Breast cancer survivors face greater cardiometabolic risks

Anew study reports that breast cancer (BC) survivors are at a greater risk for diabetes, high blood pressure, and dyslipidemia than women who have never been treated for BC. Appearing in the Journal of Clinical Oncology (doi:10.1200/JCO.21.01738), the study is based on data derived from the Pathways Heart Study at Kaiser Permanente Northern California (KPNC).

The researchers accessed the electronic health records of more than 4.5 million KPNC members at 21 hospitals and over 260 outpatient clinics in Northern California to identify women who were diagnosed with invasive BC between 2005 and 2013 and who were at least aged 21 years old. They identified 14,942 BC survivors and a control group of 74,702 women without a history of BC who had a similar age, race and ethnicity.

The researchers obtained data regarding each subject’s sociodemographic characteristics, including birth year, race, ethnicity, household income, and education level. They also included data on body mass index, menopausal status, smoking status, and whether the subjects had previously been diagnosed with a cardiometabolic condition. Clinical data for BC subjects included their tumor laterality and other characteristics, and details about their diagnosis and care, including the treatments they underwent, laboratory results, pharmacy records, and survival.

Two years after their cancer diagnosis, the cumulative incidence of hypertension in BC survivors was 10.9% versus 8.9% in the women without BC, although this difference was no longer present by 10 years post-diagnosis. A higher cumulative incidence of diabetes in BC survivors was evident after 2 years of follow-up (2.1% vs 1.7%) and remained so at 10 years of follow-up (9.3% vs 8.8%). The multivariable hazard ratio for diabetes in BC survivors (relative to control subjects) was 1.16 (95% CI, 1.07-1.26). Hazard ratios for diabetes were even higher in BC survivors who received chemotherapy (1.23; 95% CI, 1.11-1.38), left-sided radiation therapy (1.29; 95% CI, 1.13- 1.48), or endocrine therapy (1.23; 95% CI, 1.12-1.34). The multivariable hazard ratio for hypertension was not significantly higher in BC survivors overall (relative to control subjects), yet was significantly higher in subgroups of patients who had received left-sided radiation therapy (1.11; 95% CI, 1.02-1.21) and endocrine therapy (1.10; 95% CI, 1.03-1.16).

Although being overweight is associated with diabetes, hypertension, and postmenopausal breast cancer, even BC survivors who were not overweight at the time of their diagnosis faced a significantly higher risk of developing diabetes and high blood pressure relative to the control subjects without breast cancer.

“We believe our study builds on and contributes to the growing clinical field of cardio-oncology,” says Dr. Kwan. She notes that over the past decade, oncologists and cardiologists have begun to work closely together to meet the needs of patients with cancer who have received treatments that have the potential to cause heart damage. To this end, this study highlights the importance of informing patients with BC about their long-term risk for diabetes and high blood pressure. “Identifying this higher risk is the first step in improving health outcomes in patients with breast cancer,” says Dr. Kwan. “Clinicians can then talk to their patients about the importance of leading a healthy lifestyle to reduce their risk.”

Kevin C. Oeffinger, MD, a professor of medicine in the department of community and family medicine at Duke University in Durham, North Carolina, says that the study breaks new ground not only because of the number of subjects included, but also because of the adequate follow-up time and the key information available in the dataset of the health care system. “We have known for some time that breast cancer survivors have an elevated risk of cardiovascular morbidity and mortality, in part, due to the shared pathway of postmenopausal breast cancer and cardiovascular disease, and the known associations with aging, obesity, and insulin resistance. This study adds the observation that women surviving their cancer therapy are more likely to develop hypertension and/or diabetes, particularly [among] those who were treated with either left-sided radiation and/ or endocrine therapy.”

As a result, Dr. Oeffinger says it is essential for clinicians to be mindful of the cardiovascular disease risk in breast cancer survivors. “Often women are referred to the cancer specialist by their [primary care provider (PCP)] and then are followed by the oncology team for the next several years, generally with only social visits with their PCP. It is common that cardiometabolic risk factors are not addressed, as the oncology team is very focused on delivering high-quality cancer care, which can be both complicated and time consuming. Then, as PCPs often note, patients return to them after a few years with what PCPs describe as a black hole—often [patients have] only lengthy faxed notes with oncologic jargon that is difficult to decipher.”

Dr. Oeffinger says that a key message of the study is that it truly takes a team approach in the care of women with breast cancer, and that this team should include the patient’s PCP. “Then, the oncology team can focus on what they do best—achieving a cure—while the PCP, in communication with the oncology team, can manage these comorbidities. Researchers need to test interventions that enhance this team approach, aimed not only at achieving a cure but also at optimizing the patient’s longevity and quality of life.” Dr. Oeffinger says that PCPs should, “… stay involved and manage the noncancer comorbidities. Some individuals might question whether these additional PCP visits are really needed; the findings of this study suggest the answer is a definite yes.”

Dr. Oeffinger’s colleague Leah L. Zullig, PhD, MPH, an associate professor in the department of population health sciences at Duke University Medical Center, adds that for these interventions to achieve their greatest potential, they should be designed in such a way that there is the possibility of implementation in “usual” health care settings. “In other words, using resources that are available in many real-world clinical settings,” she says. “This will improve the potential for interventions to reach patients and their providers beyond the confines of a research study.