Long-term recurrence and survival data are now available from the groundbreaking TAILORx trial. With 12 years of follow-up, the updated analysis—reported by Sparano et al at the San Antonio Breast Cancer Symposium (SABCS) 2022 (Abstract GS1-05)—confirms the original findings that chemotherapy may have no benefit for a large proportion of patients with early-stage breast cancer. In addition, the longer follow-up reveals unexpected information about late recurrences. There was also a higher risk of early recurrence in Black patients.
Background
"The immediate clinical impact is that with longer follow-up, the main TAILORx study findings remain unchanged. Therefore, physicians can continue to use the 21-gene recurrence score results to guide decisions about the use of chemotherapy," highlighted lead study author Joseph A. Sparano, MD, FACP, the Ezra M. Greenspan MD Professor of Clinical Cancer Therapeutics, Deputy Director of The Tisch Cancer Center, as well Chief of the Division of Hematology and Medical Oncology at Mount Sinai Health System. Dr. Sparano is also the leader of the TAILORx trial for the Eastern Cooperative Oncology Group (ECOG)–American College of Radiology Imaging Network (ACRIN) Cancer Research Group.
Joseph A. Sparano, MD, FACP
Estrogen receptor–positive and HER2-negative breast cancer with no spread to the lymph nodes accounts for about one-half of new breast cancer cases in the United States each year. The landmark TAILORx trial gave an evidence-based answer to the question of which patients with this type of breast cancer may benefit from chemotherapy as a potentially life-saving treatment—and which may effectively pursue endocrine therapy to avoid the unnecessary side effects of chemotherapy.
The study used a molecular test that assesses the expression of 21 genes associated with breast cancer recurrence (on a scale of 0 to 100).
After following 10,273 patients for at least 5 years—with a median of 7.5 years—the TAILORx trial established that chemotherapy may safely be spared in patients with estrogen receptor–positive, HER2-negative, and lymph node–negative breast cancer with a 21-gene recurrence score of 0 to 25, who were postmenopausal or older than 50 years at diagnosis. It may also be spared in most patients with this type of breast cancer who were premenopausal or younger than 50 years.
Updated Analysis
In this updated analysis, trial volunteers were followed for an additional 3.5 years, now for an average of 11 years. The main study findings remain unchanged: chemotherapy use may be spared in many patients with estrogen receptor–positive, HER2-negative, and lymph node–negative breast cancer when guided by the 21-gene recurrence score result. As in the original analysis, the subgroup of patients younger than 51, with a score of 21 to 25 or 16 to 25, and high clinical risk derived some chemotherapy benefits that persisted out to 12 years. This cohort accounted for 7% of the trial participants.
For patients with a 21-gene recurrence score between 0 to 25, treated only with endocrine therapy, recurrence rates were very low on average—at less than 1% per year over the 12 years. However, more late recurrences occurred beyond the first 5 years after their breast cancer diagnosis than within the first 5 years.
The rates of cancer that came back with distant recurrence remained low, and overall survival rates remained high for patients with a 21-gene recurrence score between 0 to 25 when treated with endocrine therapy alone. However, there was an increasing divergence between rates of distant recurrence and invasive disease-free survival—a measure that included recurrence, death, and second primary cancers. This finding showed that the new development of second primary cancers dominated this cohort.
"There is a higher risk of developing a new breast cancer or other cancer than having a recurrence of the original cancer, pointing out the need for vigilance in cancer screening after a breast cancer diagnosis," noted Dr. Sparano.
Distant recurrence rates remained high for those with a 21-gene recurrence score between 26 to 100, despite adding chemotherapy to endocrine therapy. "More research is needed to develop more effective therapies for [patients] with a very high recurrence score who have unacceptably high recurrence risk[s] despite the use of chemotherapy,” emphasized Dr. Sparano.
Black patients were at higher risk of recurrence in the first 5 years after diagnosis, but not beyond the first 5 years. These disparities, Dr. Sparano clarified, were not explained by inequities in social determinants or health, nor by early discontinuation of endocrine therapy. "This finding adds to a growing body of evidence suggesting biological factors may contribute to the body developing resistance to endocrine therapy," he said.
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TAILORx Event Rates at 5 and 12 Years |
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Event Rate |
Arm A RS <11 ET |
Arm B RS 125 ET |
Arm C RS 11-25 Chemotherapy + ET |
Arm D RS 26-100 Chemotherapy + ET |
|
|
5-year |
94.0% |
92.8% |
93.1% |
87.6% |
Primary endpoint: Invasive Disease–Free Survival* |
|
12-year |
75.9% |
76.8% |
77.4% |
65.9% |
|
|
|
|||||
|
5-year |
99.3% |
98.0% |
98.2% |
93..0% |
Secondary endpoint: Distant Relapse–Free Interval |
|
12-year |
93.0% |
92.6% |
92.8% |
80.9% |
|
|
|
|||||
|
5-year |
98.0% |
98.0% |
98.1% |
95.9% |
Overall Survival |
|
12-year |
89.8% |
89.8% |
89.8% |
87.0% |
|
|
* Proportion alive and without breast cancer recurrence or a second primary cancer |
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| ET = endocrine therapy; RS = recurrence score. | |||||
Disclosure: The study was conducted by ECOG-ACRIN with funding from the National Cancer Institute. Other National Cancer Institute–funded network groups took part in the study. The research was supported in part by the Breast Cancer Research Foundation (https://www.bcrf.org), Susan G. Komen for the Cure, and the Breast Cancer Research Stamp.
