A study published in the October 11, 2007 issue of The New England Journal of Medicine shows that women with estrogen receptor-positive, HER2-negative breast cancer do not benefit from treatment with paclitaxel after surgery. Preliminary data from this study was reported in an abstract at the 2006 ASCO Annual Meeting.

Background

The addition of chemotherapy after surgery helps women with breast cancer live longer. The Cancer and Leukemia Group B (CALGB) clinical trial 9344 first demonstrated the benefit of adding paclitaxel (Taxol) after four cycles of doxorubicin (Adriamycin, Rubex) and cyclophosphamide (Cytoxan, Neosar) to the chemotherapy program.

In 2007, the role of proteins that are expressed by a breast cancer tumor, such as estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) play an increasingly important role in breast cancer treatment. For example, women with ER-positive breast cancer usually receive hormone therapy, such as tamoxifen (Nolvadex) or aromatase inhibitors, and women with HER2-positive breast cancer may receive anti-HER2 therapies, such as trastuzumab (Herceptin) and lapatinib (Tykerb).

The Study

In this study, 1,500 women with lymph node-positive breast cancer (meaning cancer was in the lymph nodes) were selected from 3,121 women who had received doxorubicin and cyclophosphamide, and then received no further therapy, or additional treatment with paclitaxel, in the original study. Of the 1,500 women, stored tumor tissue samples were available from 1,322 women. The researchers analyzed these samples for HER2 and ER and compared these results with disease-free survival (the length of time after treatment during which no cancer is found). The results suggest that paclitaxel helps women with HER2-positive breast cancer, as well as those with ER-negative breast cancer, regardless of the HER2 status. The study also suggests that there was very little benefit from paclitaxel for women with ER-positive and HER2-negative breast cancer, a common subtype of breast cancer.

Additional perspective

Since the time of the study, chemotherapy has improved and is given in different schedules. For example, paclitaxel is no longer given every three weeks. It is given either every two week (dose dense) or weekly, at a lower dose. A similar drug called docetaxel (Taxotere) is given every three weeks, and this schedule has been shown to be effective. Both of these treatment schedules have been shown to be better than the way paclitaxel was given in CALGB 9344 clinical trial.

According to Eric Winer, MD, Director, Breast Oncology Center at the Dana-Farber Cancer Institute, Associate Professor of Medicine at Harvard Medical School in Boston, and an author of this study, this type of study can help develop the important questions to direct the research, but the results should not lead to a change in practice at this time, especially since other trials have reached conflicting conclusions about the benefit of chemotherapy with respect to HER2 and ER.

"Women with ER-positive, HER2-negative breast cancer represent about 50% to 60% of all breast cancers. Many of these patients may not benefit from chemotherapy of any type," said Julie Gralow, MD, Chair, ASCO Cancer Communications Committee and Associate Professor of Medicine/Oncology at the University of Washington School of Medicine and Fred Hutchinson Cancer Research Center in Seattle. "However, we’ve gained a better understanding that ER status is far more complex than the simple labels of positive or negative. Additionally, optimal and reproducible HER2 testing continues to evade us. We also know that numerous other genes, tumor, and patient factors contribute to the risk of the cancer coming back and the effectiveness of chemotherapy for breast cancer."

Bottom line

"This is an interesting, provocative study, but it is premature to change the way we are treating our patients," said Gabriel Hortobagyi, MD, FACP, ASCO's Immediate Past President and Chair of the Department of Breast Medical Oncology at the University of Texas M. D. Anderson Cancer Center in Houston.

"We need to work harder to define the patients who benefit from chemotherapy, including specific types of chemotherapy, and those who don't. Until we can identify the women who can safely forego chemotherapy after surgery, oncologists should not change the way they treat their patients," Dr. Gralow said.

"We all believe that future treatment for women with breast cancer will be more individualized and will likely include less chemotherapy," added Dr. Winer, "but this study doesn't give us the answers we need to change practice."

What This Means for Patients
These results suggest that a specific group of women—those with HER2-negative and ER-positive breast cancer—may be able to skip treatment with paclitaxel. However, even in this group of women, there are patients who will likely benefit from treatment with paclitaxel. By itself, this clinical trial does not mean the treatment of women with breast cancer will change. However, this study does contribute to our developing understanding of the role of chemotherapy in preventing breast cancer from coming back.

Reference
HER2 and Response to Paclitaxel in Node-Positive Breast Cancer. The New England Journal of Medicine, 2007; 357:1496-1506.

More Information
Cancer.Net Guide to Breast Cancer
What to Know: ASCO's Guideline on HER2 Testing for Breast Cancer
Cancer.Net Feature: Understanding Chemotherapy