Anthracyclines for Breast Cancer? Who Needs Them?

Over many decades, thousands of women with early- stage breast cancer — identified as cancer isolated to the breast and sometimes the axillary lymph nodes — have participated in clinical trials that have led to lifesaving treatments for patients around the world.

Among them were trials providing clear evidence that a class of chemotherapy drugs called anthracyclines, in combination with other drugs, is active against early breast cancers. In particular, the standard in many practices is now the combination of an anthracycline, such as Adriamycin (doxorubicin); a taxane, such as Taxol (paclitaxel) or Taxotere (docetaxel); and other drugs. Modern post-surgical (adjuvant) chemotherapy using these drugs according to the best schedules can cut the rate of death by a third or more.

However, because anthracyclines can rarely bring on serious and long-lasting side effects, including leukemia and/ or heart failure, some in the medical community wonder if we can eliminate them and still treat breast cancer as effectively. At the 2016 annual meeting of the American Society of Clinical Oncology (ASCO), new data from the Anthracycline Breast Cancer Trials, or ABC Trials, was presented, shedding light on that issue.

Researchers asked two key questions: Can we identify patients with such a low risk of dying of breast cancer that we can avoid exposing them to the side effects of any chemotherapy? And, if we do use chemotherapy, do we need to use anthracyclines in all patients, or can we use other drugs that do not increase the chances of heart damage?

Three individual studies presented at the ASCO meeting offered data relevant to these critical questions. Collectively called the ABC trials, the studies were designed to be analyzed together. They tested whether the inclusion of an anthracycline in a modern taxane-containing chemotherapy regimen remained an important part of curative therapy. The primary aim of the ABC Trials was to compare treatments that used both anthracyclines and taxanes (collectively termed TaxAC) with the non-anthracycline-containing regimen of Taxotere (docetaxel) plus cyclophosphamide (TC) in terms of their ability to prevent potentially lethal breast cancer from recurring. The studies were designed to give TC its best shot at “passing the test” of not being inferior to TaxAC. Indeed, TC could have been 18 percent worse than TaxAC in terms of the rate of cancer recurrence and still be declared comparable.

The ABC Trials were very large, randomizing and treating more than 4,000 women, which increases one’s confidence in their results. The majority of these patients (69 percent) had hormone receptor-positive breast cancer, and nearly 60 percent had involvement of their axillary lymph nodes. After more than half of the patients were followed for three years, an official pre-planned analysis was conducted. An independent panel of experts recommended that the study be stopped because, while 88.2 percent of the patients getting TC were alive and free of cancer, the comparable number was 90.7 percent for those taking the TaxAC regimens. Said another way, the odds of cancer recurrence were 23 percent reduced by TaxAC when compared to TC, and this result passed a statistical test for reliability. Across all preplanned subgroups analyzed, in which the numbers of cases were adequate, the data favored TaxAC.

Not surprisingly, the magnitude of the benefit appears greatest in those patients with the highest risk of disease (i.e., those with more than four lymph nodes affected by cancer and those with triple-negative breast cancer). It might be that, for patients with very low risk of recurrence, the trade-offs between efficacy and toxicity might not justify the use of these drugs. This remains to be determined.

Moreover, these results do not prove that TaxAC is itself the best way to use taxanes and anthracyclines in the post-surgical setting. But the ABC Trials do show that anthracyclines and taxanes are useful classes of drugs, and that they both contribute to preventing the recurrence of cancer in many patients in the adjuvant setting.