Breast Cancer Risk Reduced by Bariatric Surgery in Patients With High Insulin Levels

Research finds women that undergo bariatric surgery have a reduced risk of breast cancer. | Image Credit: Visual Generation - stock.adobe.com

According to a prospective clinical trial published in JAMA Surgery, female-identifying patients with obesity had a reduced risk of breast cancer after bariatric surgery, mainly found in women with hyperinsulinemia.¹

Obesity is a major factor for breast cancer risk and as cases continuously rise, breast cancer incidence is expected to do the same. In a clinical trial led by the Women’s Health Initiative, death rates following breast cancer were higher in women considered overweight or obese (P < .001) while mortality rates were higher in women with grade 2 or 3 obesity (body mass index ≥ 35 kg/m²; P < .001).²

Previous studies have found bariatric surgery has been linked with a decreased incidence of cancer in people diagnosed with obesity.¹ The prospective clinical trial aimed to discover the associations between bariatric surgery and breast cancer in women and determine whether the treatment shows differing benefit according to baseline insulin levels.

Study Design

The study was conducted as a prospective, matched, intervention trial that included Swedish participants who were diagnosed with obesity. Around 25 public surgical departments and 480 primary health care centers in Sweden enrolled eligible participants from September 1, 1987, to January 31, 2001.

Participants in the control group were categorized as having received usual obesity care from their primary health care provider and were referred to as the usual care group (n = 1447). There were 1420 women in the surgery group, with 260 who underwent nonadjustable or adjustable gastric banding, 970 who had vertical banded gastroplasty, and 190 who had a gastric bypass.

Results

At baseline, the study population consisted of 2867 women at an average age of 48 years. There were more women in the usual care group who were experiencing menopause when measured at baseline compared with the surgery group (36.6% vs 30.5%, respectively; P = .001).

The follow-up period consisted for an average of 23.9 years, where 66 breast cancer related events occurred in the surgery group and 88 in the usual care group. Treatment groups did not find any significant differences in body mass index in women with breast cancer and without breast cancer. An unadjusted analysis found bariatric surgery showed associations with decreased risk of breast cancer compared with the usual care group. However, this relationship was not relevant once adjusted for age, body mass index, alcohol, and smoking habits.

Women had higher breast cancer incidence in the usual care group when menopausal status was stratified at baseline. Additionally, women who were premenopausal had higher breast cancer incidence compared women who were postmenopausal.

Surgical treatment benefits for breast cancer risk were greater in women with baseline insulin levels above the median 15.8 mlU/L compared with those below the median. Only 5 of the participants were excluded from the study based on incomplete data on baseline insulin.

Surgical treatment benefits were found to affect breast cancer risk in women with baseline insulin levels above the average compared with those below the average.

While the biological mechanisms by which bariatric surgery reduces the risk of breast cancer are not entirely understood, it is suggested that weight loss counteracts potential pathways where obesity may cause cancer. The Swedish study results are in line with previous data that concluded bariatric surgery as an associated factor to reduce risk of obesity-induced cancers. However, recent reports have showed data on women with obesity who experience reduced risk of both premenopausal and postmenopausal breast cancers compared with women who have not undergone surgery.

Study limitations included the nonrandomized design that resulted in several variables becoming different between the study groups at baseline; the study may have led to suboptimal matches for some individual variables. Furthermore, there was not a clear distribution of risk factors that favored either group. Each analysis was adjusted for risk factors that were associated with breast cancer. The study also included older surgical methods that are no longer in practice, and information on estrogen levels or breast cancer subtype was not included.

With the emergence of new weight loss injection drugs, like semaglutide (Wegovy), obesity treatment has become more accessible to eligible patients. Oncology experts are acknowledging the belief that weight loss drugs can assist in cancer prevention and treatment. Benjamin Liu and Cindy Lin, residents at the Case Western Reserve University School of Medicine, told The Guardian, “Our findings are significant in that they could change the paradigm of obesity management by suggesting early intervention with GLP-1 RAs [glucagon-like peptide-1 receptor agonists] could delay or prevent obesity-related cancer development.”⁴

Researchers concluded the study displayed reduced risk of breast cancer following bariatric surgery in women with diagnosed obesity, especially for those with hyperinsulinemia, which could suggest insulin as a possible predictor of the treatment effect.

References

1. Kristensson FM, Andersson-Assarsson JC, Peltonen M, et al. Breast cancer risk after bariatric surgery and influence of insulin levels: a nonrandomized controlled trial. JAMA Surg. Published online May 15, 2024. doi:10.1001/jamasurg.2024.1169

2. Santoro C. Metabolic syndrome, obesity contribute to breast cancer mortality in postmenopausal women. AJMC^®. May 13, 2024. Accessed June 25, 2024. https://www.ajmc.com/view/metabolic-syndrome-obesity-contribute-to-breast-cancer-mortality-in-postmenopausal-women

3. Chlebowski RT, Aragaki AK, Pan K, et al. Breast cancer incidence and mortality by metabolic syndrome and obesity: the Women’s Health Initiative. Cancer. Published online May 13, 2024. doi:10.1002/cncr.35318

4. Gregory A. “Enormous potential”: weight-loss drugs cut cancer risk by a fifth, research shows. The Guardian. June 4, 2024. Accessed June 25, 2024. https://www.theguardian.com/society/article/2024/jun/04/weight-loss-drugs-cut-cancer-risk-fifth-research-wegovy