Patients with hormone receptor-positive breast cancer at high risk for recurrence by traditional parameters, but with a low 21-gene Recurrence Score (RS) can safely avoid chemotherapy, according to results of the phase III PlanB trial.
In this prospective trial, patients with intermediate to high risk breast cancer receiving adjuvant chemotherapy based on RS and those receiving no adjuvant chemotherapy based on RS of 11 or less had similar 3-year disease-free survival (DFS) rates.
In patients with pN0 to 1 breast cancer, 3-year DFS was 98.4% (95% CI, 97.0% to 99.8%) for patients with RS of 11 or less (no adjuvant chemotherapy); 97.5% (95% CI, 95.9% to 99.0%) for RS of 12 to 25 (with adjuvant chemotherapy); and 94.9% (95% CI, 91.4% to 98.4%) for RS greater than 25 (with adjuvant chemotherapy) (P = .05 for RS greater than 25 vs. others).
“The most important finding in our study is the high 3-year DFS (98%) in patients with low RS (11 or less) and no chemotherapy, despite being high risk by traditional parameters. Even with an only 3-year follow-up, such a high rate of DFS almost excludes possible benefit from adjuvant chemotherapy,” wrote Dr. Oleg Gluz of the West German Study Group, Breast Center Niederrhein, Evangelical Hospital Bethesda, Germany, and colleagues (J Clin Oncol 2016 Feb 29. doi: 10.1200/JCO.2015.63.5383 ).
Univariate analysis showed RS to be a prognostic factor for DFS, along with nodal status, grade, concentration of the Ki-67 protein encoded by the MKI67 gene, estrogen and progesterone receptor status, and tumor size. In multivariate analysis, fractionally ranked RS was associated with DFS (hazard ratio [HR], 1.68; 95% CI, 1.04 to 2.74; P = .035), as were node status (pN1-3 vs. pN0: HR, 2.45; 95% CI, 1.39 to 4.29, P = .001) and centrally-determined grade (G3 vs. G1 and G2: HR, 2.27; 95% CI, 1.28 to 4.02; P = .005).
The study demonstrated substantial disagreement in grade assessment by central vs. local pathology reviews, with 44% discordance in locally HR-positive tumors. Investigators suggest that use of RS may help to make treatment decisions more homogeneous and reliable, regardless of where patients are treated.
The results suggest that patients N0 to N1 breast cancer with low RS scores derive little benefit from adjuvant chemotherapy, but benefits for patients with intermediate RS scores (12 to 25) are unclear. Prospective trials are underway to address this question.
The prospective, randomized PlanB trial recruited 3,198 patients from 93 German centers from 2009 to 2011. RS scores were available for 2,568 patients with HR-positive, HER2-negative, intermediate to high risk breast cancer. In total, 18.1% had RS of 11 or less, 60.4% had RS from 12 to 25, and 21.6% had RS greater than 25.
Research was supported by Genomic Health, Sanofi Aventis, and Amgen. Dr. Gluz reported consulting or advisory roles with Genomic Health and NanoString Technologies. Several of his coauthors reported ties to industry sources.
