Clinical Outcomes in Early Breast Cancer With a High 21-Gene Recurrence Score of 26 to 100 Assigned to Adjuvant Chemotherapy Plus Endocrine Therapy

Abstract

IMPORTANCE A high 21-gene recurrence score (RS) by breast cancer assay is prognostic for distant recurrence of early breast cancer after local therapy and endocrine therapy alone, and for chemotherapy benefit. OBJECTIVE To describe clinical outcomes for women with a high RS who received adjuvant chemotherapy plus endocrine therapy in the TAILORx trial, a population expected to have a high distant recurrence rate with endocrine therapy alone. DESIGN, SETTING, AND PARTICIPANTS In this secondary analysis of data from a multicenter randomized clinical trial, 1389 women with hormone receptor-positive, ERBB2-negative, axillary node-negative breast cancer, and a high RS of 26 to 100 were prospectively assigned to receive adjuvant chemotherapy in addition to endocrine therapy. The analysis was conducted on May 12, 2019. INTERVENTIONS The adjuvant chemotherapy regimen was selected by the treating physician. MAIN OUTCOMES AND MEASURES Freedom from recurrence of breast cancer at a distant site, and freedom from recurrence, second primary cancer, and death (also known as invasive disease-free survival [IDFS]). RESULTS Among the 9719 eligible women, with a mean age of 56 years (range 23-75 years), 1389 (14%) had a recurrence score of 26 to 100, of whom 598 (42%) had an RS of 26 to 30 and 791 (58%) had an RS of 31 to 100. The most common chemotherapy regimens included docetaxel/cyclophosphamide in 589 (42%), an anthracycline without a taxane in 334 (24%), an anthracycline and taxane in 244 (18%), cyclophosphamide/methotrexate/5-fluorouracil in 52 (4%), other regimens in 81 (6%), and no chemotherapy in 89 (6%). At 5 years, the estimated rate of freedom from recurrence of breast cancer at a distant site was 93.0% (standard error [SE], 0.8%), freedom of recurrence of breast cancer at a distant and/or local regional site 91.0% (SE, 0.8%), IDFS 87.6% (SE, 1.0%), and overall survival 95.9% (SE, 0.6%). CONCLUSIONS AND RELEVANCE The estimated rate of freedom from recurrence of breast cancer at a distant site in women with an RS of 26 to 100 treated largely with taxane and/or anthracycline-containing adjuvant chemotherapy regimens plus endocrine therapy in the prospective TAILORx trial was 93% at 5 years, an outcome better than expected with endocrine therapy alone in this population. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00310180

The 21-Gene Recurrence Score Assay and Prediction of Chemotherapy Benefit: A Propensity Score-Matched Analysis of the SEER Database

“…Given these findings, the 21-gene RS assay has already had a significant impact on treatment decisions [14][15][16], overall use of chemotherapy [16][17][18], and survival of patients [19]. For patients with an intermediate RS, results from the recent prospective Trial Assigning Individualized Options for Treatment (TAILORx) trial [20], which was designed to test whether chemotherapy is beneficial for patients with hormone receptor-positive, HER2 (human epidermal growth factor receptor 2)-negative, node-negative BC who had a mid-range 21-gene RS (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), new intermediate score), revealed that adjuvant endocrine therapy alone was non-inferior to chemo-endocrine therapy in the analysis of invasive disease-free survival (IDFS). Results from a subgroup analysis suggested that chemotherapy may be of some benefit for patients 50 years of age or younger with an RS of 16-25.…”

Prognostic Predictors Do Not Equate to Predictors of Chemotherapy Benefit in HR-Positive, HER2-Negative Breast Cancer: A Population-Based Study

“…In a secondary analysis of the TAILORx trial, 1389 patients with HR+, HER2-, N0 breast cancer who had a high RS of 26 or more were identi ed and 89 of the patients had no chemotherapy [27]. The study reported that patients without chemotherapy had a worse prognosis in invasive disease-free survival (IDFS) than patients with chemotherapy (HR with 95% CI: 0.48, 0.29-0.80), rather than freedom from recurrence at a distant site (HR with 95% CI: 0.74, 0.32-1.69).…”

A nomogram to predict the high-risk RS in HR+/HER2-breast cancer patients older than 50 years of age

“…In the current study, we set RS > 25 as the objective of prediction because this was used for de ning high-risk RS in the prospective TAILORx trial. We postulate that the chemotherapy should be included in treatment for patients with an RS of 26-30 since in the TAILORx trial those patients were assigned to use chemotherapy and had better clinical results than expected outcomes with endocrine monotherapy (18). Moreover, we only included patients > 50 years, because in patients of 50 years of age or younger some chemotherapy bene t could be found in those had an RS of 16-25 (6).…”