Primary chemoprevention of breast cancer: Are the adverse effects too burdensome?

Prasad, Vinay; Diener‐West, Marie

doi:10.1503/cmaj.141627

Cited by 10 publications

(8 citation statements)

References 19 publications

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“…Tamoxifen has been shown to increase risk for cardiovascular events, including venous thrombosis, pulmonary embolism, and stroke, and increases risk for endometrial cancer (12)(13)(14). Other side effects of tamoxifen include hot flashes, dyspareunia, depression, cataracts, weight gain, and bone loss in premenopausal women (12)(13)(14)(15). Consistent with the increased risk of endometrial cancer in humans, a 2013 study in rats showed that 13-week tamoxifen treatment increased DNA point mutations in the liver (16).…”

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confidence: 95%

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Metformin and Chemoprevention: Potential for Heart-Healthy Targeting of Biologically Aggressive Breast Cancer

Jones

Dietze

Jovanović-Talisman

et al. 2020

Front. Public Health

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Currently, tamoxifen is the only drug approved for reduction of breast cancer risk in premenopausal women. The significant cardiovascular side effects of tamoxifen, coupled with lack of a survival benefit, potential for genotoxicity, and failure to provide a significant risk-reduction for estrogen receptor-negative breast cancer, all contribute to the low acceptance of tamoxifen chemoprevention in premenopausal women at high-risk for breast cancer. While other prevention options exist for postmenopausal women, there is a search for well-tolerated prevention agents that can simultaneously reduce risk of breast cancers, cardiovascular disease, and type-2 diabetes. Metformin is a well-tolerated oral biguanide hypoglycemic agent that is prescribed worldwide to over 120 million individuals with type-2 diabetes. Metformin is inexpensive, safe during pregnancy, and the combination of metformin, healthy lifestyle, and exercise has been shown to be effective in preventing diabetes. There is a growing awareness that prevention drugs and interventions should make the "whole woman healthy." To this end, current efforts have focused on finding low toxicity alternatives, particularly repurposed drugs for chemoprevention of breast cancer, including metformin. Metformin's mechanisms of actions are complex but clearly involve secondary lowering of circulating insulin. Signaling pathways activated by insulin also drive biologically aggressive breast cancer and predict poor survival in women with breast cancer. The mechanistic rationale for metformin chemoprevention is well-supported by the scientific literature. Metformin is cheap, safe during pregnancy, and has the potential to provide heart-healthy breast cancer prevention. On-going primary and secondary prevention trials will provide evidence whether metformin is effective in preventing breast cancer.

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confidence: 95%

mentioning

confidence: 99%

Metformin and Chemoprevention: Potential for Heart-Healthy Targeting of Biologically Aggressive Breast Cancer

Jones

Dietze

Jovanović-Talisman

et al. 2020

Front. Public Health

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“…[1][2][3][4] Trials often demonstrate improvements in CSM, but not ACM. [5][6][7][8] However, reductions in CSM are often caused by a worsening of OCM, misattribution of death, and/or an increase in the frequency of assigning unknown-cause mortality. It is unclear the frequency of unknown causes of death (COD), and the potential implications of this frequency on study results focused on CSM rather than ACM.…”

mentioning

confidence: 99%

“…Trials often demonstrate improvements in CSM, but not ACM 5–8. However, reductions in CSM are often caused by a worsening of OCM, misattribution of death, and/or an increase in the frequency of assigning unknown-cause mortality.…”

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confidence: 99%

Unknown Causes of Death in Cancer Patients

Chinniah

Chiam

Mani

et al. 2023

American Journal of Clinical Oncology

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Objectives: Deaths from an unknown cause are difficult to adjudicate and oncologic studies of comparative effectiveness often demonstrate inconsistencies in incorporating these deaths and competing events (eg, heart disease and stroke) in their analyses. In this study, we identify cancer patients most at risk for death of an unknown cause. Methods: This retrospective, population-based study used cancer registry data from the Surveillance, Epidemiology, and End Results database (1992-2015). The absolute rate of unknown causes of death (COD) cases stratified by sex, marital status, race, treatment, and cancer site were calculated and a multivariable logistic regression model was applied to obtain adjusted odds ratios with 95% CIs. Results: Out of 7,154,779 cancer patients across 22 cancer subtypes extracted from Surveillance, Epidemiology, and End Results, 3,448,927 died during follow-up and 276,068 (7.4%) of these deaths were from unknown causes. Patients with an unknown COD had a shorter mean survival time compared with patients with known COD (36.3 vs 65.7 mo, P < 0.001). The contribution of unknown COD to total mortality was highest in patients with more indolent cancers (eg, prostate [12.7%], thyroid [12.3%], breast [10.7%]) and longer follow-up (eg, >5 to 10 y). One, 3, and 5-year cancer-specific survival (CSS) calculations including unknown COD were significantly decreased compared with CSS estimates excluding cancer patients with unknown COD. Conclusion: Of the patients, 7.4% died of unknown causes during follow-up and the proportion of death was higher with longer follow-up and among more indolent cancers. The attribution of high percentages of unknown COD to cancer or non-cancer causes could impact population-based cancer registry studies or clinical trial outcomes with respect to measures involving CSS and mortality.

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“…Uma vez que as estratégias farmacológicas de quimioprevenção envolvem administração sistêmica dos ativos, diversas reações adversas são possíveis, o que limita a adesão. A administração tópica pode permitir o efeito localizado dos fármacos, e a utilização de nanocarreadores, o carreamento de moléculas insolúveis, de difícil administração em decorrência de efeitos adversos ou problemas de biodisponibilidade (38).…”

Section: Administração Tópica E Nanocarreadoresunclassified

Veiculação tópica de endoxifeno e celecoxibe utilizando nanocarreadores como uma nova alternativa para a prevenção do câncer de mama

Mojeiko¹

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Veiculação tópica de endoxifeno e celecoxibe utilizando nanocarreadores como uma nova alternativa para a prevenção do câncer de mama Dissertação apresentada ao Programa de Pósgraduação em Farmacologia do Instituto de Ciências Biomédicas da Universidade de São Paulo para a obtenção do título de Mestre em Ciências. Área de concentração: Farmacologia Orientadora: Profª. Drª. Luciana Biagini Lopes Versão corrigida São Paulo 2021 RESUMO Mojeiko G. Veiculação tópica de endoxifeno e celecoxibe utilizando nanocarreadores como uma nova alternativa para a prevenção do câncer de mama. Dissertação (Mestrado em Farmacologia).

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Primary chemoprevention of breast cancer: Are the adverse effects too burdensome?

Cited by 10 publications

References 19 publications

Metformin and Chemoprevention: Potential for Heart-Healthy Targeting of Biologically Aggressive Breast Cancer

Metformin and Chemoprevention: Potential for Heart-Healthy Targeting of Biologically Aggressive Breast Cancer

Unknown Causes of Death in Cancer Patients

Veiculação tópica de endoxifeno e celecoxibe utilizando nanocarreadores como uma nova alternativa para a prevenção do câncer de mama

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