Journal Article

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

Clemens, Michael, Malter, Wolfram, Lorenz-Salehi, Fatemeh, Kreipe, Hans H., Gluz, Oleg, Just, Marianne, Nuding, Benno, Wuerstlein, Rachel, Augustin, Doris, Kuemmel, Sherko, Stefek, Andrea, Liedtke, Cornelia, Aktas, Bahriye, Christgen, Matthias, Krabisch, Petra, Shak, Steven, Reimer, Toralf, Harbeck, Nadia, Chao, Calvin, Kates, Ronald E., Nitz, Ulrike

2017

Overview

Background 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. Methods 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. Findings 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. Interpretation 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.

• Publisher: Springer US,Springer,Springer Nature B.V
• Subject: Adjuvant treatment / Adolescent / Adult / Aged / Anthracycline / Anthracyclines / Banks (Finance) / Biomarkers, Tumor / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - genetics / Breast Neoplasms - pathology / Cancer / Cancer patients / Cancer research / Care and treatment / Chemotherapy / Chemotherapy, Adjuvant / Clinical Trial / Clinical Trials, Phase III as Topic / Endocrine therapy / ErbB-2 protein / Female / Genetic Predisposition to Disease / Genetic screening / Germany / Humans / Medical prognosis / Medicine / Medicine & Public Health / Middle Aged / Multivariate analysis / Neoplasm Grading / Neoplasm Staging / Oncology / Progesterone / Prognosis / Prospective Studies / Randomized Controlled Trials as Topic / Risk / Survival / Survival Analysis / Treatment Outcome / Tumors / Workflow / Young Adult