Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer

Abstract

Background: The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score.

Methods: We performed a prospective trial involving 10,273 women with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease-free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death).

Results: Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease-free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval, 0.94 to 1.24; P=0.26). At 9 years, the two treatment groups had similar rates of invasive disease-free survival (83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group), freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local-regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). The chemotherapy benefit for invasive disease-free survival varied with the combination of recurrence score and age (P=0.004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25.

Conclusions: Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who had a midrange 21-gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger. (Funded by the National Cancer Institute and others; TAILORx ClinicalTrials.gov number, NCT00310180 .).

Figure 1.. Registration, Randomization, and Follow-up.

All the patients who met the eligibility criteria and provided written informed consent were preregistered; a primary tumor specimen was subsequently obtained and sent to the Genomic Health laboratory for the 21-gene assay. On receipt of the assay report and recurrence-score result by the treating physician, the enrolling site then assigned patients to a treatment group. If the recurrence score was 10 or lower, the patient was assigned to receive endocrine therapy alone. If the recurrence score was 26 or higher, the patient was assigned to receive chemoendocrine therapy. If the recurrence score was 11 to 25, the patient underwent randomization and was assigned to receive either endocrine therapy or chemoendocrine therapy. The stratification factors that were used in randomization were tumor size (≤2 cm vs. >2 cm), menopausal status (pre- vs. postmenopausal), planned chemotherapy (taxane-containing vs. not), planned radiation therapy (whole breast and no boost irradiation planned vs. whole breast and boost irradiation planned vs. partial breast irradiation planned vs. no planned radiation therapy for patients who had undergone a mastectomy), and recurrence-score group (11 to 15 vs. 16 to 20 vs. 21 to 25), which was added midway through the trial.

Figure 2.. Clinical Outcomes among Patients with a Recurrence Score of 11 to 25.

Kaplan–Meier estimates of survival rates in the analysis according to the assigned treatment group are shown for the group that received endocrine therapy alone and the group that received chemoendocrine therapy in the intention- to-treat analysis of invasive disease–free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death) and freedom from recurrence of breast cancer at a distant site. The hazard ratios are for the endocrine-therapy group versus the chemoendocrine-therapy group.