Tamoxifen Action in ER-Negative Breast Cancer

Liao

Geriatrics Gerontology Int

et al. 2018

Aim This study aimed to evaluate the association between tamoxifen use and hip fractures in older women with breast cancer in Taiwan. Methods We carried out a retrospective nationwide case–control study using the database of the Taiwan National Health Insurance Program. A total of 762 female patients with breast cancer aged ≥65 years newly diagnosed with hip fractures from 2000 to 2011 were identified for inclusion in the study. Additionally, 7620 female patients with breast cancer aged ≥65 years without hip fractures were randomly selected as controls. Patients were defined as having used tamoxifen if they had an existing prescription for tamoxifen before the index date. Patients were defined as having never used tamoxifen if they had never been given a prescription for tamoxifen before the index date. We used an unconditional logistic regression model to calculate the odds ratio and 95% confidence interval for the association between tamoxifen use and risk of hip fractures. Results After adjustment for confounding variables, compared with patients who did not use tamoxifen, the adjusted odds ratio of hip fracture was 2.29 for those who had used tamoxifen (95% confidence interval 1.92, 2.72). Furthermore, adjusted odds ratios were 2.74 (95% confidence interval 2.19, 3.42) among patients with a cumulative duration of tamoxifen use of >3 years. Conclusion Tamoxifen use is associated with increased risk of hip fractures among older women with breast cancer in Taiwan. Geriatr Gerontol Int 2019; 19: 56–60.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tamoxifen use correlates with increased risk of hip fractures in older women with breast cancer: A case–control study in Taiwan

Liao

Geriatrics Gerontology Int

et al. 2018

“…Interestingly, downregulation of AKT through expression of the TGFB growth factor was described as an off-target effect of tamoxifen. 49,51 Of importance, Liu et al 44 showed an induced sensitivity to tamoxifen in the triple-negative breast cancer cell line HCC-1937, when re-activating PP2A using forskolin. This suggests the potential for use of combinatory therapy for BCER+ with membranous CIP2A staining.…”

Section: Discussionmentioning

confidence: 99%

“…46 Transforming growth factor beta (TGFB) has also been known to interact with PP2A, which might contribute to the contradictory regulation of p-AKT and MYC. [47][48][49] In metastatic breast cancer (MDA-MB-231), the transition of tumour-suppressive role to tumour-promoting role of TGFB has been attributed to the nuclear factor of activated T-cells (NFAT), which is shown to drive epithelial-to-mesenchymal transition (EMT) and c-MYC expression. 50 Here, we suggest another potential mechanism for this transition.…”

Section: Discussionmentioning

confidence: 99%

CIP2A expression predicts recurrences of tamoxifen-treated breast cancer

et al. 2017

CIP2A is emerging as an oncoprotein overexpressed commonly across many tumours and generally correlated with higher tumour grade and therapeutic resistance. CIP2A drives an oncogenic potential through inhibiting protein phosphatase 2A, stabilizing MYC, and promoting epithelial-to-mesenchymal transition, although further biological mechanisms for CIP2A are yet to be defined. CIP2A protein expression was studied by immunohistochemistry in oestrogen receptor-positive primary breast cancers (n = 250) obtained from the Leeds Tissue Bank. In total, 51 cases presented with a relapse or metastasis during adjuvant treatment with tamoxifen and were regarded as tamoxifen resistant. CIP2A expression was scored separately for cytoplasmic, nuclear, or membranous staining, and scores were tested for statistically significant relationships with clinicopathological features. Membranous CIP2A was preferentially expressed in cases who experienced a recurrence during tamoxifen treatment thus predicting a worse overall survival (log rank = 8.357, p = 0.004) and disease-free survival (log rank = 21.766, p < 0.001). Cox multivariate analysis indicates that it is an independent prognostic indicator for overall survival (hazard ratio = 4.310, p = 0.013) and disease-free survival (hazard ratio = 5.449, p = 0.002). In this study, we propose the assessment of membranous CIP2A expression as a potential novel prognostic and predictive indicator for tamoxifen resistance and recurrence within oestrogen receptor-positive breast cancer.

“…Therefore, many chemotherapeutic drugs such as tamoxifen, which are used to treat certain types of breast cancer, are not effective against triple negative cells. This is because tamoxifen selectively binds to estrogen receptors, which in turn prevents estrogen from attaching to its receptor (Manna and Holz, 2016). Estrogen is required for some breast cancer cells to grow; hence, blocking the hormone will prevent the tumor *Corresponding author.…”

Section: Introductionmentioning

confidence: 99%

A novel anti-triple negative breast cancer compound isolated from medicinal herb Myrothamnus flabellifolius

Brar¹,

Fultang²,

Askey³

et al. 2018

J. Med. Plants Res.

Triple negative breast cancer (TNBC) is a disease that impacts millions of people around the world.There is an urgent need to find new therapies, specific to triple negative cancer cells with minimal effect on normal cells. This study explores the use of Myrothamnus flabellifolius as an anti-TNBC. Using High Performance Liquid Chromatography, the extract was fractionated and each fraction was tested against TNBC cells BT-549 and MDA-MB-231, and a non-malignant breast cell line MCF-10A. The results showed that fraction 7 inhibited the growth of TNBC cells starting at a dry weight concentration of 31.125 μg/mL while there was no significant cell death of the MCF-10A cell line. Using analytical techniques such as Mass Spectrometry (MS-MS) and Nuclear Magnetic Resonance (NMR), the major compound in fraction 7 was determined to be a derivative of galloyl glucose hexahydroxydiphenic acid. The results suggest that this novel compound is the primary anti-TNBC compound in M. flabellifolius and might be a potential candidate for targeted TNBC therapy.