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. 2017 Oct;165(3):573-583.
doi: 10.1007/s10549-017-4358-6. Epub 2017 Jun 29.

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

Ulrike Nitz  1   2 , Oleg Gluz  3   4 , Matthias Christgen  5 , Ronald E Kates  1 , Michael Clemens  6 , Wolfram Malter  7 , Benno Nuding  8 , Bahriye Aktas  9 , Sherko Kuemmel  10 , Toralf Reimer  11 , Andrea Stefek  12 , Fatemeh Lorenz-Salehi  13 , Petra Krabisch  14 , Marianne Just  15 , Doris Augustin  16 , Cornelia Liedtke  1   17 , Calvin Chao  18 , Steven Shak  18 , Rachel Wuerstlein  1   19 , Hans H Kreipe  5 , Nadia Harbeck  1   19
Affiliations

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

Ulrike Nitz et al. Breast Cancer Res Treat. 2017 Oct.

Erratum in

Abstract

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.

Keywords: Breast cancer; Genomic signature; IHC4; Ki-67; Oncotype DX.

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Conflict of interest statement

HK received honoraria from Roche, Genomic Health, Novartis, and Astra-Zeneca. The West German Study group provided grant for central pathology work (to HK). RW received honoraria from Roche, Celgene, Novartis, Genomic Health, Amgen, MSD, Pfizer, and Pierre Fabre. NH received honoraria from Genomic Health, Nanostring and, Agendia. OG received honoraria from Genomic Health, Nanostring, and Roche. UN (as a representative of the WSG) received grants from Genomic Health, Sanofi Aventis, and Amgen for the conduct of the trial and received honoraria from Genomic Health, Agendia, Nanostring, Amgen, and Sanofi Aventis. CL and SK received honoraria from Genomic Health. All the other authors (TR, MJ, MC, MC) have declared that they have no conflict of interest. SS is an employee and a shareholder of Genomic Health (SS patent rights assigned to Genomic Health). CC is an employee of Genomic Health. All the other authors had nothing to disclose.

Figures

Fig. 1
Fig. 1
PlanB CONSORT diagram. CT chemotherapy, ET endocrine therapy, HR hormone receptor, RS recurrence score
Fig. 2
Fig. 2
DFS for patients with RS ≤ 11, 12–25, and > 25 overall (a), node-negative patients (b), for patients with pN1 disease (c), and for patients with pN2-3 disease (d)
Fig. 3
Fig. 3
OS for patients with RS ≤ 11, 12–25, and > 25 overall (a), for node-negative patients (b), for patients with pN1 disease (c), and for patients with pN2-3 disease (d)
Fig. 4
Fig. 4
DFS in HR+/Ki-67 0–10% group (a) and in HR+/Ki-67 > 10% and <40% (b)
Fig. 5
Fig. 5
DFS by central Ki-67 expression levels in centrally HR+ patients. DFS in the triple-negative (centrally ER/PR/HER2-negative) subgroup is included for comparison
See this image and copyright information in PMC

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