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.

scholarly journals Addressing Barriers to Uptake of Breast Cancer Chemoprevention for Patients and Providers

2015 ◽  
pp. e50-e58 ◽  
Author(s):  
Katherine D. Crew
Keyword(s):  
Breast Cancer ◽  
Primary Prevention ◽  
High Risk ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Chemoprevention ◽  
The United States ◽  
Cancer Risk Assessment ◽  
Breast Cancer Risk Assessment ◽  
Breast Cancer Chemoprevention

Breast cancer is the most common malignancy among women in the United States, and the primary prevention of this disease is a major public health issue. Because there are relatively few modifiable breast cancer risk factors, pharmacologic interventions with antiestrogens have the potential to significantly affect the primary prevention setting. Breast cancer chemoprevention with selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene, and with aromatase inhibitors (AIs) exemestane and anastrozole, is underutilized despite several randomized controlled trials demonstrating up to a 50% to 65% relative risk reduction in breast cancer incidence among women at high risk. An estimated 10 million women in the United States meet high-risk criteria for breast cancer and are potentially eligible for chemoprevention, but less than 5% of women at high risk who are offered antiestrogens for primary prevention agree to take it. Reasons for low chemoprevention uptake include lack of routine breast cancer risk assessment in primary care, inadequate time for counseling, insufficient knowledge about antiestrogens among patients and providers, and concerns about side effects. Interventions designed to increase chemoprevention uptake, such as decision aids and incorporating breast cancer risk assessment into clinical practice, have met with limited success. Clinicians can help women make informed decisions about chemoprevention by effectively communicating breast cancer risk and enhancing knowledge about the risks and benefits of antiestrogens. Widespread adoption of chemoprevention will require a major paradigm shift in clinical practice for primary care providers (PCPs). However, enhancing uptake and adherence to breast cancer chemoprevention holds promise for reducing the public health burden of this disease.

scholarly journals Insulin-like growth factor-I, its binding proteins (IGFBP-1 and IGFBP-3), and growth hormone and breast cancer risk in The Nurses Health Study II

2006 ◽  
Vol 13 (2) ◽  
pp. 583-592 ◽  
Author(s):  
Eva S Schernhammer ◽  
Jeff M Holly ◽  
David J Hunter ◽  
Michael N Pollak ◽  
Susan E Hankinson
Keyword(s):  
Breast Cancer ◽  
Growth Hormone ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Premenopausal Women ◽  
Health Study ◽  
Blood Collection ◽  
Factor I ◽  
Igf I ◽  
Igfbp 3

Earlier data suggest that the relationship between circulating insulin-like growth factor I (IGF-I) levels and breast cancer risk differs according to menopausal status. We evaluated the association between IGF levels as well as the primary regulator of IGF-I production, growth hormone (GH), and breast cancer risk in the Nurses’ Health Study II (NHS II) cohort, a large cohort of primarily premenopausal women. We conducted a case-control study nested within the prospective NHS II cohort. Plasma concentrations of IGF-I, IGF binding protein (IGFBP)-3, IGFBP-1, and GH were measured in blood samples collected between 1996 and 1999. Totally 317 women were identified who had a diagnosis of invasive or in situ breast cancer between the date of blood collection and June 1 2003; 75% of these women were premenopausal at blood collection. To each of the 317 women, two controls were age-matched for a total of 634 controls. We used conditional logistic regression models to estimate the relative risk of breast cancer. Overall, plasma IGF-I, IGFBP-1, IGFBP-3, and GH levels were not associated with breast cancer risk (relative risks, top vs bottom quartile; IGF-I, 0.98, 95% confidence interval (CI), 0.69–1.39; IGFBP-1, 0.95, 95% CI, 0.63–1.41; IGFBP-3, 1.10, 95% CI, 0.78–1.54; GH, 1.09, 95% CI, 0.82–1.46). These risks were similar for premenopausal women of age 45 years or less. Further adjustment for additional breast cancer risk factors did not change these estimates. In conclusion, circulating IGF-I, IGFBP-1, IGFBP-3, and GH levels appear to have no important association with breast cancer risk in a large cohort of premenopausal women.

scholarly journals Using Breast Cancer Risk Associated Polymorphisms to Identify Women for Breast Cancer Chemoprevention

PLoS ONE ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. e0168601 ◽  
Author(s):  
Elad Ziv ◽  
Jeffrey A. Tice ◽  
Brian Sprague ◽  
Celine M. Vachon ◽  
Steven R. Cummings ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Chemoprevention ◽  
Breast Cancer Chemoprevention

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.

