Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, oestrogen receptor-positive breast cancer patients. Very late results of the ‘gruppo di ricerca per la chemio-ormonoterapia adiuvante (GROCTA)’ 01-Trial in early breast cancer

Boccardo, Francesco; Guglielmini, Pamela; Parodi, A. Ferretto; Rubagotti, Alessandra

doi:10.1007/s10549-011-1405-6

Cited by 7 publications

(2 citation statements)

References 23 publications

(22 reference statements)

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“…The most commonly used endocrine therapeutic agents that target ERα-positive breast cancers include ER modulators (e.g., tamoxifen, which selectively antagonizes ERα function), ER downregulators (e.g., fulvestrant, also known as ICI 182,780 and faslodex, which selectively downregulates ERα), and aromatase inhibitors (e.g., letrozole and anastrozole, which repress estrogen production by attenuating aromatase activity) 3 , 5 . A large body of evidence from both basic and clinical studies has now demonstrated the efficacy of tamoxifen and fulvestrant in patients with breast cancer 6 – 9 . Furthermore, comparison with 5-year exposure has confirmed that continuing tamoxifen treatment for 10 years further reduced the risk of disease recurrence and mortality in a randomized trial of patients with ER-positive breast cancer 10 .…”

Section: Introductionmentioning

confidence: 99%

A dual role of miR-22 modulated by RelA/p65 in resensitizing fulvestrant-resistant breast cancer cells to fulvestrant by targeting FOXP1 and HDAC4 and constitutive acetylation of p53 at Lys382

Wang

Filkowski

et al. 2018

Oncogenesis

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Antiestrogen resistance is a major challenge encountered during the treatment of estrogen receptor alpha positive (ERα+) breast cancer. A better understanding of signaling pathways and downstream transcription factors and their targets may identify key molecules that can overcome antiestrogen resistance in breast cancer. An aberrant expression of miR-22 has been demonstrated in breast cancer; however, its contribution to breast cancer resistance to fulvestrant, an antiestrogen drug, remains unknown. In this study, we demonstrated a moderate elevation in miR-22 expression in the 182R-6 fulvestrant-resistant breast cancer line we used as a model system, and this elevation was positively correlated with the expression of the miRNA biogenesis enzymes AGO2 and Dicer. The level of phosphorylated HER2/neu at Tyr877 was also upregulated in these cells, whereas the level of RelA/p65 phosphorylated at Ser536 (p-p65) was downregulated. Knockdown of HER2/neu led to an induction of p-p65 and a reduction in miR-22 levels. Luciferase assays identified two NF-κB binding motifs in the miR-22 promoter that contributed to transcriptional repression of miR-22. Activation of RelA/p65, triggered by LPS, attenuated miR-22 expression, but this expression was restored by sc-514, a selective IKKβ inhibitor. Inhibition of miR-22 suppressed cell proliferation, induced apoptosis and caused cell cycle S-phase arrest, whereas enhancing expression of p21Cip1/Waf1 and p27Kip1. Surprisingly, ectopic expression of miR-22 also suppressed cell proliferation, induced apoptosis, caused S-phase arrest, and promoted the expression of p21Cip1/Waf1 and p27Kip1. Ectopic overexpression of miR-22 repressed the expression of FOXP1 and HDAC4, leading to a marked induction of acetylation of HDAC4 target histones. Conversely, inhibition of miR-22 promoted the expression of both FOXP1 and HDAC4, without the expected attenuation of histone acetylation. Instead, p53 acetylation at lysine 382 was unexpectedly upregulated. Taken together, our findings demonstrated, for the first time, that HER2 activation dephosphorylates RelA/p65 at Ser536. This dephosphoryalted p65 may be pivotal in transactivation of miR-22. Both increased and decreased miR-22 expression cause resensitization of fulvestrant-resistant breast cancer cells to fulvestrant. HER2/NF-κB (p65)/miR-22/HDAC4/p21 and HER2/NF-κB (p65)/miR-22/Ac-p53/p21 signaling circuits may therefore confer this dual role on miR-22 through constitutive transactivation of p21.

