Pre-Clinical Insights into the Iron and Breast Cancer Hypothesis

Population studies, systematic reviews, and meta-analyses have revealed no relationship between iron status and breast cancer, a weak positive association, or a small protective effect of low iron status. However, in those studies, the authors concluded that further investigation was merited. The set of experiments reported here used preclinical models to assess the likely value of further investigation. The effects of iron status on the initiation and promotion stage of mammary carcinogenesis are reported. Using the classical model of cancer initiation in the mammary gland, 7,12 dimethyl-benz[α]anthracene-induced carcinogenesis was unaffected by iron status. Similarly, excess iron intake showed no effect on the promotion stage of 1-methyl-1-nitrosurea-induced mammary carcinogenesis, though iron deficiency exerted a specific inhibitory effect on the carcinogenic process. Though iron-mediated cellular oxidation is frequently cited as a potential mechanism for effects on breast cancer, no evidence of increased oxidative damage to DNA attributable to excess iron intake was found. The reported preclinical data fail to provide convincing evidence that the further evaluation of the iron–breast cancer risk hypotheses is warranted and underscore the value of redefining the referent group in population-based studies of iron–cancer hypotheses in other tissues.

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Adjuvant Hormonotherapy and Cardiovascular Risk in Post-Menopausal Women with Breast Cancer: A Large Population-Based Cohort Study

Cancers ◽

10.3390/cancers13092254 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2254

Author(s):

Matteo Franchi ◽

Roberta Tritto ◽

Luigi Tarantini ◽

Alessandro Navazio ◽

Giovanni Corrao

Keyword(s):

Breast Cancer ◽

Heart Failure ◽

Adjuvant Therapy ◽

Large Population ◽

Positive Association ◽

Population Based ◽

Study Cohort ◽

Increased Risk ◽

Post Menopausal ◽

New Diagnosis

Background: Whether aromatase inhibitors (AIs) increase the risk of cardiovascular (CV) events, compared to tamoxifen, in women with breast cancer is still debated. We evaluated the association between AI and CV outcomes in a large population-based cohort of breast cancer women. Methods: By using healthcare utilization databases of Lombardy (Italy), we identified women ≥50 years, with new diagnosis of breast cancer between 2009 and 2015, who started adjuvant therapy with either AI or tamoxifen. We estimated the association between exposure to AI and CV outcomes (including myocardial infarction, ischemic stroke, heart failure or any CV event) by a Cox proportional hazard model with inverse probability of treatment and censoring weighting. Results: The study cohort included 26,009 women starting treatment with AI and 7937 with tamoxifen. Over a median follow-up of 5.8 years, a positive association was found between AI and heart failure (Hazard Ratio = 1.20, 95% CI: 1.02 to 1.42) and any CV event (1.14, 1.00 to 1.29). The CV risk increased in women with previous CV risk factors, including hypertension, diabetes and dyslipidemia. Conclusions: Adjuvant therapy with AI in breast cancer women aged more than 50 years is associated with increased risk of heart failure and combined CV events.

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Association of Iron Status and Intake During Pregnancy with Neuropsychological Outcomes in Children Aged 7 Years: The Prospective Birth Cohort Infancia y Medio Ambiente (INMA) Study

Nutrients ◽

10.3390/nu11122999 ◽

2019 ◽

Vol 11 (12) ◽

pp. 2999 ◽

Cited By ~ 4

Author(s):

Victoria Arija ◽

Carmen Hernández-Martínez ◽

Mónica Tous ◽

Josefa Canals ◽

Mónica Guxens ◽

...

Keyword(s):

Working Memory ◽

Serum Ferritin ◽

Iron Status ◽

Population Based ◽

Maternal Serum ◽

Iron Intake ◽

Good State ◽

Trail Making ◽

Neuropsychological Outcomes ◽

Maternal Iron

Early iron status plays an important role in prenatal neurodevelopment. Iron deficiency and high iron status have been related to alterations in child cognitive development; however, there are no data about iron intake during pregnancy with other environmental factors in relation to long term cognitive functioning of children. The aim of this study is to assess the relationship between maternal iron status and iron intake during pregnancy and child neuropsychological outcomes at 7 years of age. We used data from the INMA Cohort population-based study. Iron status during pregnancy was assessed according to serum ferritin levels, and iron intake was assessed with food frequency questionnaires. Working memory, attention, and executive function were assessed in children at 7 years old with the N-Back task, Attention Network Task, and the Trail Making Test, respectively. The results show that, after controlling for potential confounders, normal maternal serum ferritin levels (from 12 mg/L to 60 mg/L) and iron intake (from 14.5 mg/day to 30.0 mg/day), respectively, were related to better scores in working memory and executive functioning in offspring. Since these functions have been associated with better academic performance and adaptation to the environment, maintaining a good state of maternal iron from the beginning of pregnancy could be a valuable strategy for the community.

