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Aromatase and breast cancer

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https://www.readbyqxmd.com/read/28529550/hormonoresistance-in-advanced-breast-cancer-a-new-revolution-in-endocrine-therapy
#1
REVIEW
Paule Augereau, Anne Patsouris, Emmanuelle Bourbouloux, Carole Gourmelon, Sophie Abadie Lacourtoisie, Dominique Berton Rigaud, Patrick Soulié, Jean Sebastien Frenel, Mario Campone
Endocrine therapy is the mainstay of treatment of estrogen-receptor-positive (ER+) breast cancer with an overall survival benefit. However, some adaptive mechanisms in the tumor emerge leading to the development of a resistance to this therapy. A better characterization of this process is needed to overcome this resistance and to develop new tailored therapies. Mechanisms of resistance to hormone therapy result in activation of transduction signal pathways, including the cell cycle regulation with cyclin D/CDK4/6/Rb pathway...
May 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28526959/adjuvant-tamoxifen-but-not-aromatase-inhibitor-therapy-decreases-serum-levels-of-the-wnt-inhibitor-dickkopf-1-while-not-affecting-sclerostin-in-breast-cancer-patients
#2
Andy Göbel, Jan D Kuhlmann, Theresa Link, Pauline Wimberger, Andrew J Browne, Martina Rauner, Lorenz C Hofbauer, Tilman D Rachner
PURPOSE: Endocrine therapies, including tamoxifen or aromatase inhibitors, are indispensable for the treatment of patients with estrogen receptor (ER)- and/or progesterone-positive breast cancer. Whereas tamoxifen displays partial ER agonistic effects in bone, aromatase inhibitors increase bone resorption and fracture risk. The Wnt inhibitors dickkopf-1 (DKK-1) and sclerostin negatively impact bone formation and are considered targets for the treatment of bone disorders. However, the effect of endocrine therapies on serum DKK-1 and sclerostin levels in patients with primary breast cancer remains elusive...
May 19, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28515111/racial%C3%A2-differences-in-adjuvant-endocrine-therapy-use-and-discontinuation-in-association-with-mortality-among-medicare-breast-cancer-patients-by-receptor-status
#3
Albert J Farias, Xianglin L Du
BACKGROUND: There are racial disparities in breast cancer mortality. Our purpose was to determine whether racial/ethnic differences in use and discontinuation of AET differed by hormone receptor status and whether discontinuation was associated with mortality. METHODS: We conducted a retrospective cohort study with SEER/Medicare dataset of women age 65 years or older diagnosed with stage I-III breast cancer in Medicare Part-D from 2007-2009, stratified by hormone receptor status...
May 17, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28512028/evaluation-of-synthesized-coumarin-derivatives-on-aromatase-inhibitory-activity
#4
Yuki Yamaguchi, Naozumi Nishizono, Daisuke Kobayashi, Teruki Yoshimura, Keiji Wada, Kazuaki Oda
In women across the world, the most common type of cancer is breast cancer. Among medical treatments, endocrine therapy based on aromatase inhibitors (AI) is expected to be effective against not only post-menopausal but also pre-menopausal breast cancer. In this study, we examined the structure-activity relationship between the aromatase inhibitory effects of 7-diethylaminocoumarin derivatives with a substituent at position 3 and coumarin derivatives with a substituent at position 7. Consequently, we found that 7-(pyridin-3-yl)coumarin (IC50 values 30...
January 25, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28510222/primary-ectopic-breast-cancer-of-the-vulva-treated-with-local-excision-of-the-vulva-and-sentinel-lymph-node-biopsy-a-case-report
#5
Takayuki Ishigaki, Yasuo Toriumi, Ryouko Nosaka, Rei Kudou, Yoshimi Imawari, Makiko Kamio, Hiroko Nogi, Hisashi Shioya, Hiroshi Takeyama
Primary breast cancer fairly infrequently occurs in ectopic breast tissue, and primary ectopic breast cancer of the vulva is particularly rare. Only 26 cases have been published in the English-language literature, and there has been no report of primary breast carcinoma of the vulva in Japan. We report a rare case of primary ectopic breast cancer of the vulva that was treated with local excision of the vulva and sentinel lymph node biopsy (SLNB). The patient was a 72-year-old woman who had noticed a right vulvar tumor 10 years earlier...
