Breast Cancer Research and Treatment

, Volume 139, Issue 3, pp 759–767 | Cite as

Molecular subtyping of early-stage breast cancer identifies a group of patients who do not benefit from neoadjuvant chemotherapy

  • Stefan Glück
  • Femke de Snoo
  • Justine Peeters
  • Lisette Stork-Sloots
  • George Somlo
Clinical trial


The aim of this study was to analyze the correlation between the pathologic complete response (pCR) rate after neoadjuvant chemotherapy and long-term outcome (distant metastases-free survival [DMFS]) in patients with early-stage breast cancer using BluePrint and MammaPrint molecular subtyping versus clinical subtyping using immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) for the determination of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 (HER2). Data were analyzed from 437 patients in four neoadjuvant chemotherapy trials. BluePrint and MammaPrint outcomes were determined from 44K Agilent arrays, the I-SPY 1 data portal, or Affymetrix U133A arrays. The pCR rate differed substantially among BluePrint molecular subgroups: 6 % in Luminal A-type, 10 % in Luminal B-type, 47 % in HER2-type, and 37 % in Basal-type patients. In the Luminal A-type group (n = 90; including seven HER2-positive patients and eight triple-negative patients by IHC/FISH), the 5-year DMFS rate was 93 %. The pCR rate provided no prognostic information, suggesting these patients may not benefit from chemotherapy. Forty-three of 107 (40 %) HER2-positive patients were classified as Luminal-type by BluePrint and may have lower response rates to targeted therapy. Molecular subtyping identified 90 of 435 (21 %) patients as Luminal A-type (BluePrint Luminal-type/MammaPrint Low Risk) with excellent survival. The pCR rate provided no prognostic information. Molecular subtyping can improve the stratification of patients in the neoadjuvant setting: Luminal A-type (MammaPrint Low Risk) patients have a good prognosis with excellent survival and do not seem to benefit from chemotherapy. We observed marked benefit in response and DMFS to neoadjuvant treatment in patients subtyped as HER2-type and Basal-type. BluePrint with MammaPrint molecular subtyping helps to improve prognostic estimation and the choice of therapy versus IHC/FISH.


BluePrint (80-gene profile) Early-stage breast cancer MammaPrint (70-gene profile) Molecular subtyping Prognosis Response 



Doxorubicin, cyclophosphamide, carboplatin, and nab-paclitaxel


Distant metastases-free survival


Estrogen receptor


Early-stage breast cancer


Food and drug administration


Fluorescence in situ hybridization


Human epidermal growth factor receptor-2


Hormone receptor




Locally advanced breast cancer


Pathologic complete response


Progesterone receptor


Docetaxel, doxorubicin, and cyclophosphamide



This study was funded by an unrestricted grant from Agendia. The City of Hope trial was supported by American Bioscience (now Celgene). The authors would like to thank Kevin De-Voy (freelance medical writer funded by Agendia) for writing support.

Conflict of interest

SG has received research support from and been an advisory board member for Agendia and Genomic Health Inc. FdS, JP, and LS-S are employees of Agendia. GS had received grants from the National Institutes of Health and has been an advisory board member and speaker for Celgene and Genentech. George Somlo has received research support from Celgene.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Stefan Glück
    • 1
  • Femke de Snoo
    • 2
  • Justine Peeters
    • 2
  • Lisette Stork-Sloots
    • 2
  • George Somlo
    • 3
  1. 1.Sylvester Comprehensive Cancer CenterUniversity of MiamiMiamiUSA
  2. 2.AgendiaAmsterdamThe Netherlands
  3. 3.Department of Medical Oncology, Therapeutics ResearchCity of Hope Cancer CenterDuarteUSA

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