scholarly journals Fenretinide (4-HPR): A Preventive Chance for Women at Genetic and Familial Risk?

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Massimiliano Cazzaniga ◽  
Clara Varricchio ◽  
Chiara Montefrancesco ◽  
Irene Feroce ◽  
Aliana Guerrieri-Gonzaga
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Protective Action ◽  
Familial Risk ◽  
Premenopausal Women ◽  
Cancer Chemoprevention ◽  
Favorable Effect ◽  
Chemopreventive Agents ◽  
Incidence And Mortality ◽  
Breast Cancer Chemoprevention

The incidence and mortality of breast cancer have been recently influenced by several new therapeutic strategies. In particular our knowledge on cancer precursors, risk biomarkers, and genetics has considerably increased, and prevention strategies are being successfully explored. Since their discovery, retinoids, the natural and synthetic derivatives of vitamin A, have been known to play a crucial role in cell and tissue differentiation and their ability to inhibit carcinogenesis has made them the ideal chemopreventive agents studied in several preclinical and clinical trials. Fenretinide (4-HPR) is the most studied retinoid in breast cancer chemoprevention clinical trials due to its selective accumulation in breast tissue and its favorable toxicological profile. This agent showed a significative reduction of the incidence of second breast tumors in premenopausal women confirmed after 15-year followups. Considering Fenretinide protective action, a similar trend on ovarian cancer, this drug warrants reevaluations as a preventive agent for high-risk young women, such as BRCA-1 and 2 mutation carriers or with a high familial risk. This favorable effect therefore provides a strong rationale for a primary prevention trial in these unaffected cohort of women.

scholarly journals Clinical trials with retinoids for breast cancer chemoprevention

2006 ◽  
Vol 13 (1) ◽  
pp. 51-68 ◽  
Author(s):  
S Zanardi ◽  
D Serrano ◽  
A Argusti ◽  
M Barile ◽  
M Puntoni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Premenopausal Women ◽  
Cancer Chemoprevention ◽  
Phase Iii ◽  
Breast Cancer Chemoprevention ◽  
Second Breast Cancer ◽  
Igfbp 3

Retinoids have been studied as chemopreventive agents in clinical trials due to their established role in regulating cell growth, differentiation and apoptosis in preclinical models. Experimental evidence suggests that retinoids affect gene expression both directly, by activating and/or repressing specific genes, and indirectly, by interfering with different signal transduction pathways. Induction of apoptosis is a unique feature of fenretinide, the most widely studied retinoid in clinical trials on breast cancer chemoprevention due to its selective accumulation in breast tissue and to its favourable toxicological profile. In a phase III breast cancer prevention trial, fenretinide showed a durable trend to a reduction of second breast malignancies in premenopausal women. This pattern was associated with a favourable modulation of circulating IGF-I and its main binding protein (IGF-binding protein-3, IGFBP-3), which have been associated with breast cancer risk in premenopausal women in different prospective studies. In a subsequent biomarker study on premenopausal women who had participated in the phase III trial, high IGF-I and low IGFBP-3 baseline levels were found to predict second breast cancer risk, although the magnitude of their changes during treatment did not fulfil the requirements for suitable surrogate end-point biomarkers. In postmenopausal women, fenretinide did not reduce second breast cancer incidence, nor did it induce significant modulation of the IGF system. Similarly, fenretinide was not found to affect risk biomarkers significantly in early postmenopausal women on hormone replacement therapy, who are at increased risk of developing breast cancer. Biomarker studies of fenretinide alone or in combination with different nuclear receptor ligands are being conducted. In particular, clinical trials of fenretinide and tamoxifen have proved to be feasible, and this combination appears to be safe and well tolerated in high-risk women, especially when low-dose tamoxifen is employed. Novel retinoid X receptor-selective retinoids, or rexinoids, have been shown to suppress the development of breast cancer in several animal models with minimal toxicity, and are being intensively studied either alone or in combination with selective oestrogen receptor modulators, both in vitro and in vivo. The rexinoid, bexarotene, has recently been approved for the treatment of patients with cutaneous T-cell lymphoma, and a biomarker trial with bexarotene in women with high breast cancer risk is currently underway.

Breast Cancer Chemoprevention: Clinical Trials and Research

Oncology ◽  
1996 ◽  
Vol 53 (3) ◽  
pp. 175-181 ◽  
Author(s):  
Masakuni Noguchi ◽  
David P. Rose ◽  
Itsuo Miyazaki
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Cancer Chemoprevention ◽  
Breast Cancer Chemoprevention

Progress in breast cancer chemoprevention.

