Metformin and breast cancer risk: A meta-analysis and critical literature review.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 25-25
Author(s):  
Nananda Col ◽  
Leslie Ochs ◽  
Vicky Springmann ◽  
Aaron K Aragaki ◽  
Rowan T. Chlebowski
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Literature Review ◽  
Cancer Incidence ◽  
Invasive Breast Cancer ◽  
Meta Analysis ◽  
Breast Cancer Incidence ◽  
Cochrane Library ◽  
Study Quality

25 Background: Observational studies have suggested that metformin, commonly used for diabetes treatment that increases insulin sensitivity and improves glycemic control, decreases the incidence of several common cancers. However, findings regarding metformin and breast cancer incidence have been mixed. To explore this issue, a systematic literature review and meta-analysis were performed with a focus on potential biases. Methods: We conducted a comprehensive literature search for all pertinent studies addressing metformin use and breast cancer risk by searching Pub Med, Cochrane Library, Scopus (which includes Embase, ISI Web of Science) using the Mesh terms: "metformin" or "biguanides" or "diabetes mellitus, type 2/therapy" and "cancer" or "neoplasms". When multiple hazard ratios (HR) or odds ratio (OR) were reported, the most adjusted estimate was used in the base-case analysis. We pooled the adjusted HR using and performed sensitivity analyses on duration of metformin use (> or < 3 years use), study quality (assessed using the GRADE system), and initial observation year of the cohort (before vs after 1997). Results: From a total of 421 citations, 13 full-text articles were considered, and 7 independent studies were included. All were observational (4 cohort and 3 case control). Our combined OR for metformin association with invasive breast cancer of all 7 studies was 0.83 (95% CI, 0.71-0.97). Funnel plot analyses did not suggest publication bias. Stronger associations were found when analyses were limited to studies estimating the impact of longer metformin duration (OR = 0.75. 95% CI, 0.62-0.91) or among studies that began observing their cohort before 1997 (OR=0.68. 95% CI, 0.55-0.84). Stratification according to study quality did not affect the combined OR but higher quality studies had smaller CI and achieved statistical significance. Interpretation is limited by the observational nature of reports and different comparison groups. Conclusions: Our analyses support a protective effect of metformin on invasive breast cancer incidence among postmenopausal women with diabetes. Clinical trials are needed to determine whether metformin reduces breast cancer risk.

scholarly journals Sleep duration and breast cancer incidence: results from the Million Women Study and meta-analysis of published prospective studies

SLEEP ◽  
2020 ◽  
Author(s):  
Angel T Y Wong ◽  
Alicia K Heath ◽  
Tammy Y N Tong ◽  
Gillian K Reeves ◽  
Sarah Floud ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Sleep Duration ◽  
Cancer Incidence ◽  
Prospective Studies ◽  
Average Duration ◽  
Meta Analysis ◽  
Breast Cancer Incidence ◽  
Weighted Average

Abstract Study Objectives To investigate the association between sleep duration and breast cancer incidence, we examined the association in a large UK prospective study and conducted a meta-analysis of prospective studies. Methods In the Million Women Study, usual sleep duration over a 24-h period was collected in 2001 for 713,150 participants without prior cancer, heart problems, stroke, or diabetes (mean age = 60 years). Follow-up for breast cancer was by record linkage to national cancer registry data for 14.3 years on average from the 3-year resurvey. Cox regression models yielded multivariable-adjusted breast cancer relative risks (RR) and 95% confidence intervals (CIs) for sleep duration categories. Published prospective studies of sleep duration and breast cancer risk were included in a meta-analysis, which estimated the inverse-variance weighted average of study-specific log RRs for short and for long versus average duration sleep. Results After excluding the first 5 years to minimize reverse causation bias in the Million Women Study, 24,476 women developed breast cancer. Compared with 7–8 h of sleep, the RRs for &lt;6, 6, 9, and &gt;9 h of sleep were 1.01 (95% CI, 0.95–1.07), 0.99 (0.96–1.03), 1.01 (0.96–1.06), and 1.03 (0.95–1.12), respectively. In a meta-analysis of 14 prospective studies plus the Million Women Study, including 65,410 breast cancer cases, neither short (RR &lt; 7 h = 0.99 [0.98–1.01]) nor long (RR &gt; 8 h = 1.01 [0.98–1.04]) versus average duration sleep was associated with breast cancer risk. Conclusions The totality of the prospective evidence does not support an association between sleep duration and breast cancer risk.

