Results from a recent study by the Breast Cancer International Research Group 006 (BCIRG-006) showed that when trastuzumab (Herceptin) treatment was paired with platinum-based chemotherapy rather than the standard anthracycline, women with HER2 positive, early-stage breast cancer lived just as long but had less risk for side effects to the heart.
Anthracycline chemotherapy medicines such as doxorubicin (Adriamycin) can cause heart damage and increase risk for future blood cancers. Trastuzumab can also cause heart damage, though at a lower rate. When anthracyclines and trastuzumab are combined, it often further increases risk to the heart.
Reason for the Study
The first studies of chemotherapy in combination with trastuzumab for advanced breast cancer showed that doxorubin could not be given safely in combination with trastuzumab in HER2 positive breast cancer. Researchers wanted to see if other medicines would work just as well with trastuzumab but provide women with greater protection from side effects to the heart.
Laboratory research also showed a positive connection between trastuzumab and two medicines: docetaxel, a taxane-based chemotherapy; and carboplatin, a platinum-based chemotherapy. This led researchers to predict that this combination of medicines might prove more effective, as well as avoid the potential heart-damaging side effects found when anthracycline chemotherapies are combined with trastuzumab.
This was the first large, randomized early stage breast cancer trial to test non-anthracycline chemotherapy with trastuzumab.
Structure of the Study
The trial included 3,222 women with HER2 positive breast cancer. Participants were randomly assigned to receive one of three post-surgical chemotherapy treatments: doxorubicin, cyclophosphamide and docetaxel (AC-T); AC-T plus trastuzumab; or docetaxel and carboplatin (Paraplatin) plus trastuzumab (TCH).
The study was designed to test the two trastuzumab-containing regimens against treatment without trastuzumab, not against each other. The question about whether one trastuzumab-containing regimen is better than the other was not considered. Instead, researchers focused on comparing differences in occurrences of breast cancer to episodes of congestive heart failure, when the heart cannot provide enough blood flow through the body.
Results of the Study
Researchers defined disease-free survival (DFS) as the length of time since enrollment in the study without a breast cancer recurrence, the development of a second primary cancer, or death from any cause. In a five-year follow-up, women in both trastuzumab groups had better five-year DFS than those who received AC-T alone. The difference between the two groups that received trastuzumab and the one that did not was statistically significant, meaning it is unlikely the differences could have happened by chance. No significant difference was found between the two groups that got trastuzumab.
A total of 144 women receiving docetaxel and carboplatin plus trastuzumab had a distant cancer recurrence. This compared to 124 women who received AC-T plus trastuzumab. This finding shows women whose treatment did not include an anthracycline had a slightly higher risk for recurrence, although the absolute difference was small.
In the group receiving AC-T plus trastuzumab, 21 had congestive heart failure, compared to four women who received docetaxel and carboplatin plus trastuzumab . This shows that including the standard anthracycline in treatment significantly increases the likelihood of heart problems.
What This Means for You
The results of this trial confirm previous findings that chemotherapy using trastuzumab improves survival in HER2 positive breast cancer. They also suggest that the docetaxel and carboplatin plus trastuzumab combination may be another option for your care.
You and your care team should weigh the risk of an increase in the potential for cancer recurrence without an anthracycline against the increased potential for heart issues with an anthracycline. You and your care team will need to discuss whether these treatment options might be useful for you, given your unique situation.
Slamon, Dennis, et. al. Adjuvant Trastuzumab in HER2-Positive Breast Cancer New England Journal of Medicine October 6, 2011 365(14):1273