Clinical Outcomes in Early Breast Cancer With a High 21-Gene Recurrence Score of 26 to 100 Assigned to Adjuvant Chemotherapy Plus Endocrine Therapy: A Secondary Analysis of the TAILORx Randomized Clinical Trial

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.

Conflict of interest statement

Conflict of interest Disclosures: Dr Sparano reported grants from National Cancer Institute during the conduct of the study. Dr Gray reported grants from National Cancer Institute and funding from Genomic Health during the conduct of the study. Dr Albain reported personal fees from Novartis, personal fees from Pfizer, personal fees from Myriad, personal fees from Genomic Health, personal fees from Genentech Roche, personal fees from Puma, and grants from Seattle Genetics outside the submitted work. Dr Badve reported speaker fees from Genomic Health outside the submitted work. Dr Wagner reported personal fees from Celgene outside the submitted work. Dr Kaklamani reported personal fees from Genomic Health, personal fees from Pfizer, personal fees from Celgene, personal fees from Genentech, personal fees from Novartis, personal fees from Puma, grants and personal fees from Eisai, personal fees from Athenex, personal fees from Amgen, personal fees from Celldex, and personal fees from AstraZeneka outside the submitted work. Dr Gomez reported personal fees from Roche, personal fees from Novartis, and personal fees from AstraZeneca outside the submitted work. Dr Mayer reported grants from Pfizer, grants and personal fees from Novartis, grants and personal fees from Genentech, personal fees from Lilly, personal fees from GSK, personal fees from AstraZeneca, personal fees from Immunomedics, personal fees from Macrogenics, and personal fees from Seattle Genetics outside the submitted work. Dr Toppmeyer reported spousal employment at Novartis and Merck outside the submitted work. Dr Brufsky reported personal fees from Genomic Health during the conduct of the study; personal fees from Agendia, personal fees from Biotheranotics, and personal fees from Myriad outside the submitted work. Dr Goetz reported personal fees from Genomic Health during the conduct of the study; grants and consulting fees from Lilly, grants and consulting fees from Pfizer, consulting fees from Novartis, grants and consulting fees from Sermonix, consulting fees from Biotheranostics, Context Pharm, and Biovica outside the submitted work. Dr Desbiens reported AD board meeting with Pfizer CIE. Dr Hayes reported grants from SWOG/NCI during the conduct of the study; personal fees from Cepheid, personal fees from Freenome, personal fees from Cellworks, grants from Agendia, grants from Merrimack, grants from Eli LIlly, grants from Menarini Silicon Biosystems, grants from Pfizer, and grants from AstraZeneca outside the submitted work; and patents held by his university, not related to this work. Dr Geyer reported grants from the National Cancer Institute during the conduct of the study. Dr Paik reports a patent issued and licensed to Genomic Health, with all rights transferred to the NSABP Foundation. No other disclosures were reported.

Figures

Figure.. Kaplan-Meier Curves for Freedom From Recurrence of Breast Cancer at a Distant Site and Invasive Disease-Free Survival (IDFS)

CMF Indicates cyclophosphamide/methotrexate/5-fluorouracil; NS, not specified; TC, taxane and cyclophosphamide.