Seventy percent of women with the most common type of newly diagnosed breast cancer can now be identified and safely skip chemotherapy, according to the results of a landmark 12-year clinical research study.
Data from the Trial Assigning Individualized Options for Treatment show that chemotherapy does not increase disease-free survival rates for women with early stage breast cancer and an intermediate risk of recurrence determined by the Oncotype DX Recurrence Score test. The study was designed to more precisely determine the effect of chemotherapy, if any, for women with hormone receptor (HR)-positive, HER2-negative, axillary lymph node-negative breast cancer.
The findings, recently presented at the American Society of Clinical Oncology annual meeting in Chicago and published in the New England Journal of Medicine, are expected to inform treatment decisions for thousands of breast cancer patients.
“TAILORx has made it possible to more precisely identify which patients do not benefit from chemotherapy and enjoy a very low risk of recurrence with endocrine therapy alone. This study represents a major advancement in precision medicine,” said study co-author and physician-researcher Charles Geyer, M.D., associate director for clinical research at VCU Massey Cancer Center. Geyer served on the TAILORx Steering Committee for 12 years and participated in the design, oversight and analysis of the trial.
“All of the women on the study benefited from receiving endocrine therapies that block the activated estrogen pathway, but only about 30 percent benefitted from also receiving chemotherapy,” Geyer said. “These results have eliminated a common area of uncertainty for patients and their oncologists.”
TAILORx, a phase three clinical trial that opened in 2006, was led by the ECOG-ACRIN Cancer Research Group under the sponsorship of the National Cancer Institute. Every adult cancer research group in the NCI's National Clinical Trials Network enrolled patients in the trial.
More than 10,000 women enrolled at approximately 1,200 sites in the United States, Australia, Canada, Ireland, New Zealand and Peru, making TAILORx the largest adjuvant breast cancer treatment trial ever conducted.
VCU Massey Cancer Center served as a participating site under the leadership of Harry Bear, M.D., Ph.D., who served as the local principal investigator of the trial. Bear is the Walter Lawrence Jr. Distinguished Professor of Oncology, chair of the Division of Surgical Oncology, and a member of the Developmental Therapeutics research program at Massey.
“Massey has a long history of participating in key phase three breast cancer clinical trials under Dr. Bear’s leadership, which for decades has provided our patients with access to this type of landmark, transformative clinical trial,” Geyer said.
TAILORx used a genomic test — Oncotype DX Breast Recurrence Score® — to assess individualized risk for breast cancer recurrence among the trial participants.
Based on previous studies, women with scores below 11 were determined to be at low risk and received only hormonal therapy. Women with scores above 25 were considered high risk for recurrence and given hormonal therapy plus chemotherapy. Midrange scores from 11 to 25 were identified in 69 percent of the participants (6,711) and were determined to have intermediate risk of recurrence.
The benefit of chemotherapy has historically been uncertain for women with intermediate scores. To address that ambiguity, these individuals were randomly assigned to receive hormonal therapy and chemotherapy or hormonal therapy alone.
Nine years after treatment, the overall group of women who received hormonal therapy alone had the same disease-free survival rate without recurrence as the women who received hormonal therapy and chemotherapy.
However, additional analyses demonstrated that the one-third of women 50 and younger at the time of their diagnosis appeared to receive benefit from chemotherapy when their scores were 16 and above. In women older than 50, the benefit from chemotherapy did not appear to be present until scores were above 26.
“This important age-related finding was only possible to detect because of the large number of women with intermediate scores who agreed to be randomized on the study. They are the real heroes of this historic study,” Geyer said.
Researchers also found that women of any age with scores of 15 and below had very low recurrence rates after nine years of receiving hormone therapy alone. This confirmed and expanded similar findings from an earlier report from TAILORx in women with scores less than 11.
Based on the results of TAILORx, thousands of women will be spared the grueling and toxic side effects of chemotherapy that is not likely to provide a benefit. Experts agree that the trial’s findings are a game-changer for breast cancer treatment and quality of life for many patients.