scholarly journals Aromatase and breast cancer susceptibility.

1999 ◽  
pp. 165-173 ◽  
Author(s):  
N M Probst-Hensch ◽  
S A Ingles ◽  
A T Diep ◽  
R W Haile ◽  
F Z Stanczyk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Incidence ◽  
Breast Cancer Incidence ◽  
Latina Women ◽  
Repeat Polymorphism ◽  
Cyp19 Gene ◽  
Functional Relevance

Based on experimental and epidemiological evidence it is hypothesized that estrogen increases breast cancer risk by increasing mitotic activity in breast epithelial cells. Aromatase is crucial to the biosynthesis of estrogens and may therefore play a role in breast cancer development. Supporting data for an etiological role of aromatase in breast tumor biology are several-fold. First, the association between weight and postmenopausal breast cancer risk may be mediated by aromatase. Secondly, a pilot study found a higher aromatase expression in normal breast adipose tissue from breast cancer cases as opposed to healthy women. Thirdly, experimental data in animals suggest that aromatase activity predisposes mammary tissue to preneoplastic and neoplastic changes. In a multiethnic cohort study conducted in Los Angeles and on Hawaii we investigated (i) whether the plasma estrone to androstenedione (E1/A) ratio in different ethnic groups was associated with ethnic differences in breast cancer incidence, and (ii) whether genetic variation in the CYP19 gene encoding the P450 aromatase protein was associated with breast cancer risk. The age- and weight-adjusted ethnic specific E1/A ratios x 100 among women without oophorectomy were 7.92 in African-Americans, 8.22 in Japanese, 10.73 in Latinas and 9.29 in non-Latina Whites (P=0.09). The high E1/A ratio in Latina women was not associated with a high breast cancer incidence; in fact Latina women had the lowest breast cancer incidence in the cohort observed so far. We found no consistent association of an intronic (TTTA)n repeat polymorphism with breast cancer risk in different ethnic groups. This polymorphism was not associated with differences in the plasma E1/A ratio in a way that would predict its functional relevance. We describe a newly identified TTC deletion in intron 5 of the CYP19 gene that is associated with the (TTTA)n repeat polymorphism. Neither this polymorphism, nor a polymorphism at codon 264 in exon VII of the CYP19 gene, was associated with breast cancer. We did not identify any genetic variation in exon VIII in 54 African-American subjects. We identified rare genetic variants of unknown functional relevance in the promoter 1.4 of the CYP19 gene in 3 out of 24 Latina women. Further investigation into the role of aromatase in breast cancer etiology is important, given that the potential use of aromatase inhibitors as breast cancer chemopreventives depends on these results.

Metformin and breast cancer risk: a meta-analysis and critical literature review

2012 ◽  
Vol 135 (3) ◽  
pp. 639-646 ◽  
Author(s):  
Nananda F. Col ◽  
Leslie Ochs ◽  
Vicky Springmann ◽  
Aaron K. Aragaki ◽  
Rowan T. Chlebowski
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Literature Review ◽  
Meta Analysis ◽  
Critical Literature

scholarly journals Risk-Reducing Salpingo-Oophorectomy and Breast Cancer Risk Reduction in the Gynecologic Oncology Group Protocol-0199 (GOG-0199)

