A follow-up assessment of data from the National Surgical Adjuvant Breast and Bowel Project B-31 (NSABP B-31) clinical trial showed that adding trastuzumab (Herceptin) to combination chemotherapy treatment raises the risk of heart problems, but they are not long-term.
Heart problems are a known risk of anthracycline-based chemotherapy. Past trials have shown that anthracycline-based chemotherapy followed by trastuzumab, the standard treatment for HER2 positive breast cancer, significantly increases the risk of heart issues.
NSABP B-31 compared the effect of the chemotherapy combination doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan), followed by paclitaxel (Taxol), or AC/T, with or without trastuzumab (Herceptin) in women with HER2 positive breast cancer. The study’s primary endpoints, or goals, were to measure which treatment had better outcomes, and to assess the effect of trastuzumab on heart function.
Women were randomly assigned to one of two treatment arms:
- In arm I, 947 women received AC every three weeks for four courses, followed by either T every three weeks for four courses, or T weekly for 12 weeks
- In arm II, 743 women received the same chemotherapy regimen, with the addition of trastuzumab given for 90 minutes on the first day of paclitaxel treatment, then 30 minutes weekly for 51 weeks
Participants were women of any age with stage II or stage IIIA HER2 positive primary breast cancer with cancer in at least one lymph node. They were in good heart health and had not been treated with chemotherapy, hormonal therapy or biologic therapy for breast cancer before the trial.
Participants who had lumpectomy were given radiation after chemotherapy; those who had mastectomy had the option of radiation therapy based on specific factors. All women with hormone-sensitive disease were given tamoxifen or another hormonal therapy for five years following treatment.
Researchers monitored each participant’s heart function before and during treatment. For the seven-year follow-up after treatment ended, data on heart function was collected and analyzed. The findings describe the number of cardiac events, which include death from heart issues; symptoms of congestive heart failure, or weakness of the heart muscle; and a decrease in blood pumped from the main chamber of the heart (LVEF).
The findings showed:
- 4 percent of women who received trastuzumab had a cardiac event, versus 1.3 percent of women who did not
- Of the 37 cardiac events in the trastuzumab arm, all but two occurred within two years of finishing treatment
- Of the 69 women who stopped trastuzumab because of a decrease in LVEF, 78 percent recovered to the normal LVEF range. Generally, "normal range" is accepted as 55 percent. For this study, 50 percent was accepted as normal range.
- One death from heart problems occurred in each treatment arm
Investigators also developed a system to estimate risk of congestive heart failure based on a person’s age and baseline LVEF before treatment.
What This Means For You
This study adds to existing findings that show anthracycline-based chemotherapy plus trastuzumab increases the risk of heart problems. But the long-term nature of this analysis also shows that though the risk of developing heart problems is higher in trastuzumab-takers, those problems that do occur usually happen during treatment or within the two years after and resolve once treatment ends. Researchers believe the benefit of adding trastuzumab to chemotherapy for HER2 positive breast cancer outweighs the potential risks of these short-term heart problems.
More research on the accuracy of the model used to predict risk of congestive heart failure is necessary before it can be used in common practice. Such a system could be useful in the future for people planning treatment with trastuzumab.
If you and your doctor are creating a treatment plan, be sure to discuss all possible side effects of the course you choose; report any new symptoms once treatment begins.
Romond, Edward H., Jeong, Jong-Hyeon, et al: Seven-Year Follow-Up Assessment of Cardiac Function in NSABP B-31, a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel (ACP) With ACP Plus Trastuzumab As Adjuvant Therapy for Patients With Node-Positive, Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. J Clin Oncol (November 2012) 30 (31): 3792-3799.