Diabetes in Breast Cancer: Diabetes mellitus (DM) and breast cancer (BCa) are two significant health concerns affecting women worldwide. To shed light on the relationship between these two conditions, a study conducted a systematic review and meta-analysis following the Preferred Reporting Item for Systematic Reviews and Meta‐analysis (PRISMA) guidelines. This study aimed to answer a fundamental research question: Does the presence of diabetes increase the risk of malignant breast cancer in women aged 18 years and older?

Table of Contents

1.     Introduction
2.     Materials and methods
3.     Results
4.     Discussion
5.     Conclusion
6.     FAQs

Diabetes in Breast Cancer: Materials and methods

The study used the Population, Interventions or Exposure, Comparator, Outcome, Study Design (PICOS) approach to formulate the research question:

• Population: Women aged 18 years or older.
• Exposure: Diabetes mellitus (excluding gestational diabetes).
• Comparison: Lack of a diabetes diagnosis prior to breast cancer detection.
• Outcome: Malignant breast cancer confirmed by self-report or medical records.
• Study Design: Cohort and case-control studies were primary, but other study designs were considered.

Literature Search

This comprehensive database search in PubMed, Embase, and Web of Science yielded 10,773 publications. By following a strict inclusion criteria list, the authors eventually included 70 studies for review and meta-analysis.

Results

This comprehensive meta-analysis yielded significant insights into the association between diabetes and breast cancer risk. Here, the study presents the results in various subsections for a comprehensive understanding.

• Overall Breast Cancer Risk

This meta-analysis demonstrated a 20% increased risk of breast cancer among women with diabetes (RR = 1.20, 95% CI: 1.11–1.29). This overall estimate provides a starting point for this analysis.

• Subgroup Analyses

Association by Study Design

• Cohort studies (RR = 1.15, 95% CI: 1.05–1.27) remained significant despite some null findings.
• Case-control studies (RR = 1.26, 95% CI: 1.13–1.40) showed a significant association, though asymmetry in the funnel plot was observed.

Association by Study Region

• Studies in Asia reported the highest association (RR = 1.34, 95% CI: 1.11–1.63), followed by Europe (RR = 1.13, 95% CI: 1.06–1.21).
• The Americas also showed a significant association (RR = 1.10, 95% CI: 1.03–1.17).
• The 3 Australian studies showed homogeneous findings, but the combined results were not statistically significant (RR = 1.15, 95% CI: 0.99–1.33).

Trends Over Time

• No significant difference was observed between studies published before and after 2012.
• The temporal cumulative meta-analysis demonstrated that the summary estimate reached statistical significance in 2001 and remained fairly constant and significant after 2005.

Effect of DM Identification Method

• The method of DM identification (self-report or medical records) did not significantly affect association estimates.
• Studies that did not adjust for basal metabolic index (BMI) yielded an equivalent summary estimate (RR = 1.21, 95% CI: 1.08–1.35) to studies controlling for BMI (RR = 1.19, 95% CI: 1.06–1.32).

Menopausal Status and BCa Risk

In analyses stratified by menopausal status:

• Postmenopausal women showed a 12% increased risk of BCa (RR = 1.12, 95% CI: 1.07–1.17).
• Premenopausal women did not exhibit a significant association (RR = 0.95, 95% CI: 0.85–1.05).

BCa Subtypes

When examining specific BCa subtypes:

• The summary estimate for 3 studies that reported data for HER2þ BCa did not reveal a statistically significant association (RR = 1.21, 95% CI: 0.52–2.82).
• The 5 studies that assessed the risk of triple negative (TN) BCa showed a significantly elevated risk related to DM (RR = 1.41, 95% CI: 1.01–1.96).
• These detailed subgroup analyses provide a nuanced view of the relationship between diabetes and breast cancer risk, highlighting variations across different study designs, regions, and BCa subtypes.

Diabetes in Breast Cancer: Discussion

The results of this systematic review and meta-analysis shed light on the complex relationship between diabetes mellitus (DM) and the risk of developing breast cancer (BCa) in women aged 18 and older. These findings have important implications for both healthcare providers and individuals.