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Phuong L Mai ◽  
Austin Miller ◽  
Mitchell H Gail ◽  
Steven Skates ◽  
Karen Lu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Incidence ◽  
Breast Cancer Incidence ◽  
Incidence Rates ◽  
Pathogenic Variant ◽  
Risk Reducing ◽  
Cancer Risk Reduction

Abstract Background Risk-reducing salpingo-oophorectomy (RRSO) has been associated with approximately 50% breast cancer risk reduction among women with a pathogenic variant in BRCA1 or BRCA2 (BRCA1/2), a finding that has recently been questioned. Methods We estimated incidence rates of breast cancer and all cancers combined during 5 years of follow-up among participants selecting RRSO or ovarian cancer screening (OCS) among women with a BRCA1/2 pathogenic variant or strong breast and/or ovarian cancer family history. Ovarian or fallopian tube or peritoneal cancer incidence rates were estimated for the OCS group. Breast cancer hazard ratios (HRs) for time-dependent RRSO were estimated using Cox regression with age time-scale (4943 and 4990 women-years in RRSO and OCS cohorts, respectively). All statistical tests were two-sided. Results The RRSO cohort included 925 participants, and 1453 participants were in the OCS cohort (381 underwent RRSO during follow-up), with 88 incident breast cancers diagnosed. Among BRCA1/2 pathogenic variant carriers, a non-statistically significant lower breast cancer incidence was observed in the RRSO compared with the OCS cohort (HR = 0.86, 95% confidence interval  = 0.45 to 1.67; P = .67). No difference was observed in the overall population or among subgroups stratified by prior breast cancer history or menopausal status. Seven fallopian tube and four ovarian cancers were prospectively diagnosed in the OCS cohort, and one primary peritoneal carcinoma occurred in the RRSO cohort. Conclusions These data suggest that RRSO might be associated with reduced breast cancer incidence among women with a BRCA1/2 pathogenic variant, although the effect, if present, is small. This evolving evidence warrants a thorough discussion regarding the impact of RRSO on breast cancer risk with women considering this intervention.

scholarly journals Breast Cancer Risk in Rheumatoid Arthritis: An Update Meta-Analysis

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Guo Tian ◽  
Jia-Ning Liang ◽  
Zhuo-Yun Wang ◽  
Dian Zhou
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Cochrane Library ◽  
Number Of Patients ◽  
The Impact

Background. The incidence of breast cancer in RA patients remains controversial. Thus we performed a meta-analysis to investigate the impact of RA on breast cancer.Methods. Published literature was available from PubMed, Embase, and Cochrane Library. Pooled standardized incidence rate (SIR) was computed by random-effect model analysis.Results. We identified 16 separate studies in the present study, in which the number of patients ranged from 458 to 84,475. We did not find the increased cancer risk in RA patients (SIR=0.86, 95%CI=0.72–1.02). However, subgroup analysis showed that breast cancer risk in RA patients was positively different in Caucasians (SIR=0.82, 95%CI=0.73–0.93) and non-Caucasians (SIR=1.21, 95%CI=1.19–1.23), respectively. In subgroup analysis by style, a reduced incidence was found in hospital-based case subjects (SIR=0.82, 95%CI=0.69–0.97). Similarly, subgroup analysis for adjusted factors indicated that in A3 (age and sex) and A4 (age, sex, and race/ethnicity) the risk was decreased (SIR=0.87, 95%CI=0.76–0.99;SIR=0.63, 95%CI=0.59–0.67).Conclusions. The meta-analysis revealed no increased breast cancer risk in RA patients. However, in the subgroup analysis, the risk of breast cancer is increased in non-Caucasians patients with RA while it decreased in Caucasian population, hospital-based case subjects, and A3 group. Such relationship may provide preference for risk of breast cancer in different population.

scholarly journals Arsenic Exposure and Breast Cancer Risk: A Re-Evaluation of the Literature

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3305
Author(s):  
Katherine Pullella ◽  
Joanne Kotsopoulos
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Incidence ◽  
Breast Cancer Incidence ◽  
Arsenic Exposure ◽  
Epidemiologic Studies ◽  
Environmental Toxins ◽  
The Public

