A study of 12,500 women treated for HER2 positive breast cancer showed an association between the use of an anthracycline, trastuzumab (Herceptin) or other chemotherapy and the development of heart failure or cardiomyopathy, disease of the heart muscle. Through analysis of existing medical records, the results support findings of past clinical trials.
Trastuzumab is now standard of care for HER2 positive breast cancer because many studies have shown significant improvement in survival when it is used with chemotherapy. However, this remarkable benefit is sometimes offset by concerns about the possibility of an increased risk of heart failure. In some cases, women choose not to take Herceptin because of concerns about the risks to their heart health.
Reason for Study
Prior studies testing the safety of anthracyclines and trastuzumab led to prescription warnings and recommendations to test heart function before and during treatment.
Often, clinical trials exclude women 70 or older or those with comorbidities, or health conditions unrelated to the cancer. These rules help researchers study the effect of medicines on a specific group and identify other factors that could affect health and outcome. But in real life, people excluded from clinical trials may receive these treatments.
Researchers wanted to explore the impact of anthracyclines and trastuzumab on heart health in actual practice, by analyzing medical records of women who had received chemotherapy treatment.
Structure of Study
Medical records were collected from 14 research centers nationwide and included all women 18 or older diagnosed with HER2 positive breast cancer from 1999 through 2007. The investigators excluded women who had heart failure or cardiomyopathy before starting chemotherapy treatment.
Researchers organized participants by type of treatment: anthracycline-based only (29.6 percent), trastuzumab-based only (0.9 percent), an anthracycline followed by trastuzumab (3.5 percent), other chemotherapy (19.5 percent) or no chemotherapy (46.5 percent). Women in the anthracycline-based only or trastuzumab-based only groups may have received additional, non-anthracycline or trastuzumab treatments. They then looked at whether the women developed heart failure or cardiomyopathy, and whether it was likely caused by treatment, or incident.
Women who received an anthracycline plus trastuzumab tended to be younger, be diagnosed at a higher stage, have fewer other illnesses and be slightly more likely to have had radiation therapy than women who received other chemotherapy.
Women who received anthracycline-based only treatment were younger (under 65), diagnosed at a higher stage, had fewer comorbidities and were more likely to have had radiation therapy than women who received other chemotherapy. Those who received trastuzumab-based only were older (over 65) and had more other illnesses than women in the other groups.
These results suggest that doctors generally prescribe treatment based on women’s ages and other health conditions, giving treatment of greatest risk to the heart to younger, more heart-healthy women. Women over 65 tended to receive no chemotherapy, a finding reflected in many clinical trials.
Overall, the researchers concluded that risk of heart failure and cardiomyopathy is higher with anthracycline-based chemotherapy, versus with other or no chemotherapy. The risk was highest when treatment included both an anthracycline and trastuzumab, reflecting seven times as much risk as with no chemotherapy.
The researchers noted that the risk of heart problems in women who received trastuzumab-based treatment alone was higher than seen in the past, especially for women under 65.
The findings have some limitations. The data relied on each centers’ past record-keeping accuracy, as well as how often it screened women for good heart function before prescribing the chemotherapy. Also, younger women who receive either anthracyclines, trastuzumab or both are more likely than those who do not to have their heart health monitored closely. That can cause detection bias, meaning that younger, more heart-healthy women – such as those on trastuzumab – may show more heart problems because doctors are looking for them.
What This Means for You
This study reinforces earlier findings that show anthracycline- and trastuzumab-based treatment may affect heart health. If you receive an anthracycline, trastuzumab or both, your doctors will monitor your heart health throughout your life. As part of your long-term survivorship care plan, make sure to share your medical history with your primary care doctor and other providers.
If you are planning treatment, talk with your doctor about your treatment plan and its side effects. Your providers will choose your plan based on many factors, including your age, your heart health and other health concerns.
Bowles, Erin J. Aiello, Wellman, Robert, et al: Risk of Heart Failure in Breast Cancer Patients After Anthracycline and Trastuzumab Treatment: A Retrospective Cohort Study. JNCI J Natl Cancer Inst (2012) 104 (17): 1293-1305