Breast Cancer Treatment May Increase Risk of Diabetes, Hypertension

Although cardiovascular disease risk is well established in survivors of breast cancer, how cardiotoxicity from treatment influences development of cardiometabolic risk factors is not.

The marked lack of research on the risk of patients with breast cancer developing cardiometabolic risk factors following treatment, along with how body mass index (BMI) contributes to that risk, underscores the great need for cardiometabolic risk factor prevention, according to new trial findings from Kaiser Permanente Northern California (KPNC).

These findings were published recently in the Journal of Clinical Oncology.

Ample evidence already exists supporting that the presence of cardiometabolic risk factors before breast cancer treatment can enhance the risk for cardiotoxic events down the line, the authors of the present study noted. Of particular concern is the potential for hypertension and diabetes and their associated mortality risk.

Using data from 89,644 women who received a breast cancer diagnosis between 2005 and 2013 within the KPNC system, the investigators divided the participants into 2 cohorts. Women with invasive breast cancer (n = 14,942) were matched 1:5 based on birth year, race, and ethnicity to noncancer controls (n = 74,702). Adjustments were made for cardiovascular disease–related risk factors and then stratified by treatment and BMI.

Cumulative higher incidence rates of diabetes were seen in the study cohort of women with invasive disease compared with the healthy controls at the 2-year mark, at 2.1% vs 1.7% and 10.9% vs 8.9%, respectively. At 5 years, this trend continued, with 4.9% and 4.4% of the groups having developed diabetes, respectively.

At the 10-year mark, rates had more than quadrupled in both groups, with the study group continuing to have a higher rate of diabetes: 9.3% vs 8.8%, respectively. The participants were followed for a mean of 7.0 (range, <1.0-13.4) years. Breaking down the numbers, this translates to 1004 cases of diabetes in the study group and 4497 in the control group, and 1790 and 9524 cases of hypertension in each group, respectively.

Additional findings on higher diabetes risk (subdistribution HR [sHR]) were also seen in connection with several variables investigated in the cancer cohort vs the noncancer cohort:

  • Overall: sHR, 1.16 (95% CI, 1.07-1.26)
  • History of chemotherapy: sHR, 1.23 (95% CI, 1.11-1.38)
  • Left-sided radiation: sHR, 1.29 (95% CI, 1.13-1.48)
  • Endocrine therapy: sHR, 1.23 (95% CI, 1.12-1.34)

Those receiving left-sided radiation or endocrine therapy also had higher risk of hypertension, at 11% (sHR, 1.11; 95% CI, 1.02-1.21) and 10% (sHR, 1.10; 95% CIU, 1.03-1.16), respectively. The risk from any chemotherapy was minimal (sHR, 0.97; 95% CI, 0.90-1.05).

All of the women in this study were participants of The Pathways Heart Study, funded by the National Cancer Institute. At baseline, the mean (SD) age was 61.2 (12.8) years in both groups, while almost equivalent results were seen for BMIs (cancer cohort: 28.5 [6.5] kg/m2; noncancer cohort: 28.3 [6.5] kg/m2) and COmorbidity Point Score, version 2, results (14.0 [15.3] and 14.2 [15.2], respectively). Sixty-five percent were non-Hispanic White, and those who had invasive breast cancer were more likely to be former smokers or nonsmokers (84% vs 76%) and classified as overweight or obese (68% vs 62%).

Additionally, when combining treatments received, risks were higher across the board for hypertension (sHR, 1.21; 95% CI, 1.07-1.37), diabetes (sHR, 1.28; 95% CI, 1.05-1.56), and any risk factors (sHR, 1.15; 95% CI, 1.01-1.30) if a member of the study cohort vs a control participant received both left-sided radiation and endocrine therapy.

“These findings highlight patients with breast cancer as a vulnerable population at higher risk of developing cardiometabolic risk factors compared with the general population without a history of [breast cancer],” the authors determined, “and support targeted cardiovascular surveillance by specific patient and treatment characteristics to mitigate these risks.”

Potential reasons for the elevated risks mentioned herein include changes in blood pressure and metabolism precipitated by chemotherapy and endocrine therapy and that left-sided radiation is more likely to affect the heart and cause systemic changes to the cardiovascular system.


Kwan ML, Cheng RK, Iribarren C, et al. Risk of cardiometabolic risk factors in women with and without a history of breast cancer: The Pathways Heart Study. J Clin Oncol. Published online January 13, 2022. doi:10.1200/JCO.21.01738

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