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Breast Cancer Research and Treatment

, Volume 167, Issue 1, pp 59–71 | Cite as

Outcome after neoadjuvant chemotherapy in estrogen receptor-positive and progesterone receptor-negative breast cancer patients: a pooled analysis of individual patient data from ten prospectively randomized controlled neoadjuvant trials

  • Marion T. van MackelenberghEmail author
  • Carsten Denkert
  • Valentina Nekljudova
  • Thomas Karn
  • Christian Schem
  • Frederik Marmé
  • Elmar Stickeler
  • Christian Jackisch
  • Claus Hanusch
  • Jens Huober
  • Peter A. Fasching
  • Jens-Uwe Blohmer
  • Sherko Kümmel
  • Volkmar Müller
  • Andreas Schneeweiss
  • Michael Untch
  • Gunter von Minckwitz
  • Karsten E. Weber
  • Sibylle Loibl
Clinical trial

Abstract

Purpose

The estrogen receptor (ER) is involved in control of progesterone receptor (PgR) expression and lack of PgR may be also a surrogate of altered growth factor signaling. The aim of this study was therefore to investigate PgR expression as predictive factor for response to neoadjuvant therapy and long-term outcome.

Methods

Five thousand and six hundred and thirteen patients with primary breast cancer and positive ER expression from ten German neoadjuvant trials of anthracycline and taxane-based chemotherapy were included. Pathologic complete response (pCR), disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and local recurrence-free survival (LRFS) were compared according to PgR expression.

Results

The lack of PgR expression (1172 patients) was associated with grade 3 (38.4 vs. 26.3%; p < 0.001), nodal involvement (>cN2) (6.8% vs. 4.7%; p = 0.004), and HER2 positivity (36.2 vs. 22.3%; p < 0.001). pCR rates of PgR-negative tumors were higher in the entire cohort (13.8 vs. 7.5%; p < 0.001) and in the HER2-negative subgroup (11.2 vs. 5.8%; p < 0.001). In multivariable logistic regression, PgR negativity was an independent predictive factor for pCR overall (OR 1.76; p < 0.001) and in the HER2-negative patients (OR 1.99; p < 0.001). Patients with PgR-negative disease had significantly worse outcome (p < 0.001, respectively). Multivariable Cox regression analysis revealed that PgR was an independent prognostic factor for DFS, OS, DDFS, and LRFS.

Conclusion

ER-positive/PgR-negative breast carcinomas are associated with higher response but also worse long-term outcome after neoadjuvant therapy. PgR negativity is an independent predictive factor for pCR after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer.

Keywords

Breast cancer Progesterone receptor Neoadjuvant chemotherapy Outcome 

Notes

Acknowledgements

We would like to thank all patients, investigators, and study personnel who supported the trials and the German Breast Group for support.

Funding

This study was supported by a Grant from the German Cancer Aid (Translational Oncology project 111536, TransLuminal-B).

Compliance with ethical standards

Conflict of interest

Peter Fasching is a consultant for Novartis, Pfizer, and Roche and receives funding from Novartis. Claus Hanusch is a consultant for Roche, Pfizer Amgen, Asrazeneca, Celgene, and Novartis. Sherko Kuemmel is a consultant for Roche, Amgen, Novartis, Genomic Health, Cellgene, Tewa, and Dairdi-Saulay and receives funding from Roche. Frederik Marme acts as a consultant for Roche, AstraZeneca, Novartis, Amgen, and Genomic Health and receives remuneration from the aforementioned companies. All remaining authors declare that there exists no conflict of interest.

Supplementary material

10549_2017_4480_MOESM1_ESM.docx (268 kb)
Supplementary material 1 (DOCX 268 kb)
10549_2017_4480_MOESM2_ESM.docx (270 kb)
Supplementary material 2 (DOCX 269 kb)

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Marion T. van Mackelenbergh
    • 1
    • 4
    Email author
  • Carsten Denkert
    • 2
  • Valentina Nekljudova
    • 1
  • Thomas Karn
    • 3
  • Christian Schem
    • 4
  • Frederik Marmé
    • 5
  • Elmar Stickeler
    • 6
  • Christian Jackisch
    • 7
  • Claus Hanusch
    • 8
  • Jens Huober
    • 9
  • Peter A. Fasching
    • 10
  • Jens-Uwe Blohmer
    • 2
  • Sherko Kümmel
    • 11
  • Volkmar Müller
    • 12
  • Andreas Schneeweiss
    • 5
  • Michael Untch
    • 13
  • Gunter von Minckwitz
    • 1
  • Karsten E. Weber
    • 1
  • Sibylle Loibl
    • 1
  1. 1.German Breast Group, c/o GBG Forschungs GmbHNeu-IsenburgGermany
  2. 2.Charite Berlin, Institute of Pathology and German Cancer Consortium (DKTK), Partner SiteBerlinGermany
  3. 3.Universitätsklinikum FrankfurtFrankfurtGermany
  4. 4.Universitätsklinikums Schleswig-Holstein KielKielGermany
  5. 5.Universitätsklinikum HeidelbergHeidelbergGermany
  6. 6.Universitätsklinikum AachenAachenGermany
  7. 7.Sana Klinikum OffenbachOffenbachGermany
  8. 8.Universitätsklinikum MünchenMunichGermany
  9. 9.Universitätsklinikum UlmUlmGermany
  10. 10.Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMNFriedrich-Alexander University Erlangen-NurembergErlangenGermany
  11. 11.Kliniken Essen MitteEssenGermany
  12. 12.Universitätsklinikum HamburgHamburgGermany
  13. 13.Helios Kliniken Berlin-BuchBerlinGermany

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