Diabetes Positively Associated With Risk of Developing Breast Cancer

A positive association has been found between diabetes mellitus (DM) and increased risk of developing breast cancer, particularly several molecular subtypes of the disease, according authors of a systematic review and meta-analysis published in Diabetes/Metabolism Research and Reviews.

Although DM can increase the risk for many chronic diseases, its impact on breast cancer risk is not well-established. However, experts have hypothesized that due to metabolic dysfunction, DM can be related to breast cancer risk. Therefore, the authors sought to assess the association between diabetes mellitus (DM) and breast cancer risk.

Following PRISMA guidelines, they searched PubMed, Embase, and Web of Science databases for English-language cohort and case-control studies from inception until December 10, 2021 that evaluated possible associations between DM and breast cancer. Initially, 8396 studies were identified.

Excluded from the analysis were studies in which DM was diagnosed at the same time as breast cancer, or afterwards; studies of patients who developed gestational DM; cohort or case-control studies including fewer than 10 participants with breast cancer or diabetes, respectively; and studies that did not distinguish between benign and malignant tumors.

A total of 70 independent studies met the authors’ criteria for inclusion in the final meta-analysis. The study population included women aged 18 years or older who had been diagnosed with DM before their breast cancer was detected.

The primary outcome was the incidence of malignant breast cancer among patients with DM. Across all 70 studies, there was a 20% increased risk for breast cancer among patients with DM (risk ratio [RR], 1.20; 95% CI, 1.11-1.29).

There was substantial heterogeneity among studies (I², 97.9%; P-heterogeneity <.001). Regarding research findings based on study type, 24 case-control studies demonstrated a stronger association between DM and breast cancer (RR, 1.26; 95% CI, 1.13-1.40) compared with the 46 cohort studies evaluated (RR, 1.15; 95% CI, 1.05-1.27).

Studies that reported on breast cancer risk with DM based on menopausal status showed a higher risk for breast cancer among menopausal women (RR, 1.12; 95% CI, 1.07-1.17). No association was found between DM and breast cancer in premenopausal women (RR, 0.95; 95% CI, 0.85-1.05).

The authors also noted an association between DM and significantly increased risk of certain breast cancer subtypes, including the following:

• Estrogen receptor (ER) positive breast cancer (RR, 1.09; 95% CI, 1.00-1.20)
• ER negative breast cancer (RR, 1.16; 95% CI, 1.04-1.30)
• Triple-negative breast cancer (RR, 1.41; 95% CI, 1.01-1.96)

Limitations of this review include selection bias (related mainly to studies restricting inclusion to older women, thereby maximizing the number of DM and/or breast cancer cases), the inability to differentiate between type 1 and type 2 diabetes, and a lack of information regarding specific diabetes treatments, which could potentially affect the relationship between DM and breast cancer risk.

“In conclusion,” the authors wrote, “this updated systematic review and meta-analysis confirms prior findings of an increased risk of BCa [breast cancer] in women with DM. In addition, our results suggest that women with DM may have a higher risk of diagnosis with an aggressive molecular subtype of BCa compared with women without DM.” They cautioned, “Further high‐quality evidence is needed to verify the relationship between DM and BCa receptor expression, understand the underlying mechanisms of breast carcinogenesis in women with DM, and eventually provide evidence-based recommendations for BCa prevention and treatment.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Endocrinology Advisor