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Section: Introductionmentioning

confidence: 99%

A dual role of miR-22 modulated by RelA/p65 in resensitizing fulvestrant-resistant breast cancer cells to fulvestrant by targeting FOXP1 and HDAC4 and constitutive acetylation of p53 at Lys382

Wang

Filkowski

et al. 2018

Oncogenesis

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“…that reducing functional androgen signalling levels further than standard castrate (50 ng/ml) may alter the efficacy of chemotherapy? This strategy certainly has not been beneficial in breast cancer [39,40], but there is the theoretical potential that exposure to a highly androgen-deficient state, either prior to or simultaneous with chemotherapy, may reduce the efficacy of subsequent taxane-based chemotherapy as taxanes may exert part if not all of their effect [41] by blocking AR nuclear translocation, an effect that may be lost [42] with alternative AR growth pathways activated. To date, this concept has been most closely modelled in the neoadjuvant studies of androgen withdrawal and docetaxel which to date indicate that clinically relevant disease remains despite combination therapies [43,44], and to date, the histological outcomes are no different from neoadjuvant hormonal therapy alone.…”

Section: How Long Should Abiraterone Acetate Be Continued After Progrmentioning

confidence: 99%

Beyond Castration—Defining Future Directions in the Hormonal Treatment of Prostate Cancer

Niraula¹,

N.²,

Joshua³

2011

HORM CANC

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It is now almost 70 years since Charles Huggins described the relationship between testosterone and the prostate gland. Arguably defining one of the first targeted therapies, the reduction of testosterone to castrate levels remains unaltered as the standard of care for men with metastatic prostate cancer. The failure of castration to permanently control the growth of prostate cancer leads to a state called castration-resistant prostate cancer (CRPC).

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Stratified treatment recommendation or one-size-fits-all? A health economic insight based on graphical exploration

et al. 2018

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Objectives We sought to explore to what extent the use of Subpopulation Treatment Effect Pattern Plot (STEPP) may help to identify efficient treatment allocation strategy. Methods The analysis was based on data from the COACH study, in which 1023 patients with heart failure were randomly assigned to three treatments: care-as-usual, basic support, and intensive support. First, using predicted 18-month mortality risk as the stratification basis, a suitable strategy for assigning different treatments to different risk groups of patients was developed. To that end, a graphical exploration of the difference in net monetary benefit (NMB) across treatment regimens and baseline risk was used. Next, the efficiency gains resulting from this proposed subgroup strategy were quantified by computing the difference in NMB between our stratified approach and the best performing population-wide strategy. Results The analysis using STEPPs suggested that a differentiated approach, based on offering intensive support to low-risk patients (18-month mortality risk ≤ 0.16) and basic support to intermediate- to high-risk patients (18-month mortality risk > 0.16) would be an economically efficient treatment allocation strategy. This was confirmed in the subsequent cost-effectiveness analysis, where the average gain in NMB resulting from the proposed stratified approach compared to basic support for all was found to be €1312 (95% CI €390–€2346) per patient. Conclusions STEPP provides a systematic approach to assess the interaction between baseline risk and the difference in NMB between competing interventions and to identify cutoffs to stratify patients in a health economically optimal manner.

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Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, oestrogen receptor-positive breast cancer patients. Very late results of the ‘gruppo di ricerca per la chemio-ormonoterapia adiuvante (GROCTA)’ 01-Trial in early breast cancer

Abstract: 2 ABSTRACT Background and study purposes: firstly, to evaluate whether the benefits of combined chemotherapy (CT) and

Cited by 7 publications

References 23 publications

A dual role of miR-22 modulated by RelA/p65 in resensitizing fulvestrant-resistant breast cancer cells to fulvestrant by targeting FOXP1 and HDAC4 and constitutive acetylation of p53 at Lys382

A dual role of miR-22 modulated by RelA/p65 in resensitizing fulvestrant-resistant breast cancer cells to fulvestrant by targeting FOXP1 and HDAC4 and constitutive acetylation of p53 at Lys382

Beyond Castration—Defining Future Directions in the Hormonal Treatment of Prostate Cancer

Stratified treatment recommendation or one-size-fits-all? A health economic insight based on graphical exploration

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