Most Early Breast Cancer Patients Do Not Need Chemotherapy
By Mark L. Fuerst
CHICAGO—Most women with early breast cancer do not benefit from the addition of chemotherapy to hormone therapy when guided by a diagnostic test, according to a new study.
For women with the most common type of breast cancer—hormone receptor-positive, HER2-negative, axillary node-negative, early-stage breast cancer—who have a mid-range score on a 21-tumor gene expression assay (Oncotype DX Breast Recurrence Score), treatment with chemotherapy and hormone therapy after surgery is not more beneficial than treatment with hormone therapy alone. The findings are expected to have an immediate impact on clinical practice, sparing thousands of women the side effects of chemotherapy.
“Half of all breast cancers are hormone receptor-positive, HER2-negative, and axillary node-negative. Our study shows that chemotherapy may be avoided in about 70 percent of these women when its use is guided by the test, thus limiting chemotherapy to the 30 percent who we can predict will benefit from it,” said lead author Joseph A. Sparano, MD, Associate Director for Clinical Research at the Albert Einstein Cancer Center and Montefiore Health System in New York City.
“Before TAILORx, there was uncertainty about the best treatment for women with a mid-range score of 11-25 on the Oncotype DX Breast Recurrence Score test. The trial was designed to address this question, and provides a very definitive answer.” Sparano reported on the results of the study at a press briefing at the American Society of Clinical Oncology Annual Meeting (Abstract LBA1).
Up to 30 percent of women with this breast cancer have incurable recurrence by 10 years. Adjuvant chemotherapy is recommended, but the benefit is small, in about 3-5 percent of patients, he said. “Most patients are over-treated, and estrogen therapy alone is adequate. Some are under-treated and some who did not receive chemotherapy could have benefited,” said Sparano.
Based on evidence from several prior studies, the 21-gene expression assay has been widely used to analyze tumors and provide prognostic information about the risk of breast cancer recurrence within 10 years, and to predict which patients are most likely to benefit from chemotherapy. Women with a low score (0-10) typically receive only hormone therapy and those with a high score (26-100) receive hormone therapy and chemotherapy.
The Trial Assigning IndividuaLized Options for TReatment (TAILORx) enrolled 10,273 women with hormone receptor-positive, HER2-negative, axillary node-negative breast cancer at 1,182 sites in the U.S., Australia, Canada, Ireland, New Zealand, and Peru. Women who had a mid-range recurrence score of 11-25 (6,711 women) were randomly assigned to receive hormone therapy alone or hormone therapy and chemotherapy.
At a median follow-up of 7.5 years, the study met its primary endpoint of disease-free survival (DFS), indicating that hormone therapy alone was not less-effective than chemotherapy plus hormone therapy in women with a Breast Recurrence Score of 11-25. Nine-year rates were similar in the two treatment arms for DFS (83.3% vs. 84.3%), distant recurrence (94.5% vs. 95%), and overall survival (93.9% vs. 93.8%), indicating no benefit from adding chemotherapy to hormone therapy.
When the researchers analyzed premenopausal women and those younger than 50 years old at the higher end of the intermediate-risk range (16-25) separately, the results showed there may be a small benefit from chemotherapy. These women should consider chemotherapy with their doctor, he said. However, it is unclear if this benefit is due to the effect of chemotherapy or to endocrine suppression caused by chemotherapy-induced menopause.
Women with a recurrence score of 10 or less had very low recurrence rates with hormone therapy alone, irrespective of age or other clinical factors (3%). In addition, those with a recurrence score of 26 or higher had a distant recurrence rate of 13 percent despite chemotherapy and hormone therapy, indicating the need to develop more effective therapies for women at high risk of recurrence.
The findings suggest, said Sparano, that chemotherapy may be spared in about 70 percent of women with HR-positive, HER2-negative, node-negative breast cancer who are:
• older than 50 and with a recurrence score of 11–25 (45%)
• any age with a recurrence score of 0-10 (16%)
• 50 years old or younger with a recurrence score of 11-15 (8%)
The findings suggest that chemotherapy may be considered for the remaining 30 percent of women who are:
any age with a recurrence score of 26-100 (17%)
50 years old or younger with a recurrence score of 16-25 (14%)
“Any woman with early-stage breast cancer 75 years or younger should have the test and discuss the results of TAILORx with her doctor to guide her decision regarding chemotherapy after surgery to prevent recurrence,” said Sparano.
ASCO Expert Harold Burstein, MD, PhD, Associate Professor of Medicine at Harvard Medical School, commented: “These data provide critical reassurance to doctors and patients that they can use genomic information to make better treatment decisions in women with early-stage breast cancer. Practically speaking, this means that thousands of women will be able to avoid chemotherapy, with all of its side effects, while still achieving excellent long-term outcomes.
“The most challenging decision for clinicians with these women is whether to add adjuvant chemotherapy. The vast majority of women who have tests on their tumors can now be told they do not need chemotherapy. The goal is to tailor treatment. This allows us to individualize therapy.”
In addition, Burstein said, “even in the highest risk group, 10-year DFS was 87 percent. We have made extraordinary progress in the way we manage breast cancer. Women who get modern therapy do extremely well.”