2002 ◽  
pp. 15-32 ◽  
Author(s):  
B Arun ◽  
G N Hortobagyi
Keyword(s):  
Breast Cancer ◽  
New Technologies ◽  
Cancer Chemoprevention ◽  
Chemopreventive Agents ◽  
The Past ◽  
Breast Cancer Chemoprevention ◽  
Clinical Breast ◽  
Prevention Trials ◽  
First Time ◽  
Made In

Over the past years there have been significant advances in breast cancer treatment and early detection. For the first time, a decrease in cancer mortality has been observed. Recently, much progress has been made in the understanding of carcinogenesis partly due to available new technologies to detect early molecular changes in the tissue. The knowledge of breast cancer carcinogenesis has provided possible opportunities to prevent breast cancer. Currently, several clinical breast cancer prevention trials are ongoing. This paper reviews issues related to breast cancer chemoprevention including identification of high risk cohorts, endpoint biomarkers, current and new chemopreventive agents as well as models to evaluate these agents.

scholarly journals Bioactive Compounds and Metabolites from Grapes and Red Wine in Breast Cancer Chemoprevention and Therapy

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3531 ◽  
Author(s):  
Danielly C. Ferraz da Costa ◽  
Luciana Pereira Rangel ◽  
Julia Quarti ◽  
Ronimara A. Santos ◽  
Jerson L. Silva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Bioactive Compounds ◽  
Molecular Mechanisms ◽  
Red Wine ◽  
Cancer Chemoprevention ◽  
Breast Cancer Chemoprevention ◽  
Structure And Metabolism

Phytochemicals and their metabolites are not considered essential nutrients in humans, although an increasing number of well-conducted studies are linking their higher intake with a lower incidence of non-communicable diseases, including cancer. This review summarizes the current findings concerning the molecular mechanisms of bioactive compounds from grapes and red wine and their metabolites on breast cancer—the most commonly occurring cancer in women—chemoprevention and treatment. Flavonoid compounds like flavonols, monomeric catechins, proanthocyanidins, anthocyanins, anthocyanidins and non-flavonoid phenolic compounds, such as resveratrol, as well as their metabolites, are discussed with respect to structure and metabolism/bioavailability. In addition, a broad discussion regarding in vitro, in vivo and clinical trials about the chemoprevention and therapy using these molecules is presented.

scholarly journals Methylseleninic acid is a novel suppressor of aromatase expression

2011 ◽  
Vol 212 (2) ◽  
pp. 199-205 ◽  
Author(s):  
Ruijuan Gao ◽  
Lijuan Zhao ◽  
Xichun Liu ◽  
Brian G Rowan ◽  
Martin Wabitsch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Aromatase Inhibitors ◽  
Low Cost ◽  
Cancer Chemoprevention ◽  
Chemopreventive Agents ◽  
First Line Therapy ◽  
Methylseleninic Acid ◽  
Estrogen Receptor Positive ◽  
Breast Cancer Chemoprevention

Elevated circulating estrogen levels, as a result of increased peripheral aromatization of androgens by aromatase, have been indicated to underlie the association between obesity and a higher risk of breast cancer in postmenopausal women. Although aromatase inhibitors have been used as a first-line therapy for estrogen receptor-positive breast cancer in postmenopausal women, their potential as breast cancer chemopreventive agents has been limited due to toxicities and high costs. It is therefore imperative to develop new aromatase-inhibiting/suppressing agents with lower toxicities and lower costs for breast cancer chemoprevention, especially in obese postmenopausal women. The expression of the aromatase gene,CYP19, is controlled in a tissue-specific manner by the alternate use of different promoters. In obese postmenopausal women, increased peripheral aromatase is primarily attributed to the activity of the glucocorticoid-stimulated promoter, PI.4, and the cAMP-stimulated promoter, PII. In the present study, we show that methylseleninic acid (MSA), a second-generation selenium compound, can effectively suppress aromatase activation by dexamethasone, a synthetic glucocorticoid, and forskolin, a specific activator of adenylate cyclase. Unlike the action of aromatase inhibitors, MSA suppression of aromatase activation is not mediatedviadirect inhibition of aromatase enzymatic activity. Rather, it is attributable to a marked downregulation of promoters PI.4- and PII-specific aromatase mRNA expression, and thereby a reduction of aromatase protein. Considering the low-cost and low-toxicity nature of MSA, our findings provide a strong rationale for the further development of MSA as a breast cancer chemopreventive agent for obese postmenopausal women.

scholarly journals Evaluation of CYP2D6 and Efficacy of Tamoxifen and Raloxifene in Women Treated for Breast Cancer Chemoprevention: Results from the NSABP P1 and P2 Clinical Trials

2011 ◽  
Vol 17 (21) ◽  
pp. 6944-6951 ◽  
Author(s):  
Matthew P. Goetz ◽  
Daniel J. Schaid ◽  
D. Lawrence Wickerham ◽  
Stephanie Safgren ◽  
Taisei Mushiroda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Cancer Chemoprevention ◽  
Breast Cancer Chemoprevention
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