Effects of low dose tamoxifen on normal breast tissue from premenopausal women

Lima, Geraldo Rodrigues de; Facina, Gil; Shida, Jorge Yoshinori; Chein, M.B.C.; Tanaka, P.; Dardes, Rita C.; Jordan, V. Craig; Gebrim, Luíz Henrique

doi:10.1016/s0959-8049(02)00530-0

Cited by 74 publications

(60 citation statements)

References 32 publications

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“…Our findings are in agreement with those of de Lima et al (55) who studied the effects of low doses (5 or 10 mg daily) of tamoxifen for 50 days in women with nonmalignant breast disorders and demonstrated comparable antiproliferative activity between conventional and low doses of tamoxifen in normal epithelial breast tissue.…”

Section: Discussionsupporting

confidence: 93%

Tamoxifen and Metabolite Concentrations in Serum and Breast Cancer Tissue during Three Dose Regimens in a Randomized Preoperative Trial

Kisanga

Gjerde

Guerrieri-Gonzaga

et al. 2004

Clinical Cancer Research

182

124

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Purpose: Both therapeutic and adverse effects of tamoxifen may be related to its tissue concentrations. We investigated concentrations of tamoxifen, 4-hydroxytamoxifen, Ndesmethyltamoxifen, and N-didesmethyltamoxifen in serum, normal breast, and breast cancer tissues during conventional dosage and two low-dose regimens. Furthermore we studied tamoxifen effects on the cancer proliferation marker Ki-67, and on sex hormone-binding globulin (SHBG).Experimental Design: From September 1999 to August 2001, 120 breast cancer patients were randomized to 20-, 5-, or 1-mg tamoxifen daily. We measured serum and tissue concentrations of tamoxifen and three metabolites after 28 days of treatment, and the changes between baseline and post-treatment levels of SHBG and Ki-67.Results: The median (range) tamoxifen concentrations (ng/ml) at doses of 1, 5, and 20 mg daily (n ‫؍‬ 38, 37, and 36) were 7.5 (2.9 -120.9), 25.2 (1.9 -180.9), and 83.6 (8.7-134.4) in serum, and 78.2 (35.9 -184), 272.3 (122-641), and 744.4 (208.6 -2556) in breast cancer tissue, respectively. Tamoxifen levels followed a dose-concentration relationship. The concentrations of tamoxifen and metabolites were related to each other. Serum and tissue concentrations of tamoxifen were associated with corresponding changes of SHBG levels, whereas changes of Ki-67 levels were not related. Conclusions:Estrogen agonistic effects of tamoxifen on SHBG decreased with lower dosage, whereas tamoxifen effects on Ki-67 expression did not change. This together with a >10-fold variation in serum tamoxifen concentrations and a serum to tissue concentration relationship suggest that tamoxifen treatment may be improved by administration of lower doses and therapeutic drug monitoring.

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Section: Discussionsupporting

confidence: 93%

Tamoxifen and Metabolite Concentrations in Serum and Breast Cancer Tissue during Three Dose Regimens in a Randomized Preoperative Trial

Kisanga

Gjerde

Guerrieri-Gonzaga

et al. 2004

Clinical Cancer Research

182

124

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“…The same results have also been reported for the normal epithelium which is adjacent to fibroadenomas [21]. It is really characteristic that Ki67 is expressed exclusively in estrogen receptor (ER)-negative cells, which means that ER-positive cells do not proliferate under normal circumstances.…”

Section: Ki67 and Breast Tissuesupporting

confidence: 77%

Correlation between Ki67 and Breast Cancer Prognosis

Kontzoglou¹,

Palla

Karaolanis³

et al. 2013

Oncology

117

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Background: Ki67 is an immunohistochemical proliferation marker in many types of cancer and has been widely studied among breast cancer patients mostly through retrospective studies. Methods: The MEDLINE/PubMed database was searched for publications with the medical subject heading ‘Ki 67’ and the key words ‘breast’, ‘cancer’, and ‘prognosis’. We restricted our search to articles published until 2012. Results: In this review, we included 78 articles and abstracts that were accessible and available in English. An effort to further explain the role of Ki67 in the prognosis of breast cancer has been made. Conclusions: The debate on the prognostic role of Ki67 in breast cancer is still open, although most of the studies have established a relation between Ki67 and overall and disease-free survival. Further research should be made in order to establish Ki67 as a standard prognostic marker in breast cancer.

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“…Other side effects include liver cancer, venous thrombosis, pulmonary emboli, and an ocular effect includes retinopathy and corneal opacities. [11][12][13][14] To overcome such severe side effects, in our research work we have mainly concentrated on the parenteral sustained release delivery of Tamoxifen citrate in nanoparticles so that they can penetrate in the tumor tissue and can be taken up well by endocytosis into the affected cells.…”

Section: Introductionmentioning

confidence: 99%

Preparation and characterization of Tamoxifen citrate loaded nanoparticles for breast cancer therapy

Maji¹,

Dey²,

Satapathy³

et al. 2014

IJN

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Background Four formulations of Tamoxifen citrate loaded polylactide-co-glycolide (PLGA) based nanoparticles (TNPs) were developed and characterized. Their internalization by Michigan Cancer Foundation-7 (MCF-7) breast cancer cells was also investigated. Methods Nanoparticles were prepared by a multiple emulsion solvent evaporation method. Then the following studies were carried out: drug-excipients interaction using Fourier transform infrared spectroscopy (FTIR), surface morphology by field emission scanning electron microscopy (FESEM), zeta potential and size distribution using a Zetasizer Nano ZS90 and particle size analyzer, and in vitro drug release. In vitro cellular uptake of nanoparticles was assessed by confocal microscopy and their cell viability (%) was studied. Results No chemical interaction was observed between the drug and the selected excipients. TNPs had a smooth surface, and a nanosize range (250–380 nm) with a negative surface charge. Drug loadings of the prepared particles were 1.5%±0.02% weight/weight (w/w), 2.68%±0.5% w/w, 4.09%±0.2% w/w, 27.16%±2.08% w/w for NP1–NP4, respectively. A sustained drug release pattern from the nanoparticles was observed for the entire period of study, ie, up to 60 days. Further, nanoparticles were internalized well by the MCF-7 breast cancer cells on a concentration dependent manner and were present in the cytoplasm. The nucleus was free from nanoparticle entry. Drug loaded nanoparticles were found to be more cytotoxic than the free drug. Conclusion TNPs (NP4) showed the highest drug loading, released the drug in a sustained manner for a prolonged period of time and were taken up well by the MCF-7 breast cancer cell line in vitro. Thus the formulation may be suitable for breast cancer treatment due to the good permeation of the formulation into the breast cancer cells.

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Effects of low dose tamoxifen on normal breast tissue from premenopausal women

Cited by 74 publications

References 32 publications

Tamoxifen and Metabolite Concentrations in Serum and Breast Cancer Tissue during Three Dose Regimens in a Randomized Preoperative Trial

Tamoxifen and Metabolite Concentrations in Serum and Breast Cancer Tissue during Three Dose Regimens in a Randomized Preoperative Trial

Correlation between Ki67 and Breast Cancer Prognosis

Preparation and characterization of Tamoxifen citrate loaded nanoparticles for breast cancer therapy

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