TAILORx-RxPONDER Clinical Research Extension Award: Advancing Progress, Precision, and Equity in Breast Cancer Care
Abstract
Estrogen-receptor positive, HER2-negative breast cancer is the most common breast cancer subtype, accounting for about 70% of all individuals who present with early-stage breast cancer. This type of early-stage breast cancer is potentially curable with surgery, radiation, and anti-estrogen therapy given for a period of at least 5 years after surgery. Anti-estrogen therapy, also commonly referred to as endocrine therapy, is recommended for all individuals with estrogen-receptor positive early breast cancer in order to reduce recurrence risk in the breast, regional lymph nodes, and other organs. Adjuvant chemotherapy given after surgery also reduces the risk of disease recurrence, especially in those at higher recurrence risk with positive axillary lymph nodes, although not all individuals benefit equally from chemotherapy, and some derive no benefit. The 21-gene Oncotype DX Recurrence Score assay is a diagnostic test performed on breast tumor tissue that was developed to identify those at highest risk of recurrence and most likely to benefit or not benefit from adjuvant chemotherapy. The test measures the RNA levels in the tumor for 21 specific genes, with the level of RNA expression correlating with the activity of DNA that comprise genes in the tumor. The result is reported as a score ranging from 0-100, where a score of 26 or higher is associated with a very high recurrence risk and chemotherapy benefit, and a score of 25 or lower associated with a lower recurrence risk and no or little chemotherapy benefit. TAILORx and RxPONDER are two landmark federally funded clinical trials that were designed to test whether the Recurrence Score could be used to guide chemotherapy use. The two trials collectively included 14,827 women with ER-positive, HER2-negative early breast cancer and either O (TAILORx; n=9719) or 1-3 (RxPONDER; n=5108) positive axillary nodes. Prior to the availability of the test and the trial results, most women were advised to receive adjuvant chemotherapy. The studies showed that cancer recurrence rates were similar for adjuvant endocrine therapy compared with chemotherapy plus endocrine therapy for women with a RS 11-25 and O positive nodes (TAILORx), and also in postmenopausal women with a RS 0-25 and 1-3 positive nodes (RxPONDER); recurrence rates were also very low with endocrine therapy alone in those with a RS 0-10 and O positive axillary nodes (TAILORx). However, there was some benefit for chemotherapy in premenopausal women in RxPONDER and a RS of 0-25 (with higher RS in this range associated with greater chemotherapy benefit), and in a subset of premenopausal women in TAILORx, including those with a RS 21-25 or RS 16-20 and high clinical risk features (eg, larger tumor size, higher tumor grade). Racial disparities in outcome were noted in both trials, despite similar adherence to endocrine therapy, with Black women exhibiting significantly higher recurrence rates. In addition, a recent update of the TAILORx results indicated that there was a 2.5-fold higher risk of late recurrence more than 5 years after diagnosis compared with early recurrence within 5 years, and that Black women had higher rates of early but not late recurrence. Patients with RS of 26-100 were excluded from RxPONDER, although 471 patients enrolled at U.S. trial sites provided written informed consent to be contacted for future research. RNA extracted for the 21-gene RS assay required for trial entry has been stored in accordance with best practices, is of sufficient quantity and quality from both trials for additional gene expression assays, and will be used for this project. Our ultimate goals for this project are: (Aim 1) to have as complete follow-up as possible out to 15 years for TAILORx, and 10 years for RxPONDER (including the RS 26-100 group); and (Aim 2) to perform a prospective validation study of the new gene expression test, called the Sensitivity to Endocrine Therapy (SET) Index, to allow great
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310573
Entities
People
- William Symmans
Organizations
- The University of Texas MD Anderson Cancer Center
- United States Army