genotoxicity-risk-and-dna-repair-capacity-in-breast-cancer-patients-using-anastrozole
#16
Tugce Yesil Devecioglu, Fatih Aydogan, Gulden Zehra Omurtag, Nuran Senel Bese, Semra Sardas
OBJECTIVE: Breast cancer is the most common cancer in women worldwide and the incidence increases in postmenopausal women. Anastrozole is a non-steroidal (type II), third-generation aromatase inhibitor (AI) that is used in the treatment of postmenopausal estrogen-related breast cancer. Several studies have been conducted to assess the efficacy, safety, and superiority of AIs to tamoxifen; however, a literature search did not reveal a study that investigated the genotoxic potential of AIs...
2018: Northern Clinics of Istanbul
https://www.readbyqxmd.com/read/29584567/preliminary-clinical-application-of-an-aromatase-inhibitor-and-a-gonadotropin-releasing-hormone-agonist-combination-for-inoperable-endometrial-cancer-patients-with-comorbidities-case-report-and-literature-review
#17
Mengting Dong, Su Jiang, Wenyan Tian, Ye Yan, Chao Gao, Jinping Gao, Yan Sheng, Yingmei Wang, Fengxia Xue
BACKGROUND: Endometrial cancer (EC) occurs most commonly after menopause. A proportion of patients present with advanced age and comorbidities, and become ineligible for surgery. The optimal treatment strategy of these patients remains a clinical challenge. Aromatase inhibitor (AI) combined with Gonadotropin-releasing hormone agonist (GnRH-a) possesses profound effect in suppressing the estrogen level, has become a valid treatment in the breast cancer. However, the combined use of an AI and a GnRH-a in EC has rarely been studied...
March 27, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29582246/current-treatment-patterns-among-postmenopausal-women-with-hr-her2-metastatic-breast-cancer-in-us-community-oncology-practices-an-observational-study
#18
Deborah Goldschmidt, Anand A Dalal, Hela Romdhani, Sneha Kelkar, Annie Guerin, Genevieve Gauthier, Eric Q Wu, Polly Niravath, Tania Small
INTRODUCTION: Recent approval of novel agents has changed the treatment landscape for post menopausal women with hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) metastatic breast cancer (mBC). The objective of this study was to describe contemporary treatment patterns among postmenopausal women with HR+/HER2- mBC in the real-world setting. METHODS: Data were collected from 64 community oncologists in the US between February and June 2017 using an online medical records extraction tool...
March 26, 2018: Advances in Therapy
https://www.readbyqxmd.com/read/29581979/current-strategies-of-endocrine-therapy-in-elderly-patients-with-breast-cancer
#19
REVIEW
Suk-Young Lee, Jae Hong Seo
Currently, the growing population of the elderly is one of biggest problems in terms of increase in geriatric diseases. Lack of data from large prospective studies on geriatric breast cancer patients often makes it difficult for clinicians to make treatments decisions for them. Because both benefit and risk of treatment should be taken into account, treatment is usually determined considering life expectancy or comorbidities in elderly patients. Treatment of breast cancer is differentiated according to histologic classifications, and hormone therapy is even adopted for patients with metastatic breast cancer if tumor tissue expresses hormone receptors...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29581135/er-breast-cancers-resistant-to-prolonged-neoadjuvant-letrozole-exhibit-an-e2f4-transcriptional-program-sensitive-to-cdk4-6-inhibitors
#20
Angel Guerrero-Zotano, Thomas Stricker, Luigi Formisano, Katherine E Hutchinson, Daniel G Stover, Kyung-Min Lee, Luis J Schwarz, Jennifer M Giltnane, Monica V Estrada, Valerie M Jansen, Alberto Servetto, Joaquín Gavilá, José Alejandro Pérez-Fidalgo, Ana Lluch, Antonio Llombart-Cussac, Mohamed Amine Bayar, Stefan Michiels, Fabrice Andre, Monica Arnedos, Vicente Guillem, Amparo Ruiz-Simon, Carlos L Arteaga
PURPOSE: This study aimed to identify biomarkers of resistance to endocrine therapy in ER+ breast cancers (BC) treated with prolonged neoadjuvant letrozole. Experimental Design: We performed targeted DNA and RNA-sequencing in 68 ER+ BC from patients treated with preoperative letrozole (median 7 months). Results:Twenty-four tumors (35%) exhibited a PEPI score ≥4 and/or recurred after a median of 58 months and were considered endocrine resistant. Integration of the 47 most upregulated genes (log FC>1, FDR<0...
March 26, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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