Bariatric surgery may protect against development of breast cancer in women with obesity

By Vijay Kumar MalesuReviewed by Danielle Ellis, B.Sc.May 20 2024

In a recent study published in the JAMA Surgery, a group of researchers investigated the association between bariatric surgery and breast cancer incidence in women and determined if baseline insulin levels influence the benefit of bariatric surgery on breast cancer risk.

Background 

Breast cancer is one of the most common cancers in women and a leading cause of cancer-related death. Obesity, a major risk factor, worsens disease outcomes and is rising globally, increasing breast cancer incidence. Insulin, a cellular growth factor, mediates cancer risk in obesity.

Bariatric surgery, effective for weight loss and reducing insulin levels, has shown reduced overall cancer incidence, particularly female-specific cancers. Retrospective studies suggest bariatric surgery reduces breast cancer incidence, but further research is needed to verify this reduction and understand the underlying biological mechanisms.

About the study 

The present Swedish Obese Subjects (SOS) study enrolled 4,047 participants with obesity, aged 37 to 60 years, with a body mass index (BMI) of 34 or greater for men and 38 or greater for women. Participants were recruited in Sweden from 1987 to 2001. The surgery group included 2010 participants undergoing various bariatric procedures, while a matched control group of 2037 participants received usual care. 

Baseline and follow-up examinations were conducted at multiple intervals up to 20 years, including blood samples and questionnaires. Breast cancer events identified through the Swedish Cancer Registry were analyzed using International Classification of Diseases, Seventh Revision (ICD-7) code 170. The surgery group included 1,420 women (260 with gastric banding, 970 with vertical banded gastroplasty, 190 with gastric bypass), and the usual care group had 1447 women. 

Statistical analyses compared treatment groups using t-tests and Fisher exact tests, with Kaplan-Meier estimates and Cox proportional hazards models for breast cancer risk. Adjustments were made for baseline age, BMI, alcohol use, and smoking status. Subgroup analyses evaluated the effect of insulin and metabolic variables on breast cancer risk. Sensitivity analyses considered menopausal state and undiagnosed baseline breast cancer. Analyses used R and Stata software.

Study results 

The study population consisted of 2,867 women with a mean (SD) age of 48.0 (6.2) years. Baseline characteristics of the surgery group (n = 1420) and the usual care group (n = 1447) showed significant differences in 12 out of 17 characteristics. A higher proportion of women in the usual care group were menopausal at baseline compared to the surgery group (36.6% vs 30.5%, respectively; P = 0.001).

In the surgery group, mean BMI changes were −10.4, −7.7, −7.5, and −7.8 after 2, 10, 15, and 20 years of follow-up, respectively. The usual care group showed minimal BMI changes during follow-up.

During a median follow-up of 23.9 years, there were 154 breast cancer events, with 66 in the surgery group and 88 in the usual care group (log-rank test: χ₁² = 5.63; Probability Value (P) = 0.02).

There were no significant differences in BMI during follow-up among participants with and without breast cancer diagnoses within the treatment groups.

Unadjusted analysis indicated bariatric surgery was associated with a reduced risk of breast cancer compared to usual care (Hazard Ratio (HR), 0.68; 95% Confidence Interval (CI), 0.49-0.94; P = 0.02), though this association was not significant after adjusting for age, BMI, alcohol, and smoking status (adjusted HR, 0.72; 95% CI, 0.52-1.01; P = .06).

The proportional hazard assumption was not violated (adjusted P = .16). When breast cancer events were excluded within the first three years of study inclusion, the association remained significant (adjusted HR, 0.67; 95% CI, 0.47-0.95; P = 0.02).

Stratifying by menopausal status at baseline, breast cancer incidence was higher in the usual care group than in the surgery group after adjustment (adjusted HR, 0.64; 95% CI, 0.42-0.99; P = 0.045) for premenopausal women but not for postmenopausal women (adjusted HR, 0.84; 95% CI, 0.49-1.45; P = 0.54).

The cumulative incidence of breast cancer was stratified by median baseline insulin levels (15.8 μIU/L). Five participants were excluded due to missing insulin data.

The surgical treatment benefit was greater in women with insulin levels above the median. The interaction between insulin and treatment was significant (χ₁² = 5.11; P = 0.02). Excluding early breast cancer events, results were unaltered.

The homeostasis model assessment-estimated insulin resistance (HOMA-IR) was also significantly associated with surgical treatment benefit (χ₁² = 4.82; P = 0.03). No interactions were found between other risk factors and treatment. Excluding early breast cancer events, results remained similar, except for blood glucose (χ₁² = 4.25; P = 0.04).

Conclusion

In conclusion, bariatric surgery is associated with a reduced incidence of breast cancer in women with obesity, especially those with high baseline insulin levels. This suggests that insulin levels may help predict the protective benefit of bariatric surgery against breast cancer.