December 2017: Surgical Case Reports
https://www.readbyqxmd.com/read/28494403/her2-status-predicts-for-upfront-ai-benefit-a%C3%A2-trans-aiog-meta-analysis-of-12-129-patients-from%C3%A2-atac-big-1-98-and-team-with-centrally-determined-her2
#6
John M S Bartlett, Ikhlaaq Ahmed, Meredith M Regan, Ivana Sestak, Elizabeth A Mallon, Patrizia Dell'Orto, Beat Thürlimann, Caroline Seynaeve, Hein Putter, Cornelis J H Van de Velde, Cassandra L Brookes, John F Forbes, Giuseppe Viale, Jack Cuzick, Mitchell Dowsett, Daniel W Rea
BACKGROUND: A meta-analysis of the effects of HER2 status, specifically within the first 2-3 years of adjuvant endocrine therapy, has the potential to inform patient selection for upfront aromatase inhibitor (AI) therapy or switching strategy tamoxifen followed by AI. The pre-existing standardisation of methodology for HER2 (immunohistochemistry/fluorescence in situ hybridization) facilitates analysis of existing data for this key marker. METHODS: Following a prospectively designed statistical analysis plan, patient data from 3 phase III trials Arimidex, Tamoxifen, Alone or in Combination Trial (ATAC), Breast International Group (BIG) 1-98 and Tamoxifen Exemestane Adjuvant Multicentre Trial (TEAM)] comparing an AI to tamoxifen during the first 2-3 years of adjuvant endocrine treatment were collected and a treatment-by-marker analysis of distant recurrence-free interval-censored at 2-3 years treatment - for HER2 status × AI versus tamoxifen treatment was performed to address the clinical question relating to efficacy of 'upfront' versus 'switch' strategies for AIs...
May 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28491147/a-clinical-guide-to-the-management-of-genitourinary-symptoms-in-breast-cancer-survivors-on-endocrine-therapy
#7
REVIEW
Mariana S Sousa, Michelle Peate, Sherin Jarvis, Martha Hickey, Michael Friedlander
There is increasing attention and concern about managing the adverse effects of adjuvant endocrine therapy for women with early breast cancer as the side effects of therapy influence compliance and can impair quality of life (QoL). Most side effects associated with tamoxifen (TAM) and aromatase inhibitors (AIs) are directly related to estrogen deprivation, and the symptoms are similar to those experienced during natural menopause but appear to be more severe than that seen in the general population. Prolonged estrogen deprivation may lead to atrophy of the vulva, vagina, lower urinary tract and supporting pelvic structures, resulting in a range of genitourinary symptoms that can in turn lead to pain, discomfort, impairment of sexual function and negatively impact on multiple domains of QoL...
April 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28489882/preparation-of-a-novel-antiserum-to-aromatase-with-high-affinity-and-specificity-its-clinicopathological-significance-on-breast-cancer-tissue
#8
Naoki Kanomata, Shiro Matsuura, Tsunehisa Nomura, Junichi Kurebayashi, Taisuke Mori, Jo Kitawaki, Takuya Moriya
Aromatase inhibitors have been widely used for the endocrine treatment of estrogen-dependent breast cancer in postmenopausal patients. However, clinicopathological studies of aromatase have been limited due to unsatisfactory specificity and/or restricted availability of anti-aromatase antibodies. Here, we have generated a polyclonal antiserum with high affinity and specificity for human aromatase using a monoclonal antibody tagged immunoaffinity chromatography on an industrial production scale. Our preliminary immunohistochemical analysis of 221 invasive breast cancer cases indicated that 87...
2017: PloS One
https://www.readbyqxmd.com/read/28489562/incidence-of-menopausal-symptoms-in-postmenopausal-breast-cancer-patients-treated-with-aromatase-inhibitors
#9
Hong Dongsheng, Bi Ling, Zhou Jun, Tong Ying Hui, Zhao Qingwei, Chen Jing, Lu Xiaoyang
Aromatase inhibitors (AIs) are the standard of care for postmenopausal women with estrogen receptor-positive breast cancer. Here, we performed a meta-analysis to evaluate the occurrence of menopausal symptoms in breast cancer patients receiving the AI therapy. Patients treated with AIs had an increased risk of all-grade arthralgia (1.63 [95% CI: 1.34-1.98]) and insomnia (1.24 [95% CI: 1.14-1.34]). The overall incidence of hot flashes, fatigue, arthralgia, sweating, and insomnia in patients receiving AIs was 30...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28488183/palbociclib-a-review-in-hr-positive-her2-negative-advanced-or-metastatic-breast-cancer
#10
REVIEW
Esther S Kim, Lesley J Scott
Oral palbociclib (Ibrance®) is a first-in-class, highly selective inhibitor of cyclin-dependent kinases 4 and 6 (i.e. a CDK4/6 inhibitor). It is indicated for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer, in combination with an aromatase inhibitor as initial endocrine-based therapy, and in combination with fulvestrant (with or without a luteinizing hormone-releasing hormone agonist) in those previously treated with endocrine therapy. In clinical trials, palbociclib in combination with letrozole as initial endocrine-based therapy in postmenopausal women (PALOMA-1 and PALOMA-2), or in combination with fulvestrant in pre-, peri-, or postmenopausal women with disease progression after endocrine therapy (PALOMA-3), significantly prolonged progression-free survival (PFS) and improved clinical benefit response (CBR) rates...
