Breast Cancer Survivors and Their Oncologists Need to Think About Cardiovascular Health

Many women who survive breast cancer spend a lot of time worrying about the risk of recurrence, but a study presented at the ASCO Breast Cancer Symposium in San Francisco suggests at least three-quarters of the women have as much risk of suffering a serious cardiovascular event, such as heart attack or stroke, in the first decade after treatment. Aditya Bradia, MD, a fellow at Johns Hopkins School of Medicine, presented the data from the study, which was a 2009 Breast Cancer Symposium Merit Award Recipient.

“Breast cancer survivorship is becoming an increasingly important issue,” said Dr Bradia. He displayed a slide that indicated there are at least 2 million breast cancer survivors in the United States, a rate expected to increase. In addition, 42% of new breast cancers are diagnosed in women aged >65 years. “With the aging population, as well as improved breast cancer therapies, the issue of breast cancer survivorship is becoming increasingly more important and the role of other health conditions should be considered in treatment decision-making,” he said. Cardiovascular disease (CVD) is the leading cause of death in men and women, accounting for one-quarter of US deaths, and a lifelong risk for many cancer survivors.

The long-term cardiovascular risks associated with anthracycline treatment are well established, but the risks associated with aromatase inhibitors have not been determined. “One study suggested a slight increase in CVD risk,” Dr Bradia said, “But other studies have found no association.” Aromatase inhibitors are often recommended instead of or in sequence with tamoxifen in postmenopausal women with hormone—receptor (HR)-positive breast cancer.

The aim of the study was to compare the 10-year risk of breast cancer recurrence with the 10-year risk of CVD among postmenopausal women with early stage HR-positive breast cancer who initiate treatment with an AI. They used data from a trial that took place at 3 sites, in which 500 women with stage 0 to III breast cancer were randomized to exemestane (Aromasin) or letrozole (Femara) for 2 years, either as a first-line treatment or after 3 to 5 years of tamoxifen. CVD risk factor data was collected at baseline, and this data was used to compute the 10-year CVD risk.

The 10-year risk of a serious CVD event was computed based on a modified Framingham score that uses age, diabetes, smoking, blood pressure, body mass index (BMI), and total cholesterol (including HDL). This also provided a composite endpoint called “heart age,” which Dr Bradia described as the estimated age of the patient’s heart based on these factors. To calculate 10-year breast cancer recurrence risk, the investigators used Adjvuant! Online, a prognostic tool that relies on patient age, size and grade of tumor, and lymph node status. Dr Bradia said they defined 3 categories, which they applied to both CVD event and breast cancer recurrence risk: low risk, <10%; moderate risk, 10% to 25%; high risk, >25%.

In the CVD study, they only had access to data from 2 of the trial sites, so their analysis included 242 women with a mean age of 61 years at diagnosis.

Approximately 42% of women had a low 10-year breast cancer recurrence risk, 55% had a moderate risk, and 3% had a high risk. CVD risk was 36% low, 52% moderate, and 12% high.

CVD Risk Factors

Mean BMI, 29

Mean cholesterol, 202 mg/dl

Mean HDL, 62 mg/dl

Mean heart age, 68

Breast Cancer Characteristics

Median tumor size, 1.6 cm

Lymph node-negative, 78.1%

Grade 2, 57.7%

Stage I, 64%

They then compared the 10-year breast cancer risk with the 10-year CVD risk and found that 22% of women had a greater chance of experiencing breast cancer recurrence than a serious CVD event in the next 10 years. For 43% of women, the risks were equal. Approximately 35% had a greater risk of having a serious CVD event than a recurrence of their breast cancer. In other words, Dr Bradia said, “three-fourths of the population had a cardiovascular risk equal to or higher than the breast cancer recurrence risk.”

As might be expected, women with disease factors commonly associated with reduced risk for breast cancer recurrence were more likely to have a risk of CVD events exceeding their breast cancer risk in comparison to their counterparts. Women identified as having a heart age >65 years were 16 times more likely to have a serious CVD event than breast cancer recurrence. “These women,” said Dr Bradia, “should be counseled appropriately.”

Dr Bradia outlined some limitations of the study; namely, that the estimates relied on prognostic tools rather than actual patient outcome data. In addition, Adjuvant! Online does not incorporate obesity and diabetes data, factors Dr Bradia said are believed to affect the risk of breast cancer recurrence. He also noted that the effect of therapy with aromatase inhibitors is not well known and is not part of the Framingham score. When data from the third trial site is available, the team plans to update their calculations. “We should identify interventions that could modulate both breast cancer and CVD risk,” he said. “In other words, kill two birds with one stone.” He also recommended developing education strategies for clinicians and patients with breast cancer.

Rowan Chlebowski, MD, PhD, Harbor-UCLA Medical Center in Los Angeles, California, chaired the session. “Breast cancer patients need more attention to cardiovascular health regardless of their risk level,” he said. Dr Chlebowski added that oncologists need to have more interaction with cardiologists. This might include referring high-risk patients for cardiac care. Abstract No. 133.