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

scholarly journals Oxidative Stress and Breast Cancer Risk in Premenopausal Women

Epidemiology ◽  
2017 ◽  
Vol 28 (5) ◽  
pp. 667-674 ◽  
Author(s):  
Hazel B. Nichols ◽  
Chelsea Anderson ◽  
Alexandra J. White ◽  
Ginger L. Milne ◽  
Dale P. Sandler
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Premenopausal Women

scholarly journals Circulating growth factor concentrations and breast cancer risk: a nested case-control study of IGF-1, IGFBP-3, and breast cancer in a family-based cohort

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Kelsey R. Monson ◽  
Mandy Goldberg ◽  
Hui-Chen Wu ◽  
Regina M. Santella ◽  
Wendy K. Chung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Average Risk ◽  
Breast Cancer Family ◽  
Cancer Family ◽  
Cancer Family History ◽  
Breast Cancer Family History ◽  
Igfbp 3

Abstract Background Insulin-like growth factor 1 (IGF-1) and binding protein 3 (IGFBP-3) are associated with breast cancer in women at average risk of cancer. Less is known whether these biomarkers also predict risk in women with breast cancer family history. Methods We conducted a nested case-control study within the New York site of the Breast Cancer Family Registry (BCFR, n = 80 cases, 156 controls), a cohort enriched for breast cancer family history. Using conditional logistic regression, we estimated the association between IGF-1 and IGFBP-3 levels and breast cancer risk and examined whether this risk differed by predicted absolute breast cancer risk based on pedigree models. Results The overall association between IGF-1 or IGFBP-3 elevation (≥ median in controls) and breast cancer risk was elevated, but not statistically significant (IGF-1 OR = 1.37, 95% CI = 0.66–2.85; IGFBP-3 OR = 1.62, 95% CI = 0.81–3.24). Women with elevated predicted absolute 10-year risk ≥ 3.4% and elevated IGFBP-3 (≥ median) had more than a 3-fold increased risk compared to women with lower predicted absolute 10-year risk (< 3.4%) and low IGFBP-3 (OR = 3.47 95% CI = 1.04–11.6). Conclusions These data offer some support that the overall magnitude of the associations between IGF-1 and IGFBP3 seen in average risk cohorts may be similar in women enriched with a strong breast cancer family history.

scholarly journals Assessment of Breast Cancer Risk Based on Mammary Gland Volume Measured with CT

2010 ◽  
Vol 4 ◽  
pp. BCBCR.S5248 ◽  
Author(s):  
Megumi Kuchiki ◽  
Takaaki Hosoya ◽  
Akira Fukao
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Patients ◽  
Odds Ratio ◽  
Premenopausal Women ◽  
Breast Cancer Patients ◽  
History Of ◽  
The Relationship

We investigated the relationship between mammary gland volume (MGV) of the breast as measured with three-dimensional chest computed tomography (CT) and breast cancer risk. Univariate analysis was used to assess the relationship between MGV and known risk factors in 427 healthy women. A case control study (97 cases and 194 controls) was conducted to assess breast cancer risk. MGV was significantly smaller for postmenopausal women than for premenopausal women, and was significantly larger for women with a family history of breast cancer than for women without. MGV, body mass index (BMI), and rate of family history of breast cancer were significantly higher among breast cancer patients than among healthy women, and number of deliveries was significantly lower among breast cancer patients. In postmenopausal women, age at menarche was significantly younger for breast cancer patients. MGV correlated well with breast cancer risk factors. The highest odds ratio was 4.9 for premenopausal women with the largest MGV. Regardless of menopausal status, the greater the MGV, the higher the odds ratio. Our results constitute the first reliable data on the relationship between MGV and breast cancer obtained through exact volume analysis.

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