May 9, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28487654/the-association-of-cyp19a1-variation-with-circulating-estradiol-and-aromatase-inhibitor-outcome-can-cyp19a1-variants-be-used-to-predict-treatment-efficacy
#11
REVIEW
Dylan M Glubb, Tracy A O'Mara, Jannah Shamsani, Amanda B Spurdle
After menopause, estradiol is primarily synthesized in peripheral tissues by the enzyme aromatase, encoded by CYP19A1. CYP19A1 variation associates with circulating estradiol in postmenopausal women and this variation is best represented by the intronic variant rs727479. This variation appears to have pleiotropic effects as it also associates with endometrial cancer risk. Indeed, estradiol plays an important role in the development of breast and endometrial cancer. Aromatase inhibitor (AI) drugs are used in the treatment of both diseases, however, response rates for AIs are low and there is currently no way to identify breast or endometrial cancer patients who are more likely to receive a clinical benefit...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28469437/predicting-adherence-to-aromatase-inhibitor-therapy-among-breast-cancer-survivors-an-application-of-the-protection-motivation-theory
#12
Monita Karmakar, Sharrel L Pinto, Timothy R Jordan, Iman Mohamed, Monica Holiday-Goodman
The purpose of this observational study was to determine if the Protection Motivation Theory could predict and explain adherence to aromatase inhibitor (AI) therapy among breast cancer survivors. Purposive sampling was used to identify 288 survivors who had been prescribed AI therapy. A valid and reliable survey was mailed to survivors. A total of 145 survivors completed the survey. The Morisky scale was used to measure adherence to AI. The survivors reported a mean score of 6.84 (±0.66) on the scale. Nearly 4 in 10 survivors (38%) were non-adherent...
2017: Breast Cancer: Basic and Clinical Research
https://www.readbyqxmd.com/read/28467729/long-term-follow-up-of-the-intergroup-exemestane-study
#13
James P Morden, Isabel Alvarez, Gianfilippo Bertelli, Alan S Coates, Robert Coleman, Lesley Fallowfield, Jacek Jassem, Stephen Jones, Lucy Kilburn, Per E Lønning, Olaf Ortmann, Claire Snowdon, Cornelis van de Velde, Jørn Andersen, Lucia Del Mastro, David Dodwell, Stig Holmberg, Hanna Nicholas, Robert Paridaens, Judith M Bliss, R Charles Coombes
Purpose The Intergroup Exemestane Study, an investigator-led study of 4,724 postmenopausal patients with early breast cancer (clinical trial information: ISRCTN11883920), has previously demonstrated that a switch from adjuvant endocrine therapy after 2 to 3 years of tamoxifen to exemestane was associated with clinically relevant improvements in efficacy. Here, we report the final efficacy analyses of this cohort. Patients and Methods Patients who remained disease free after 2 to 3 years of adjuvant tamoxifen were randomly assigned to continue tamoxifen or switch to exemestane to complete a total of 5 years of adjuvant endocrine therapy...
May 3, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28464211/osteoporosis-therapy-and-outcomes-for-postmenopausal-patients-with-hormone-receptor-positive-breast-cancer-ncic-ctg-ma-27
#14
Allan Lipton, Judith-Anne W Chapman, Kim Leitzel, Ashwani Garg, Kathleen I Pritchard, James N Ingle, G Thomas Budd, Matthew J Ellis, George W Sledge, Manuela Rabaglio, Lei Han, Catherine R Elliott, Lois E Shepherd, Paul E Goss, Suhail M Ali
BACKGROUND: Breast cancer patients in the MA.27 trial had similar outcomes with steroidal aromatase inhibitor (AI) exemestane and nonsteroidal anastrozole. AIs increase the risk of osteoporosis. This study examined the effects of self-reported osteoporosis and osteoporosis therapy (OPT) on outcomes. METHODS: The MA.27 phase 3 adjuvant trial enrolled 7576 postmenopausal women. The primary outcome was event-free survival (EFS), and the secondary outcome was distant disease-free survival (DDFS)...
May 2, 2017: Cancer
https://www.readbyqxmd.com/read/28459598/practices-and-attitudes-regarding-women-undergoing-fertility-preservation-a-survey-of-the-national-physicians-cooperative
#15
Pietro Bortoletto, Rafael Confino, Brigid M Smith, Teresa K Woodruff, Mary Ellen Pavone
PURPOSE: To describe physician attitudes and variations in oncofertility treatment strategies. METHODS: An exploratory online survey administered between December 1, 2014 and January 27, 2015 to 185 members of the National Physicians Cooperative (NPC). RESULTS: Twenty-eight percent (52 of 185) of NPC members responded to the online survey. Fifty percent of respondents were obstetrician-gynecologists working largely in academic medical centers...
