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Aromatase and breast cancer

Toshiyuki Okumura, Kazuhiro Ikeda, Takafumi Ujihira, Koji Okamoto, Kuniko Horie-Inoue, Satoru Takeda, Satoshi Inoue
Endocrine therapy using antiestrogens and aromatase inhibitors is usually efficient to treat patients with hormone-sensitive breast cancer. Many patients with endocrine therapy, however, often acquire resistance. In the present study, we performed functional screening using short hairpin RNA library to dissect genes involved in antiestrogen tamoxifen resistance in MCF-7 breast cancer cells. We identified seven candidate genes that are associated with poor prognosis of breast cancer patients based on clinical dataset...
August 3, 2017: Journal of Biochemistry
Narayan Shivapurkar, Eveline E Vietsch, Erin Carney, Claudine Isaacs, Anton Wellstein
BACKGROUND: Serial analysis of biomarkers in the circulation of patients undergoing treatment ("liquid biopsies") can provide new insights into drug effects. In particular the analysis of cell-free, circulating nucleic acids such as microRNAs (miRs) can reveal altered expression patterns indicative of mechanism of drug action, cancer growth, and tumor-stroma interactions. RESULTS: Here we analyzed plasma miRs in patients with hormone receptor positive, metastatic breast cancer with prior disease progression during aromatase inhibitor therapy (n = 8) in a phase I/II trial with the multiple tyrosine kinase inhibitor dovitinib (TKI258)...
October 4, 2017: Clinical and Translational Medicine
Jyoti Bajpai, Anant Ramaswamy, Arun Chandrasekharan, Surya Mishra, Tanuja Shet, Sudeep Gupta, R A Badwe
INTRODUCTION: Biomarkers predictive of response to mechanistic target of rapamycin (mTOR) inhibitor, everolimus, in endocrine receptor (ER)-positive metastatic breast cancer (MBC) are a work in progress. We evaluated the feasibility of directly measuring mTOR activity and phosphatase and tensin homolog (PTEN) expression and correlating their expression with response and survival. MATERIALS AND METHODS: MBC patients who received everolimus with endocrine therapy (ET) after progression on an aromatase inhibitor and had adequate tissue preservation for estimation of mTOR activity and PTEN expression were selected for analysis from a prospectively maintained database...
July 2017: South Asian Journal of Cancer
Susmitha Apuri
Breast cancer remains the most common cancer in women in the United States, the second most common cause of cancer death, and the main cause of death in women ages 45 to 55 years. Molecular analyses have shown that breast cancer is divided into several subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 [HER2] enriched, and basal-like), based on microarray techniques. Patients diagnosed as having breast cancer may undergo adjuvant or neoadjuvant chemotherapy, depending on the tumor size, hormone receptor, HER2/neu status, and desire for breast preservation...
October 2017: Southern Medical Journal
E M Van der Weijden-Van Doornik, Dagmar E Slot, Chris Burtin, G A van der Weijden
Background: Adjuvant endocrine therapy in breast cancer has increased survival rates; however, it is not without musculoskeletal side effects. Purpose: The purpose of this review was to systematically and critically appraise the available scientific evidence concerning the effect of adjuvant endocrine treatment on grip strength in women being treated for breast cancer. Data sources and study selection: The National Library of Medicine (MEDLINE-PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), Excerpta Medical Database by Elsevier (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Physiotherapy Evidence Database (PEDro) were searched from inception to February 2017 for appropriate papers that could answer the focused question...
September 1, 2017: Physical Therapy
Matthew P Goetz, Masakazu Toi, Mario Campone, Joohyuk Sohn, Shani Paluch-Shimon, Jens Huober, In Hae Park, Olivier Trédan, Shin-Cheh Chen, Luis Manso, Orit C Freedman, Georgina Garnica Jaliffe, Tammy Forrester, Martin Frenzel, Susana Barriga, Ian C Smith, Nawel Bourayou, Angelo Di Leo
Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting...
October 2, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Eskinder Eshetu Ali, Ka Lok Cheung, Chee Ping Lee, Jo Lene Leow, Kevin Yi-Lwern Yap, Lita Chew
OBJECTIVE: The success of oral adjuvant endocrine therapy (OAET) is greatly influenced by patients' level of adherence to treatment. The objective of this study is to measure the prevalence and determinants of adherence to OAET among breast cancer patients in Singapore. METHODS: A cross-sectional survey of patients supplemented by analysis of their prescription records was used to collect data. Adherence to OAET was assessed using the Morisky Medication Adherence Scale-4 items and evaluation of refill gaps...