Arsenic is a widespread environmental contaminant and recognized carcinogen for the skin, bladder and lungs. In recent years, there has been an increasing number of studies that have investigated the effects of arsenic exposure and cancer risk at other sites, including the breast. However, to date, the association between arsenic exposure and breast cancer risk remains unclear. This article will provide an overview of arsenic metabolism, the clinically important biomarkers commonly used to assess arsenic exposure, and review the epidemiologic studies examining the role of arsenic exposure on breast cancer risk. Given the large burden of disease associated with breast cancer, it is of the upmost importance to identify risk factors and preventative strategies that could reduce cancer incidence. Limiting exposure to endemic environmental toxins, such as arsenic, represents one such strategy. More studies are required to better ascertain this relationship and to develop the public policy necessary to significantly reduce breast cancer incidence.

Physical activity and risk of postmenopausal breast cancer defined by hormone receptor status and histology: A large prospective cohort study with 18 years of follow up

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1002-1002 ◽  
Author(s):  
A. Bardia ◽  
A. H. Wang ◽  
L. C. Hartmann ◽  
J. E. Olson ◽  
C. M. Vachon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Physical Activity ◽  
Risk Factors ◽  
Cohort Study ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Incidence ◽  
Breast Cancer Incidence ◽  
Histological Subtypes

1002 Background: Physical activity is a modifiable breast cancer risk factor, perhaps mediating risk reduction through regulation of estrogen metabolism. Evidence regarding effect of physical activity is conflicting partly because breast cancer is a heterogenous constellation of different tumor subtypes with differing etiologies. No prospective study has examined the relationship between physical activity and breast cancer incidence based on ER/PR status or histological subtype. Objective: Examine effect of physical activity on breast cancer incidence based on ER/PR status and histological subtypes of breast cancer. Methods: The Iowa Women’s Health Study is a prospective cohort study of postmenopausal women (N=41,837). Physical activity was self-reported on baseline questionnaire, and three levels (high, medium and low) were defined. Breast cancer incidence, histologic subtype and ER/PR status, through 18 years of follow-up, were ascertained by linkage with the Iowa SEER Cancer Registry. Cox proportional hazards models were used to estimate multivariate relative risks (RRs) and 95% confidence intervals (CIs) of breast cancer, adjusting for other breast cancer risk factors. Results: During 554,819 person-years of follow-up, 2548 incident cases of breast cancer were observed. High physical activity was associated with decreased risk for breast cancer (RR 0.91, 95 % CI 0.81–1.01) compared to low activity. The protective effect was most marked in ER+/PR− (RR 0.66, CI 0.46–0.94), intermediate in ER−/PR− (RR 0.80, CI 0.56–1.15), weakest in ER+/PR+ (RR 0.94, CI 0.81–1.08), and elevated in ER-/PR+ (RR 1.42, CI 0.67–3.01) tumors. Higher physical activity was also associated with a decreased risk of invasive ductal/lobular carcinoma (RR 0.90, CI 0.80–1.02), but not with invasive breast cancer with a favorable histology (RR 1.19, CI 0.78–1.81). Conclusions: Higher physical activity was associated with a 10% decreased risk of breast cancer. Unexpectedly, risk reduction was most marked in PR- tumors, particularly ER+/PR-, and the more aggressive histologic forms. Further studies are needed to confirm these findings, and also evaluate other risk factors based on ER/PR status and histological subtypes. No significant financial relationships to disclose.

scholarly journals Redefining the impact of nutrition on breast cancer incidence: is epigenetics involved?