May 1, 2017: Journal of Adolescent and Young Adult Oncology
https://www.readbyqxmd.com/read/28451964/prospective-assessment-of-patient-reported-outcomes-and-estradiol-and-drug-concentrations-in-patients-experiencing-toxicity-from-adjuvant-aromatase-inhibitors
#16
Kunal C Kadakia, Kelley M Kidwell, Nicholas J Seewald, Claire F Snyder, Anna Maria Storniolo, Julie L Otte, David A Flockhart, Daniel F Hayes, Vered Stearns, N Lynn Henry
PURPOSE: Aromatase inhibitors (AI), which decrease circulating estradiol concentrations in post-menopausal women, are associated with toxicities that limit adherence. Approximately one-third of patients will tolerate a different AI after not tolerating the first. We report the effect of crossover from exemestane to letrozole or vice versa on patient-reported outcomes (PROs) and whether the success of crossover is due to lack of estrogen suppression. METHODS: Post-menopausal women enrolled on a prospective trial initiating AI therapy for early-stage breast cancer were randomized to exemestane or letrozole...
April 27, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28445992/interaction-between-the-estrogen-receptor-and-fibroblast-growth-factor-receptor-pathways-in-non-small-cell-lung-cancer
#17
Jill M Siegfried, Mariya Farooqui, Natalie J Rothenberger, Sanja Dacic, Laura P Stabile
The estrogen receptor (ER) promotes non-small cell lung cancer (NSCLC) proliferation. Since fibroblast growth factors (FGFs) are known regulators of stem cell markers in ER positive breast cancer, we investigated whether a link between the ER, FGFs, and stem cell markers exists in NSCLC. In lung preneoplasias and adenomas of tobacco carcinogen exposed mice, the anti-estrogen fulvestrant and/or the aromatase inhibitor anastrozole blocked FGF2 and FGF9 secretion, and reduced expression of the stem cell markers SOX2 and nanog...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443693/confounder-factors-masking-a-leydig-cell-ovarian-tumor-in-a-post-menopausal-woman-treated-for-androgen-positive-receptor-breast-cancer
#18
Felipe Scipião Moura, Flávia A Costa-Barbosa, Sydney Correia Leao, Sergio Mancini Nicolau, Claudio E Kater, Patrícia T Monteagudo
Post-menopause hyperandrogenism is a condition that needs careful evaluation. Aromatase inhibitors (AI), which are important in the management of positive estrogen breast cancer, and chronic kidney disease (CKD) can puzzle the evaluation of this condition. A postmenopause female with type-2 diabetes and advanced CKD was attended due to progressive virilization, which has started after the introduction of an AI for breast cancer 5 years earlier. Clinical and radiological investigation has confirmed a pure Leydig cell tumor as source of hyperandrogenism...
April 26, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28439796/adjuvant-endocrine-therapy-in-breast-cancer-evolving-paradigms-in-premenopausal-women
#19
REVIEW
Lorenzo Rossi, Olivia Pagani
In the last few years, new adjuvant endocrine treatment options have become available in young women with early breast cancer, such as the addition of ovarian function suppression to tamoxifen or aromatase inhibitors. Treatment duration has been also adapted in the latest guidelines based on the individual risk of recurrence. The oncologist is therefore challenged to precisely assess the risk of recurrence according to currently available predictive and prognostic factors in order to offer the most appropriate therapeutic option to the individual patient, considering also potential side effects, quality of life, pregnancy planning and patients' preferences...
May 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28438054/evaluation-of-active-hexose-correlated-compound-ahcc-in-combination-with-anticancer-hormones-in-orthotopic-breast-cancer-models
#20
Lata Mathew, Anjali Gaikwad, Anneliese Gonzalez, Elizabeth K Nugent, Judith A Smith
OBJECTIVE: To determine the impact on antitumor activity when active hexose correlated compound (AHCC) in combination with anticancer hormonal agents in orthotopic mouse models of human estrogen receptor positive breast cancer and evaluate impact of AHCC on aromatase activity. METHODS: The study consisted of 7 treatment arms (n=10) conducted in 2 breast cancer mouse models: MCF-7 and ZR-75. Treatment groups included untreated, vehicle, AHCC 50 mg/kg, AHCC 50 mg/kg + tamoxifen 10 mg/kg, tamoxifen 10 mg/kg, AHCC 50 mg/kg + letrozole 10 µg/mouse, or letrozole 10 µg/mouse...
April 1, 2017: Integrative Cancer Therapies
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