October 2017: Asia-Pacific Journal of Oncology Nursing
A F de Groot, C J Kuijpers, J R Kroep
Breast cancer (BC) is responsible for 14% of cancer-related deaths in women [1]. Cyclin-dependent kinase (CDK) 4/6 inhibitors are a new class of selective drugs, offering an effective and tolerable treatment. CDK4/6 inhibitors induce cell cycle arrest in the G1 phase, and may thereby prevent tumour progression. Three CDK4/6 inhibitors have been tested in clinical BC trials: palbociclib, ribociclib, and abemaciclib. The Food and Drug Administration (FDA) and European Commission (EMA) have approved palbociclib for the treatment of patients HR+ HER2- locally advanced or metastatic BC (aBC) in combination with an aromatase inhibitor as initial therapy in postmenopausal women or in combination with fulvestrant in women who have received prior endocrine therapy...
September 20, 2017: Cancer Treatment Reviews
Suthat Chottanapund, M B M Van Duursen, Anne Zwartsen, Supatchaya Timtavorn, Panida Navasumrit, Prasat Kittakoop, Sanya Sureram, Mathuros Ruchirawat, Martin Van den Berg
Naturally occurring depsidones from the marine fungus Aspergillus unguis are known to have substantial anti-cancer activity, but their mechanism of action remains elusive. The purpose of this study was to examine the anti-aromatase activity of two common depsidones, unguinol and aspergillusidone A, in a co-culture system of human primary breast adipose fibroblasts and hormonal responsive T47D breast tumor cells. Using this in vitro model it was shown that these depsidones inhibit the growth of T47D tumor cells most likely via inhibition of aromatase (CYP19) activity...
2017: Toxicology Reports
Vincenzo Monda, Gelsy A Lupoli, Giovanni Messina, Rosario Peluso, Annalisa Panico, Ines Villano, Monica Salerno, Francesco Sessa, Francesca Marciello, Fiorenzo Moscatelli, Anna Valenzano, Leonardo Molino, Roberta Lupoli, Francesco Fonderico, Anna Tortora, Agata Pisano, Maria Ruberto, Marsala Gabriella, Gina Cavaliere, Giovanna Trinchese, Maria P Mollica, Luigi Cipolloni, Giuseppe Cibelli, Marcellino Monda, Giovanni Lupoli, Antonietta Messina
The endocrine therapy is the new frontiers of many breast cancers hormone sensitive. Hormone therapy for treating women with hormone receptor-positive cancer suppresses breast cancer growth either by reducing estrogen synthesis or by interfering with the action of estrogen within tumor cells. In this prospective randomized observational study we investigate the effect of adjuvant anastrozole in monotherapy or associated with risedronate on bone physiology and quality of life in postmenopausal, hormone-sensitive early breast cancer women at mild to moderate risk of fragility fractures...
2017: Frontiers in Pharmacology
Ying L Liu, Anurag Saraf, Benjamin Catanese, Shing M Lee, Yuan Zhang, Eileen P Connolly, Kevin Kalinsky
BACKGROUND: Obesity may negatively affect survival in breast cancer (BC), but studies are conflicting, and associations may vary by tumor subtypes and race/ethnicity groups. METHODS: In a retrospective review, we identified 273 women with invasive BC administered Adriamycin/Taxane-based neoadjuvant chemotherapy from 2004 to 2016 with body mass index (BMI) data at diagnosis. Obesity was defined as BMI ≥30. Associations between obesity and event-free survival (EFS), using STEEP events, and overall survival (OS), using all-cause mortality, were assessed overall and stratified by tumor subtype [[Hormone Receptor Positive (HR+)/HER2-, HER2+, and Triple-Negative Breast Cancer (TNBC])] in our diverse population...
September 25, 2017: Breast Cancer Research and Treatment
Iman Doostan, Cansu Karakas, Mehrnooh Kohansal, Kwang Hui Low, Matthew J Ellis, John A Olson, Vera Suman, Kelly Hunt, Stacy Moulder-Thompson, Khandan Keyomarsi
PURPOSE: Preoperative aromatase inhibitor (AI) therapy has demonstrated efficacy in hormone receptor (HR)-positive postmenopausal breast cancer. However, many patients have disease that is either intrinsically resistant to AIs or that responds initially but develops resistance after prolonged exposure. We have shown that patients with breast tumors expressing the deregulated forms of cyclin E (low molecular weight forms [LMW-E]) have poor overall survival. Herein, we hypothesize that LMW-E expression can identify HR-positive tumors that are unresponsive to neoadjuvant AI therapy due to the inability of AIs to induce a cytostatic effect...
September 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Claus M Schlotter, Lothar Tietze, Ulf Vogt, Carlos Villena Heinsen, Antje Hahn
Background Core needle biopsy plays a crucial role as diagnostic tool for BC. Both Ki67 and likely tumor-infiltrating lymphocytes (TILs) in the near future are determining the kind of systemic therapy. The role of TILs in BC is still an issue for clinical research, albeit preliminary results of neoadjuvant and adjuvant clinical studies already now highlight the crucial impact of TILs on therapy response and survival. Methods Evaluation of related publications (pubmed) and meeting abstracts (ASCO, SABCS). Results The monoclonal antibody Ki67 recognizing a nuclear antigene in proliferating cells is a positive marker of therapy response and superior survival...