Understanding the Association

The 20% increased risk of BCa among women with DM, as indicated by this meta-analysis, underscores the importance of recognizing the potential link between these two prevalent conditions. This finding aligns with previous studies and suggests that DM may act as a contributing factor in the development of BCa. While the association is modest, it signifies the need for vigilance, particularly among diabetic women.

Subgroup Variations

This study delved into various subgroups to uncover nuanced associations. Notably, the risk varied by study design, with both cohort and case-control studies demonstrating significant associations. Case-control studies, in particular, displayed a stronger association, although the funnel plot revealed potential publication bias. These variations emphasize the importance of considering study design when interpreting results.

Additionally, authors examined the impact of geographic regions. Studies conducted in Asia reported the highest association, followed by Europe and the Americas. This regional variation may be influenced by diverse lifestyles, genetics, and healthcare systems. The lack of statistical significance in Australian studies suggests the need for further investigation within specific populations.

Effect of Menopausal Status and BCa Subtypes

The analysis by menopausal status revealed that postmenopausal women with DM had a 12% increased risk of BCa. In contrast, no significant association was observed among premenopausal women. This suggests that hormonal changes associated with menopause may play a role in the relationship between DM and BCa.

Furthermore, the analysis of BCa subtypes revealed intriguing results. While the association with hormone receptor-positive (ER+) and hormone receptor-negative (ER-) BCa was significant, the association with human epidermal growth factor 2-positive (HER2+) BCa was inconclusive. However, the risk of triple-negative (TN) BCa was significantly elevated in diabetic women. These subtype-specific associations provide valuable insights for future research.

Clinical Implications

Understanding the link between DM and BCa is of paramount importance for healthcare providers. Diabetic individuals, especially postmenopausal women, may benefit from tailored breast cancer screening programs and preventive measures. Early detection can lead to improved outcomes.

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Diabetes in Breast Cancer: Conclusion

In conclusion, this meta-analysis confirms a modest yet significant positive association between diabetes mellitus and breast cancer risk in women aged 18 and older. This association varies by study design, geographic region, and BCa subtype. The findings underscore the importance of diabetes management, regular breast cancer screenings, and tailored interventions for diabetic individuals, particularly postmenopausal women. Further research is needed to unravel the underlying mechanisms driving this association and to refine preventive strategies. Diabetes in Breast Cancer.

FAQs

Q1: Is there a proven link between diabetes mellitus (DM) and breast cancer (BCa)?

A1: Yes, this systematic review and meta-analysis has found a modest but significant association between DM and an increased risk of developing BCa in women aged 18 and older. The risk is approximately 20% higher among diabetic individuals.

Q2: How does the association of Diabetes in Breast Cancer vary by study design?

A2: This analysis shows that both cohort and case-control studies suggest a positive association between DM and BCa risk. Case-control studies demonstrate a stronger association, although there may be some publication bias in these findings.

Q3: Does the risk of BCa associated with DM differ based on geographic region?

A3: Yes, this study reveals regional variations. Studies conducted in Asia report the highest association, followed by Europe and the Americas. However, Australian studies did not show a statistically significant association.

Q4: Does menopausal status influence of Diabetes in Breast Cancer?

A4: Yes, this analysis indicates that postmenopausal women with DM have a 12% increased risk of BCa. However, there is no significant association observed among premenopausal women.

Q5: Are there differences in the association between DM and different BCa subtypes?

A5: Indeed, the association varies by BCa subtype. DM is associated with both hormone receptor-positive (ER+) and hormone receptor-negative (ER-) BCa. However, the association with human epidermal growth factor 2-positive (HER2+) BCa is inconclusive, and the risk of triple-negative (TN) BCa is significantly elevated.

Q6: What are the clinical implications of this association of Diabetes in Breast Cancer?

A6: The findings suggest that diabetic individuals, especially postmenopausal women, may benefit from tailored breast cancer screening programs and preventive measures. Early detection can lead to improved outcomes.

Q7: Diabetes in Breast Cancer: What should future research focus on in this area?

A7: Future research should delve into the underlying mechanisms driving the association between DM and BCa, explore potential interventions, and investigate the impact of diabetes management on BCa risk. Additionally, further studies within specific populations can help refine preventive strategies.