scholarly journals Accumulation of p53 is prognostic for aromatase inhibitor resistance in early-stage postmenopausal patients with ER-positive breast cancer

2015 ◽  
pp. 549 ◽  
Author(s):  
Xiao-Qing Jia ◽  
Guangyu Liu ◽  
Qi Hong ◽  
Jingyi Cheng ◽  
Jianwei Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitor ◽  
Early Stage ◽  
Er Positive ◽  
Aromatase Inhibitor Resistance ◽  
Inhibitor Resistance ◽  
Positive Breast Cancer

scholarly journals MIR2052HG regulates ERα levels and aromatase inhibitor resistance through LMTK3 by recruiting EGR1

2019 ◽  
Author(s):  
Junmei Cairns ◽  
James N. Ingle ◽  
Krishna R. Kalari ◽  
Lois E. Shepherd ◽  
Michiaki Kubo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitor ◽  
Direct Role ◽  
Adjuvant Trial ◽  
Aromatase Inhibitor Treatment ◽  
Aromatase Inhibitor Resistance ◽  
Inhibitor Resistance ◽  
Inhibitor Treatment ◽  
Positive Breast Cancer

AbstractOur previous GWAS using the MA.27 aromatase inhibitors (AIs) adjuvant trial identified SNPs in the lncRNA MIR2052HG associated with breast cancer free interval. Here we report that MIR2052HG depletion in breast cancer cells results in a decrease in LMTK3 expression and cell growth. Mechanistically, MIR2052HG interacts with EGR1 and facilitates its recruitment to the LMTK3 promoter. LMTK3 sustains ERα levels by reducing PKC activity, resulting in increased ESR1 transcription mediated through AKT/FOXO3 and reduced ERα degradation mediated by the PKC/MEK/ERK/RSK1 pathway. MIR2052HG regulated LMTK3 in a SNP- and aromatase inhibitor - dependent fashion: the variant SNP increased EGR1 binding to LMTK3 promoter in response to androstenedione, relative to wild-type genotype, a pattern that can be reversed by aromatase inhibitor treatment. Finally, LMTK3 overexpression abolished the effect of MIR2052HG on PKC activity and ERα levels. These results reveal a direct role of MIR2052HG in LMTK3 regulation and raise the possibility of targeting MIR2052HG or LMTK3 in ERα-positive breast cancer.

Controversies in Adjuvant Endocrine Therapy for Breast Cancer

2012 ◽  
pp. 20-26
Author(s):  
Stephen R. Johnston
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Aromatase Inhibitors ◽  
Early Stage ◽  
Premenopausal Women ◽  
Adjuvant Endocrine Therapy ◽  
Risk Of Recurrence ◽  
Er Positive ◽  
Added Benefit ◽  
Positive Breast Cancer

Overview: Adjuvant endocrine therapy for early-stage breast cancer has had the single biggest impact on improving survival from the disease—with tamoxifen alone contributing to saving many thousands of lives. In postmenopausal women, additional progress has been made by the incorporation of aromatase inhibitors into the treatment of early-stage, estrogen receptor (ER)–positive breast cancer, as several large well-conducted trials have established either “up-front” or “switch” strategies that are now widely used. To date, both have been shown to be beneficial when compared with tamoxifen alone, although controversy exists as to which approach is superior. Increasingly, extended adjuvant therapy is being considered, as “longer may be better” for some women who have an ongoing risk of recurrence beyond 5 years. However, controversy remains as to how long adjuvant endocrine therapy should be given for; in clinical practice, clinicians balance the level of risk for individual patients versus any ongoing toxicity concerns. For premenopausal women, with ER-positive breast cancer, tamoxifen remains the gold standard with uncertainty in the added overall benefit of ovarian suppression. Important clinical trials have recently been completed that may help answers this question, including whether complete estrogen deprivation using a luteinizing hormone releasing hormone (LHRH) agonist plus aromatase inhibitors (AIs) is of added benefit. In recent years, molecular profiling of ER-positive breast cancer has started to distinguish those women with a low risk of recurrence on endocrine therapy who may not need chemotherapy. Thus, with more therapy options and greater tumour stratification, modern, adjuvant endocrine therapy is becoming increasingly personalised to suit each individual patient's risk.

Aromatase inhibitor-induced joint symptom in patients with breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11070-11070 ◽  
Author(s):  
Y. Yamamoto ◽  
T. Kawasoe ◽  
M. Ibusuki ◽  
K. Kai ◽  
S. Tomita ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitor ◽  
Postmenopausal Women ◽  
Joint Stiffness ◽  
Onset Time ◽  
Initial Symptom ◽  
Joint Symptom ◽  
Joint Symptoms ◽  
Er Positive ◽  
Positive Breast Cancer

11070 Background: Aromatase inhibitor (AI) are superior to tamoxifen (TAM) for postmenopausal women with estrogen receptor (ER)-positive breast cancer. Toxic profiles are different between AI and TAM. The frequency of bone fracture and joint symptom are high in AI compared with TAM. However, there is little report concerning a detailed joint symptom. Methods: From January 2002 to March 2006, 120 postmenopausal women with ER-positive breast cancer were treated with anastrozole 1mg or exemestane 25mg daily at our hospital. We studied retrospectively the incidence, onset, type, sites, grade, and change of joint symptom. We also investigated the incidence of discontinuation due to joint symptoms and correlation between patient’s characteristics and joint symptoms. Results: Median follow-up time is 590 days and median age is 63 years old. Forty-seven (39.1%) of 120 patients complained of joint symptom. Median onset time of the symptom was 90 days of starting AI. All cases with the symptom complained of joint stiffness and 33 (70.2%) of 47 patients with the symptom have joint pain. In decreasing order, the most commonly affected sites were hand, knee, wrist, ankle, shoulder and elbow. The joint symptom was mostly grade 1/2, and most symptom ware resolved with exercise. Most common feature is morning digital stiffness like initial symptom of rheumatoid arthritis. Some patients experienced severe joint symptom. Subsequently, 15 (12.5%) patients had to discontinue AI because of the severe symptom. Discontinuation of AI led to improvement of symptoms, and patients received TAM in stead of AI also led to resolution of symptoms. AI-induced joint symptom was significantly correlated with young age, prior chemotherapy and switching from TAM to AI. Conclusions: Most AI-induced joint symptom is modest, and this symptom can lead to resolution with exercise. However, some patients lead to discontinue AI because of AI-induced severe joint symptom. We should inform patients treated with AI about AI- induced joint symptom and observe patient’s symptom in detail because severe joint symptom can prevent maintenance of quality of life and compliance. No significant financial relationships to disclose.

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