Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial

• DOI: 10.1007/s10549-017-4358-6
• Publication Date: 2017-06-29T16:53:14Z
• Authors: Ulrike Nitz; Oleg Gluz; Matthias Christgen; Ronald E. Kates; Michael Clemens; Wolfram Malter; Benno Nuding; Bahriye Aktas; Sherko Kuemmel; Toralf Reimer; Andrea Stefek; Fatemeh Lorenz-Sa...; Petra Krabisch; Marianne Just; Doris Augustin; Cornelia Liedtke; Calvin Chao; Steven Shak; Rachel Wuerstlein; Hans H. Kreipe; Nadia Harbeck
• Keywords: Adult; Risk; Adolescent; Medizin; Breast Neoplasms; Middle Aged; Clinical Trial; Survival Analysis; Workflow; 3. Good health; Treatment Outcome; Clinical Trials, Phase III as Topic; Chemotherapy, Adjuvant; Germany; Biomarkers, Tumor; Humans; Female; Genetic Predisposition to Disease; Prospective Studies; Neoplasm Grading; Aged; Neoplasm Staging; Randomized Controlled Trials as Topic

The prospective phase 3 PlanB trial used the Oncotype DX® Recurrence Score® (RS) to define a genomically low-risk subset of clinically high-risk pN0-1 early breast cancer (EBC) patients for treatment with adjuvant endocrine therapy (ET) alone. Here, we report five-year data evaluating the prognostic value of RS, Ki-67, and other traditional clinicopathological parameters.A central tumour bank was prospectively established within PlanB. Following an early amendment, hormone receptor (HR)+ , pN0-1 RS ≤ 11 patients were recommended to omit chemotherapy. Patients with RS ≥ 12, pN2-3, or HR-negative/HER2-negative disease were randomised to anthracycline-containing or anthracycline-free chemotherapy. Primary endpoint: disease-free survival (DFS). PlanB Clinicaltrials.gov identifier: NCT01049425.From 2009 to 2011, PlanB enrolled 3198 patients (central tumour bank, n = 3073) with the median age of 56 years, 41.1% pN+, and 32.5% grade 3 EBC. Chemotherapy was omitted in 348/404 (86.1%) eligible RS ≤ 11 patients. After 55 months of median follow-up, five-year DFS in ET-treated RS ≤ 11 patients was 94% (in both pN0 and pN1) versus 94% (RS 12-25) and 84% (RS > 25) in chemotherapy-treated patients (p < 0.001); five-year overall survival (OS) was 99 versus 97% and 93%, respectively (p < 0.001). Nodal status, central/local grade, tumour size, continuous Ki-67, progesterone receptor (PR), IHC4, and RS were univariate prognostic factors for DFS. In a multivariate analysis including all univariate prognostic markers, only pN2-3, central and local grade 3, tumour size >2 cm, and RS, but not IHC4 or Ki-67 were independent adverse factors. If RS was excluded, IHC4 or both Ki-67 and PR entered the model. The impact of RS was particularly pronounced in patients with intermediate Ki-67 (>10%, <40%) tumours.The excellent five-year outcomes in clinically high-risk, genomically low-risk (RS ≤ 11) pN0-1 patients without adjuvant chemotherapy support using RS with standardised pathology for treatment decisions in HR+ HER2-negative EBC. Ki-67 has the potential to support patient selection for genomic testing.