2012 ◽  
Vol 25 (1) ◽  
pp. 68-95 ◽  
Author(s):  
Dorothy Teegarden ◽  
Isabelle Romieu ◽  
Sophie A. Lelièvre
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Dna Methylation ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Incidence ◽  
Breast Cancer Incidence ◽  
Dietary Factors ◽  
Transcription Control ◽  
The Impact

Breast cancer incidence is rising worldwide with an increase in aggressive neoplasias in young women. Possible factors involved include lifestyle changes, notably diet that is known to make an impact on gene transcription. However, among dietary factors, there is sufficient support for only greater body weight and alcohol consumption whereas numerous studies revealing an impact of specific diets and nutrients on breast cancer risk show conflicting results. Also, little information is available from middle- and low-income countries. The diversity of gene expression profiles found in breast cancers indicates that transcription control is critical for the outcome of the disease. This suggests the need for studies on nutrients that affect epigenetic mechanisms of transcription, such as DNA methylation and post-translational modifications of histones. In the present review, a new examination of the relationship between diet and breast cancer based on transcription control is proposed in light of epidemiological, animal and clinical studies. The mechanisms underlying the impact of diets on breast cancer development and factors that impede reaching clear conclusions are discussed. Understanding the interaction between nutrition and epigenetics (gene expression control via chromatin structure) is critical in light of the influence of diet during early stages of mammary gland development on breast cancer risk, suggesting a persistent effect on gene expression as shown by the influence of certain nutrients on DNA methylation. Successful development of breast cancer prevention strategies will require appropriate models, identification of biological markers for rapid assessment of preventive interventions, and coordinated worldwide research to discern the effects of diet.

scholarly journals Use of systemic glucocorticoids and risk of breast cancer in a prospective cohort of postmenopausal women

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Manon Cairat ◽  
Marie Al Rahmoun ◽  
Marc J. Gunter ◽  
Pierre-Etienne Heudel ◽  
Gianluca Severi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Postmenopausal Women ◽  
Invasive Breast Cancer ◽  
Cox Regression ◽  
Breast Cancer Incidence ◽  
Breast Cancers ◽  
Systemic Glucocorticoid ◽  
Systemic Glucocorticoids

Abstract Background Glucocorticoids could theoretically decrease breast cancer risk through their anti-inflammatory effects or increase risk through immunosuppression. However, epidemiological evidence is limited regarding the associations between glucocorticoid use and breast cancer risk. Methods We investigated the association between systemic glucocorticoid use and breast cancer incidence in the E3N cohort, which includes 98,995 women with information on various characteristics collected from repeated questionnaires complemented with drug reimbursement data available from 2004. Women with at least two reimbursements of systemic glucocorticoids in any previous 3-month period since January 1, 2004, were defined as exposed. We considered exposure as a time-varying parameter, and we used multivariable Cox regression models to estimate hazard ratios (HRs) of breast cancer. We performed a competing risk analysis using a cause-specific hazard approach to study the heterogeneity by tumour subtype/stage/grade. Results Among 62,512 postmenopausal women (median age at inclusion of 63 years old), 2864 developed breast cancer during a median follow-up of 9 years (between years 2004 and 2014). Compared with non-exposure, glucocorticoid exposure was not associated with overall breast cancer risk [HR = 0.94 (0.85–1.05)]; however, it was associated with a higher risk of in situ breast cancer and a lower risk of invasive breast cancer [HRinsitu = 1.34 (1.01–1.78); HRinvasive = 0.86 (0.76–0.97); Phomogeneity = 0.01]. Regarding the risk of invasive breast cancer, glucocorticoid exposure was inversely associated with oestrogen receptor (ER)-positive breast cancer [HRER+ = 0.82 (0.72–0.94); HRER− = 1.21 (0.88–1.66); Phomogeneity = 0.03]; it was also inversely associated with the risk of stage 1 or stage 2 tumours but positively associated with the risk of stage 3/4 breast cancers [HRstage1 = 0.87 (0.75–1.01); HRstage2 = 0.67 (0.52–0.86); HRstage3/4 = 1.49 (1.02–2.20); Phomogeneity = 0.01]. Conclusion This study suggests that the association between systemic glucocorticoid use and breast cancer risk may differ by tumour subtype and stage.

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