Adjuvant Chemoendocrine Therapy Ups CV Risk : Resting echocardiography may not be sufficiently sensitive to detect subtle cardiac dysfunction.


SAN ANTONIO — Breast cancer patients who receive adjuvant chemoendocrine therapy experience a marked reduction in cardiac reserve and diminished peak oxygen consumption, placing them at increased long-term risk for cardiovascular events, Dr. Mark Haykowsky reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

This risk is further compounded by a tendency for worsening lipid profiles in women on aromatase inhibitors, which are increasingly replacing 5 years of tamoxifen as the standard for adjuvant endocrine therapy.

Indeed, as breast cancer mortality continues to decline because of earlier diagnosis and improved therapies, late-occurring cardiovascular disease is becoming an increasingly important source of competing mortality in the estimated 2.3 million U.S. women living with a history of breast cancer, added Dr. Haykowsky of the University of Alberta, Edmonton.

He reported on 47 postmenopausal patients who had hormone receptor-positive early-stage breast cancer treated with surgery followed by adjuvant radiotherapy, anthracycline-containing chemotherapy, and endocrine therapy. All participants had completed radiation and chemotherapy at the time of the cardiac function study. Of the total, 26 women were on adjuvant tamoxifen for their endocrine therapy, while 21 were on an aromatase inhibitor; 11 age-matched healthy women served as controls.

The mean peak oxygen consumption in the breast cancer patients was 17.9 mL/kg per minute, significantly worse than the 22.2 mL/kg per minute in controls.

This impairment in peak oxygen consumption appeared to result from a lower stroke volume and cardiac output at peak exercise. Stroke volume at peak exercise was 68 mL/beat in the breast cancer patients, compared with 76 mL/beat in controls. Cardiac output at peak exercise averaged 10.4 L/minute in the cancer patients and 11.7 L/minute in controls. And cardiac reserve averaged 1.7 watts (W) in women with breast cancer, compared with 2.4 W in controls. All of this adds up to diminished oxygen delivery to skeletal muscles in breast cancer patients receiving standard adjuvant therapies.

The patients' low stroke volume was probably the result of impaired ventricular preload, since systemic vascular resistance as reflected in peak heart rate and afterload didn't differ between patients and controls, Dr. Haykowsky continued.

Of note, the breast cancer patients with the greatest impairment in peak oxygen consumption also tended to have the worst cardiovascular risk profiles. And those on an aromatase inhibitor had worse lipid profiles and higher levels of C-reactive protein, insulin, and glucose than did those on tamoxifen.

This study was the first to scrutinize the mechanisms responsible for exercise limitation in recipients of chemoendocrine therapy for early-stage breast cancer. An important clinical implication of the results is that resting echocardiography—the imaging tool oncologists and clinical trialists most often turn to in order to check cancer patients' heart function—appears to be insufficiently sensitive for early detection of treatment-associated subtle cardiac dysfunction.


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