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Dietary glycemic index and glycemic load in relation to risk of breast cancer

Public Health Nutrition ◽

10.1017/s1368980021004018 ◽

2021 ◽

pp. 1-20

Author(s):

Somaye Rigi ◽

Asma Salari-Moghaddam ◽

Sanaz Benisi-Kohansal ◽

Leila Azadbakht ◽

Ahmad Esmaillzadeh

Keyword(s):

Breast Cancer ◽

Glycemic Index ◽

Menopausal Status ◽

Glycemic Load ◽

Positive Association ◽

Population Based ◽

Significant Positive Association ◽

The Status ◽

Dietary Glycemic Index ◽

Stratified Analysis

Abstract Objective: Previous studies on the association between glycemic index (GI) and load (GL) in relation to breast cancer risk are contradictory. The aim of this study was to examine the association between dietary GI and GL and risk of breast cancer in Iranian women. Design: Population-based case-control. Dietary GI and GL were assessed using a validated Willett-format 106-item semi-quantitative food frequency questionnaire. Setting: Isfahan, Iran. Participants: Cases were 350 patients with newly diagnosed stage I-IV breast cancer, for whom the status of breast cancer was confirmed by physical examination and mammography. Controls were 700 age-matched apparently healthy individuals who were randomly selected from general population. Results: After controlling for potential confounders, individuals in the highest tertile of dietary GI had 47% higher odds of breast cancer than women in the lowest tertile (OR: 1.47; 95% CI: 1.02-2.12). Stratified analysis by menopausal status showed such association among postmenopausal women (OR: 1.51; 95% CI: 1.02-2.23). We found no significant association between dietary GL and odds of breast cancer either before (OR: 1.35; 95% CI: 0.99-1.84) or after adjustment for potential confounders (OR: 1.24; 95% CI: 0.86-1.79). In addition, stratified analysis by menopausal status revealed no significant association between dietary GL and odds of breast cancer. Conclusions: Our findings showed a significant positive association between dietary GI and odds of breast cancer. However, we observed no significant association between dietary GL and odds of breast cancer.

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Iron intake, body iron status, and risk of breast cancer: a systematic review and meta-analysis

BMC Cancer ◽

10.1186/s12885-019-5642-0 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 14

Author(s):

Vicky C. Chang ◽

Michelle Cotterchio ◽

Edwin Khoo

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Iron Status ◽

Meta Analysis ◽

Iron Intake ◽

Body Iron

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Serum estrogen receptor bioactivity and breast cancer risk among postmenopausal women

Endocrine Related Cancer ◽

10.1530/erc-13-0233 ◽

2013 ◽

Vol 21 (2) ◽

pp. 263-273 ◽

Cited By ~ 10

Author(s):

Vanessa W Lim ◽

Jun Li ◽

Yinhan Gong ◽

Aizhen Jin ◽

Jian-Min Yuan ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Postmenopausal Breast Cancer ◽

Positive Association ◽

Serum Levels ◽

Population Based ◽

Health Study ◽

Baseline Serum

The estrogen levels of Asian women are different from those of Western women, and this could affect estrogen receptor (ER) bioactivity and breast cancer risk. We conducted a case–control study in 169 postmenopausal breast cancer cases and 426 matched controls nested within a population-based prospective cohort study, the Singapore Chinese Health Study, to evaluate the serum levels of estrogens and their receptor (ERα and ERβ)-mediated estrogenic activities in relation to breast cancer risk. Breast cancer cases had higher levels of estrogens and ER-mediated bioactivities in baseline serum than the controls. Compared with those in the lowest quartile, women in the highest quartile for estrone (E1) or ERα-mediated bioactivity had increased breast cancer risk. After additional adjustment for ERβ bioactivity, free estradiol, and E1levels, serum ERα-mediated bioactivity remained associated with increased breast cancer risk. Compared with those in the lowest quartile, women in the highest quartile for ERα-mediated bioactivity had an odds ratio of 2.39 (95% CI=1.17–4.88;Pfor trend=0.016). Conversely, the positive association between E1and cancer risk became null after adjustment for ERα-mediated bioactivity, suggesting that the effect of E1could be mediated through ERα. Factor(s) contributing to increased ERα-mediated estrogenic bioactivity in serum and its role as a predictor for breast cancer risk need to be validated in future studies.

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