Women whose breast cancer is positive for HER-2 are most likely to benefit from adding paclitaxel to their chemotherapy regimen, whereas women whose tumors are estrogen-receptor-positive but HER-2-negative do not benefit from added paclitaxel, according to an article in the October 11 issue of the New England Journal of Medicine.

The multicenter study was led by University of Michigan Comprehensive Cancer Center researchers. About 15 percent to 20 percent of breast cancers express HER-2, and as many as three quarters of breast cancers are estrogen-receptor-positive.

“In general, chemotherapy for breast cancer has been a one-size-fits-all approach. Our decision to recommend it is based on whether a woman is at high risk of the breast cancer recurring, without any idea of whether she would benefit from the additional therapy. With this data we hope we will be able to focus chemotherapy on patients whom it’s most likely to help,” said lead study author Daniel Hayes, MD, clinical director of the breast oncology program at the U-M Comprehensive Cancer Center. Hayes was the lead investigator on the study, which was run by the Cancer and Leukemia Group B through the Breast Cancer Intergroup of North America.

The study looked at tissue samples and data from 1,500 women who had previously participated in a study looking at the benefit of adding paclitaxel after four cycles of doxorubicin and cyclophosphamide. Cancer had spread to the lymph nodes in all women.

All the women were given combination chemotherapy for four cycles, after which half the women received four cycles of paclitaxel and the other half did not receive additional chemotherapy. A previous analysis had shown that adding paclitaxel decreased the chances of recurrence and improved survival when all patients were considered, with no consideration of HER-2 status.

However, previous studies have also suggested that women whose tumors were estrogen-receptor-positive did not seem to benefit as much from chemotherapy as those women whose tumors were negative for the receptors.

In the current analysis, researchers found that the addition of paclitaxel improved survival rates in women who were HER-2-positive regardless of estrogen receptor status. However, women whose tumors were HER-2-negative and estrogen-receptor-positive had no additional benefit. More than half of the patients in the study fell into the latter category.

The researchers do not recommend a change in treatment at this point, stating that more research must be done to confirm that paclitaxel does not benefit estrogen-receptor-positive breast cancer.

“This is the first such observation that has been made, and it was made retrospectively, meaning we looked backwards instead of forwards. We are not recommending at this time that women with positive lymph nodes, for whom we would currently recommend paclitaxel, but who are estrogen receptor-positive and HER-2-negative not take the paclitaxel. We think the stakes are too high,” Hayes said.

“We’ve seen mortality from breast cancer dropping in recently years because we have applied these new and better therapies. But now we believe, if these results are confirmed and validated in other studies, that perhaps we could pull out half the patients in that study and save them from the toxicities and the cost of receiving a drug that might not do them any good,” he continued.

“Determining who does not need chemotherapy and can be spared some portion of toxic therapy is one of the biggest issues facing breast cancer today,” said senior study author Donald Berry, PhD, professor and head of the Division of Quantitative Sciences at The University of Texas M. D. Anderson Cancer Center. “In oncology, we are very good at adding therapies to a patient’s regimen, but we are not as confident subtracting treatment. Hopefully, in time, we’ll be able to limit therapies to those that will truly benefit from the additional regimen.”