In Older Breast Cancer Survivors, CVD Risk May Fly Below the Radar

In older women diagnosed with early-stage breast cancer, cardiovascular disease poses a mortality risk that may be underrecognized, according to a large, population-based study. One in six deaths over the follow-up period of more than 6 years were related to cardiovascular causes. 

“Breast cancer is a scary diagnosis and for many women it may assume the focus of their attention toward their health,” the study’s lead author, Husam Abdel-Qadir, MD (University of Toronto, Canada), told TCTMD. “But, as our study shows, cardiovascular risk is an important issue in this population.”

The study, published online October 12, 2016, ahead of print in JAMA Cardiology, looked at deaths over a period of more than 6 years among 98,999 women enrolled in the Ontario Cancer Registry who had a diagnosis of early-stage breast cancer. Of these, 6.6% had a prior history of cardiovascular disease.

The mortality rate was 21.3%, with a median time to death of 4.2 years. Most deaths (49.9%) were due to breast cancer, while cardiovascular disease accounted for about one in six deaths (16.3%). However, the majority of the cardiovascular deaths—nearly 90%—occurred among women aged 66 years or older at diagnosis.

Compared with younger women, those 66 or older had a greater than 10-fold increase in the cause-specific hazard for cardiovascular death. Additionally, women older than 75 years had 42 times the risk of cardiovascular death relative to those who were 55 years or younger at time of diagnosis.

In women who had a previous history of cardiovascular disease, the risk of dying from breast cancer or cardiovascular causes was similar for the first 5 years of follow-up, but cardiovascular disease became a more important driver of mortality after that point, accounting for 16.9% of deaths at 10-year follow-up compared with 14.6% for breast cancer.

Abdel-Qadir said the message regarding older women and those with prior cardiovascular disease is that their competing risks for mortality should be taken into consideration and that they are good candidates to benefit from cardio-oncology programs, especially since their risk of cardiovascular death would be expected to continue to rise, becoming more of a determinant of overall survival.

For women who were younger and had no cardiovascular risk factors prior to their cancer diagnosis, the risk of dying from cardiovascular disease was less than 1 in 200, Abdel-Qadir said.

“This tells us that in women such as these, the primary focus of their care should be their breast cancer,” he observed. “However, you want to provide appropriate therapy to prevent cardiovascular disease [and] among these women it would probably be less wise to try to limit chemotherapy because of concern about cardiovascular disease and survival.”

Future research, Abdel-Qadir added, should focus on finding ways to match cancer treatment with individual risk of cardiovascular death, something that he says is “doable.” But that will require a more thorough understanding of the type of management strategies that are needed.

“We can’t assume that what we know about the natural history of cardiovascular disease applies in a population who has cancer,” he noted.

Cardiac Assessments Lacking in Cancer Patients

Commenting on the study for TCTMD, Daniel J. Lenihan, MD (Vanderbilt University Medical Center, Nashville, TN), said the data are important given the dearth of information on patients with cancer and cardiovascular disease. Two of the largest papers published to date on cardiovascular disease in breast cancer patients, he noted, used billing codes to track heart failure outcomes. While those studies showed that heart failure was a comorbid and fairly frequent condition, the new study strengthens and adds to the association by showing disease-specific causes of death.

“This is an important observation,” Lenihan said. “All the breast cancer studies historically have not ascertained underlying heart disease at baseline. There needs to be at least some assessment of cardiovascular risk at the beginning of therapy.”

Lenihan said cancer survivor guidelines due out soon from the American Society of Clinical Oncology are expected to include recommendations for that type of assessment. As to who should do the assessment, he said the emphasis should be on cardiologists and oncologists working together, instead of expecting oncologists to do all the work.

“It’s not right to say to an oncologist ‘you need to be thinking about heart disease and you need to do these tests in your visit.’ That’s not the way to approach this,” Lenihan added. “Cardiologists need to be helpful in this setting. They need to be more proactive and ascertain the presence of cardiac issues in these patients. This study shows you why that’s important.”

Cezar A. Iliescu, MD (MD Anderson Cancer Center, Houston, TX), told TCTMD in an interview that the extent of undiagnosed CAD in breast cancer patients is hard to categorize, but studies such as this are contributing to “a shift in understanding the importance of treating all the additional comorbidities.”

Likewise, it also provides a message to women to stay on top of their risk factors such as hypertension, diabetes, obesity, and depression both during and after breast cancer treatment, he noted.

“Data from studies like this are very welcome, and this is an excellent foundation for so many more things to come,” Iliescu said. Among those possibilities are understanding more about vascular toxicity in cancer treatment and how certain drugs and radiation may contribute to vascular aging, as well as how additional stressors from cancer exacerbate established cardiovascular disease, he said.