Type 2 diabetes, breast cancer specific and overall mortality: Associations by metformin use and modification by race, body mass, and estrogen receptor status

Lee, Kyung Na; Torres, Mylin A.; Troeschel, Alyssa N.; He, Jiabei; Gogineni, Keerthi; McCullough, Lauren E.

doi:10.1371/journal.pone.0232581

Cited by 19 publications

(12 citation statements)

References 55 publications

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“…18 Recently, several studies reported that type 2 diabetes and impaired glucose metabolism were associated with the prognosis of breast cancer. [19][20][21][22] In our study, an IGT was associated with SLN metastasis. Our findings suggest that having IGT may lead to LN progression despite early breast cancer.…”

Section: Discussionsupporting

confidence: 55%

Predictive Factors Among Clinicopathological Characteristics for Sentinel Lymph Node Metastasis in T1-T2 Breast Cancer

Minami

Sakimura

Irie

et al. 2021

CMAR

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Section: Discussionsupporting

confidence: 55%

Predictive Factors Among Clinicopathological Characteristics for Sentinel Lymph Node Metastasis in T1-T2 Breast Cancer

Minami

Sakimura

Irie

et al. 2021

CMAR

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“…Of note, metformin is consistently shown to be associated with lower mortality in a range of conditions (e.g., breast cancer [ 45 ], not just COVID-19). These associations are not presumed to be causal, and these findings should not be immediately interpreted as suggesting that metformin has a protective effect in COVID-19 illness without further investigation.…”

Section: Resultsmentioning

confidence: 99%

Risks of and From SARS-CoV-2 Infection and COVID-19 in People With Diabetes: A Systematic Review of Reviews

Hartmann‐Boyce

Rees²,

Perring

et al. 2021

Diabetes Care

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BACKGROUND This review was commissioned by the World Health Organization and presents a summary of the latest research evidence on the impact of coronavirus disease 2019 (COVID-19) on people with diabetes (PWD). PURPOSE To review the evidence regarding the extent to which PWD are at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and/or of suffering its complications, including associated mortality. DATA SOURCES We searched the Cochrane COVID-19 Study Register, Embase, MEDLINE, and LitCOVID on 3 December 2020. STUDY SELECTION Systematic reviews synthesizing data on PWD exposed to SARS-CoV-2 infection, reporting data on confirmed SARS-CoV-2 infection, admission to hospital and/or to intensive care unit (ICU) with COVID-19, and death with COVID-19 were used. DATA EXTRACTION One reviewer appraised and extracted data; data were checked by a second. DATA SYNTHESIS Data from 112 systematic reviews were narratively synthesized and displayed using effect direction plots. Reviews provided consistent evidence that diabetes is a risk factor for severe disease and death from COVID-19. Fewer data were available on ICU admission, but where available, these data also signaled increased risk. Within PWD, higher blood glucose levels both prior to and during COVID-19 illness were associated with worse COVID-19 outcomes. Type 1 diabetes was associated with worse outcomes than type 2 diabetes. There were no appropriate data for discerning whether diabetes was a risk factor for acquiring SARS-CoV-2 infection. LIMITATIONS Due to the nature of the review questions, the majority of data contributing to included reviews come from retrospective observational studies. Reviews varied in the extent to which they assessed risk of bias. CONCLUSIONS There are no data on whether diabetes predisposes to infection with SARS-CoV-2. Data consistently show that diabetes increases risk of severe COVID-19. As both diabetes and worse COVID-19 outcomes are associated with socioeconomic disadvantage, their intersection warrants particular attention.

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“…Obesity and metabolic disease poses a deepening challenge in the United States, where the burden of Type 2 diabetes (T2D) or pre-diabetes affects over 100 million adults ( 1 – 4 ). Critically, these diseases are implicated in a variety of cancers, both with an obesogenic environment, such as endometrium, colon, and kidney, as well as less common malignancies such as leukemia, multiple myeloma, and non-Hodgkin’s lymphoma ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

The crosstalk within the breast tumor microenvironment in type II diabetes: Implications for cancer disparities

et al. 2022

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Obesity-driven (type 2) diabetes (T2D), the most common metabolic disorder, both increases the incidence of all molecular subtypes of breast cancer and decreases survival in postmenopausal women. Despite this clear link, T2D and the associated dysfunction of diverse tissues is often not considered during the standard of care practices in oncology and, moreover, is treated as exclusion criteria for many emerging clinical trials. These guidelines have caused the biological mechanisms that associate T2D and breast cancer to be understudied. Recently, it has been illustrated that the breast tumor microenvironment (TME) composition and architecture, specifically the surrounding cellular and extracellular structures, dictate tumor progression and are directly relevant for clinical outcomes. In addition to the epithelial cancer cell fraction, the breast TME is predominantly made up of cancer-associated fibroblasts, adipocytes, and is often infiltrated by immune cells. During T2D, signal transduction among these cell types is aberrant, resulting in a dysfunctional breast TME that communicates with nearby cancer cells to promote oncogenic processes, cancer stem-like cell formation, pro-metastatic behavior and increase the risk of recurrence. As these cells are non-malignant, despite their signaling abnormalities, data concerning their function is never captured in DNA mutational databases, thus we have limited insight into mechanism from publicly available datasets. We suggest that abnormal adipocyte and immune cell exhaustion within the breast TME in patients with obesity and metabolic disease may elicit greater transcriptional plasticity and cellular heterogeneity within the expanding population of malignant epithelial cells, compared to the breast TME of a non-obese, metabolically normal patient. These challenges are particularly relevant to cancer disparities settings where the fraction of patients seen within the breast medical oncology practice also present with co-morbid obesity and metabolic disease. Within this review, we characterize the changes to the breast TME during T2D and raise urgent molecular, cellular and translational questions that warrant further study, considering the growing prevalence of T2D worldwide.

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Type 2 diabetes, breast cancer specific and overall mortality: Associations by metformin use and modification by race, body mass, and estrogen receptor status

Cited by 19 publications

References 55 publications

Predictive Factors Among Clinicopathological Characteristics for Sentinel Lymph Node Metastasis in T1-T2 Breast Cancer

Predictive Factors Among Clinicopathological Characteristics for Sentinel Lymph Node Metastasis in T1-T2 Breast Cancer

Risks of and From SARS-CoV-2 Infection and COVID-19 in People With Diabetes: A Systematic Review of Reviews

The crosstalk within the breast tumor microenvironment in type II diabetes: Implications for cancer disparities

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