September 22, 2017: Hormone Molecular Biology and Clinical Investigation
Richard J Santen, Cynthia A Stuenkel, Susan R Davis, JoAnn V Pinkerton, Anne Gompel, Mary Ann Lumsden
Objective: Review evidence to guide the management of menopausal signs and symptoms in women after breast cancer and make recommendations accordingly. Evidence: Randomized controlled clinical trials, observational studies, evidence- based guidelines, and expert opinion from professional societies. Background: Several symptoms and clinical problems associated with estrogen depletion -sleep disorders, vulvovaginal atrophy (VVA), vasomotor symptoms (VMS), mood changes, depressive symptoms, cardiovascular disease, osteopenia and osteoporosis- confront the estimated 9...
August 2, 2017: Journal of Clinical Endocrinology and Metabolism
Hany A Abdel-Hafiz
Breast cancer is one of the most common cancers and the second leading cause of cancer death in the United States. Estrogen receptor (ER)-positive cancer is the most frequent subtype representing more than 70% of breast cancers. These tumors respond to endocrine therapy targeting the ER pathway including selective ER modulators (SERMs), selective ER downregulators (SERDs) and aromatase inhibitors (AIs). However, resistance to endocrine therapy associated with disease progression remains a significant therapeutic challenge...
July 6, 2017: Diseases (Basel)
Erik J Blok, Judith R Kroep, Elma Meershoek-Klein Kranenbarg, Marjolijn Duijm-de Carpentier, Hein Putter, Joan van den Bosch, Eduard Maartense, A Elise van Leeuwen-Stok, Gerrit-Jan Liefers, Johan W R Nortier, Emiel J Th Rutgers, Cornelis J H van de Velde
Background: The optimal duration of extended endocrine therapy beyond five years after initial aromatase inhibitor-based adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer is still unknown. Therefore, we conducted a clinical trial to compare two different extended endocrine therapy durations. Methods: In the randomized phase III IDEAL trial, postmenopausal patients with hormone receptor-positive breast cancer were randomly allocated to either 2...
January 1, 2018: Journal of the National Cancer Institute
Hadar Goldvaser, Tristan A Barnes, Boštjan Šeruga, David W Cescon, Alberto Ocaña, Domen Ribnikar, Eitan Amir
Background: A number of randomized controlled trials (RCTs) have reported improvement in breast cancer outcomes from extending treatment with aromatase inhibitors (AIs) beyond the initial five years after diagnosis. However, the toxicity profile of extended AIs is uncertain. Methods: We identified RCTs that compared extended AIs to placebo or no treatment using MEDLINE and a review of abstracts from key conferences between 2013 and 2016. Odds ratios (ORs), 95% confidence intervals (CIs), absolute risks, and the number needed to harm (NNH) were computed for prespecified safety and tolerability outcomes including cardiovascular events, bone fractures, second cancers (excluding new breast cancer), treatment discontinuation for adverse events, and death without recurrence...
January 1, 2018: Journal of the National Cancer Institute
Céline Gérard, Kristy A Brown
One in eight women will develop breast cancer over their lifetime making it the most common female cancer. The cause of breast cancer is multifactorial and includes hormonal, genetic and environmental cues. Obesity is now an accepted risk factor for breast cancer in postmenopausal women, particularly for the hormone-dependent subtype of breast cancer. Obesity, which is characterized by an excess accumulation of body fat, is at the origin of chronic inflammation of white adipose tissue and is associated with dramatic changes in the biology of adipocytes leading to their dysfunction...
September 15, 2017: Molecular and Cellular Endocrinology
M J Yapura, E M Zwiefelhofer, R A Pierson, G P Adams
Numerous treatments and protocols have been used to control the reproductive cycle in cattle, with varying effectiveness and many involving the administration of steroid hormones. Steroid hormones, such as estradiol, are perceived as having a negative impact on consumer health. This internationally shared opinion has led to a ban on the use of steroid hormones in food producing animals in many countries (i.e., European Union, New Zealand, and Australia). Letrozole, a non-steroidal aromatase inhibitor, inactivates the aromatase enzyme responsible for the synthesis of estrogens by reversibly binding to the "heme" group of the P450 subunit...
September 11, 2017: Theriogenology
A Chandra, N S Rao, K P Malhotra, M Rastogi, R Khurana
Recently, everolimus (Evl) has been introduced in the management of hormone receptor-positive metastatic breast cancer, in combination with aromatase inhibitors. Evl-induced acute kidney injury has hitherto been described in other malignancies, especially renal cell cancer, but only once before in a patient with breast cancer. We describe two cases of Evl-associated nephrotoxicity in patients with breast cancer, one of whom underwent a renal biopsy showing acute tubular necrosis. Both our patients improved after withdrawal of the offending agent and have normal renal functions on follow-up...
September 2017: Indian Journal of Nephrology
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