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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

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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.

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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).

Author information

Authors and Affiliations

  1. German Breast Group, c/o GBG Forschungs GmbH, Martin-Behaim-Straße 12, 63263, Neu-Isenburg, Germany

    Marion T. van Mackelenbergh, Valentina Nekljudova, Gunter von Minckwitz, Karsten E. Weber & Sibylle Loibl

  2. Charite Berlin, Institute of Pathology and German Cancer Consortium (DKTK), Partner Site, Berlin, Germany

    Carsten Denkert & Jens-Uwe Blohmer

  3. Universitätsklinikum Frankfurt, Frankfurt, Germany

    Thomas Karn

  4. Universitätsklinikums Schleswig-Holstein Kiel, Kiel, Germany

    Marion T. van Mackelenbergh & Christian Schem

  5. Universitätsklinikum Heidelberg, Heidelberg, Germany

    Frederik Marmé & Andreas Schneeweiss

  6. Universitätsklinikum Aachen, Aachen, Germany

    Elmar Stickeler

  7. Sana Klinikum Offenbach, Offenbach, Germany

    Christian Jackisch

  8. Universitätsklinikum München, Munich, Germany

    Claus Hanusch

  9. Universitätsklinikum Ulm, Ulm, Germany

    Jens Huober

  10. Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

    Peter A. Fasching

  11. Kliniken Essen Mitte, Essen, Germany

    Sherko Kümmel

  12. Universitätsklinikum Hamburg, Hamburg, Germany

    Volkmar Müller

  13. Helios Kliniken Berlin-Buch, Berlin, Germany

    Michael Untch

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  1. Marion T. van Mackelenbergh
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Corresponding author

Correspondence to Marion T. van Mackelenbergh.

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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.

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van Mackelenbergh, M.T., Denkert, C., Nekljudova, V. et al. 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. Breast Cancer Res Treat 167, 59–71 (2018). https://doi.org/10.1007/s10549-017-4480-5

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